Can Urban Universities Be Better Neighbors? Proteinases and Their Inhibitors

Vol. 20 / No. 2 / February 2021

Can urban universities be better neighbors? Proteinases and their inhibitors

Feb. 24–26

This meeting covers diverse and vibrant fields of protease research, such as mechanistic studies on proteases in their molecular, cellular and organismic context. Sessions include: • proteolysis in cancer • proteolysis in neurosignaling and neurodegeneration • proteolysis in blood coagulation • discovery of protease substrates • mechanisms and engineering of proteases, ligases, their substrates and inhibitors

Regular registration deadline: Feb. 22

Learn more and register at: asbmb.org/meetings-events/proteinases-and-their-inhibitors CONTENTS

NEWS FEATURES PERSPECTIVES

2 28 46 PRESIDENT’S MESSAGE CAN URBAN UNIVERSITIES #BLACKINX TWITTER MOVEMENT Miller named ASBMB executive director BE BETTER NEIGHBORS? CREATES VISIBILITY 3 FOR BLACK SCIENTISTS MEMBER UPDATE 38 SECURING SPACE FOR 48 THE EVOLUTION OF PROTEINS BLACK WOMEN SCIENTISTS FROM MYSTERIES TO MEDICINES 10 IN A CROOKED ROOM IN MEMORIAM 50 11 41 LEARNING TO BE NEWS ‘EVERY EXPERIMENT AND EVERY A SCIENCE SUPERHERO 11 Establishing connections — BREAKTHROUGH MATTERS’ from people to synapses 54 12 10 young scientists win ESSAY PROLAB awards Project SHORT shares know-how 15 Sewer scholarship program funding doubled 18 Increasing diversity to improve 55 health care — for all of us FIVE QUESTIONS Douglas Storts: Giving labs the tools 20 to be successful JOURNAL NEWS 20 The vaccine race heats up 21 Vision health depends on fat 22 A mold’s dangerous responses to its environment 23 From the journals 28 46

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FEBRUARY 2021 ASBMB TODAY 1 PRESIDENT’S MESSAGE

Vol. 20 / No. 2 / February 2021

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Miller named ASBMB THE MEMBEROFFICERS MAGAZINE OFCOUNCIL THE AMERICAN MEMBERS SOCIETY FOR BIOCHEMISTRY ANDSuzanne MOLECULAR Barbour BIOLOGY Toni M. Antalis President Joan Broderick executive director Charles Craik GeraldOFFICERS Hart COUNCIL MEMBERS Matt Gentry PastGerald President Hart Squire J. Booker Susanna Greer President Victoria J. DeRose By Toni Antalis Wei Yang AudreyBlake Lamb Hill Secretary Jennifer DuBois JamesAudrey M. Ntambi Lamb Secretary n behalf of the American Joan Conaway TakitaJames Felder M. Ntambi Sumter Celia A. Shiffer Society for Biochemistry and Toni TreasurerM. Antalis Kelly Ten–Hagen Treasurer Takita Felder Sumter OMolecular Biology Council, I Kelly Ten-Hagen EX-OFFICIO MEMBERS ASBMBJoAnn TODAY Trejo EDITORIAL am pleased to announce that Stephen EX-OFFICIO MEMBERS Robert S. Haltiwanger ADVISORY BOARD Miller, deputy executive director and Rajini Rao RobertCarla S. Haltiwanger Koehler ASBMB TODAY EDITORIAL chief financial officer of the ASBMB, Co-chairs, 2020/2021Carla Annual Koehler ChairADVISORY BOARD Co-chairs, 2020 Annual Meeting Program Committee AnaRajini Maria Rao Barral will be appointed to the position of Meeting Program Committee Cheryl Bailey NatashaChair Brooks executive director upon the retire- Chair, Education andCheryl Professional Bailey KellyFloyd Chacón “Ski” Chilton ment of the current executive director, DevelopmentChair, Education Committee and BerondaHenrik Montgomery Dohlman Professional Development Daniel Raben BillPeter Sullivan J. Kennelly Barbara Gordon. Committee Chair, Meetings Committee MelissaBeronda Vaught Montgomery Steve joined the society in July Daniel Raben A. Maureen Rouhi Sonia Flores Binks Wattenberg 2004 as the financial controller. Dur- STEPHEN MILLER Chair,Chair, Meetings Minority Committee Affairs Melissa Vaught CommitteeSonia Flores ASBMBBinks TODAY W. Wattenberg ing the succeeding years of his service Chair,Nicole Minority Woitowich Affairs Angela Hopp to the ASBMB, he held the positions leadership and move to open access. Chair, Science OutreachCommittee and ASBMB TODAY Executive Editor of director of finance and then chief In his new capacity as executive CommunicationSusannna Committee Greer Angela Hopp [email protected] Editor Chair,Terri Public Goss KinzyOutreach financial officer. He has become director, Steve will be shepherding the [email protected] Chair, PublicCommittee Affairs Comfort Dorn ManagingComfort Editor Dorn more involved in the journals and transition to open access for the AdvisoryMatthew Committee S. Gentry [email protected] Editor society operations as deputy executive ASBMB journals, developing a strate- Chair,Ed EisensteinPublic Affairs [email protected] Chair, MembershipAdvisory Committee Committee Laurel Oldach director. gic plan to guide the society through ScienceJohn Writter Arnst Sandra Weller Susan Baserga [email protected] Writer The ASBMB Council began the the next several years, and expanding Chair, WomenChair, in Biochemistry Publications [email protected] process of identifying a new executive the opportunities and benefits the and MolecularCommittee Biology Ed LaurelMarklin Oldach Committee WebScience Editor Writter director upon the announcement of society provides for its members. Lila M. Gierasch [email protected] Editor-in-chief,Sandra Weller JBC [email protected] Barbara’s retirement. With the major We warmly thank Barbara for her Chair, Publications Ed Marklin A. L. Burlingame Allison Frick Committee MultimediaWeb Editor and Social Media move of our journals to open access, many years of service and for her Editor, MCP [email protected] Lila M. Gierasch Content Manager as well as other anticipated op- long-lasting legacy in bringing the so- Nicholas O. Davidson Editor-in-chief, JBC [email protected] Frick Editor-in-chief, JLR Media Specialist erational enhancements, the council ciety to where it is today. We are also Barbara Gordon A. L. Burlingame [email protected] Kerry-AnneEditor, MCP Rye Executive Director considered continuity and experience deeply thankful for the commitment Editor-in-chief, JLR [email protected] Gordon Nicholas O. Davidson Executive Director with society operations to be critically and dedication of all of the ASBMB Editor-in-chief, JLR [email protected] important during this transition pe- staff during this time of transition as Kerry-Anne Rye riod. Based on Steve’s deep knowledge we open an exciting new chapter for Editor-in-chief, JLR of and commitment to the society, the the society. ForFor information information on on advertising, advertising, contact contact Pharmaceutical Pharmaceutical council made the decision to ask him Media Inc. at 212-904-0374 or [email protected]@pminy.com.. to take on the role of executive direc- Toni Antalis Toni Antalis tor, and we are delighted that he has ([email protected]) agreed to serve in this position for the is a professor of physiology next several years. at the University of Maryland School of Medicine, where she In early 2023, the ASBMB Coun- www.asbmb.org/asbmbtoday is also the associate director www.asbmb.org/asbmbtoday cil plans to initiate a wide-ranging for training and education PRINT ISSNISSN 2372-0409 2372-0409 search for the next, longer-term for the Greenebaum Cancer Center and the director of the ArticlesArticles published published in ASBMB in ASBMB Today Today reflect reflect solely solely the authors’the authors’ views viewsand not executive director. This plan will allow theand official not the official positions positionsof the American of the SocietyAmerican for BiochemistrySociety for Biochemistry and Molecular and graduate program in molecular BiologyMolecular or Biologythe institutions or the institutions with which with the authorswhich the are authors affiliated. are affiliated. Mentions of for an orderly transition of the society medicine. productsMentions or of services products are or not services endorsements. are not endorsements.

2 ASBMB TODAY FEBRUARY 2021 MEMBER UPDATE

Steitz receives and the American Academy of and international relations. Alrubaye, Microbiology and a member of the who teaches microbiology, animal Microbiology Society prize National Academy of Sciences and the bacteriology and prokaryote biology Joan Steitz, the Sterling professor National Academy of Medicine, Steitz to about 900 students annually and of molecular biophysics and biochem- has received many honors, including who recently was inducted into the istry at Yale University and a Howard the Lasker–Koshland Special Achieve- university’s teach- Hughes Medical Institute investigator, ment Award in Medical Science, ing academy, won will receive the 2021 prize medal from the National Medal of Science, the the faculty award. the United Kingdom’s Microbiology American Society for Cell Biology’s Alrubaye earned Society. E.B. Wilson Medal and the American bachelor’s and “Britain and British science Society for Biochemistry and Mo- master’s degrees have occupied a special spot in my lecular Biology’s 2015 Herb Tabor from the University heart ever since I was a postdoc- Research Award. of Baghdad in the toral researcher at the Laboratory for Steitz will receive her award and ALRUBAYE early 2000s. He Molecular Biology in Cambridge in present a lecture at the Microbiology went on to earn 1967–70,” Steitz told the Microbiol- Society’s annual conference in April, his master’s in secondary education ogy Society. “So much of my subse- which will be held online. and his Ph.D. in cell and molecular quent life and science were shaped biology at the University of Arkansas by my experiences Alrubaye wins award for Fayetteville campus, where he also there.” international education completed a postdoctoral stint. Steitz is known He has won numerous teaching for her studies Adnan Alrubaye of the University awards, including the university’s involving RNA, of Arkansas won the 2020 Hoyt H. Most Outstanding Faculty Member including insights Purvis Award for Service in Interna- award in 2019. into how ribo- tional Education. somes interact Alrubaye, a research assistant Fierke joins STEITZ with messenger professor and the associate director Brandeis leadership RNA and the for the university’s cell and molecular splicing of introns by small nuclear ri- biology program, is credited with Carol Fierke, who was until bonucleic proteins, or snRNPs, which having helped double the size of the recently a provost and executive vice occur in eukaryotes. As a postdoc, graduate program through recruit- president at Texas A&M Univer- she studied translation initiation in ment of students from the Middle sity, is now provost, executive vice bacterial systems. After joining the East and elsewhere. He has made president and chief faculty at Yale, she published her find- numerous trips abroad to meet with academic officer at ings demonstrating that ribosomes prospective students, government of- Brandeis Univer- use complementary base pairing to ficials and administrators at academic sity in Waltham, identify the start site on mRNA. Her and research institutes. Massachusetts. She discovery of the role of snRNPs and In a statement, Dean Patricia Koski assumed her new the related small nucleolar RNPs in said, “He has been a leader in com- duties Jan. 1. splicing explains why humans have munity international relations and in Fierke earned only double the number of genes of the Muslim community on campus, FIERKE her doctorate in a fruit fly. Her work could provide and he is dedicated to bringing differ- biochemistry at insights into diagnosis and treatment ent religions together for peace and Brandeis in 1984 and conducted of autoimmune disorders that develop understanding.” postdoctoral research at Pennsylvania when patients make anti-nuclear The Purvis award, which was State University. Her first faculty antibodies against their own DNA, issued to three members of the position was at Duke University, after snRNPs or ribosomes. university community during a Nov. which she spent almost 20 years as a A fellow of the National Associa- 19 ceremony online, is named after professor at the University of Michi- tion for the Advancement of Science an emeritus professor of journalism gan. Prior to moving to Texas A&M,

FEBRUARY 2021 ASBMB TODAY 3 MEMBER UPDATE

she served as Michigan’s chemistry departments where she has worked. itz praised Fierke’s management, department chair, vice provost and She received the 2020 Mildred research and mentoring skills in dean. Cohn Award in Biological Chemis- an article on the university’s website, Fierke’s research group studies try from the ASBMB and also has saying, “As a consensus builder with metalloenzymes in yeast and human been recognized with the American a demonstrated commitment to cells, including structural studies Chemical Society’s Repligen Award making institutions more diverse, of metal ions and substrates in the in the Chemistry of Biological Pro- equitable and inclusive, Dr. Fierke active site of catalytic RNAs and cesses and the Protein Society’s Emil is already a champion of the values proteins. She also has been com- Thomas Kaiser Award. that have defined the Brandeis committed to advancing diversity in the Brandeis President Ron Liebow- munity since 1948.”

York named Impossible Foods CSO Cortez takes over Vanderbilt John York, previously chair of the Vanderbilt Univer- biochemistry department sity department of biochemistry, recently left that role to David Cortez, Richard Armstrong professor for become the chief science officer at Impossible Foods. innovation in biochemistry at Vanderbilt University, The startup, founded by biochemist Pat Brown and is serving as the interim chair of Vanderbilt’s based in Oakland, California, department of biochemistry, effective Jan. 1. develops and markets plant- “The people in this department and at Vanderbilt based imitation meat. The make it special, and I will do everything I can to company has put consider- support them as they pursue their goals,” Cortez able effort into biochemical stated in a Vanderbilt press release. research to re-create the expe- Cortez received his Ph.D. from Duke University rience of eating meat, notably in molecular cancer biology, conducted postdoctoral incorporating a heme protein research at the Baylor College of Medicine, and from soy. The company is joined Vanderbilt as a young professor in 2002. outspoken about its mission His lab has studied YORK to combat climate change replication stress, DNA and other environmental damage responses problems by reducing meat consumption. and other pathways “The opportunity to use biochemistry to save the that control genome planet is a spectacular motivation,” York stated in a press stability and works release from Impossible Foods. on developing cancer York came to Vanderbilt from Duke University, where therapeutics that target he was a professor for 16 years and a Howard Hughes DNA damage pathways. Medical Institute investigator. In eight years at Vander- Cortez is also bilt, he pursued a long-standing interest in inositol associate director for CORTEZ phosphate signaling. He also developed a line of research basic sciences research into the effect of reductive sulfur fixation on iron ho- at the Vanderbilt–Ingram Cancer Center. He has meostasis and physiology after the lab identified a family received awards from the National Cancer Institute, of proteins including both inositol phosphatases and the MD Anderson Cancer Center and the Pew sulfur-assimilation enzymes. According to a press state- Charitable Trust. In 2017, he became a fellow of ment from Vanderbilt, York deepened the university’s the American Association for the Advancement of focus on basic science and helped make the biochemistry Science. department the most funded by the National Institutes of Health in 2019.

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New IUBMB award named in the laboratory of David Barford toral fellowship with Paul Nurse, at the Medical Research Council where she began her career-long use for Whelan Laboratory of Molecular Biology in of S. pombe as a model organism. The International Union of Cambridge, England. She studies She started as an assistant professor Biochemistry and Molecular Biol- spindle assembly checkpoint activa- at the Salk Insti- ogy announced recently that it had tion. She is the granddaughter of tute for Biological established a new award named after Edmond Fischer, Nobel laureate and Studies and be- its former president William “Bill” Whelan’s longtime friend. came an associate J. Whelan. The IUBMB Whelan Élyse Fischer will give a talk at professor there, Young Investigator Award will be the IUBMB’s 2022 Young Scien- cross-appointed issued annually to tists Program, which will be held to the University a promising early- in conjunction with the organiza- of California, San career scientist. tion’s 25th congress. She also will be FORSBURG Diego, prior to Whelan is a invited to contribute a review article joining the faculty pioneer in the to IUBMB Life and will receive a at the University of Southern Cali- study of glyco- cash prize, a certificate and a physi- fornia in 2004. gen synthesis. cal award. Forsburg is a member of the He discovered ASBMB Public Affairs Advisory WHELAN glycogenin, which Forsburg named Committee. She is a fellow of the provided the American Association for the Ad- then-missing link in the biosynthetic distinguished professor vancement of Science, the Califor- pathway that converts glucose into Susan Forsburg, the University nia Academy of Sciences and the glycogen. of Southern California Dornsife Association of Women in Though he retired in 2019 from professor of biological sciences, has Science. She is an elected member the University of Miami School been named a distinguished profes- of the American Academy of of Medicine, where he served for sor of USC. Microbiology. many years as the biochemistry Forsburg’s lab studies chromo- department chairman, he remains some duplication and segregation Rye receives UNSW co-editor-in-chief of the journal using Schizosaccharomyces pombe, Medicine research award IUBMB Life. or fission yeast, which is distinct He is a fellow of the Royal Soci- from the familiar brewer’s yeast, Kerry-Anne ety of London, an honorary member Saccharomyces cerevisiae. Using Rye, a professor at of the Royal College of Physicians a toolbox that includes molecular the University of of London and a fellow of the biology and microscopy, her team New South Wales American Association of Academic researches the molecular checkpoints in Sydney, Austra- Scientists, among other honors. and repair activities that keep fission lia, and co-editor- The IUBMB also has a fellow- dividing smoothly or cut it off in in-chief of the ship, established case of disruption. They study what Journal of Lipid in 1983, in happens when replication stalls, RYE Research, has his name: the potentially destabilizing the genome. received the Uni- IUBMB Wood- The response to replication stress is versity of New South Wales Faculty Whelan Research the first barrier to malignant trans- of Medicine Award for Academic Fellowship. formation in humans, making this Research Excellence. He has been simple yeast an unexpected model Rye, who received her Ph.D. a member of the for cancer research. from Flinders University in South FISCHER ASBMB since After earning her Ph.D. in genet- Australia and was a postdoc at the 1965. ics at the Massachusetts Institute of University of Illinois at Urbana– The first winner of the award, Technology in 1989, Forsburg went Champaign, has been a research Élyse Fischer, is a graduate student to Oxford University for a postdoc- professor at UNSW since 2013.

FEBRUARY 2021 ASBMB TODAY 5 MEMBER UPDATE

She is deputy head of the School of throughs including the discovery Eureka Therapeutics. Medical Sciences, where she studies of the mRNA 5’ cap-binding Schekman shared the Nobel Prize the mechanisms by which diabetes protein eIF4E, the rate-limiting in physiology or medicine in 2013 for can lead to heart disease. She was component of the eukaryotic discoveries of machinery regulating the first to report that the athero- translation apparatus. Eukaryotic vesicle traffic, particularly his work protective high-density lipoproteins translation ini- that began in the 1970s to character- in human plasma inhibit inflamma- tiation factor 4E ize the yeast secretory pathway. His tion in coronary arteries and that overexpression lab subsequently discovered a protein these HDLs also have anti-diabetic is prominent in complex key for vesicle budding properties. many cancers, called COPII. He also is known This is not the first time the suggesting its widely for founding the journal eLife UNSW has honored Rye, who was utility as a tumor in 2012 and for his continued calls for recognized as the UNSW School marker and publishing reform and open science. of Medical Sciences Researcher of SONENBERG anti-cancer drug In recent years, Schekman’s the Year in 2016. Among her other target. The lab lab has continued to characterize awards are several nods for research now works on translational control the formation and trafficking of and mentoring from the American in cancer; oncolytic viruses as anti- vesicles, paying particular attention Heart Association’s Atherosclerosis, cancer drugs; microRNA control to extracellular vesicles that contain Thrombosis and Vascular Biology of translation; and translational small RNAs and Council. She is also an editorial control of plasticity, learning and to the molecular board member of two AHA journals memory, and brain disease. mechanisms of and has held multiple leadership Sonenberg is a foreign associate autophagy. roles within that organization. of the National Academy of Sci- Schekman’s ences, an international member of honors include Sonenberg receives the National Academy of Medicine the Lewis S. honorary doctorate and an international honorary Rosenstiel Award member of the American Acad- SCHEKMAN for Distinguished The Institut national de la recher- emy of Arts and Sciences. He has Work in Basic che scientifique in Quebec awarded received the Killam Prize in Health Medical Research, the Gairdner an honorary doctorate to McGill Sciences, the Robert L. Noble International Award, the Eli Lilly University biochemist Prize from the National Cancer Award in Microbiology from the Nahum Sonenberg during the Institute of Canada, the Wolfe American Society for Microbiology, INRS virtual graduation ceremony Prize in Medicine, the Rosenstiel and the Albert Lasker Award in Basic in November. Award, the McLaughlin Medal of Medical Research. He is a member of Sonenberg holds the Gilman the Royal Society of Canada, the the National Academy of Sciences and Cheney chair in the department Order of Canada and the Canada the American Academy of Arts and of biochemistry and the Good- International Gairdner Award. Sciences. man Cancer Research Centre at Eureka Therapeutics was founded McGill. He earned his Ph.D. in in San Francisco in 2006 by industry biochemistry from the Weizmann Schekman joins Eureka veteran Cheng Liu, who previously Institute of Science in 1976 and scientific board worked in antibody therapeutics at held a Chaim Weizmann postdoc- a company now owned by Novartis. toral fellowship at the Roche Insti- Randy Schekman, a professor Liu, who earned his Ph.D. at UC tute of Molecular Biology before at the University of California, Berkeley, said in a press release that joining McGill University in 1979. Berkeley, and an investigator he and Schekman have known each The Sonenberg lab’s primary with the Howard Hughes other for over 20 years. Eureka research is on the translational Medical Institute, has joined the Therapeutics develops T cell therapies control of protein synthesis. His scientific advisory board of clinical- to target cancer cells, with particular work has led to a number of break- stage biotechnology company focus on solid cancers.

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AAAS fellows announced Of the 489 members of the American Association for the Advancement of Science elected as fellows this year, 33 are members of the American Society for Biochemistry and Molecular Biology. The tradition of electing AAAS fellows began in 1874. Since then, the recognition has gone to thousands of distinguished scientists. Two 2020 Nobel laureates, Jennifer Doudna and Charles Rice, are both AAAS fellows and ASBMB members. The AAAS will hold a virtual induction ceremony for the newly elected fellows on Feb. 13. The honorees will receive certificates and rosette pins in gold and blue, colors symbolizing science and engineering, by mail. The ASBMB members who are 2020 AAAS fellows are listed below by section.

Section on Biological Sciences Patricia Kiley | University of Wisconsin–Madison: For Suresh K. Alahari | Louisiana State University Health distinguished contributions to understanding Sciences Center School of Medicine: For distinguished mechanisms that regulate E. coli’s lifestyle in different contributions in cancer research and teaching, with a oxygen environments, specifically how transcription focus on signal transduction. factors exploit Fe-S metal centers for oxygen responses. Samuel J. Landry | Tulane University School of Diana M. Downs | University of Georgia: For distinguished Medicine: contributions to the field of bacterial metabolism and For distinguished contributions to the field of physiology, particularly metabolic pathway integration structural and molecular immunology, particularly for and stress. the analysis of protein immunogenicity and CD4+ T cell epitope prediction. Gloria Cruz Ferreira | University of South Florida: For Rodney L. Levine | National Heart, Lung and Blood distinguished contributions to the field of iron-heme Institute: metabolism, particularly using enzymology and For distinguished contributions to our spectroscopy to study heme synthesis and the molecular understanding of the effects of oxidative modifications basis of heme-related disorders. of proteins. Beronda L. Montgomery | Michigan State University: Michael William Gray | Dalhousie University (Canada): For For distinguished contributions to the field of molecular distinguished contributions to plant biology and evolution, particularly in the area of endosymbiosis, microbiology, particularly using photobiological organelle origins, molecular biology and genomics. analyses to investigate physiological and morphogenic adaptation of photosynthetic organisms. Ursula Jakob | University of Michigan: For seminal Katsuhiko (Katsu) Murakami | Penn State: discoveries of how reactive oxygen species play pivotal For roles in a range of biological processes and for method outstanding contributions in the field of structural development to identify redox-regulated proteins/ biology, particularly the role of RNA polymerase in pathways. prokaryotic gene regulation.

FEBRUARY 2021 ASBMB TODAY 7 MEMBER UPDATE

AAAS fellows continued Phillip E. Klebba | Kansas State University: For distinguished contributions to the understanding of the Rama Natarajan | City of Hope National Medical membrane transport mechanisms of bacteria relevant to Center: For distinguished contributions to the field of their practical applications in human health. diabetes and its vascular complications, particularly Raymond C. Stevens | University of Southern for studies showing the roles of epigenetics and California: For the development of technologies to noncoding RNAs. significantly accelerate drug discovery and protein Basil Nikolau | Iowa State University: For distinguished structure determination, including of G protein– contributions to the field of biochemistry, particularly coupled receptors, that have led to new biological for the characterization of novel metabolic processes. insights and therapeutics.

Franklin Wayne Outten | University of South Section on Dental and Oral Health Sciences Carolina: For distinguished research contributions deciphering the mechanisms for iron sulfur cluster Renny Theodore Franceschi | University of Michigan: For biogenesis, its regulation, and its roles in microbial distinguished contributions to the fields of physiology and stress responses. transcriptional control mechanisms of bone formation, signaling and extracellular matrix biology of osteoblast William S. Reznikoff | Marine Biological Laboratory: For differentiation as well as teaching and service. deciphering the molecular details of transposition by studying a model bacterial transposon. Section on Medical Sciences Charles Rock | St. Jude Children’s Research Hospital: For cutting-edge research on bacterial lipid Ronald W. Davis | Stanford University: For pioneering metabolism, the results of which have advanced the work in functional genomics and clinical genomics, and promise of fatty acid synthesis inhibitors as new in particular his development of novel technologies. bacterial antibiotics. Catherine Drennan | Massachusetts Institute of James V. Staros | University of Massachusetts Technology: For her structures of metalloenzymes and Amherst: For distinguished contributions in cell insights that show how nature harnesses and redirects biology on the mechanisms by which binding of the reactivity of enzyme metallocenters to perform polypeptide hormones to their surface receptors is challenging reactions. transduced into signals. Hudson Freeze | Sanford Burnham Prebys Medical Vassie Ware | Lehigh University: For contributions Discovery Institute: For identifying and characterizing to understanding ribosomes and for outstanding the mechanistic underpinnings of many glycosylation initiatives in undergraduate science education. diseases and work toward new treatments.

Thomas H. Haines | City College of New York (retired): Section on Chemistry For initiating and setting up the CUNY Medical School at City College of New York to educate Joan Blanchette Broderick | Montana State minority and disadvantaged students. University: For distinguished contributions to the field of bioinorganic chemistry, particularly for Shan-Lu Liu | Ohio State University: For distinguished elucidating the novel chemistry of iron–sulfur clusters contributions to our understanding of virus–host in biological radical initiation. interaction and viral pathogenesis as well as impact on scientific communication, diversity and international collaboration.

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Rodger P. McEver | Oklahoma Medical Research Foundation: For services to cardiovascular biology and hematology, and in particular to understanding the forces that govern cell–cell adhesion, and for distinguished scientific leadership. Don’t forget to renew your Alan Saghatelian | Salk Institute for Biological Studies: ASBMB membership! For mass spectrometry–centered work identifying Over the past 100 years, the ASBMB has grown and novel endogenous peptides and lipids in cells and changed with the times to become the supportive determining their regulation and targets. community of discoverers that it is today.

Jerrold Ross Turner | Brigham and Women’s Hospital/ ASBMB members are driven to better understand what Harvard Medical School: For distinguished contributions makes life work. With patience, perseverance and to cell biology, physiology, pathobiology and diagnosis insatiable curiosity, and through collaboration and hard in gastrointestinal science, particularly for defining work, we seek to uncover the secrets of life. functions, regulatory mechanisms and molecular Thank you for your membership. therapies targeting mucosal barriers. If you need to renew your ASBMB membership, you can Section on Neuroscience do so here: society.asbmb.org/SignInRenew Alan L. Goldin | University of California, Irvine: For distinguished contributions in understanding the function of sodium channels and their role in seizure susceptibility, and for promoting the development of physician–scientists.

Linda Jo Van Eldik | University of Kentucky College of Medicine: For distinguished contributions on how aberrant glia-neuronal interactions impact neurodegenerative processes, focusing on identification of signal transduction pathways that mediate neuroinflammatory responses of activated glia.

Section on Pharmaceutical Sciences

Patricia Babbitt | University of California, San Francisco: For distinguished contributions to the field of computational biology and bioinformatics, particularly related to protein structure/function and applications to drug target identification and drug design.

Walter H. Moos | University of California, San Francisco: For distinguished contributions to the fields of pharmaceutical sciences and medicinal chemistry targeting human health and disease.

FEBRUARY 2021 ASBMB TODAY 9 IN MEMORIAM

Raoul Carubelli Charles M. Radding

Raoul Carubelli, a research Charles M. Radding, a pro- scientist whose work ranged fessor emeritus of genetics at from ribosomes and cyto- Yale University, died Oct. 20 at chromes to cancer and cata- age 90. He was a member of the racts, died in June at age 90. American Society for Biochem- Born in Cordoba, Argentina, istry and Molecular Biology for to Italian immigrant parents in 40 years. 1929, Carubelli served in the Argentine army engineers as Born June 8, 1930, in Springfield, Massachusetts, Rad- a young man, reaching the rank of second lieutenant in the ding earned an M.D. from Harvard Medical School in 1956. reserves before he was discharged in 1949. He served a medical internship in Boston and a research After leaving the army, he attended Argentina’s Univer- fellowship at the National Institutes of Health before sidad Nacional de Cordoba, earning bachelor’s degrees in conducting postdoctoral research at Stanford University pharmacy and biochemistry while working as a laboratory with Arthur Kornberg. Radding joined the faculty at the instructor. He went on to graduate school at the University of University of Michigan before moving to Yale in 1967. Minnesota. In his lab, Radding characterized cellular proteins that He worked as a research scientist at the Oklahoma Medi- mediate DNA recombination, focusing on the recA protein cal Research Foundation for 37 years, from 1957 to 1994, from E. coli. By purifying and studying proteins, he was able and thereafter at the Dean A. McGee Eye Institute. On two to reconstitute key steps of recombination in the lab. He yearlong sabbaticals in Germany, he visited the Max Planck and his colleague Matthew Meselson of Harvard formulated Institute for Virus Research in Tübingen and the German the articulation of a new general model of recombination Cancer Research Center in Heidelberg. known as the Meselson–Radding Model. Carubelli’s first grant was a research career develop- Radding was elected into the National Academy of Sci- ment award from the National Institutes of Health awarded ences in 1995 and served for many years as an editor of the in 1968. Over the years his research covered many topics. journal Proceedings of the National Academy of Sciences. Early on, he studied how ribosomes and cytochromes embed According to a Yale School of Medicine profile, Radd- in the membranes of the endoplasmic reticulum and the ing is remembered as an outstanding teacher, engaging nucleus and how they could be disrupted chemically. Later, lecturer, and dedicated and inspiring mentor: “He often he became interested in glycosylation, with particular focus accessorized his lectures with props: long rubber tubes on the enzyme neuraminidase and how it changes during the representing DNA strands to illustrate difficult-to-visualize development of cancer. In his later years, as a member of the concepts like positive and negative DNA supercoiling and Dean McGee Eye Institute, he studied the molecular changes DNA strand exchange. Occasionally, the tubing got into a behind the development of corneal lesions and cataracts. hopeless tangle, to the great amusement of the class!” Carubelli loved to travel for work and pleasure; he His interests outside the lab included classical music, presented at many international meetings and took his wife literature, fine food and languages, with a special fondness and two children on numerous international vacations. While for French, the profile states, and “he was always happy at home, his family wrote, he spent time fishing, hunting and with little urging to speak French, or, for that matter, any writing letters to the editor of The Daily Oklahoman. of a series of ersatz languages and accents that sounded Carubelli is survived by his wife, Barbara, to whom he was surprisingly authentic.” married for 60 years; son Michael and daughter Cecilia; two Radding is survived by his wife of more than 65 years, grandchildren; great-grandchildren; and family in Oklahoma, Natalie, as well as three daughters and a grandson. Cordoba and Canada.

10 ASBMB TODAY FEBRUARY 2021 STUDENT CHAPTERS Establishing connections — from people to synapses COURTESY OF JOSÉ ZEPEDA By Jaclyn Brennan with their questions and ability to pick up the material so quickly.” hen José Zepeda was in his He also continued to be fascinated early teens, his mother was by the human brain. Now a first-year Wdeported, and his family Ph.D. student pursuing neurophar- moved from Cambridge, Massachu- macology at Vanderbilt University, setts, to San Luis Río Colorado in Zepeda seeks to help develop cures Sonora, Mexico. There he witnessed and treatments for neurological the poisoning access to drugs in a disorders and diseases. He specifically border town. “I saw friends who went focuses his scientific attention on through that and struggled,” he said. “I always wondered what I could do neuroplasticity, studying the brain’s to help.” ability to reorganize itself through the As a youngster, Zepeda was an formation of new neural connections. avid reader of science and nonfiction Zepeda’s interest in connections José Zepeda, former president of the UMass goes beyond scientific inquiry. From books. By high school, he had turned Boston ASBMB Student Chapter, is now a Ph.D. his desire to help his teenage friends his attention to books on philosophy student in neuropharmacology at Vanderbilt to engaging with eighth graders in and neuroscience, wanting to know University. more about the brain’s involvement in the study of science, leading a strong addiction. The ASBMB-UMB chapter pro- executive board and organizing pro- Looking to satisfy his curiosity vides resources to those interested in fessional development events, Zepeda about brain signals, rationality and biochemistry and molecular biology has a passion for forging connections. the function of biological organisms — both within and outside the uni- And he urges others to do the same. at their core, Zepeda returned to his versity. As chapter president in 2019, If more scientists would go out of home state for college, pursuing a Zepeda started biweekly journal clubs their way to engage with the public, degree in biochemistry at the Univer- to discuss articles in the ASBMB’s Zepeda believes they could improve sity of Massachusetts Boston. He had Journal of Biological Chemistry and the credibility of science and over- the opportunity to work in neurosci- triweekly professional development come its politicization. ence labs at Harvard Medical School events including CV, resume and in- “Since the COVID-19 outbreak, and MIT, where he was exposed to terviewing workshops. He also led the there has been a lot of distrust be- studies of molecular neuroscience and chapter’s partnership with the local tween the outside community and the synaptic plasticity. — and underfunded — McCormick scientific community,” he said, “and He also joined the UMass ASBMB Middle School, where members teach as scientists, we have an obligation to Student Chapter, first as a general a class of eighth graders general sci- build that trust with the communities member, then becoming vice presi- ence topics through lectures and labs, we serve.” dent and, in his final year, president. everything from thermodynamics to He initially was attracted to being the structure and function of small Jaclyn Brennan (jabrennan@ gwmail.gwu.edu) is a post- around like-minded individuals and molecules. doctoral researcher at George receiving mentorship about working “Working with eighth graders was Washington University, where her in a lab. However, Zepeda said the extremely rewarding,” Zepeda said. research focuses on electrophysi- ology of the cardiac conduction outreach component of the club was “Their energy and curiosity for science system. Follow her on Twitter what he loved the most. are enviable. I was deeply impressed @jaclynb_phd

FEBRUARY 2021 ASBMB TODAY 11 NEWS 10 young scientists win PROLAB awards

By Angela Hopp

en early-career researchers have won travel grants Giuliano Tomás Antelo is a Ph.D. student at the Fun- from the Promoting Research Opportunities for dación Instituto Leloir in the Ciudad Autónoma de TLatin American Biochemists program. They will use Buenos Aires, Argentina. He studies “how the molecular the awards to conduct research in academic laboratories in evolution of transcriptional regulators in pathogenic the United States and Canada. bacteria gave rise to new resistance mechanisms against Since 2012, the American Society for Biochemistry and antibiotics and the immune system.” He will spend time Molecular Biology, the Pan-American Society for Bio- in the lab of Da- chemistry and Molecular Biology, and the International vid P. Giedroc at Union for Biochemistry and Molecular Biology have Indiana Univer- issued about 100 travel awards to young biochemists. sity’s chemistry This year’s PROLAB travel grants are going to Ph.D. department. “I’m students and postdoctoral fellows from Argentina, Brazil, grateful for this Chile and Uruguay. All but one will work in the United opportunity that States. will allow me to learn cutting-edge Carolina Alberca is a Ph.D. student at the Univer- nuclear magnetic sidad de Buenos Aires in Argentina. She is a member of resonance spectro- the neuroepigenetics lab in the department of biological scopic techniques chemistry. “The main objective of my Ph.D. thesis is to and grant me identify the cellular and molecular mechanisms underly- access to equipment not yet available in my country,” ing the cognitive deficits derived from perinatal protein Antelo said. “I believe this will be an extraordinary experi- malnutrition in mice and the effects of reversion due to ence to expand our knowledge on the role of internal a stimulating growth protein dynamics in bacterial resistance and to strengthen environment, with the international collaboration between our labs.” special emphasis on the epigenetic mecha- Melisa Antinori, a Ph.D. student at the Universidad nisms,” she said. She Nacional de Rosario in Argentina, is working on a thesis will spend time in the project focused on the mechanism of activation of the lab of Reid S. Alisch vraSRT system of Staphylococcus aureus, which results in at the University of resistance to β-lactam and glycopeptide antibiotics. She Wisconsin School of will be joining the lab of Gerry Wright at McMaster Uni- Medicine and Public versity in Canada. At McMaster’s Michael G. DeGroote Health. The grant, she Institute for Infectious Disease Research, she plans to con- said, “will allow me to tinue studies of bacterial resistance to antibiotics. “This learn about novel techniques and will provide me tools to research stay will allow me to use unique compounds to broaden and enhance my specialization in the neurobiol- evaluate whether there is direct interaction of vancomycin ogy field.” or of cell-wall–derived fragments with the proteins of the

12 ASBMB TODAY FEBRUARY 2021 NEWS

Biology and Regenerative Medicine, she looks forward to getting “experience in state-of-the-art techniques and a deeper understanding of the biological processes underlying the reversion of aging.”

Pablo Cruz Núñez is a Ph.D. student at the Facul- tad de Medicina of the Universidad de Chile. He studies ion channels and is particularly interested in how post-translational modifications regulate store-operated Ca2+ entry components. He will be visiting the lab of James S. Trimmer at the University of California, Davis. “This award means to me a great challenge and opportunity to expand my knowledge in molecular and cell biology of ion channels. I expect to learn a lot from great researchers in a collaborative environment, which could vraSRT system,” she said. “I will be working in one of mean, in the future, an opportunity for the develop- the most renowned laboratories in my area of research, ment of high-impact studies,” Cruz said. in contact with experts in the subject, which will greatly contribute to my formation as a scientist.” Maria Florencia González Lizárraga is a postdoctoral researcher at the Dayana Benchoam is a Ph.D. student at the Universi- Instituto de Investig- dad de la República in Uruguay who studies the reactiv- ación en Medicina ity of biological persulfides. Molecular y Celular She will spend time in the Aplicada in Argen- lab of Ruma Banerjee at the tina. She is studying University of Michigan. “This the proteins involved visit is a valuable opportunity in neurodegenerative to transition from my stud- diseases and will be ies on low–molecular-weight working in the lab persulfides to proteins with an of Rodrigo Mail- expert in the field,” Benchoam lard at Georgetown said. “It will nurture my doc- University “on the toral training and broaden my knowledge, allowing me to characterization of the interaction between α-synuclein bring back expertise that would be useful in the research and tau proteins using optical tweezers.” She added: setting in my own country.” “This approach will allow us (to better understand) the cross-talk between these proteins at the level of single Priscila Chiavellini is molecules. This will also help to identify novel targets a Ph.D. student studying for designing therapeutic interventions in a variety of aging at the Universidad neurodegenerative diseases.” Nacional de La Plata in Ar- gentina. She’ll be joining the Marisol León Cabrera is a Ph.D. candidate at the lab of Vittorio Sebastiano Universidade de São Paulo in Brazil, where she’s work- at Stanford University. At ing to understand the metabolic impacts of maternal the Institute for Stem Cell obesity on prenatal development in a mouse model

FEBRUARY 2021 ASBMB TODAY 13 NEWS

using multimodal imaging. She will be visiting the lab of Kimberly K. Buhman at Purdue University. “The PRO- LAB scholarship (will make) my dream to (go) to Purdue University to perform chemical imaging experiments come true,” León said. “My research quality and impact will greatly improve. Also, the mentorship I will receive in this international experience will certainly play a major role in my future academic career.” Ian Silva is a Ph.D. student at the Facultad de Medicina of the Universidad de Chile, where he studies the role of transient receptor potential channels on Ca2+ signaling and cellular migration. He will be visiting the lab of Madesh Muniswamy at the University of Texas Health Science Center at San Antonio. “During this rotation, using a model of colon cancer cells, I will evaluate whether two TRP channels are involved in the regulation of mitochondrial function,” Silva said. “Thus, this rotation will give me the opportunity not only to learn new methodologies to address mitochondrial functions, but will lay the foundations for future collaborations.”

About the awards Maria Florencia Rossetti is a postdoctoral The ASBMB welcomes applications for PROLAB scholar- researcher at the Universidad Nacional del Litoral ships from trainees and new investigators (not more than in Santa Fe, Argentina. “The general objective of five years past postdoctoral work) from all countries in my research project is to explore the importance of the Pan-American Society for Biochemistry and Molecular Biology, including Spain and Portugal. maternal nutritional environment during prenatal and early postnatal life on brain functions and to The awards offset the costs of travel and living expenses provide novel mechanisms through which such for one to six months up to a maximum of $5,000. early experiences may lead to the onset of metabolic For more information, go to the Career Resources section syndromes, neurodevelopmental disorders and other (awards, grants and fellowships) at asbmb.org. brain disorders later in life,” she said. She will be joining the lab of Nancy G. Forger at Georgia State University. “My project in the Forger lab will address how information about the maternal microbiota is Angela Hopp ([email protected]) is executive editor conveyed to the offspring brain. This training will of ASBMB Today and communications director for the ASBMB. Follow her on Twitter @angelahopp. give me new tools for gut microbiota and microglial practices and the possibility to interact with foreign students and scientists resulting in a professional and cultural enriched experience.”

14 ASBMB TODAY FEBRUARY 2021 NEWS Sewer scholarship program funding doubled Meet the 2020 recipients of this ASBMB diversity award

By Stephanie Paxson England Biolabs means we are able to do more. NEB’s commitment to diver- he American Society for sity in STEM and their support of the Biochemistry and Molecular Marion B. Sewer scholarship mission TBiology’s Marion B. Sewer in promoting inclusion and equality in Distinguished Scholarship for Under- the life sciences is reflected through this graduates has the potential to double generous donation.” its reach this year. The award honors Marion B. Sewer, The ASBMB’s Minority Affairs who was an ASBMB member and past Committee created the scholarship in deputy chair of the Minority Affairs 2015 to support students who excel Committee when she died in January academically and are dedicated to en- 2016 at age 43. Sewer was a principal hancing diversity in science. This year investigator on projects devoted to the MAC and the Student Chapters MARION B. SEWER increasing participation among under- Steering Committee will be able to se- represented minorities and furthering lect up to 10 undergraduate students ous social and financial challenges,” student training. She also wrote about to receive up to $2,000 toward tuition Saleh said. “Not surprisingly, the vast issues that URM scientists face, such instead of the usual five, thanks to a majority of the applicants are from as impostor syndrome. Sewer’s work donation to the scholarship fund from underrepresented groups in STEM. reflected her commitment to diversity New England Biolabs. While there were many qualified can- and inclusivity of underrepresented Lana Saleh, a member of the didates in the past years, we had the minorities in science, technology, engi- MAC, has worked to expand the resources to offer five $2000 schol- neering and math. program. “Every year, the Marion B. arships. This resulted in us turning Here, the latest five recipients of Sewer Scholarship program receives down qualified applicants who were the Sewer scholarship describe their a substantial number of applications in dire need of this financial assistance personal goals and how they promote from talented undergraduates who are to complete their degrees. Receiving diversity. Their statements have been working diligently to overcome seri- a donation of $10,000 from New edited.

2020 RECIPIENTS Faria Afreen, Brandeis University molecular level. Cancer’s heterogene- reduce any distrust of health My long-term goal is to become a ity makes it a mammoth of a disease professionals. physician–scien- to treat, but I am optimistic that my Additionally, as someone who tist with a lab that future lab, in collaboration with other entered college not having prior re- focuses on creat- clinical, scientific and bioinformatical search experience or family members ing personalized research groups, can create treatments in science, I am driven to give other cancer treatment that will reduce patient suffering. I students, particularly those under- by researching hope that, as a physician, I am able represented in science, the tools and one of the many to explain clearly to my patients their resources they need to be successful. mechanisms of pathogenesis at a illness and treatment plans to help There is a leaky pipeline in both

FEBRUARY 2021 ASBMB TODAY 15 NEWS

science and medicine. I hope to play program to earn a Ph.D. and M.D. to research. My career goal is to push the a role in fixing it by creating a culture begin the long and arduous process of field of IBD treatment and research so that values compassion, teamwork becoming a physician and biomedical that one day we no longer will think and mentorship and practices inclu- scientist. of the colon as a question mark. sive teaching styles. I decided to choose this career path because I hope that I can bring some Prashit Parikh, Vassar College Jennifer Burdette, Tidewater Community positive change to the world by lead- I am currently a senior at Vassar College ing a breakthrough in science, answer- College studying biochemistry. Fol- For the past few years, I have been ing science’s most plaguing questions lowing graduation, I hope to pursue a student at or finding a cure for some of the an M.D.–Ph.D. Tidewater Com- world’s most aggressive diseases. in computational munity College, biology in order attending classes Alisha Holden, California State to become a phy- to earn my associ- University, Northridge sician– ate degree in sci- Currently working on my B.S. in scientist. ence to ultimately biochemistry, My goal is to transfer to a four-year university. This I eventually combine my interests in public health past spring, I completed my studies plan to go on to and medicine with modern computa- toward my associate, and I have been grad school and tional techniques to advance human accepted to the University of Virginia, earn a master’s health and disease. By combining where I plan to obtain a bachelor’s degree, prefer- my medical practice and research degree in the field of biochemistry. ably in chemistry. experience, I believe that I will be able Afterward, I plan to apply to be a My career goals include becoming a to institute positive change not only part of a medical scientist training scientific researcher in the biomedical for my patients but also the scientific field as well as, in the future, becom- community at large. ing a chemistry teacher. As I have par- Ultimately, I also would like to About the Sewer ticipated in a research project focused start a program where students from scholarship on cellular signaling, I am currently disadvantaged backgrounds would interested in research on that topic. be able to shadow physicians and The Marion B. Sewer Distinguished conduct research, giving them the Scholarship for Undergraduates Rishi Mehta, University of Cincinnati provides up to $2,000 toward tuition opportunity to explore their research to students who demonstrate an My professional goal is to lead a interests and to understand better interest in the fields of biochemistry clinical research laboratory aimed at what being a medical professional and molecular biology and enhance uncovering data- entails. Overall, I am excited to the diversity of science. Students driven insights to contribute to the forefront of science whose social, educational or economic treat pediatric in- and medicine. background adds to the diversity of flammatory bowel the biomedical workforce or who show disease. To do so, Stephanie Paxson (spaxson@ commitment to enhancing academic I aim to attend asbmb.org) is the diversity and undergraduate education coor- success of underrepresented students medical school are eligible. Deadline to apply is June 1, dinator at the ASBMB. Follow her at a top research institution with the on Twitter @stephaniepaxson. 2021. See details at asbmb.org/diver- goal of becoming a clinician investiga- sity/undergraduate-scholarship tor and conducting patient-focused

Send us your news! Have you recently been promoted or honored? Do you have good news to share with your fellow ASBMB members? Email it to us at [email protected] and don’t forget to include a photo!

16 ASBMB TODAY FEBRUARY 2021 PLEASE DONATE

Marion B. Sewer Distinguished Scholarship for Undergraduates This scholarship provides ﬁnancial support to students who will diversify the scientiﬁc workforce.

Make a donation to help the ASBMB achieve our goals.

The late Marion Sewer was a leader in the ﬁeld of steroid hormone biosynthesis at the University of California, San Diego and deputy chair of the ASBMB Minority Aairs Committee. Just 43 years old when she died, Dr Sewer worked to make science more inclusive and retain talented students and scientists of color.

Your gift will honor Marion Sewer’s memory and help support the newest members of the scientiﬁc enterprise.

Visit asbmb.org/donate to make your tax-deductible donation.

May 4–5, 2021 | Virtual

PDB50: A special symposium celebrating the 50th anniversary of the Protein Data Bank

Abstract and early registration deadline: March 15

Learn more at asbmb.org/meetings-events/pdb50

FEBRUARY 2021 ASBMB TODAY 17 NEWS Increasing diversity to improve health care — for all of us

By Jack Lee

iversity is at the core of the centers are partnerships led by Baylor officer for the Genetic Counseling National Institutes of Health’s College of Medicine and the Broad Resource with the All of Us Research DAll of Us Research Program. Institute. Program. The program aims to gather All of Us “has had a focus from “We’re really trying to reflect medical records, survey responses and the start on enrollment of diverse the diversity of the United States,” DNA samples from 1 million or more populations,” Jarvik said, “with the Wise said. So far, more than 80% individuals of different races, eth- recognition that those populations of the contributed biosamples are nicities, ages and geographic regions. are underserved in medicine, and in from members of underrepresented Researchers will be able to use this particular, in genomics.” communities. In addition to racial large body of data to identify how Genetic data, such as whether an and ethnic minorities, this includes biological, lifestyle and environmental individual has a specific version of a individuals from other groups that factors impact human health. gene, can provide valuable insight into typically haven’t been part of research, All of Us began through the forma- a person’s health. Certain versions of such as sexual and gender minorities tion of a precision medicine working the BRCA1 and BRACA2 genes, for and members of low-income group in 2015. After a period of in- example, can indicate people with households. frastructure development and testing, a higher risk of developing certain The All of Us Research Program the program opened enrollment across cancers, such as breast and ovarian encourages inclusion in a number of the United States in 2018. Since then, cancer. Polygenic risk scores go a ways, including the use of imagery more than 270,000 participants have step further, combining details about that reflects diverse communities provided biosamples — such as blood, multiple genes to predict the risk of and preparation of information in urine and saliva — carrying genetic an individual developing a disease. multiple languages. The program also information. These scores, however, have generally has national community engagement Gail Jarvik, a medical geneticist at been developed based on populations partners that increase public aware- the University of European ancestry, Jarvik said. ness and encourage participation of Wash- The larger, more diverse data set be- by members of underrepresented ington, is a ing developed through All of Us could groups. One of these organizations is co-leader of be used to make new and improved the Delta Research and Educational the Northwest predictions of health risks for people Foundation. Based in Washington, Genomics of other ancestry groups. For example, D.C., DREF promotes research on Center, one of there may be versions of genes more issues affecting African American the three All common in people of non-European women and their families. of Us genome ancestry that haven’t been studied yet. “The All of Us Research Program GAIL JARVIK centers. She Additionally, by including electronic offers a vital opportunity to increase and her col- medical records and information the number of African American par- leagues Deborah Nickerson and Evan about lifestyle factors, the new data set ticipants in biomedical research and Eichler are spearheading efforts to will help researchers better understand lead a path towards closing the health sequence participants’ samples and health outcomes for people of many disparity gap,” DREF President Caro- return information about their DNA. different backgrounds. lyn Lewis stated in a press release. The other two All of Us genome Anastasia Wise is the NIH program Regina Locust, the DREF Re-

18 ASBMB TODAY FEBRUARY 2021 NEWS MARCUS ANNABLE

Among the early researchers on the All of Us project at Northwest Genomics Center were, left to right, Ashley Kang, Jeff Weiss, Marcus Annable, Alison Schiele and Matt Richardson.

search Matters program manager, has environmental factors affect an indi- to traits such as earwax type and ci- planned and presented events that vidual’s health. “That’s how we then lantro preference. The program plans engage with African Americans and tie in the importance of understand- to provide participants with health- inform them about science research. ing and participating in research,” related information in the future. Initially, these events were in-person Locust said. All of Us also plans to begin mak- and of all sizes, from book clubs and In addition to providing valu- ing genetic data that’s stripped of per- fellowship groups to the Essence able data for research purposes, sonal details available to researchers in Festival and national conventions. The participants can decide if they want about a year. NIH officials hope that COVID-19 pandemic has forced a to receive details about their genetic broadening the data that’s available shift to a virtual format. ancestry and traits. In November, All to researchers will accelerate research “When we interact with minority of Us began returning genetic results discoveries, making health care more communities, we engage in everyday to participants. useful for all, Wise said. conversations,” without unfamiliar “Our participants are really acronyms or complicated terminology, partners in the research,” Wise said. Locust said. These conversations then The program developed an informed Jack Lee (jackjleescience@ can lead to dialogue about precision consent process, allowing participants gmail.com) is a freelance science writer. Read more of his work at medicine and the All of Us Research to choose the results they want to get. jackjleescience.com/writing and Program. For example, talking about At this stage, participants are receiv- follow him on Twitter @jackjlee. depression can lead to a discussion ing information about their genetic about how lifestyle, behavior and ancestry as well as several genes linked

FEBRUARY 2021 ASBMB TODAY 19 JOURNAL NEWS The vaccine race heats up Researchers address distribution challenges by prioritizing higher temperature tolerance, ease of manufacturing By Guananí Gómez–Van Cortright

esearchers around the world are refrigeration. racing to develop COVID-19 Instead, they Rvaccine options at a record focused their pace, but the logistical challenge of efforts on getting vaccines to everyone who developing a needs them remains daunting. Most protein-based vaccine formulas must be kept at very vaccine, which low temperatures during their journey takes longer from assembly to a person’s arm, a to develop but major obstacle for those living in is easier and remote locations or underserved com- more afford- munities without access to long-term able to produce. The target proteins remains viable after a month at 37 refrigeration. are the coronavirus’ spikes, the C and would be straightforward and In a recent paper in the Journal distinctive points of the virus’ crown inexpensive to manufacture, it could of Biological Chemistry, research- that allow it to bind to the receptors become an accessible and portable ers at the Molecular Biophysics Unit known as ACE-2 on the surface of vaccine option. at the Indian Institute of Science in host cells. “Certainly, other people along Bengaluru, India, address distribution “Once the virus is able to come with us and before us have also made challenges by designing a coronavirus close to the cell, that binding of the related protein subunit vaccines with vaccine that can withstand four weeks spike protein is the beginning of the similar fragments, but nobody had at temperatures as high as 37 degrees infection,” Varadarajan said. “There- looked at the temperature stability Celsius (about 98 degrees Fahrenheit) fore, if your body is able to create to this degree,” Varadarajan said. “In as well as 90 minutes at 100 C (212). antibodies that block this interaction, that sense we were fortunate — that Raghavan Varadarajan, the project’s you can prevent infection.” we looked for this property, and it principal investigator, is pleased by the The portion of the spike protein turned out to exist.” vaccine candidate’s hardiness. “The needed for binding is the receptor Varadarajan’s team is continuing most exciting thing that we didn’t ex- binding domain, or RBD. Varada- to develop their vaccine with chal- pect is that we could keep this protein rajan’s team engineered a protein lenge trials of mRBD and improved at very high temperatures and it was fragment in its image. They expressed variants in hamsters, which are also still viable,” Varadarajan said. “We this fragment in mammalian cells, susceptible to SARS-CoV-2, as the lab hadn’t tried it before, and we wanted creating mRBD (m for mammalian- strives to immunize those who may be to see how far we could push things.” expressed), and then tested its ability out of other vaccines’ reach. In addition to temperature toler- to stimulate the immune system of DOI: 10.1074/jbc.RA120.016284 ance, Varadarajan’s team considered guinea pigs to make antibodies that ease and accessibility of manufactur- could block the coronavirus’ spike Guananí Gómez–Van Cortright ing. The first COVID-19 vaccines on proteins from interacting with host ([email protected]) is an outdoor educator and freelance the market are messenger RNA–based, receptors. science writer. but India lacks facilities with the Because mRBD stimulates an expertise to make mRNA vaccines, immune response with good yields and the technique requires extensive of receptor-blocking antibodies,

20 ASBMB TODAY FEBRUARY 2021 JOURNAL NEWS Vision health depends on fat

By Jaclyn Brennan ELISA VIDAL

ur eyes are rich in fatty acids that help the retina receive, Oconvert and send light signals to the brain. Healthy ocular fatty acid content relies on a diet rich in omega-3 long-chain polyunsatu- rated fatty acids, or LC-PUFAs, but guidelines for obtaining these dietary fats to maintain vision health remain controversial and incomplete. Compared to a control diet, an omega-3 supplementary diet rich in phospholipids increases docosa- To understand better how dietary hexaenoic acid (green) content in the optic nerve. omega-3 supplementation can modify the content of fatty acids in the reti- phospholipids or triglycerides — can Holistically, this study unravels na, researchers at Louisiana State Uni- effectively influence bioavailability fundamental questions. In the rat, versity and the Université Bourgogne and distribution in retina.” “EPA and DHA provided as dietary Franche-Comté investigated how The creative collaboration be- supplements can enhance DHA con- lipids and lipid metabolism intervene tween the Neuroscience Center tent in the retina and trigger changes in the function and dysfunction of of Excellence at LSU and the Eye in spatial organization of fatty acids the retina. The results of their study and Nutrition Research Group in in the outer retina,” Vidal said. This are detailed in the Journal of Lipid Dijon, France, afforded research- can help provide guidance on what Research. ers the chance to investigate LC- sources of dietary fatty acids might be The study began by looking at di- PUFA changes that followed different beneficial for preventing irreversible etary guidelines in Western countries, omega-3 rich diets. The human body visual impairments. which recommend consuming 500 cannot make alpha linolenic acid, The researchers next want to mg of fatty acids per day to reduce the precursor of EPA and DHA, and understand better the mechanisms the risk of developing age-related is inefficient at making these fatty regulating how fatty acids contain- macular degeneration, or AMD, the acids. To investigate the effects of ing phospholipids or triglycerides most common cause of blindness in supplements, the researchers created travel — from oral uptake, through the elderly of developed countries. experimental diets of five lipid blends the digestive tract, and to the retina A diet rich in two key fatty acids — using varying concentrations of both and retinal pigment epithelial cells. docosahexaenoic acid, or DHA, and fish and plant oils (such as sunflower, Molecular changes in the eyes are one eicosapentaenoic acid, or EPA — has palm, rapeseed and herring roe). Fed thing, but functional consequences been shown to be associated with a to rats, these different mixtures of in the retina are crucial to prevent the lower risk of AMD development, but EPA and DHA were analyzed after effects of aging. the 500 mg per day recommendation eight weeks for their uptake in rodent DOI: 10.1194/jlr.RA120001057 does not take into account a number plasma, red blood cells and the retina. of key factors, according to the study’s “Using mass spectrometry molecu- lead author, Elisa Vidal. lar imaging and other approaches, Jaclyn Brennan (jabrennan@ gwmail.gwu.edu) is a post- “This recommendation is not we showed, for the first time that the doctoral researcher at George precise for the chemical forms or content of fatty acids in the photore- Washington University, where her source of EPA and DHA in dietary ceptor layer can indeed be modified research focuses on electrophysi- ology of the cardiac conduction supplements,” Vidal said, “despite the by an omega-3 food supply,” Vidal system. Follow her on Twitter fact that the chemical form —aka, said. @jaclynb_phd

FEBRUARY 2021 ASBMB TODAY 21 JOURNAL NEWS A mold’s dangerous responses to its environment

By Laurel Oldach JANICE HANEY CARR AND ROBERT SIMMONS

flatoxins are among the most dangerous of natural products. AAt a high dose, the toxins can cause fatal liver failure; at lower doses, by forming adducts with guanine bases in DNA, they can cause mutations that lead to liver cancer. The toxins are made by filamen- tous fungi in the Aspergillus family found in soil and are able to colonize the grains and seeds that constitute many of the world’s most important food crops. Aspergilli don’t need aflatoxins to survive; they activate aflatoxin synthesis in response to A scanning electron micrograph shows the fruiting body of an Aspergillus fungus. environmental conditions, especially heat and moisture. Since hotter days to identify peptides detected through the new genes. are coming worldwide, research- mass spectrometry, the team discov- Based on homology to other, ers would like to find strategies to ered over 700 new protein-coding better-annotated proteins in the lit- reduce aflatoxin production. genes. erature, the authors think that they The genome of Aspergillus flavus, “The authors provide a significant may have identified new metabolic the chief culprit in introducing improvement to the genome annota- enzymes, signaling proteins and aflatoxin to human and animal tion in Aspergillus and demonstrate stress response factors. They have not food supplies, first was sequenced the use of proteogenomics as a tool yet determined whether any of the in 2006. But there’s a difference especially in organisms lacking high- new genes are involved in aflatoxin between knowing what sequences are quality genome annotations,” one production. in a genome and knowing what they anonymous peer reviewer wrote. According to the researchers, do; many sections of the A. flavus Researchers cultured the fungus follow-up studies of the new protein- genome have not been annotated, under cold, salty and oxidative stress coding genes and when and where meaning that researchers have had conditions to maximize phenotypic they are expressed may improve our little insight into their function. variability, and they were rewarded: understanding of when and why In a recent article in the journal The fungi expressed a smorgasbord aflatoxin is produced. Molecular & Cellular Proteomics, of proteoforms, including over 200 DOI: 10.1074/mcp.RA120.002144 researchers at the Fujian Agriculture new-to-science splice variants, some

and Forestry University in China, single-amino-acid variants and a few Laurel Oldach (loldach@ led by Mingkun Yang, report on a unexpected intergenic peptides. In asbmb.org) is a science writer for proteogenomic analysis of A. flavus. follow-up quantitative PCR experi- the ASBMB. Follow her on Twitter @LaurelOld. By using the whole fungal genome ments, the researchers observed that instead of only its known coding stressful conditions substantially sequences as the reference database affected the expression of some of

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From the journals By Nuala Del Piccolo, Lisa Nicole Learman, Laurel Oldach & Anand Rao

We offer summaries of papers thors, places limitations on the utility uptake led to lower levels of LDL-in- recently published in the Journal of and trustworthiness of certain spike-in duced atherogenic signaling cascades. Biological Chemistry, the Journal normalization methods as well as The authors used the same concen- of Lipid Research and Molecular & published results utilizing them. trations of adiponectin found in the Cellular Proteomics. A paper recently published in the human body, strongly supporting the Journal of Biological Chemistry de- idea that blocking atherogenic LDL ChIP-ing away at ChIP-Seq scribes the authors’ approach — called uptake is a physiological function of the sans-spike-in method for quantita- the protein and not just something pain points tive ChIP-sequencing, or siQ-ChIP that occurs in artificial laboratory con- Chromatin immunoprecipitation — which may prompt changes in ditions. Overall, the results provide followed by next-generation sequenc- community practice of ChIP-Seq, insights into how adiponectin protects ing, or ChIP-Seq, is used widely to data reporting and analysis. us from developing fatty arteries and identify genomewide DNA binding DOI: 10.1074/jbc.RA120.015353 offer a new therapeutic target in the sites and enrich chromatin modifica- treatment of atherosclerosis-related tions. Cheap and relatively easy to set How adiponectin fights diseases. up, ChIP-Seq has become a corner- fatty plaques DOI: 10.1194/jlr.RA120000767 stone of epigenetics research. For all its merits, however, researchers still The formation of fatty plaques in How to keep Staph haven’t found an appropriate method the arteries, called atherogenesis, can from sticking for defining a quantitative scale for lead to problems such as heart attack, ChIP-Seq data analysis. stroke or even death. Fat cells, called Staphylococcus aureus, a bacterium Bradley Dickson of the Van Andel adipocytes, secrete a protein called ad- that can cause pneumonia and heart Research Institute and collaborators iponectin into the bloodstream, where infections, often adheres to skin, caus- determined that a commonly used it can block these fatty plaques from ing the blisters and abscesses known method for comparing ChIP-Seq forming, but researchers do not yet as staph infection. The adhesins that signal strength with external refer- know how adiponectin performs this bind the bacteria to host skin ligands ences — spike-in normalization — protective function. In a recent study are a promising therapeutic target. may be flawed, leading to inaccurate in the Journal of Lipid Research, However, researchers are unable to conclusions. To address this issue, investigator Akemi Kakino from Shin- develop anti-adhesives without ef- the authors appealed to the physics shu University and a team of Japanese ficient methods for studying S. aureus exploited by ChIP-Seq to develop researchers describe how adiponectin adhesion. a physical model that produces a protects against atherogenesis by In a recent paper published in the quantitative scale for ChIP-Seq result blocking the uptake of specific types Journal of Biological Chemistry, comparison. To test their model and of low-density lipoprotein, or LDL, Laurenne E. Petrie and colleagues at demonstrate this scale, the researchers that have atherogenic properties. the University of Guelph describe examined the impacts of an enhancer These atherogenic varieties, such how they developed and validated a of zeste homolog 2, or EZH2, inhibi- as oxidized LDL and electronega- high-throughput assay that enables tor using ChIP-Seq; their experimen- tive LDL, enter cells via scavenger the large-scale profiling of S. aureus tal results were predicted accurately receptors and trigger a cell signaling adhesion to host ligands. The authors by the model but not by conventional cascade that causes plaque forma- profiled a sequence-defined S. aureus spike-in–based indications. The re- tion. The researchers found that the transposon mutant library, identifying searchers also found a sensitivity issue more adiponectin there was in the cell mutants that had reduced adhesion in spike-in normalization practices culture medium, the less efficiently to the human-derived extracel- that has not been considered in the LDL could gain entry into the cells. lular matrix molecules fibronectin, literature. This, according to the au- The decrease in plaque-causing LDL keratin and fibrinogen. To compare

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the genetic requirements of adhesion to each host ligand, the researchers Gastric bypass affects microRNA production generated an S. aureus genetic adhesion Over one-third of people in the United States are obese, putting network, which identified a core gene them at increased risk for heart disease, stroke, diabetes and certain set involved in adhesion to all three cancers. Bariatric surgeries, procedures performed on the stomach or host ligands, as well as unique genetic intestines to induce weight loss, can help these individuals lose weight. signatures. The most commonly performed weight loss surgery, a gastric bypass, With the new assay, researchers can creates a small pouch from the stomach that connects directly to the do high-throughput screens capable of small intestine. After SHARAD PATIL/NIH FLICKR identifying new anti-adhesives. the surgery, the usable DOI: 10.1074/jbc.RA120.015360 portion of the stomach is very small, limiting Unraveling a cancer the amount a person stem cell inhibitor can eat. In addition, swallowed food bypasses Much like healthy stem cells, cancer most of the stomach stem cells are capable of self-renewal, and some of the small dormancy and generation of multiple intestine, causing less tissue-specific cell types. Since they food to be absorbed. maintain malignant tumors instead Even before they lose of healthy tissue, they are an enticing weight, patients’ meta- but elusive therapeutic target. Recent bolic and cardiovascular studies identified a small molecule — systems function better napabucasin — that inhibits cancer after the surgery. Jan During a gastric bypass surgery, the top portion of the stem cell activity. Researchers hypoth- stomach is made into a small pouch and connected directly Hoong Ho at the Uni- esize that napabucasin targets the Stat3 to the small intestine, a process that decreases nutrient versity of Manchester signaling pathway, which regulates absorption and eventually leads to weight loss. and a team of British wound healing, tissue integrity and tu- and Australian research- mor proliferation. However, they have ers have discovered how high-density lipoprotein, or HDL, the so-called not yet characterized the drug’s precise “good cholesterol,” might be involved in this phenomenon. mechanism of action. Molecular & Cellu- Lipoproteins are small particles that carry cholesterol, other lipids, A new study in lar Proteomics proteins and nucleic acid cargo between cells. HDL is considered examines protein–drug helpful because it transports cholesterol out of tissues and to the liver, interactions following napabucasin where it can be neutralized. However, researchers do not yet understand treatment in zebrafish. Led by Niels exactly how HDL controls the removal of cholesterol from tissues. Leijten from Utrecht University and Recently, researchers have found that HDL particles can carry microR- Petra Bakker from the Hubrecht Insti- NAs, short RNAs that impede the expression of genes. In a recent study tute, the authors analyzed the whole in the Journal of Lipid Research, Ho and colleagues demonstrate that organism using thermal proteome the microRNAs within HDL particles may confer the protective effects profiling. With this new technique, of gastric bypass. they identified binding events — for The group showed that HDL’s cholesterol efflux capacity is improved example, of a protein to a drug — after gastric bypass, independent of weight loss, and that this improved through changes in the thermostabil- function correlates with the levels of certain microRNAs within the ity of folded protein structures. The HDL particle. The discovery of microRNAs that regulate the removal of researchers found that napabucasin ac- cholesterol from tissues gives researchers a potential therapeutic avenue tivates aldehyde dehydrogenases, a class in the treatment of obesity and metabolic disorders. of enzymes responsible for metabolism DOI: 10.1194/jlr.RA120000963 of vital biomolecules including the — Lisa Learman morphogen retinoic acid, but does not change Stat3 signaling. They plan

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to explore further the relationship between napabucasin, aldehyde de- hydrogenase activity and cancer stem Ataxin-2 to RNA’s rescue cell viability in future experiments. Spinocerebellar ataxia type II, or SCA2 — a hereditary neurological DOI: 10.1074/mcp.RA120.002273 disorder characterized by the progressive loss of muscle control — is among the most common forms of spinocerebellar ataxias. Individuals Ceramide anchors with SCA2 first experience problems with coordination and balance, cilia proteins speech, swallowing, and eye control. Over time, symptoms also include weakness in limbs, muscle wasting, uncontrolled muscle tensing Cellular cilia depend on an axle- and involuntary jerking movements. People diagnosed with SCA2 and-spoke arrangement of microtu- often survive only 10 to 20 years after showing initial symptoms. bules for structural integrity, meaning Nearly 25 years ago, researchers identified the root genetic cause that to generate cilia, a cell must syn- of SCA2 as mutations in the Ataxin-2 gene. Ataxin-2, a cytoplasmic chronize microtubule and membrane protein that binds and stabilizes a number of mRNA sequences and is extension. The plasma membrane expressed widely throughout the brain, is involved in several trans- lipid ceramide regulates the length lation-related processes including the regulation of RNA stability/ of cilia and transport along growing translation, suppression of harmful R-loop formation, involvement in cilia, but researchers have been uncer- cellular stress response, and germline and circadian rhythm forma- tain of how ceramide concentration is tion. However, researchers have not yet uncovered the direct role of sensed. Ataxin-2 in translation. In a recent article in the Journal Polyadenylation is an important feature in the pre-processing of of Lipid Research, Priyanka Tripathi mRNA. It refers to the addition of multiple adenosine monophos- and a team from the University of phate to an RNA transcript, creating what is known as a poly(A) tail. Kentucky report that lipid modifica- Using transcriptional pulse chase analyses, Hiroto Inagaki of Nagoya tion of cysteine residues on a microtu- City University and colleagues found that Ataxin-2 promotes post- bule protein allows direct binding to transcriptional polyadenylation of its target mRNAs. The researchers ceramide in the membrane. Micro- also conducted a polysome profile analysis, providing direct evidence tubules are made up of two subunits, that Ataxin-2 enhances translation of its target mRNAs. By doing so, alpha tubulin and beta tubulin, each Ataxin-2 stabilizes the RNA molecule, preventing its degradation. of which can be post-translationally The researchers describe this work in a recent paper in the Journal modified. A subset of acetylated alpha of Biological Chemistry. They believe their findings show new ways tubulin is palmitoylated, and the that Ataxin-2 may be involved in the pathological processes of not just researchers showed using immunopre- SCA2 but also amyotrophic lateral sclerosis and other neurodegenera- cipitation and fluorescence microsco- tive diseases. py that palmitoylation allows tubulin DOI: 10.1074/jbc.RA120.013835 to bind to ceramide. It also helps — Anand Rao tubulin recruit a GTPase involved in protein transport into the cilia. The authors report that the interaction between ceramide and palmitoyl-tubulin is required for new cilia to form in human-derived neural progenitor cells, where they eventually mature into dendrites and axons. The interaction is also necessary for a distantly related eukaryotic algae to grow flagella. DOI: 10.1194/jlr.RA120001190 CONTINUED ON PAGE 26

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CONTINUED FROM PAGE 25 Noninvasive tool provides oral cancer prognosis Oral squamous cell carcinoma, which affects about 34,000 people Discovering an old DoGs’ in the U.S. each year, is found in the cells lining the lips and mouth. new trick Metastasis to the lymph nodes is a sign of disease progression and may be accompanied by changes in proteolytic activity. During proteolysis, Heterotrimeric G proteins regulate enzymes cut up proteins into short fragments called peptides. Recent a variety of signaling pathways that work suggests that characterizing the sequence and abundance of these control cell development and influ- molecules — a method dubbed peptidomics — might provide new in- ence cell morphology via actin/cyto- sight on cancer biology and in the clinic. In a recent paper in the journal skeleton remodeling. There are four Molecular & Cellular Proteomics, Leandro Xavier Neves of the Brazil- main families of G proteins: Gi/Go, ian Biosciences National Laboratory and a team of Brazilian clinicians Gq, Gs and G12/13. Researchers long and scientists describe their analysis of oral squamous cell carcinoma have thought that Gs, unlike its family patient saliva using peptidomics. members, is coupled specifically and After extracting peptides from saliva samples, the research team ana- exclusively to adenylyl cyclases. lyzed and compared the peptide content in samples from patients with In a new study published in the and without metastasis to the lymph nodes. They found more than 1,000 Journal of Biological Chemistry, uniquely expressed peptides in each group and an additional 1,628 pep- Alejandro Castillo–Kauil of the tides expressed by both groups. A series of statistical analyses identified Center for Research and Advanced 77 peptides of particular interest; all of these peptides are overexpressed Studies of the National Polytechnic in samples from patients with lymph node metastasis, which supports the Institute and collaborators challenge hypothesis that proteolytic activity increases in metastatic disease. Ten of this dogmatic view by identifying a these peptides also correlated with clinical features of metastatic tumors. new Gs target. Using biochemical, The researchers used a panel measuring the abundance of five peptides to molecular biological and chemo- classify patients according to metastatic state. genetic approaches, the researchers To predict which enzymes generated this distinctive saliva peptidome, demonstrated that the Gαs subfamily the team compared the sequences of peptides and full-length proteins to of G proteins can regulate the activity identify the most common cleavage sites. Many of the predicted en- of Rho GTPases such as Rho guanine zymes are associated with the lysosome or vacuole, linked to immunity nucleotide exchange factor, or Rho- or present in the oral microbiome. They then examined the expression GEF. The interaction identified by the CDC/UNSPLASH of these enzymes in group activates the small G protein publicly available oral Cdc42 by Gs-coupled GPCRs, stimu- squamous cell carcinoma lating a rearrangement of the cyto- tissue data. This analysis skeleton and inducing formation of showed that enhanced fingerlike protrusions called filopodia. expression of enzymes — These results provide new insight but not the proteins they into G protein activity and define a target — associates with new role for RhoGEF coupling in G metastasis and reduced protein function. survival, further bolster- DOI: 10.1074/jbc.AC120.015204 ing the link between Peptidomics analyses of saliva samples from oral proteolytic activity and A pathogen’s proteins target squamous cell carcinoma patients correlate with disease disease progression. metastasis. The technique may be a useful noninvasive mitochondria prognostic tool. Together, these analyses of proteolysis in oral The tick-borne pathogen Coxiella squamous cell carcinoma may be useful for patient prognosis. burnetii causes Q fever, or query fever, DOI: 10.1074/mcp.RA120.002227 a rare flulike disease that can spread — Nuala Del Piccolo to humans who inhale dust particles contaminated by infected farm or

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domestic animals. When C. burnetii molecules linked to PAK1. Nuala Del Piccolo (ndelpiccolo@ infects a human macrophage, it Jae-Hong Kim of Kyungpook ucdavis.edu) is a science writer transfers as many as 150 effector National University and a team of in- in the biomedical engineering proteins into the host cell. Research- ternational collaborators used genetic department at the University of California, Davis. She earned her ers know these proteins change the transformation screens, RNAi, phar- Ph.D. in materials science and host’s physiology to support the macological inhibition and migration engineering at Johns Hopkins infection. However, they know little assays to characterize PAK1-mediated University. about the contributions of the indi- signal transduction pathways thor- vidual effector proteins, partly due to oughly. The researchers selected 19 Lisa Nicole Learman (llearman@ their diversity and scarcity. candidate PAK1 genetic interactions jhmi.edu) is a Ph.D. candidate Laura Fielden and colleagues at that had human orthologs and were studying molecular neuroscience at Johns Hopkins University the University of Melbourne hy- expressed in glioma for further ex- School of Medicine. Follow her on pothesized that C. burnetii effector amination in mammalian cells, brain Twitter @LearmanLisa. proteins target the mitochondria — slice cultures and orthotopic glioma known as the powerhouse of the cell models. RNAi and pharmacological — because that organelle is crucial inhibition of potential PAK1 interac- in cellular homeostasis. To test this, tors confirmed the importance of Laurel Oldach (loldach@ the team isolated mitochondria several genes related to the mitotic asbmb.org) is a science writer for the ASBMB. Follow her on Twitter from human macrophages infected spindle, proteolysis, autophagy and @LaurelOld. with C. burnetii and analyzed the metabolism in PAK1-mediated glioma proteins using high-sensitivity mass cell migration, drug resistance and spectrometry. proliferation. The team’s recent paper in the These results, published in the journal Molecular & Cellular Journal of Biological Chemistry, Anand Rao ([email protected]) Proteomics identified seven C. provide a comprehensive view of is an ASBMB science communi- burnetii proteins associated with PAK1-mediated signal transduction cator. Follow him on Twitter @AnandRaoPhD. the mitochondria, including two pathways and identify new drug not previously found in the organ- targets for glioma therapy. elle. They found that one of these DOI: 10.1074/jbc.RA120.014831 effector proteins, MceC, moves to the inner mitochondrial membrane and interacts with mitochondrial proteins involved in quality control and metabolic function. This study presents an adapt- able method for characterizing the contributions of a pathogen’s effector Wednesdays | 12 p.m. EST proteins. DOI: 10.1074/mcp.RA120.002370 Lipid Research Division Seminar Series

Pinpointing therapies Presentations from researchers highlighting in PAK pathways their recent work in the field of lipids. Hosted by the ASBMB’s Lipid Research Division. The serine/threonine kinase P21-activated kinase-1, or PAK1, LEARN MORE AT: influences cancer-related biological processes such as cell migration, asbmb.org/meetings-events/lrd-seminar-series invasion and angiogenesis. However, researchers have not completely delineated the network of signaling

FEBRUARY 2021 ASBMB TODAY 27 28 ASBMB TODAY FEBRUARY 2021 FEATURE Can urban universities be better neighbors?

By Laurel Oldach

avarian Baldwin began studying universities’ impact on their neighborhoods two decades ago, when he stumbled across a case study in real time at the University of Chicago, where he was visiting as a junior professor to Ddo archival research. After a day in the university’s research library, he went

outside and found a protest underway. DISCOSOUR/FLICKR “The university was in the process of taking a historic blues club in the historically Black community of Bronzeville … and moving it to the campus neighborhood of Hyde Park,” Baldwin said. Local activists were in the process of objecting. The Checkerboard Lounge did end up moving to Hyde Park and stayed open there for a dozen years before closing in 2015. For Baldwin, now a professor at Trinity College, the story kindled a long-standing academic interest. “I found out that this was just the tip of the iceberg of the ways that the University of Chicago had control of the South Side,” he said. “They were the biggest employer; they were the Chicago’s Checkerboard Lounge in 2003, before it largest health care provider; they were the largest landholder on the South was moved to Hyde Park. Side; and they were the biggest policer.” With the decline of manufacturing, universities have become a significant economic force in many cities. According to one estimate, 11% of jobs in American cities today are at universities and hospitals, sometimes called “eds LEFT: GELAREH VINUEZA | RIGHT: FLICKR, ELI POUSSON and meds.” “Universities are among the most powerful institutions in advanced society,” said Ira Harkavy, an associate vice president and founding director of the Netter Center for Community Partnerships at the University of Penn- sylvania. As such, Harkavy and many colleagues see an ethical imperative for universities to do more to contribute to their local communities. The idea has caught on in academic administration; dubbed the anchor movement, this approach to managing the business of running a university also takes the community into account.

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The defensive moat strategy large philanthropy that works to improve life for American children and In some ways the conflict between youth. The foundation was looking to town and gown is as old as universi- data-informed approaches to expand ties. The expression comes from tradi- opportunity for young people grow- tional attire in Europe, where students ing up in poor urban neighborhoods. were required to attend lectures in When Rutheiser and his colleagues capes and mortarboards that set them visited grant sites, they noticed a apart from neighbors not affiliated striking pattern. with the university. “In many of those distressed, The divide remains apparent, disinvested communities, there was minus the quaint costumes, in many either a university or a hospital, or U.S. universities today. At urban cam- sometimes both, located either smack puses and medical centers in cities like dab in the middle or immediately Philadelphia, Chicago and Baltimore, adjacent to the community — but badge-wearing students and staff for all intents and purposes, that board free, liveried campus shuttles institution might have been on Mars,” while nonaffiliated residents wait for Rutheiser, who is now a senior associ- the city bus. Campus security guards ate at Casey, said. are posted at building entrances or As American cities struggled with on street corners. University staff and shrinking populations, job loss, students are disproportionately white poverty, crime and disinvestment and Asian, while the people who live through the mid-20th century, both in nearby neighborhoods are dispro- Baldwin and Rutheiser said, universi- portionately Latino and Black. ties were ill-equipped to pick up and In the early 2000s, not long before leave. Instead, they adopted a bunker Davarian Baldwin stumbled across mentality that lingered for decades. The University of Pennsylvania, shown here, the Checkerboard Lounge protest, “As I witnessed firsthand in Baltimore launched a center for community engagement Charles Rutheiser began working with during the 1980s and 1990s, this in 1992. the Annie E. Casey Foundation, a defensive posture … generated deep mistrust, hostility and conflict between institutions and communities,” Rutheiser said. Tragedy reoriented one elite university away from trying to shut out the city and its many problems. At the University of Pennsylvania in the mid-1990s, Rutheiser said, increasing crime near campus that culminated in the murder of a graduate student “led the university to rethink whether it should be in West Philly at all.” Penn leaders “realized that current business as usual was just not sustain- able, that the defensive moat strategy was not working,” Rutheiser said. “The institution made a commitment: No, we’re going to stay, and we’re going to make a renewed effort,” both to integrate with the community in

30 ASBMB TODAY FEBRUARY 2021 FEATURE STEVE GEER/ISTOCK West Philadelphia and to improve the neighborhood. “Why do universities exist? They exist to improve the world,” Har- kavy said, adding that the ethical obligation to alleviate community suffering is stronger given universities’ nonprofit status. “Whatever we have done has, in my judgment, been significantly insufficient given the state of our world and the state of our community.” The center for community engagement that he leads was founded in 1992 as part of Penn’s effort, which also involved significant investments in neighborhood safety, affordable housing and a few local schools. “The University of Pennsylvania, in shape. “Universities are doing all Boarded-up commercial buildings in Chicago’s doing it, actually showed it could be this work in communities — but Englewood neighborhood, one of the neighborhoods near University of Chicago’s campus that it done,” Rutheiser said. who are they hiring for their jobs? has prioritized for investment. And where are they purchasing their Anchoring neighborhoods goods from? Once we took a look at that, we realized there was a lot of The idea of a university as an an- improvement that could be done.” chor for its community — as depart- Alyssa Berman–Cutler, executive ment stores used to anchor shopping director of community develop- malls — started at the fringes of aca- ment in the University of Chicago’s demia in the early 2000s, supported Office of Community Engagement, initially by philanthropic investment runs the university’s anchor initia- The idea of a university as tive. “We think about our anchor from the Annie E. Casey Founda- an anchor for its community tion. Over time, the term has become mission work … as how we leverage widespread in university administra- our role as a large employer and — as department stores tive circles, mentioned in reports from large purchaser on the South Side the Obama administration’s Depart- (of Chicago) to be a good partner used to anchor shopping ment of Housing and Urban Devel- in community economic develop- malls — started at the fringes opment and cited as a key strategy ment,” she said. in a National Academies of Sciences, Historically, in communities of academia in the early Engineering and Medicine report on around the university, she said, 2000s, supported initially by improving health disparities. A domi- “There was definitely a sense that the nant model for how an institution can university was a little bit Other: that philanthropic investment from benefit its community has emerged, we might have been their neighbor, focusing on how a university’s corpo- but we weren’t really part of the the Annie E. Casey Foundation. rate functions might be localized. community.” “It really centered on the areas of Six years ago, the university hiring and purchasing,” said Bob- launched an effort called UChi- bie Laur, executive director of the cago Local, which aims to hire Coalition of Urban and Metropolitan more people from and purchase Universities, or CUMU, about how more from companies located in the anchor institution concept took nine neighborhoods around the

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CAMILO J VERGARA from community leaders that former offenders may view the check as a sign that it isn’t worth their time to apply. There, she said, is an opportunity for better communication. The university also seeks to buy from local businesses and writes into contracts that a certain percentage of subcontractors must be locally owned. Food and transportation purchasing are especially suited to local procurement. Still, “It can’t be charity,” Berman–Cutler said. Except in a few cases where a business’s mission clearly aligns with the university’s social mission — she cited a biodegrad- able cutlery company with a strong training program in manufacturing — local vendors must offer competitive pricing. According to CUMU’s Laur, An intersection several blocks south of the university’s campus. With hire-local, helping small companies scale up and University of Chicago’s campus, in the Woodlawn buy-local and live-local components, compete is part of many universi- neighborhood, shown in 2019. the program maps directly onto the ties’ anchor missions. “In order for a priorities that the CUMU initiative small vendor to support such a large espouses. At least one other university, institution, they need to have the Johns Hopkins, has a program similar business practices in place to be able in scope and design, and many more to do so,” she said. That could include have local hiring or procurement bookkeeping, accounting and billing, initiatives. or it could involve business plan- With more than 15,000 employ- ning. “Many of our members have ees, the University of Chicago is the been working for years to support seventh-largest employer in the city. programs that help build that capacity About 30% of its faculty and staff live and help smaller ventures within our in the nine priority neighborhoods; cities to be competitive.” Berman–Cutler said the program aims The third arm of UChicago Local, to raise that to 40%. Her office en- the live-local program, envisions courages hiring managers to identify university staff and faculty as residents and interview local job applicants, of the communities surrounding work with nearby job-training and the campus. The university offers placement organizations, and talk to forgivable loans to help university community groups to identify barriers employees purchase homes in those to employment. neighborhoods. For example, a background check “I’m a community-development is part of the hiring process for all professional first,” said Berman–Cut- employees. The university does ler, who spent 10 years at the non- not automatically disqualify candi- profit Uptown United before coming dates with criminal records, instead to the University of Chicago. “I feel considering each case individually, like this is an incredibly impactful but Berman–Cutler said she learned way to do that work.”

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Alex Goldenberg, the director of a University studying the role of loca- community organizing group called tion in health. Before he moved to Southside Together Organizing for Oregon, he spent a few years working Power based in Chicago’s Wood- for the Baltimore health department. lawn neighborhood, has watched It troubled Petteway that the the university’s relationship with its department’s headquarters was across neighbors change since he came to the street from a public housing de- the city in 2002, when he said that velopment but completely disengaged It troubled Petteway that the the university had a “history of being from it. “I grew up in public housing department’s headquarters extremely closed off and really not myself,” he said. “I’ve always known engaging at all with its neighbors. … no one gives a shit about us.” were across the street I’ve seen it move from that to (say- To counter the impression of ing), ‘No, we want to engage with our uncaring institutions, Petteway went from a public housing surroundings in a more meaningful door to door to meet the public development but completely way.’” whose health he was working to He credits strong leadership in the improve. During one of these walks, disengaged from it. university’s civic engagement office he and a local public housing resident for the changes and noted that hiring got to talking about Johns Hopkins, organizers like Berman–Cutler who whose medical campus was just a are expert at building relationships block or two away. The resident’s has been an important part of the comments were “a shared sentiment program’s success. Goldenberg said for pretty much everyone I talked to,” the university’s procurement work is Petteway said. especially impactful. “In the science “If they had a working relation- library, the coffee shop is owned by ship, where Hopkins was somehow a local South Side operator, which supporting their organization with a when I first came to the university grant, it was kind of like, ‘OK, we’ll was unheard of — just not the kind get along because you’re providing Baltimore’s Douglas Homes public housing project, of thing that happened.” resources.’ Outside of that I didn’t where Ryan Petteway went door-to-door to Still, Goldenberg said, he feels talk to anybody in these communities canvass residents. The development is across the that the university should do more. that thought highly of Hopkins at street from the Johns Hopkins Medical Center.

“While it’s good, it still pales in com- GELAREH VINUEZA parison to what would be needed to truly address the decades of systemic disinvestment, displacement and destabilizing impacts that the university has had on the community.” Fraught histories weigh on the present “People’s past history and experience of each other, and each other’s institutions, also informs how they show up and what they expect and what they suspect of each other,” Rutheiser said. Building trust is a delicate business. Ryan Petteway is an assistant professor of public health at Portland State

FEBRUARY 2021 ASBMB TODAY 33 FEATURE

“That was my read of that context.” Slavery and reparations Rutheiser said that things have changed at Hopkins in the past 10 In addition to efforts to build wealth in surround- years. University leaders have worked ing neighborhoods, some universities are reckoning to redress some specific historical with their own history of the severest racial inequity: harms, for example, launching twice- holding slaves. annual symposia commemorating American studies professor Davarian Baldwin Henrietta Lacks, a Black cancer pa- credits Ruth Simmons, former president of Brown tient whose cells, taken without con- University, for bringing attention to this academic sent at Hopkins in 1951, became the history. “In 2003, when she said ... ‘we’re going to immortal HeLa cell line, and offering grapple with our roots in slavery,’ that was huge, Johns Hopkins full scholarships for high-performing that was heroic, and people thought that she was graduates of Baltimore city schools. crazy,” he said. Today, dozens of universities in the U.S., Canada and the In Petteway’s experience of conver- U.K. belong to a coalition called Universities Studying Slavery. sations about inequality, he said, “It’s Scholars recently found census documents from 1850 proving that always about going forward and how Johns Hopkins, the founder of the eponymous university, counted at least we can build equity and justice … four people as his property. The find disproved a popular belief that Hop- and not thinking about how we can kins, and his parents before him, were avid abolitionists. The discovery was repair harms in the past.” Later he part of a historical examination project called the Hopkins Retrospective, added, “If whatever is happening is launched in 2013, that aimed to reexamine the university’s history. The not done from a restorative-justice news was released with an earnest open letter from the presidents of the perspective, then I don’t think it’s re- university, medical school and hospital, promising to reckon with the finding alistic for us to expect any real change and why the university accepted the story of Hopkins as abolitionist without in the level of rapport and trust.” question for so long. They also promised to join the Universities Studying Slavery. Not all aboard Georgetown University — which sold 270 people in 1838 to raise funds — formally apologized in 2017. By way of making reparations, the school Not all academic administrators has offered since 2016 legacy consideration for admission to anyone de- like the anchor movement. scended from one of the people the university sold. “There are some institutions that have been completely immune to this,” Rutheiser said, citing Colum- all ... there’s a community awareness bia University in New York as an of the harms that Hopkins had done example. Some universities, he said, historically and a sense of the harms consider local community service they’re doing right now.” ancillary to their key constituents Along that walk, he said, looking and their mission of teaching and down a street from the housing proj- research. “They serve their students, ect toward campus, he saw a hiring their staff, science as a whole, and so ad for new security guards, clearly forth, and not the people living across designed to be seen by passersby. It the street.” might have been a university effort to Harkavy, too, said he has seen offer employment opportunities to “fear of a kind of mission drift” when local residents: advertising entry-level trying to persuade colleagues to invest jobs close to home for disadvantaged substantial resources locally. “Univer- potential applicants. To Petteway, it sities feel that they’re doing (benefi- read very differently. “If you want to cial) things, and they don’t often see come on this campus, the only way how doing this more centrally fulfils you can come on this campus is if their mission.” you’re one of our sentinels,” he said. Even if a university leader supports

34 ASBMB TODAY FEBRUARY 2021 FEATURE

an anchor mission in principle, it can MAX COHEN / THE DAILY PENNSYLVANIAN be challenging to execute. Academia is known for its inertia and fondness for tradition. A case study published in the journal Higher Education Policy found that research faculty incentives are not well aligned with community benefits. Universities are decentralized, and different orienta- tions toward the community across departments and units can make for a complex overall picture. Finally, while counting changes in employee or vendor locations may be straightforward, measuring the impact of a community-oriented mission on a local economy or population subject to hundreds of other factors can be very difficult. For some leaders in academia, seeing institutions launch anchor commitments, and seeing such commitments as prestige projects, has been relations, said. Thanks to this clas- Participants in a 2018 protest in support compelling, Rutheiser said. The Carn- sification in the tax code, universities of PILOTs outside of the University of Pennsylvania’s Ben Franklin College Hall. egie Foundation for the Advance- generally do not pay property taxes on ment of Teaching, which developed what they own, despite some being the widely used classification system major urban landholders. Baldwin for colleges based on size, research and some others argue that this, in activity and highest degree conferred, effect, robs cities of revenue, especially has launched a special classification when universities lease property to Many universities make for-profit businesses. to recognize institutions with strong voluntary contributions community commitments. Partly in response to such critiques, many universities make voluntary to their city governments contributions to their city govern- Compulsory vs. voluntary known as payments in lieu contributions ments known as payments in lieu of taxes, or PILOTs. PILOTs are assessed of taxes, or PILOTs. PILOTs The University of Pennsylvania was as a portion of the taxes that would an early adopter and an important be owed on the property universities are assessed as a portion front-runner in the anchor institution hold, and institutions can write off movement. Yet, in the past year, the services that provide social good. In of the taxes that would university has been deeply embattled the 1990s, when Philadelphia was on be owed on the property over what it owes its community. the brink of bankruptcy, Penn, like “Universities are identified as an many nonprofits, contributed in the universities hold, and inherent public good … because they form of PILOTs. But later the univer- institutions can write off provide services to their cities or their sity dropped the practice. communities that would normally In recent years, university students services that provide have to be procured by the govern- and school-based community groups ment,” Davarian Baldwin, the Ameri- in Philadelphia, led by the nonprofit social good. can studies scholar who recently has Jobs with Justice, campaigned to published a book on university–city get the university to return to the

FEBRUARY 2021 ASBMB TODAY 35 FEATURE

practice. A Penn spokesperson told Pep Marie, a lifelong Philadelphia the student newspaper last summer resident and activist who co-led the that the university’s contributions to Pay Your Fair Share movement with school programs and financial con- a parents’ organization called Philly Penn donated $250,000 to tributions to two schools outweighed SUN, was not impressed by the gift. what it might do with PILOTs. (The “I think UPENN likes to position support businesses near its paper reported that the school district itself as a savior to Philly,” she wrote campus; Hopkins gave over had received about $861,000 from the in an email, “by providing a lot of university in cash assistance the prior resources no one asked for instead of $2 million; and the University year.) paying their taxes or responding to of Chicago contracted In 2020, with a new push by asks from school communities.” activists, a group of staff and faculty Summers traced a connection with local caterers and launched a petition called Penn for between the anchor movement and PILOTs. The organization calculated how universities contribute to their with its own food service that if the university were to pay cities’ bottom lines. “The idea of call- staff to coordinate a food- 40% of the property tax rate on the ing them anchor institutions is saying, land it owns, the annual total would ‘The cities lost … their factories; now distribution program in be $40 million, or about 0.35% of they can depend on universities and the early months of the the university’s annual revenues. (If medical centers.’ But if that’s what passed through directly to the school this new economy is going to look pandemic. system, the sum would represent a like, these big institutions … have to 2.5% increase in funding from the support the public institutions that local government, which covers about everybody needs.” half of the system’s annual operating She anticipates that growing politi- expenses.) cal pressure — such as a bill in the The petition happened to launch Pennsylvania state legislature that just weeks before George Floyd’s mur- would exempt nonpublic buildings der sparked a national wave of social- such as dormitories and gyms from justice activism. It was signed by more the public good classification — than 1,100 faculty and staff. might incentivize universities to pay “The two really came together,” PILOTs eventually. said Mary Summers, one of the fac- Harkavy said he sees PILOTs as ulty members who organized the Penn very far from a settled question in for PILOTs campaign. “I remember Penn’s ongoing effort to support its one faculty person said, ‘A man community. “It’s one of a number kneeling on someone’s neck for eight of activities that are on the table, in minutes is a clear example of racism. terms of ‘What should institutions But so is a child that’s not learning to do?’” read in an underfunded, overcrowded school with lead and asbestos.’” A tumultuous year In November, Penn pledged to donate $100 million over 10 years to Laur expects the Black Lives Matter remove asbestos and lead from Phila- movement to prompt greater invest- delphia public schools. It wasn’t what ment in anchor work. “Layering in Penn for PILOTs was asking for, but anti-racism and trying to think about it was a significant investment. Sum- trying to address systemic inequities mers said, “We see it as a first step,” has always been a part of what we’ve adding she felt certain the pressure talked about.” activists put on the university had a Meanwhile, universities face dif- real impact. ficult financial decisions. A November

36 ASBMB TODAY FEBRUARY 2021 FEATURE

headline in the Chronicle of Higher Education read, “Colleges have shed A kaleidoscopic movement a tenth of their employees since the pandemic began.” Student enroll- This article focuses on three large, private universities in majority-Black ment has dropped, and revenues cities. These schools have a lot in common, including an outsized effect on have followed. Some institutions their postindustrial cities’ economies, since each is among its city’s largest have frozen hiring during the private employers. But they represent just one slice of the anchor movement. pandemic, and procurement is “It’s not just the Hopkinses, UPenns and UChicagos of the world,” paused with many students living Charles Rutheiser of the Annie E. Casey Foundation said; smaller colleges off campus and many staff working with less substantial endowments, and in some cases large public from home. universities, have also expressed anchor commitments. If universities are in crisis, their As the concept has gained popularity, the number of institutions pursuing cities may be even worse off. Ac- an anchor mission has grown. They’ve organized into several groups, cording to a recent estimate, 12 including the Anchor Institutions million Americans are behind on Task Force, which includes rent by an average of almost $6,000, libraries, hospitals and museums and close to half of almost 9 mil- in addition to universities and lion renters surveyed expected to colleges, and an anchor learning network run by the Coalition of Urban be evicted within months. Busi- and Metropolitan Universities of about 30 universities. Those universities nesses have closed, homicides have and colleges are diverse in location and size, including state and private increased, and, for many children, universities and ranging in size from just 2,200 students education has been disrupted for at Wagner College in New York to almost 28,000 at close to a year. All this in addition California State University in Los Angeles. to the psychological impacts of a “What really binds everybody together,” said year of isolation raises deeply con- Coalition of Urban and Metropolitan Universities cerning questions about the future. executive Bobbie Laur, “is a clear commitment Community-engagement offices to place.” at major universities have helped out as they can. Laur said that many universities in the anchor network have acted as trusted conveners ordinate a food-distribution program purchasing more equitably will stay during the pandemic, connecting in the early months of the pandemic. in place. individuals or schools in need of “It was a really nice win-win-win The anchor movement addresses services to the government agencies that we were able to stand up very a number of complex problems that or foundations that can help them. quickly, in part because we had rela- have yet to be resolved — and that At the University of Chicago, Alyssa tionships with some of these business- Harkavy believes society must face. “If Berman–Cutler’s office has worked es earlier on,” Berman–Cutler said. you look at the world today, at what to support businesses with which Still, some projects have halted. In the profound problems are … issues they have relationships, offering light of budget uncertainty, Chicago’s like extreme inequality, social justice them free marketing and adminis- live-local forgivable loans for em- and racial justice, issues related to trative support in applying for loans ployee housing have been suspended, environmental degradation; these are and grants. at least for 2021. issues that occur in their most sharp Then there’s direct support: Laur said that she doubts the pan- and clear form in America’s cities.” Penn donated $250,000 to support demic will end the anchor movement. businesses near its campus; Hop- “The university’s success is tied to Laurel Oldach (loldach@ kins gave over $2 million; and the the success of our cities,” she said. As asbmb.org) is a science writer for University of Chicago, in addition such, she expects that even if the scale the ASBMB. Follow her on Twitter @LaurelOld. to making $680,000 in grants, of hiring or purchasing at universi- contracted with local caterers and ties changes, the processes the anchor with its own food service staff to co- movement has inspired for hiring and

FEBRUARY 2021 ASBMB TODAY 37 FEATURE Securing space for Black women scientists in a crooked room

By Courtney Chandler SPELMAN COLLEGE

imberly Jackson noticed as a graduate student that when Kshe attended scientific meetings, she was one of the only Black women in the room. She remembers feeling discouraged, but she also saw it as a challenge — one she’s worked intentionally to address and change. “I decided early on in my career that I didn’t have to be the only Black woman in the room,” she says. “I could bring other Black women with me into this space.” Jackson is now chair of the department of chemistry and biochem- As chair of the department of chemistry and biochemistry and director of the food studies program istry and director of the food studies at Spelman College, Kimberly Jackson studies cancer therapeutics and drug discovery. A Fulbright program at Spelman College, a Scholar, she also works with her colleagues to develop approaches that train and retain Black women historically Black college for women in STEM fields. in Atlanta, Georgia. In addition to her research on cancer therapeutics can American women earned only the National Science Foundation as and drug discovery, she and her col- 6.2% of all Ph.D. degrees granted the leading producer of Black women leagues have worked hard to develop to women in 2019. When looking who go on to earn doctorates in the approaches that train and retain at life sciences specifically, the total sciences. Black women in science, technology, number of women earning Ph.D.s Jackson and others have published engineering and math fields. increased 12% from 2010 to 2019. on practices they’ve identified that Jackson has written about how Yet the number of female African support the success of Black women lasting discrimination and stereo- Americans earning Ph.D.s in life in STEM, guiding the way for other types have left the STEM space as sciences increased only 1% in the colleges and institutions to follow. a proverbial “crooked room” for same time span. In fact, in several But Jackson doesn’t think many women of color. They often are life science fields including marine institutions are using these resources forced either to contort themselves biology, astrophysics, applied physics — despite her work and Spelman in order to fit in an atmosphere in and neuropsychology, not a single students’ success, she says she isn’t see- which their abilities are diminished doctorate went to an African Ameri- ing widespread impact. or to decide to stand straight in a can man or woman in 2019. “We should have more institutions space that is disorienting, uncom- Spelman’s success at righting knocking down Spelman’s door to fortable or both. In these unlevel the crooked room for its students ask questions and listen about how to environments, lack of opportunity is well documented. Spelman is a successfully make these changes, yet it and recognition diminishes women’s Department of Defense Center of hasn’t happened,” she said. achievements. Excellence for Minority Women in Instead, she sees institutions look- The data reflect this reality. Afri- STEM and has been recognized by ing to Spelman not to emulate its

38 ASBMB TODAY FEBRUARY 2021 FEATURE COURTESY OF ALISON BROWN success but to feed off its student “It was an amazing experience pool. Spelman prides itself on creat- to be surrounded by so many other ing accomplished students who come Black woman-scientists (at Spel- from an encouraging environment. man) and live in a community But the spaces they move to next are where I did not have to question my often not the same. worth because of my identity,” Van “Instead of re-engineering their says. She credits Jackson with teach- environment to welcome our stu- ing her the importance of standing dents, many of these institutions try in her identity and confidently to change (our students) as if they’re pursuing her future. the deficit,” Jackson says, citing first- “The research community is hand accounts she’s heard from past slowly striving towards inclusion trainees and focus group data she’s and diversity,” Van said. “But they collected. “We can produce wonder- are also struggling to maintain these ful students but if they go into a students and assure they are in a space where they’re not conformable, safe space to not only strive for suc- it can be extremely derailing.” cess but to speak up without fear.”

Life after Spelman Strategies for change Alison Brown received a 40 Under 40 Health Alison Brown, program director at Award from the National Minority Quality Forum In response to these lasting the National Heart, Lung and Blood in 2018 at the same time she was experiencing challenges, Jackson continues to Institute’s Division of Cardiovascular microagressions in her Ph.D. program at Tufts identify strategies that can be used Sciences and a Spelman alumna, says University. to create spaces where Black women her experience as an African Ameri- in STEM can thrive. She’s writing a can woman in STEM largely has betics in a predominantly African paper on how cohorting, in which been influenced by her environment. American community in Boston was programs or institutions accept at When she was pursuing a master’s dismissed completely by classmates. least two Black candidates together, degree at Columbia University, she Instead of conforming to their proj- can be used to help support women said, she felt comfortable, partially ect ideas, she set out and completed of color during their education or due to the diversity of New York the project on her own. careers. City. But as a Ph.D. at Tufts Uni- “Although I excelled in the proj- Mentor and mentee training is versity in Boston, she had a different ect, it was hurtful, being dismissed another institution-level change experience. and having to do the project com- that could help provide a secure “I definitely experienced those pletely by myself,” she said. “I had space for Black women. Mentors moments of microaggressions when many experiences like that.” and mentees can get the tools they eye contact is avoided in meetings or Brown earned her Ph.D. in 2017, need to form mindful and produc- where your competency or quality of but many Black students in STEM tive relationships in many places, work is questioned, especially during still have similar experiences. Destiny Jackson said, including the National group projects,” Brown says. “Body Van, another Spelman alumna, Research Mentoring Network. The language and responsiveness to ideas now a second-year Ph.D. student NRMN provides anti-racism and all play a role in feeling dismissed or in Cornell University’s biochemis- unconscious bias training modules, diminished.” try, molecular and cellular biology among others, that could help men- She was the only African Ameri- program, said it’s still difficult to tors ensure an inclusive environ- can Ph.D. student in the food policy find Black women represented in the ment for women of color. and applied nutrition program, a STEM research community outside Jackson hopes institutions that field dominated by white women. of historically Black institutions. Van are committed to reengineering She remembers one group project in says this lack of widespread represen- their STEM spaces to be inclusive particular where her idea to develop tation can make it seem overwhelm- and supportive of Black woman a nutrition intervention for dia- ing to continue in a STEM career. can look to Spelman as a guide

FEBRUARY 2021 ASBMB TODAY 39 FEATURE COURTESY OF DESTINY VAN

Destiny Van, a second-year Ph.D. student in Cornell University’s biochemistry, molecular and cellular biology program, said it’s still difficult to find Black women represented in the STEM research community outside of historically Black institutions.

I think there needs to be and partner. She thinks continued that the next generation of Black ‘‘ lines of communication between women will continue to advocate for re-hauling of the entire these institutions and Spelman can their space in STEM. scientific enterprise. We need be critical to driving and sustaining “They speak up for themselves,” change. Jackson says. “My generation was a to change how people perceive As an example, Jackson points to bit quieter and more reserved, but this what a scientist should look the Leadership Alliance, a consor- generation is more expressive about tium of colleges, universities and pri- their feelings and what they’re going like and then make changes to vate institutions aimed at supporting through — they won’t hesitate to blast underrepresented students during you on social media.” support this diversity.” their education and research careers. Students can’t take on the burden As a member of the alliance, Spel- of changing the STEM space on their KIMBERLY JACKSON man works to increase the readiness own. Despite their advocacy and the and competitiveness of its scholars as efforts of Jackson and others, Spelman they enter careers in the biomedical grads know work is still needed to workforce. right the crooked room permanently. These focused efforts will be criti- “We’ve moved the needle, but not cal, but Jackson believes more global far enough,” Brown said. “We still changes are needed to secure space have a long way to go.” fully for Black women in STEM. “I think there needs to be re- Courtney Chandler hauling of the entire scientific enter- ([email protected]) is a prise,” she said. “We need to change postdoctoral researcher at the department of biochemistry and how people perceive what a scientist molecular biology at the Johns should look like and then make Hopkins University School of changes to support this diversity.” Public Health and an industry careers columnist for ASBMB While a scientific overhaul is out Today. Follow her on Twitter @ of her hands, Jackson is optimistic CourtneyCPhD.

40 ASBMB TODAY FEBRUARY 2021 FEATURE ‘Every experiment and every breakthrough matters’ An interview with NYMC dean Marina K. Holz By Angela Hopp

arina K. Holz, a researcher She has continued her studies of NEW YORK MEDICAL COLLEGE and dean at New York LAM at her new lab at NYMC, where MMedical College, started she heads up the Graduate School of her scientific career with her eye on Basic Medical Sciences and directs its cancer for both scientific and personal integrated Ph.D. program. reasons. In observance of Rare Disease Day As a Ph.D. student at Harvard on Feb. 28, ASBMB Today talked to Medical School, she studied the serine/ Holz about her work on therapies for threonine kinase mTOR. It regulates LAM, one of which is being tested on a cell growth and, when its pathway goes small number of patients, and with the awry, can contribute to tumor progres- LAM Foundation, which funds research sion. At the same time, her mother was and advocates for patients. undergoing treatment, which ultimately failed, for breast cancer. “Her experience created the desire Q. Tell me a bit about your lab’s for me to pursue this area of research work. and to focus on diseases that affect A. My lab studies the mechanisms of women,” Holz told NYMC’s annual cell growth and proliferation. We are Chironian Magazine in 2019. specifically interested in the mTOR Marina K. Holz is dean of New York Medical So that’s what she did. Her first fac- signaling pathway and its crosstalk College’s Graduate School of Basic Medical ulty position was at Yeshiva University with estrogen signaling. mTOR is a Sciences and directs its integrated Ph.D. program. in New York City. There, she built a lab master regulator of cell growth and She is a member of the American Society for thus important for development and Biochemistry and Molecular Biology’s Women in that studied signaling pathways and progression of several diseases. Biochemistry and Molecular Biology Committee. growth factors in breast cancer. Estrogen is a hormone that regu- Within a few years, however, the lates reproductive functions and is science led Holz in a new direction. She crucial for the development of many followed it from a disease that affects diseases, such as breast cancer. We many to one that affects very few: the would like to uncover how the two pathways work in concert to regu- rare disease lymphangioleiomyoma- late gene expression at the level of tosis, or LAM for short, a metastatic transcription as well as translation, neoplasm that affects the lungs in fine-tuning the cellular responses in women of childbearing age. homeostasis and disease.

FEBRUARY 2021 ASBMB TODAY 41 FEATURE

What specifically interested Q. How did you begin to get supplementation quite soon, while ‘‘ involved with rare disease others do not. The diversity in the me about LAM was the obvious research? disease progression is in itself an area connection to estrogen, since of active investigation. For some, lung A. In the early 2000s, pioneering transplantation is eventually needed. the disease mainly manifests work of several labs, including John The decrease in the quality of life Blenis’, where I was doing my Ph.D., for women, who are usually diagnosed in women of childbearing age uncovered the connection between in their 20s to 40s, is devastating. and is exacerbated during mTOR and a rare genetic disease Moreover, patients who require oxy- called tuberous sclerosis complex, or gen have to face rude behavior from pregnancy. I felt that my lab TSC. (Editor’s note: Blenis moved strangers in public who assume that from Harvard to Weill Cornell in could draw on many lessons the harm is self-inflicted because of 2014.) smoking. from our breast cancer work Mutations in genes TSC1 or TSC2 lead to TSC, which causes benign Q. What are their treatment to develop new insights into tumors called hamartomas in many options? LAM.” organs as well as central nervous A. system manifestations, including TSC1/2 mutations cause abnormal epilepsy and autism. activation of mTOR. The mTOR Some patients with TSC develop inhibitor sirolimus, an analog of the pulmonary lymphangioleiomyoma- naturally derived agent called rapamy- tosis, a rare disease in which TSC1 or cin, is approved by the Food and TSC2 mutations metastasize, causing Drug Administration for the treat- cystic lung destruction. Pulmonary ment of LAM. LAM is seen in 30% to 40% of adult The therapy strikingly stabilizes TSC patients. lung function and improves quality of However, LAM can also arise spo- life. So, while having any rare disease radically in women with no history is an enormous health challenge, of TSC, and sporadic LAM affects LAM is exceptional in the rare disease women almost exclusively. space because of the availability of a What specifically interested me life-extending treatment. about LAM was the obvious con- Like many drugs, however, it is not nection to estrogen, since the disease without side effects, which include mainly manifests in women of child- some immunosuppression, mouth bearing age and is exacerbated during sores, gastrointestinal issues, etc., and pregnancy. I felt that my lab could unfortunately some women either draw on many lessons from our breast don’t tolerate it well or their disease cancer work to develop new insights still progresses while on the drug. into LAM. Q. You won a grant from the LAM Q. What’s life like for women with Foundation in 2013, and that was LAM? the start of a long relationship A. with the organization. How did The initial symptoms are ambigu- that play out? ous and include shortness of breath and bronchitislike symptoms, fatigue A. I attended a LAM research sympo- and chest pains, and some women sium — LAMposium — to accept the experience pneumothoraxes. There is award, and what was so remarkable a progressive decline in lung function. about it was the prominent role and Many women require oxygen the participation of the patients, who

42 ASBMB TODAY FEBRUARY 2021 FEATURE NEW YORK MEDICAL COLLEGE

were an integral part of the event. the medical community, increasing Holz earned her bachelor’s degree in microbiology Sitting in sessions with these the likelihood that women get proper and immunology at McGill University in Montreal amazing women, who asked diagnoses when they present with in 2001 and her Ph.D. in cell and developmental detailed and informed questions some of the ambiguous symptoms of biology at Harvard Medical School in 2006. Since 2018, she has been a professor of cell biology and about the nitty-gritty of research, LAM. anatomy and dean at New York Medical College. talking to them during meals and dancing with them at the gala Q. The work you began with that crystalized for me something that I one-year pilot grant led to clinical previously felt only intuitively: how trials of a new combination much every experiment and every treatment. Tell us about that. breakthrough matters to real people who depend on these advances to A. This trial is led by Dr. Nishant save their lives. Gupta, my wonderful collaborator at I went on to join the scien- the University of Cincinnati. tific advisory board of the LAM It is built on preclinical work from Foundation, which for the past 25 my lab that showed that adding resve- years has been funding research ratrol, a naturally derived compound, into LAM as well as engaging in to rapamycin (an mTOR inhibitor patient advocacy and building a used for treatment of LAM), specifi- clinical care network in the U.S. cally causes death of TSC-deficient and worldwide. cells. The efforts of the LAM Foun- We hope that, unlike rapamycin, dation have led not only to an which stops disease progression but FDA-approved treatment but also doesn’t eradicate the TSC-mutant greater awareness of the disease in cells, with disease resuming upon ces-

FEBRUARY 2021 ASBMB TODAY 43 FEATURE NEW YORK MEDICAL COLLEGE sation of treatment, the combination I realized that the setback to women’s would allow patients to stop treat- careers was enormous and would ment without disease progression. have effects for years to follow. So This is a first trial in humans, I’m glad that this article was read and and it’s still ongoing, but some data shared widely. should come soon. I feel strongly about advocating for women in science at all career Q. How has the COVID-19 levels, and I am proud to be part of pandemic affected your work at the American Society for Biochemis- NYMC? try and Molecular Biology’s Women in Biochemistry and Molecular Biol- A. Like most institutions around ogy Committee, whose mission is to the country, NYMC shuttered the increase participation, visibility and research labs in March of 2020. We status of women within the scientific gradually reopened in May but are community. working at a slower pace due to our efforts to give space to researchers Q. Any final thoughts? and reduce the time they have to spend together. I am really grateful A. There is still much more to be to my team, who continue to do done in understanding the origins research despite the risks. of sporadic LAM, improving the quality of life of LAM patients and Q. How has the pandemic developing curative treatments, but affected LAM patients or the hope is on the horizon. In 2013, Holz won the LAM Foundation’s Pilot foundation’s work? I am also optimistic about the Award to study mTORC1 and S6K1 signaling in future of science in general. In the LAM and the connections between S6K1 and A. A highly infectious and deadly past year, we experienced great lows estrogen in LAM cells. She is shown here at the respiratory disease is a huge concern but also amazing highs — several foundation’s annual conference, known as the to patients who already have a lung Nobel prizes awarded to women and LAMposium, with patient and board member disease. Some of the precautions two vaccines approved for prevention Eden Pontz. like wearing masks are challenging of COVID-19. for people who are on oxygen and Like most scientists, I miss my struggle to breathe. colleagues and the collaborations The LAM Foundation did an that are forged at conferences and amazing job holding virtual educa- breakthroughs that happen in in- tional events for patients as well as stitute hallways. But scientific work research symposia and even an online must go on, because there are real gala, which allowed it to fund a new people who depend on us to deliver slate of researchers for its 2020 grant the treatments for diseases we know cycle. and, as we unfortunately discovered, ones yet to come. Q. Over the summer, you wrote an article for us about how the pandemic was affecting women Angela Hopp (ahopp@ in science. It was one of our asbmb.org) is executive editor most-read articles in 2020! of ASBMB Today and communications director for the A. I am not a prolific writer, but I ASBMB. Follow her on Twitter @angelahopp. felt compelled to speak up, because right from the onset of the pandemic

44 ASBMB TODAY FEBRUARY 2021 CALL FOR SUBMISSIONS Contribute to the ASBMB Today REIMAGINING ISSUE

The world after COVID-19 will be a different place. Let’s reimagine ways the scientific enterprise could be more sensible and just.

Think about the systems around you for teaching, funding, doing and publishing science. Can they be improved? Should they be replaced?

In 500 to 1,500 words, tell us what you would do to make them better.

Send submissions to [email protected] or go to the submissions page at asbmb.org/asbmbtoday.

Deadline: March 15

Share your aha moments! Call for essay submissions.

The ASBMB's three journals — Journal of Biological Chemistry, Molecular & Cellular Proteomics and Journal of Lipid Research — are now open access. To celebrate this important change, ASBMB Today is hosting an essay contest that showcases scientists' "aha moments."

Learn more and submit your essay at: asbmb.org/journals-news/open-access

ASBMB ournals move to open access open to move ournals ASBMB Received for publication, March 7, 2020, and in revised form, June 21, 2020 Published, Papers in Press, June 22, 2020, DOI 10.11118.asbmb.00044727681 DOI 2020, 22, June Press, in Papers Published, 2020 21, June form, revised in and 2020, 7, March publication, for Received he American Society for Biochemistry and Molecular Biology Molecular and Biochemistry for Society American he

FEBRUARY 2021 ASBMB TODAY 45 PERSPECTIVES #BlackInX Twitter movement creates visibility for Black scientists

By Martina Efeyini

n honor of Black History Month, I am showcasing Black scientists Iwho have careers outside of academia or industry. This is my career story as well. I am a toxicologist, science communicator and science education advocate. As a Black woman in science, I grew up not seeing people who looked like me in spaces where I wanted to be, especially in the media. Now we are slowly seeing more Black scientists represented on television KISHANA TAYLOR and social media and in different industries. Twitter movements, last year the other #BlackinX weeks, and the Last year as the COVID-19 CrossTalk.Cell.com published goal was to showcase and celebrate pandemic started, we also were going multiple lists of 100, 100 more and Black chemists. During #BlackinAs- through a racial reckoning. During 1,000 inspiring Black scientists in tro, founded by Ashley Walker (an in- this time, the #BlackInX Twitter America. I encourage you to follow tern at NASA movements were on the rise; more and collaborate with more Black sci- Goodard people were speaking up about the entists this year. As a Black scientist, Flight Center racial injustices, challenges and lack of I am grateful these movements were and #Black- visibility of Black scientists. Currently, created and that the next generation inChem there are more than 30 #BlackInX of scientists will have many Black co-founder), I Twitter movements. science role models. I look forward to tweeted that I I am focusing on two: #BlackInMi- the growth of these movements. would love to cro and #BlackInChem. Both move- curate #Black- ASHLEY WALKER ments started because the organizers #BlackInChem inChem, if I realized that they did not see scientists found some help.” who looked like them, and they Devin Swiner, a Ph.D. candidate Soon other grad students and wanted that to change. These move- at Ohio State University, shared how professionals started chiming in on ments made learning about Black putting out a Twitter. Swiner did not expect to scientists more accessible and changed call for action get all these responses. From there, the narrative of what a scientist looks on Twit- the group of co-organizers formed like. They also created a safe space and ter started to make #BlackInChem. Along with an environment where encouraging a chemistry Swiner and Walker, the organizers the next generation of Black scientists movement: included Ayanna Jones, a Ph.D. stu- was at the forefront. “#Black- dent at Emory University; Kathleen In addition to the growth of InChem was Muloma Rink, a National Society of #sciencetwitter and the #BlackInX DEVIN SWINER inspired by all Black Physicists associate; Natérica

46 ASBMB TODAY FEBRUARY 2021 PERSPECTIVES

das Neves Rodrigues Lopes, a Marie infection and Curie research fellow at Lipotec subsequent SAU; Samantha Theresa Mensah, a development Ph.D. candidate at UCLA; and Heidi of Nelson–Quillin, a scientist at the COVID-19. Azimuth Corp. “Ear- “It started because of a need to lier this spring center Black people doing chemistry,” and through- ARIANGELA J. KOZIK Swiner said. “We saw it as a great op- out the portunity to show the world that we summer, there were many movements exist and do great science.” formed in the wake of continued Learn #BlackInChemWeek was created racial inequality and violence,” Kozik to bring more visibility to Black said. “In the academic community, something chemists and build a community. The this included #ShutDownSTEM, virtual events ran Aug. 10–15 and #BlackBirdersWeek, and others that new. included virtual events and Twitter gathered a coalition of scientists and chats featuring different chemistry STEM professionals to speak out specialties, an elevator pitch competi- more openly about the challenges Watch on-demand tion, a career journey panel and a net- faced by their Black colleagues and to webinars and events working event. After this successful amplify the presence of Black scholars including scientific week, @BlackInChem has over 6,200 in their fields. Twitter followers and is continuing “In the context of a pandemic with presentations and to grow. disproportionate impacts on the Black discussions on topics Visit their Twitter page, community along with widespread related to career @BlackInChem, and website, misinformation about microbiology, development, Blackinchem.com. we also felt a sense of urgency,” she education, funding added. and more. #BlackInMicro Others felt it too; a week later, 30 people coming from different career Ariangela J. Kozik and Kishana levels in microbiology came together asbmb.org/ Taylor, two Black women postdoc to organize #BlackInMicroWeek. meetings-events/ microbiologists, were encouraged by Running from Sept. 30 through Oct. #BlackInX to start #BlackInMicro. 4, it included a roll call and discus- on-demand Kozik has a Ph.D. in comparative sions about STEM education dispari- pathobiology from Purdue University. ties in the Black community, vaccines, She is a postdoctoral research fellow virology, and HIV and the Black at the University of Michigan Medical queer community. @BlackInMicro School in the division of pulmonary has over 7,100 Twitter followers and critical care. She conducts research is continuing to grow. in Yvonne Huang’s laboratory on Visit their Twitter page, @BlackIn- how the respiratory microbiome is Micro, and website, Blackinmicrobi- involved in the presentation and ology.org. pathogenesis of asthma. Taylor has a Ph.D. in interdis- Martina Efeyini (mefeyini@ ciplinary biomedical sciences from gmail.com) is a toxicologist, science communicator and advocate the University of Georgia. She is a for the next generation of scien- postdoctoral fellow at Carnegie Mel- tists. She works at the University lon University in Elizabeth Wayne’s of Maryland, Baltimore, CURE Scholars Program and is a ca- lab. Her research focuses on the role reers columnist for ASBMB Today. of macrophages in SARS-CoV-2 Follow her on Twitter @mefeyini.

FEBRUARY 2021 ASBMB TODAY 47 PERSPECTIVES The evolution of proteins from mysteries to medicines

By Ken Hallenbeck

hat does the word “protein” make you think of? Steak Wand eggs, or a health food diet, perhaps? What about a cancer drug? Today, advanced medicines are often a purified protein rather than something synthesized by a chemist. Proteins, built within our cells from individual amino acids, are an intricate class of biomolecules that fulfill a wide array of functions in human biology. That is why a healthy diet includes a constant stream of protein: to fuel the maintenance of our trillions of internal biomolecule machines. Their core role in our biology is also why protein dysfunction leads to many human diseases. Fortunately, over the last 50 years, molecular biology research uncovered acceptable therapeutic profile. For scientists have uncovered how to use the structure of DNA and how DNA example, the first versions of human proteins themselves as drugs to treat is translated into protein molecules. insulin degraded so quickly that the diseases they cause. These and other advances led to the injections were required many times It didn’t start fancy, though. In invention of recombinant protein per day. Optimization took decades the late 1800s, doctors researching technologies: methods to insert into and continues today with the grow- diabetes narrowed down the problem DNA the code for any protein that ing interest in automated insulin to the pancreas. In the 1920s, Freder- can be read by bacteria and other delivery systems. ick Banting, Charles Best and J.J.R. lab-friendly microorganisms. For the One important class of biolog- Macleod discovered that reinjecting first time, our own molecules could ics is antibodies. Antibodies are an patients with pancreas extracts con- be synthesized at large enough scale to essential part of the mammalian taining the protein insulin restored be explored as therapeutics. immune system, so when robust blood glucose regulation. They won You might think that what fol- antibody production methods were the 1923 Nobel Prize for their experi- lowed was an explosion in the use invented in the 1970s, intensive ments, and the first protein drug was of proteins as medicines. However, research ensued. The result was the born. But extracting insulin from biologics (as they now are called) are first approval of an antibody drug by animal pancreases for therapeutic use challenging molecules to develop the Food and Drug Administration was difficult and inconsistent, and and administer to patients. They in 1986: muromonab-CD3 to treat it would take researchers decades to often suffer from stability or solubil- the rejection of kidney transplants. learn how to produce human insulin ity problems, and countless small Other similar treatments soon fol- for use as a medicine. First, basic variations often are tested to find an lowed. However, these first-

48 ASBMB TODAY FEBRUARY 2021 PERSPECTIVES

generation antibody therapies proteins for use as drugs. DNA- proteins from mysterious biological often induced immune reactions encoded libraries now can screen machines to molecules we can use to in patients because the hybridoma vast numbers of protein variants treat disease. I firmly believe the next method used for their production (more than 10 billion), enabling 50 years will bring breakthroughs of takes advantage of a mouse antibody the rapid discovery of antibodies similar importance. As technologi- scaffold. Using human hybridomas or peptides with high affinity for cal developments enable new ways was untenable, so researchers devel- drug targets. Paired with decades to discover drugs, the effectiveness of oped methods to graft human and of production and humanization the treatments we can develop will animal scaffolds together in chimeras method development, the pipeline continue apace. that reduced the immunogenicity of for turning an antibody into a drug the resulting antibody molecule, all candidate is faster than ever before. (This article was written to mark without compromising the portion The frontiers of biologic drug National Protein Day, Feb. 27. Find that attacks the drug target. The development now lie in new ways more science and health observances at resulting humanized antibodies now to engineer and modify proteins asbmb.org/asbmbtoday.) represent the most profitable and themselves. For example, antibod- rapidly growing class of approved ies can be made bispecific or have Ken Hallenbeck (k.hallenbeck@ drugs in the United States. drug payloads conjugated directly to gmail.com) earned a Ph.D. in Since the turn of the century, them. Small proteins and peptides pharmaceutical sciences from advances in protein-based medi- can incorporate nonnatural amino the University of California, San Francisco, and now is an early cines have continued. The push to acids and succeed where larger bio- drug discovery researcher. He sequence the entirety of the human logics fail — some are being tested serves on the board of directors genome led to large advances in in clinical trials now. of ReImagine Science and is the life sciences lead at TerraPrime. DNA sequencing technology, which Over the last 50 years, basic re- Follow him on Twitter in turn enabled new ways to discover search discoveries have transformed @ kenkhallenbeck.

Upcoming ASBMB events and deadlines

FEBRUARY Black History Month 7 Periodic Table Day 11 International Day of Women and Girls in Science

ARY 14 Cancer testis antigens virtual event 22 Regular registration deadline for Proteinases and their inhibitors

FEBRU 24–26 Proteinases and their inhibitors 27 National Protein Day 28 Rare Disease Day

MARCH Women’s History Month 15 Abstract deadline for PDB50: A special symposium celebrating the 50th anniversary of the Protein Data Bank

MARCH 15 Early registration deadline for PDB50: A special symposium celebrating the 50th anniversary of the Protein Data Bank

APRIL 12 Early registration deadline for the 2021 ASBMB Annual Meeting

APRIL 27–30 2021 ASBMB Annual Meeting

FEBRUARY 2021 ASBMB TODAY 49 PERSPECTIVES Learning to be a science superhero

By Alison Smith COURTESY OF ALLIE SMITH

hen I was about 7 years old, I knew I wanted to be a Wsuperhero who uses science (specifically, I wanted to be able to shrink down really small and fight bad bacteria like the main character in my favorite movie, “Osmosis Jones”), even though I didn’t know what a scientist was. I thought there was nothing cooler than being able to be microscopic and fight the bacteria and parasites that plague us in real life. I was fascinated by the natural world around me, but I believed that was the case for everyone. My parents had high school diplomas but could not afford to go to college. I was raised by a single mother in rural Massachusetts, and it was not until high school that I realized college was an option for anyone other Allie Smith poses with Andrew, a camper at Camp Sunshine in Casco, Maine, in 2015. Andrew has than aspiring doctors or lawyers. As hypoplastic left heart syndrome, and after working with him, Smith wanted to become a cardiothoracic I went through a high school where surgeon. most graduates went on to attend college, I began to understand what great), I became passionate about to many schools on my own, and college was and why people decided HLHS. I decided that I wanted to I didn’t feel as if my family was in to go, but I thought it was out of my go to college and become a car- a financial position to help. With financial reach. diothoracic surgeon to study the this in mind, I narrowed down The summer before my senior mechanisms of this congenital heart my choices by finding the suc- year in high school, I volunteered defect. cessful teachers at my high school at Camp Sunshine, a place that Not only was tuition expensive, and applying to their alma maters. provides respite for children with but even applying for college was a Thanks to my AP chemistry teacher, life-threatening illnesses and their financial burden; taking SATs and I applied to Stonehill College, a families. There I met 18-month-old sending scores, requesting transcripts private college in Easton, Mas- Andrew, a child with hypoplastic and submitting the Common App sachusetts, where I was accepted left heart syndrome, or HLHS. all cost money my family couldn’t and received various scholarships From working with Andrew (who is spare. Even working 20-plus hours such that I could afford to attend. It now in fourth grade and doing just a week, I couldn’t afford to apply was there at Stonehill College that

50 ASBMB TODAY FEBRUARY 2021 PERSPECTIVES

I met Bronwyn Heather Bleakley, COURTESY OF ALLIE SMITH who introduced me to the world of research. In my second semester at Stone- hill, I took an introductory biology class with Dr. Bleakley. During a lesson about Trypanosoma cruzi, a parasite that causes a disease in humans that weakens heart walls, I asked why a similar mechanism couldn’t be used to break down the heart muscle in cardiomyopathy patients. Instead of dismissing my question, Dr. Bleakley recom- mended I do some research. This led to a conversation about postgraduate plans. I told her I wanted to become a cardiothoracic surgeon to study the mechanisms of HLHS. She told me about other postgraduate careers in science that I didn’t know existed. She told me about graduate school Allie Smith, right, and Bronwyn Heather Bleakley at Stonehill College convocation in fall 2016. Bleakley and earning a master’s degree or had been awarded professor of the year and asked Smith to introduce her. This photo was taken after Ph.D. and the many doors those de- their speeches. grees open — doors such as becoming a senior scientist in a laboratory, would be able to ask and answer ques- the genetics of social behavior in becoming a principal investigator or tions by doing hands-on research. It guppies, Poecilia reticulata. I spent a lecturer at a university, or working was then that I decided I did not want three years and two full summers in science policy. All careers where I to be a doctor. Instead, I became pas- doing research in that lab, learning

COURTESY OF ALLIE SMITH sionate about going every technique and concept I could, into research and then quite literally, get my hands on. I academia, hoping that had found a place where I could one day I could be bloom as a scientist. even half as good a re- After graduation, I moved to searcher and professor La Romana, a coastal city in the as Dr. Bleakley. Dominican Republic, for a year of After I completed service at the Hogar del Niño for the the intro biology class, Patronato Beneficio Oriental. This Dr. Bleakley let me school serves more than 1,700 of the join her lab, studying most economically vulnerable children in La Romana, ranging in age from 14 days through high school. Juniors at Hogar del Niño It is the only school in that entire learn English and science region for people who are deaf; at the same time. They did an experiment with ooblek children who are deaf are taught (a mixture of cornstarch Dominican Sign Language as well as and water), and Allie Smith all mainstream subjects so they can had them describe the be integrated full time into the class- experiences of their five room in eighth grade. The children senses in English. who can hear also learn Domini-

FEBRUARY 2021 ASBMB TODAY 51 PERSPECTIVES COURTESY OF ALLIE SMITH hands-on science while also reinforc- ing their English communication about science topics. I used my $60-per-month stipend to buy household items we could use in our science experiments. On Wednesdays we would go outside to the playground area, where we extracted DNA from fruit, hypothesizing which fruit we would get the most DNA from (it was mangos), or dissolved the eggshell off an egg. The 15 students in each of my classes soon were joined by all the science teachers and then by students outside of my classrooms. Random students I had never even met started telling me about their eggs at home and how someone from my class was Allie Smith takes a selfie with a group of sophomores in the outside science classroom at Hogar del Niño. showing everyone in their neighborhood the experiment. What started as can Sign Language to decrease the from seventh to 12th grade at all a few students turned into a science language barrier across peers as the levels of English proficiency. The revolution. children who are deaf are integrated intermediate level was my per- My year in La Romana quickly into extracurriculars from preschool sonal favorite; they had the passion came to an end, and I moved to on. The school offers medical, dental, for English and lots of room for Bloomington, Indiana, to start my psychological and sociological services growth. During this year, due to Ph.D. That was more than two years as well as three meals a day and cloth- the economic demand in the city, ago, but to this day, I am still search- ing for each child. the school increased its acceptance ing for funding that will allow me and At the Hogar del Niño, I taught rate until the student-to-teacher a few fellow graduate students to fly English to more than 330 students ratio was about 35:1, squeezed in annually to the Dominican Republic classrooms that didn’t allow for to train science teachers how to do Allie Smith purchased household items to do much, if any, movement. hands-on science experiments they experiments on Science Wednesdays at Hogar del With the space constraints and can perform using everyday house- Niño — such as dissolving the shell off an egg. little funding, hands-on science

COURTESY OF ALLIE SMITH hold items. experiments were not an option. What’s better than a world full of I thought back to my child- superheroes? A world full of superhe- hood when I had wanted to be a roes who use science. superhero who uses science. I had (This essay was written to mark the wanted to be a superhero because I International Day of Education, Jan. didn’t know that I really wanted to 24. Find more observances at asbmb. be a scientist. And now I couldn’t org/asbmbtoday.) stop thinking about the more than 1,700 children at the school. How many of them also wanted to be Alison (Allie) Smith ([email protected]) is a Ph.D. superheroes who use science? candidate in the Genome Cell With this in mind, I started and Developmental Biology Science Wednesdays in my English Program at Indiana University Bloomington, in Justin Kumar’s classroom of about 15 students. lab. Follow them on Twitter I wanted to give them access to @EctopicEyeQueer.

52 ASBMB TODAY FEBRUARY 2021 Images in Lipid Research A new article format in the Journal of Lipid Research

The editors of the Journal of Lipid Research are pleased to announce the adoption of a new article format: “Images in Lipid Research.” Each peer-reviewed, one-page article contains a single horizontal image, a 400-word caption and up to four references.

In creating the “Images in Lipid Research” format, we hope to celebrate scientists and the images they create. These articles will be easy to read and eective in communicating discoveries in lipid research. “Images in Lipid Research” will appear in PubMed and will be citable.

Learn more at jlr.org/images-in-lipid-research

FEBRUARY 2021 ASBMB TODAY 53 ESSAY Project SHORT shares know-how

By Lauren Fields COURTESY OF LAUREN FIELDS

didn’t have enough money to go through the Ph.D. application Iprocess more than once, so I set out to make my one-and-only application as competitive as I could. I spent hours watching videos, reading blogs, listening to podcasts and asking questions on social media until I felt Lauren Fields meets with Jigar Sethiya, one of her mentees, via Zoom to work on preparing his grad versed enough to begin preparing my school application. application. I learned about attending Ph.D. admission seminars, emailing My first mentee is a second-year sought out computational and virtual professors and reaching out to current undergraduate and already eager research opportunities to compensate graduate students. It was a hands-on to prepare himself for a chemistry for the loss of in-person research she process and very time-consuming, graduate program. Because he won’t was counting on for her grad school so I did not want all my newfound graduate for a couple of years, we application. I now am working with knowledge to fall by the wayside once crafted an email to a potential re- her to revise her personal statements I began my Ph.D. journey. search advisor, asking about opportu- as well as locate and apply for fee Looking for ways to share my nities to gain undergraduate research waivers. know-how with future graduate experience, which will allow him to Project SHORT’s services provide school applicants, I discovered Project be a more competitive applicant for my mentees with a contact who can SHORT, an organization founded graduate programs. I told him about answer questions readily, minimizing in 2019 by Hannah Loo, a Ph.D. the National Science Foundation’s the often intimidating task of consult- student at the University of Pennsyl- Research Experience for Undergradu- ing with professors on the application vania. The name stands for Student ates. We also worked together to find process. I believe these relationships Health Opportunities and Research conferences where he could present are helping students who otherwise Training, and the program matches his work, such as the Society for might have been provided with little prospective graduate students with a Advancement of Chicanos/Hispan- information about admissions to be mentor who provides free consulting ics and Native Americans in Science, better prepared to gain admission to to help navigate the application pro- better known as SACNAS. grad school. cess. Mentees also get help with pro- Another mentee of mine bal- Undergraduate students interested gram selection, feedback on personal ances being a single mother, work- in being mentored by Project SHORT statements and mock interviews. As ing and attending school. I was a and graduate students, postdocs and of December, the graduate school arm first-generation college student who others interested in becoming mentors of Project SHORT had 374 mentors worked full-time through much of can find information and applications serving 378 mentees. my undergraduate education, so I at project-short.com. As a Project SHORT mentor, I could relate. We worked together (Marya S. Sabir and Hannah K. have partnered with future gradu- to craft her personal statements in Loo, both of Project SHORT, assisted ate students at various stages in the a way that highlights how profes- with critical revision of this article.) application process to help them con- sional experiences can be beneficial firm that graduate school is right for in a graduate school program. When Lauren Fields ([email protected]) is a chemis- them and work with them to become the COVID-19 pandemic disrupted try graduate student studying genetically encodable strong candidates for admission. her undergraduate research, we sensors at the University of Wisconsin–Madison.

54 ASBMB TODAY FEBRUARY 2021 QFive Questions Giving labs the tools to be successful

By Laurel Oldach Whatever they find at a crime scene, in whatever quantity, they want to or almost three decades, Doug- test it: telephones, bloodspots, bodies las Storts has been developing — anything. Ftools for genetic amplification at the reagent supply company Pro- mega in Madison, Wisconsin. “I’ve enjoyed working on lots of projects,” H ow did you come to he said. “There’s been a huge variety work at Promega? over the years.” 3I recognized early on that I was not According to Storts, the through- interested in an academic position. line that ties his group’s work on After I received my Ph.D. and did genetic changes in astronauts to a postdoc, I went to a small startup cancer diagnostics is that they company in Austin, Texas, for about always are working to solve puzzles. two years. I transferred to Promega Douglas Storts ASBMB Today caught up with him in 1991 based on a recommendation for the latest in our series on indus- from a recruiter. I have not looked CURRENT POSITION try careers. This interview has been back. Head of Research, Nucleic condensed and edited. Acid Technologies, Promega Corporation As the head of research in W hat traits do you look CAREER PATH nucleic acids at Promega, for in a potential hire? Ph.D., microbiology, Miami what do you work on? No. 1 skill: communication. It University, 1980 4 Postdoctoral research: University I manage a group of about two would be great to have somebody 1 of Chicago dozen scientists working on projects come in with a technical background related to nucleic acid amplification exactly aligned with what I need. FIRST JOB OUTSIDE OF ACADEMIA and genotyping. The products we That rarely happens. So what I want Ambion, a molecular biology develop are used for forensic testing, is somebody who has good commu- startup in Austin, Texas molecular diagnostics and also in nication skills who can take direction FAVORITE MOLECULE the life science research community. without being offended and can reach DNA We develop tools that we can give out for help when they have any to laboratories across the world and questions. I can teach anyone to do enable them to be successful. almost anything. They have to be able W hat career advice to listen. do you give young This second skill is being able to scientists? W hat’s most challenging think outside the box. If somebody about your work? 5Work hard. Be creative. Be a team thinks A plus B must equal C, then if member. My perception is there are a With some of these assays, we’re A plus B equals anything other than 2 lot of folks that have a big gap in one looking at 30 or more different C, they’re totally flustered. When you of those three areas. targets in the genome in a single show them they’ve walked into this amplification reaction that has to with a box around their thoughts and Laurel Oldach (loldach@asbmb. be extremely robust and extremely the data clearly indicate the answer org) is a science writer for the efficient. We need to reliably detect lies outside of the box, they begin ASBMB. Follow her on Twitter @LaurelOld. copies of DNA every time, time to understand: You’ve got to think after time. In forensic tests, the outside the box to solve complex samples are almost unimaginable. problems.

FEBRUARY 2021 ASBMB TODAY 55 ASBMB Journals are now open access.

Journal of Biological Chemistry Molecular & Cellular Proteomics Journal of Lipid Research

The American Society for Biochemistry and Molecular Biology’s three journals are open access beginning in January.

asbmb.org/journals-news/open-access

56 ASBMB TODAY FEBRUARY 2021 classifieds

Postdoctoral Position Available Process Development Technician — Department of Tropical Medicine at Tulane University Enzyme Manufacturing Watchmaker Genomics

A NIH-funded postdoctoral position is im- Watchmaker Genomics is an mediately available to join the Scaraffia re- early-stage life science company search group. Scaraffia´s lab is particularly based in Boulder, Colorado. Our interested in unraveling the physiological, team is passionate about in- biochemical, and molecular basis underlying the regulation of nitrogen novation and values collaboration, creativity and scientific rigor. We and carbon metabolism in mosquitoes, as well as in discovering new metabolic targets that can be used for the design of better mosquito–control believe the intersection of biology, engineering and computer sci- strategies. The successful candidate will apply traditional and modern ence presents exciting opportunities for developing novel technolo- biochemical approaches to investigate the mechanistic regulation of am- gies that promote research and improve human health. Watchmaker monia metabolism in Aedes aegypti mosquitoes. Genomics specializes in the design, development and production of DNA- and RNA-modifying enzymes that enable high-growth applica- ASBMB Journals are Requirements tions in genomics, molecular diagnostics and personalized medicine. • PhD degree in biochemistry or related discipline with a strong background in protein biochemistry, and metabolic signaling We are inviting applications for the full-time position of Process • Research experience in metabolic studies Development Technician — Enzyme Manufacturing. This position now open access. reports to the Production Manager — Enzyme Manufacturing, and • Documented experience in biochemical techniques including western will support existing enzyme manufacturing procedures and assist blotting, immunoprecipitation and immunofluorescence microscopy in the development of novel upstream and downstream techniques • Excellent communication skills and ability to work independently as well utilizing the latest advancements in chromatography and instru- as part of a team mentation. This position will interface directly across all aspects of To apply, submit a single PDF file to [email protected] with the production, including quality control, logistics and technical support. subject Postdoc Application and include: https://careers.asbmb.org/job/process-development-technician- Journal of Biological Chemistry (1) a cover letter describing research interests (no more than1 page); enzyme-manufacturing/55716975/ (2) your curriculum vitae; and Molecular & Cellular Proteomics (3) contact information for three references. Journal of Lipid Research Proteomics Mass Spectrometry Chemist ImmunogeneticsApplied BioMath, Clinical LLC Lab Manager VRS Recruitment UCLASenior Scientist, Health Mathematical Modeler The American Society for Biochemistry and Molecular Biology’s three journals Exciting opportunity to join an internationally You will be a key leader within the renowned Healthcare Diagnostics company in David Geffen School of Medicine for beautiful Maine! The successful candidate will the Immunogenetics Center, an inter- are open access beginning in January. be responsible for developing new Proteomics nationally-respected center of clinical, and Metabolomics workflows using HRMS in support of diagnostic and academic and research innovation and excellence. Within our 24-hour therapeutic R&D. laboratory environment, you will provide administrative, programmatic and personnel management while overseeing development, productiv- Primary Responsibilities: ity, materials management and regulatory compliance. We’re looking to asbmb.org/journals-news/open-access • Lead analytical projects supporting internal teams developing cutting you to promote interdisciplinary cooperation as you work closely and edge diagnostic tools and therapeutics collaboratively with faculty to develop operating principles, goals and • Develop and optimize high-res LC/MS methods for protein, peptide, priorities. You will: and metabolite identification / quantification • Oversee daily laboratory operations • Maintain and troubleshoot Thermo LC-MS instrumentation • Process data, compile results, and present project findings • Develop, implement and monitor budgets Candidate Qualifications: • Ensure compliance with all relevant laws, regulations and standards for safety, human resources, accreditation, permitting, licensure, and • PhD or MSc in Analytical Chemistry, Biochemistry, Biology (or similar) certification with a background in mass spectrometry • Experience in the use of LC-MS instrumentation; preferably Thermo • Facilitate staff growth while also pursuing self-development • Familiarity with peptide/protein assay development and informatics is • Maintain and model technical expertise a PLUS! • MUST be self-sufficient and able to manage your own work, including • Ensure the delivery of high quality, efficient, cost effective clinical instrument troubleshooting and maintenance services https://careers.asbmb.org/job/proteomics-mass-spectrometry- https://careers.asbmb.org/job/immunogenetics-clinical-lab- chemist/55716861/ manager/55190988/

To see a full list of jobs, please visit careers.asbmb.org The 2021 ASBMB Annual Meeting will be virtual!

LearnJoin us more April at 27–30asbmb.org/annual-meeting Advance registration deadline: April 12 Learn more at asbmb.org/annual-meeting

The ASBMB annual meeting is held in conjunction with Experimental Biology.