Vol. 20 / No. 5 / May 2021

FIRST CLASS Meet the inaugural ASBMB FELLOWS Planning a scientific conference? The ASBMB is here to help.

LEARN MORE: asbmb.org/meetings-events/propose-event CONTENTS

NEWS FEATURES PERSPECTIVES

2 32 44 EDITOR’S NOTE TARGETING 20,000 PROTEINS WINNERS OF THE ‘AHA MOMENTS’ Planning a scientific conference? ‘Share your aha moments!’ BY 2035 ESSAY CONTEST 44 Finding a common ancestor 4 38 45 Dreaming of Western blots MEMBER UPDATE EXPLORING UNDERAPPRECIATED 46 Beauty in brown The ASBMB is here to help. MOLECULES AND NEW CITIES 47 Fringe inspiration 8 47 A life filled with aha moments IN MEMORIAM 48 The first to know 49 The right experiment 9 49 Prepared mind leads to life-saving RETROSPECTIVE medical advice Remembering Curtiss, former JLR associate editor 50 Superhero science 51 Not quite out of the box 10 MEMBER NEWS 52 First class: Meet the inaugural FIVE QUESTIONS ASBMB fellows Alanna Mitsopoulos: “I could be happy doing other things” 20 LIPID NEWS Ceramides’ role in liver disease 10 16 JOURNAL NEWS 21 JLR names new junior associate editors 23 Study reveals experimental targets for lymphoma research 24 Researchers target cell membrane for cancer research 25 Parasitic secretions create 32 microenvironment for survival 44 26 From the journals

LEARN MORE: 20 38 asbmb.org/meetings-events/propose-event 52 MAY 2021 ASBMB TODAY 1 EDITOR’S NOTE

Vol. 20 / No. 5 / May 2021

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY ‘Share your aha moments!’ THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRYOFFICERS ANDCOUNCIL MOLECULAR MEMBERS BIOLOGY Suzanne Barbour Toni M. Antalis By Allison Frick President Joan Broderick OFFICERS CharlesCOUNCIL Craik MEMBERS Gerald Hart Gerald Hart MattSquire Gentry J. Booker Past President President SusannaVictoria Greer J. DeRose ’m not a scientist. My back- Fast-forward to January 2021, Wei Yang Blake Hill Jennifer DuBois Audrey Lamb Secretary Audrey Lamb ground is in broadcast jour- when ASBMB’s journals made Secretary JamesJames M. M. Ntambi Ntambi nalism. When I came to the the transition to gold open access. Joan Conaway Takita Felder Sumter I Toni M. Antalis Celia A. Shiffer Treasurer American Society for Biochemistry Papers published in the Journal of Treasurer KellyTakita Ten–Hagen Felder Sumter Kelly Ten-Hagen and Molecular Biology in 2015, Biological Chemistry, the Journal JoAnn Trejo EX-OFFICIOEX-OFFICIO MEMBERS MEMBERS ASBMB TODAY EDITORIAL it was from a local TV station, of Lipid Research, and Molecular ADVISORY BOARD RobertRobert S. HaltiwangerS. Haltiwanger where I covered high school sports & Cellular Proteomics were going RajiniASBMB Rao TODAY EDITORIAL CarlaCarla Koehler Koehler ChairADVISORY BOARD online and worked with reporters to be published immediately and be Co-chairs,Co-chairs, 2020/2021 2020 Annual Annual AnaRajini Maria Rao Barral MeetingMeeting Program Program Committee Committee and producers on related TV ele- permanently available for everyone Chair Cheryl Bailey Natasha Brooks Cheryl Bailey ments. Biochemistry and molecular to read, download, copy, distribute Chair, Education and Professional KellyFloyd Chacón “Ski” Chilton Chair, Education and Henrik Dohlman Development Committee Beronda Montgomery biology were a far cry from Friday and reuse. In preparation for the Professional Development Peter J. Kennelly DanielCommittee Raben BillBeronda Sullivan Montgomery night lights. I was nervous to enter change, our marketing and com- Chair, Meetings Committee Daniel Raben MelissaA. Maureen Vaught Rouhi a new realm of content, but, more munications teams were tasked with Chair, MeetingsSonia Committee Flores BinksMelissa Wattenberg Vaught Chair, Minority Affairs importantly, I was excited for a new coming up with a plan to share the Sonia Flores Binks W. Wattenberg Committee Chair, Minority Affairs ASBMB TODAY challenge. news. Nicole Woitowich Committee AngelaASBMB Hopp TODAY The thing that I absolutely love Last fall, Joanna Kotloski, then Chair, Science Outreach and ExecutiveAngela Editor Hopp CommunicationSusannna Committee Greer the most about working in commu- our digital and content marketing Chair, Public Outreach [email protected] Editor Terri Goss Kinzy [email protected] nications is hearing people’s stories. manager; Anand Rao, our publica- Committee Comfort Dorn Chair, Public Affairs Comfort Dorn Matthew S. Gentry Managing Editor I love learning about how they’ve tions department’s science com- Advisory Committee Managing Editor Chair, Public Affairs [email protected] [email protected] navigated life. In fact, when I was municator; and I all hopped on AdvisoryEd Eisenstein Committee Chair, Membership Committee LaurelJohn Oldach Arnst a kid, I really wanted to grow up Zoom one afternoon and started Sandra Weller Science Writter Susan Baserga Science Writer Chair, Publications [email protected]@asbmb.org to be an actress. My logic: I’d never brainstorming. We wanted to come Chair, Women in BiochemistryCommittee and Molecular Biology Ed LaurelMarklin Oldach have to choose just one job. I could up with a fun way to encourage Lila CommitteeM. Gierasch WebScience Editor Writter Editor-in-chief, JBC [email protected]@asbmb.org try everything if I was an actress. scientists to share their discoveries in Sandra Weller Ed Marklin A. L. Burlingame It turns out performing is not my ASBMB journals. I love these brain- Chair, Publications AllisonWeb EditorFrick CommitteeEditor, MCP Multimedia [email protected] and Social Media forte, but I never lost that passion storming sessions and admire Joan- NicholasLila M. O. Gierasch Davidson ContentAllison Manager Frick for storytelling and learning about na and Anand for their creativity. As [email protected] Editor-in-chief,Editor-in-chief, JBC JLR Media Specialist the human experience. we talked about what motivates us A. L.Kerry-Anne Burlingame Rye [email protected] F. MIller Editor-in-chief,Editor, MCP JLR ExecutiveBarbara Director Gordon Once I got to the ASBMB and to connect with organizations and [email protected] Director Nicholas O. Davidson [email protected] began working as a multimedia remember content, TikTok came Editor-in-chief, JLR content specialist and sharing to mind. Then Joanna remembered Kerry-Anne Rye articles from ASBMB Today on one of her favorite commercials Editor-in-chief, JLR our social media channels, I started from Southwest Airlines, and as the ForFor information information on on advertising, advertising, contact contact Pharmaceutical Pharmaceutical getting to know our members and ideas kept coming, we landed on the Media Inc. at 212-904-0374 or [email protected]@pminy.com.. the scientific community. I quickly slogan “Share your aha moments!” learned that scientists have fascinat- That was the beginning; we’d make ing stories. From their personal a TikTok-inspired video with our experiences to their research, they members passing papers to one www.asbmb.org/asbmbtodaywww.asbmb.org/asbmbtoday are inspired to figure out how this another and a second video with PRINTPRINT ISSN ISSN 2372-0409 2372-0409 world works. I knew I was going to words of encouragement about the hear some amazing stories working opportunities offered by publishing ArticlesArticles published published in ASBMB in ASBMB Today Today reflect reflect solely solely the authors’the authors’ views viewsand not theand official not the official positions positionsofthe American of the SocietyAmerican for BiochemistrySociety for Biochemistry and Molecular and here, and I have. in an ASBMB journal. BiologyMolecular or Biologythe institutions or the institutions with which with the authorswhich the are authors affiliated. are affiliated. Mentions of productsMentions or of services products are or not services endorsements. are not endorsements.

2 ASBMB TODAY MAY 2021 EDITOR’S NOTE ASBMB

ess 681 7 cc a 11118.asbmb.0004472 . open o t e v ess, June 22, 2020, DOI 10 DOI 2020, 22, June ess, r P in s r ape P orm, June 21, 2020 Published, Published, 2020 21, June orm, f vised e o m r in and 2020, journals , 7 ch ASBMB Biology r a M ation, c r olecula M and publi r o f ed v ei c e R y Biochemistr r o f y t e Soci an c Ameri The - n o c d n a l u f e r a c s a w s s ce e e w s, n o i t a er o r p g n i k a m n- o si i c e d ur O b i l e d g n o s-l h t n o m ur Ngee Kiat “Jake” Chua encouraged his fellow We recruited help from our select the winners. We’re publishing o g n i r u D . e v i t a t l u s journals’ associate editors and JBC’s the winning essays in this issue, start- ASBMB members to share their aha moments. early-career reviewers. They showed ing on page 44. We hope you enjoy up and went above and beyond to them as much as we did. bring this to life. I have to thank When I reflect on my own career, Ray Blind, Craig Cameron, George I realize my first few months at the Carman, Courtney Chandler, Ngee ASBMB were huge for me. Before We’re publishing the winning Kiat “Jake” Chua, Michel Geovanni starting here, I’d taken steps toward essays in this issue, starting on Santiago–Martínez and Catherine changing fields. I wasn’t sure com- Goodman for graciously appearing munications was right for me, but my page 44. We hope you enjoy them in these videos. Their performances experience at the ASBMB reminded were outstanding! You can see for me how much I love storytelling and as much as we did. yourself on the ASBMB’s YouTube multimedia. It was career-changing. channel. Working here was my aha moment, From there, another element and to this day, not a month goes by of the “Share your aha moments!” when I’m not reminded I’m in the project came to life, and for this, right place. This month, that’s thanks we have Angela Hopp to thank. She to these essays. Thank you for sharing created an essay contest, asking our your stories and aha moments with us members to reflect on their careers and reminding me just how grateful I or those of scientists they respect am for mine. and to write about the aha moment that sparked a shift in their work. It could be any kind of revelation Allison Frick (africk@ asbmb.org) is the ASBMB’s that changed the trajectory of their multimedia and social media research or life. We received dozens content manager. Follow her on of submissions. Wow. Thank you to Twitter @allisonfrick. all who contributed. It wasn’t easy to

MAY 2021 ASBMB TODAY 3 MEMBER UPDATE

Hanawalt, Nagata and for cellular apoptosis.” Nagata and that university’s new Fisher Center his lab described a membrane protein named professorship for neurode- Regev named AACR fellows called the Fas receptor as a cell death generative disease research. The American Association for receptor; after binding to its ligand, Strickland’s lab studies the con- Cancer Research announced in March which Nagata’s lab also identified, tribution of vascular dysfunction to the new class of Fas initiates an extrinsic cell death the development fellows in its AACR pathway that is crucial for immune of Alzheimer’s dis- Academy, which control of tumors. ease; they found recognizes scientists Nagata is a member of the Japan that beta-amyloid whose contribu- Academy and a foreign associate of protein can tions have led to the U.S. National Academy of Sci- promote clotting progress against ences. and inflammation cancer. Three Aviv Regev has been the executive in the brain by in- HANAWALT American Society vice president of Genentech Research STRICKLAND teracting with fi- for Biochemistry and Early Development since 2020. brinogen and acti- and Molecular Biology members — The AACR honors her for “devel- vating coagulation factor FXII. The Philip Hanawalt, Shigekazu Nagata oping and applying sophisticated work has suggested new molecular and Aviv Regev — are among the computational modeling techniques mechanisms for the widely studied class of 25 fellows. and algorithms to understand mo- β-amyloid protein to contribute to Philip Hanawalt is an emeritus lecular circuits and predict cellular Alzheimer’s pathogenesis and has professor of biology at Stanford Uni- behavior.” While linked the disease to other common versity. The AACR is honoring him a professor at the maladies of aging, such as hyperten- for his contributions to DNA damage Broad Institute and sion and cardiovascular disease. repair. He co-discovered the ubiqui- Massachusetts In- The position, funded by the Fish- tous process of DNA excision repair stitute of Technol- er Center for Alzheimer’s Research in 1964 and also discovered transcrip- ogy and a Howard Foundation, will support research tion-coupled repair, which removes Hughes Medical into neurodegenerative diseases. It transcription-blocking damage from Institute investiga- extends the Fisher Center’s partner- the template strands of expressed REGEV tor, Regev led a ship with Rockefeller University; genes. His work has furthered our un- lab that developed the university is also home to the derstanding of the role of unrepaired high-throughput single-cell sequenc- foundation’s flagship lab of 40 scien- DNA damage in ing technologies and conducted tists focused on Alzheimer’s disease. oncogenesis. systems modeling to understand cells’ Strickland has been a member of Hanawalt is a responses to varying stimuli. She co- the Fisher Center’s neuroscience fellow of the Ameri- leads the Human Cell Atlas project, advisory committee since 2019. can Academy of a multinational research consortium Arts and Sciences, that aims to define each cell type in Blind recognized by GSA a member of the the human body. National Academy Regev is a member of the National Raymond D. Blind, an assistant NAGATA of Sciences, and a Academy of Sciences and the National professor at Vanderbilt Univer- past member of the Academy of Medicine. sity, was named in early March a AACR’s board of directors. He is a member of the inaugural cohort for senior editor for the journal Cancer Strickland to hold the Genetics Society of America’s Research. new professorship Presidential Membership Initiative. Shigekazu Nagata is a distinguished This competitive program aims professor of biochemistry and immu- Sidney Strickland, a professor, to diversify the GSA membership nology at the Immunology Frontier dean of graduate and postgraduate while providing professional-devel- Research Center of Osaka University studies, and vice president for educa- opment programming and support in Japan. He is honored by the AACR tional affairs at Rockefeller Univer- for early-career scientists. for “categorizing crucial steps required sity, will be the first person to hold Blind’s lab studies how nuclear

4 ASBMB TODAY MAY 2021 MEMBER UPDATE

inositides and inositols regulate chro- in biology from Williams College, a metabolite converted into NADH matin-bound proteins. He recently master’s degree in biology from Case during cellular respiration. NAD+ completed a two-year stint as a junior Western Reserve University and a declines with age in both mice and associate editor for the Journal of Ph.D. in genetics from the University the roundworm Caenorhabditis el- Lipid Research, an American Society of Wisconsin. egans. When it is for Biochemistry and Molecular Biol- Research in the Hazelbauer lab missing, glycolysis ogy publication. at the MU School of Medicine and can slow down. Blind gave a talk the College of Agriculture, Food McReynolds’ titled “The acyl and Natural Resources focuses on research explores chains of phos- elucidating molecular mechanisms of how the result- phoinositides alter transmembrane receptors and sensory ing energy deficit the structure and transduction in bacterial chemotaxis. might contribute function of nuclear A number of recent projects have used MCREYNOLDS to cellular ageing receptor steroido- the emerging technology of nanodiscs and whether it BLIND genic factor-1” at a to manipulate membrane proteins in can be reversed. She also has pub- special session on a water-soluble state. lished extensively on mentoring and lipid diversity and disease at the 2021 Hazelbauer is making an initial improving the equity of scientific ASBMB Annual Meeting. $20,000 donation to LTHS this year, training. which will support creative projects of The move is a homecoming Hazelbauer pledges several of the school’s science teach- of sorts: McReynolds earned her ers. He has pledged to give at least the Ph.D. in biochemistry, molecular $1 million to high school same amount each year while he and biology and microbiology at Penn Gerald Hazelbauer, a curators’ his wife are alive, State in 2017. She served as the distinguished professor emeritus of prior to the $1 mil- president of the Black Graduate biochemistry at the University of lion posthumous Student Association during her Missouri, plans to donate $1 million donation. time in State College. She arrived to foster innovative science teaching A member of the at Penn State through a Bridges to at Lyons Township High School in American Society the Doctorate program with Alcorn Illinois. for Biochemistry State University in Hazelbauer, a 1962 graduate of and Molecular Mississippi, where she earned her the school, is making the bequest in HAZELBAUER Biology since 1984, bachelor’s and master’s degrees. Her honor of Ruth Wenner, his fresh- Hazelbauer is also awards as a graduate student in- man biology teacher, according to a fellow of the American Association cluded an award from the Alfred P. an article in the Riverside/Brookfield for the Advancement of Science Sloan Foundation Minority Ph.D. Landmark. and of the American Academy of Program; as a postdoc, she has Wenner, described by Hazelbauer Microbiology. received a Howard Hughes Medical as an innovative and challenging Institute Hanna Gray fellowship teacher who treated her students McReynolds to join faculty and the Burroughs Wellcome Fund like scientists, arranged for him to Postdoctoral Enrichment Program accompany her to some laboratory at Penn State award. sessions of a summer course for Melanie McReynolds, a postdoc- Department chair Wendy teachers at the Illinois Institute of toral fellow at Princeton University, Hanna–Rose was McReynolds’ Technology after his freshman year. will join the faculty at Pennsylvania dissertation adviser. “Dr. McReyn- The following year, she gave him the State University’s department of olds is a creative and collaborative opportunity to be student leader of a biochemistry and molecular biology, researcher of exceptional promise,” high school research project funded taking a named early-career chair, in she stated in a Penn State news by the National Science Teachers’ January of next year. release. “As a graduate student, she Association through the Future Sci- McReynolds studies the metabolic was well known and recognized entists of America Foundation. He changes that occur during aging, across campus for her activism and went on to earn a bachelor’s degree focusing on NAD+, the essential leadership.”

MAY 2021 ASBMB TODAY 5 MEMBER UPDATE

Passano Foundation Goldberg’s wide-ranging work has Each year, the Alfred P. Sloan had a major impact on many areas Foundation provides fellowships honors Goldberg of biology, medicine and biotech- to promising scientific researchers Alfred Goldberg, professor of nology. whose achievements and potential cell biology at Harvard Medical place them among the next genera- School, won the Derbyshire named tion of scientific leaders in the U.S. 2021 Passano and Canada. Winners each receive Award, which Sloan fellow $75,000, which may be spent over is presented Emily Derbyshire, an assistant a two-year term on any expense by the Passano professor of chemistry at Duke supportive of their research. Foundation to a University, is one of 128 early- researcher who career scholars who are winners Kornfeld and Dahms has made an of the 2021 Sloan Research named to M6P board GOLDBERG exceptional con- fellowships. tribution to the Derbyshire earned her Ph.D. The Missouri-based biotechnol- advancement of medical science. from the University of California, ogy company M6P Therapeutics, Goldberg was recognized for in- Berkeley, in which develops enzyme and gene troducing the proteasome inhibitor 2008 and then therapies for lysosomal storage MG132, now very widely used as held a National disorders, has appointed a scien- a research tool, and initiating the Institutes of tific advisory board of geneticists research that led to the develop- Health postdoc- and glycobiologists including two ment of the inhibitor bortezomib, toral fellowship American Society for Biochemistry which is used worldwide in the in biological and Molecular Biology members, primary treatment of the blood chemistry and Stuart Kornfeld and Nancy cancer multiple myeloma. DERBYSHIRE molecular Dahms. Goldberg’s major discoveries pharmacology The company is named for have concerned the biochemical at Harvard Medical School from the sugar mannose-6-phosphate, mechanisms and physiological 2009 to 2014. She was a scholar in which acts as regulation of protein breakdown residence in the chemistry depart- a signal flag to in cells and the importance of this ment at Duke’s Trinity College of promote traffick- process in human disease. Arts and Sciences before joining ing of enzymes His laboratory first discovered the faculty. She is also an assistant destined for the ATP-dependent system for professor in molecular genetics and the lysosome. protein breakdown, now termed microbiology and an associate of Without the the ubiquitin–proteasome path- the Duke Initiative for Science and sugar, enzymes way. They first demonstrated the Society. KORNFELD don’t make it to involvement of the proteasomes Derbyshire’s lab studies novel the lysosome — in this process and discovered the aspects of malaria parasite biology and absence of certain enzymes can ATP-dependent proteases respon- with the aim of identifying drug- cause lysosomal buildup of their sible for protein degradation in gable targets. They develop pheno- substrates. Lysosomal storage disor- bacteria and mitochondria. typic and target-based screens to ders are generally rare diseases but Also of great impact have been discover small molecules that can can be very serious. The company his findings about the mechanisms be leveraged to elucidate biological is developing a gene therapeutic for the excessive protein degrada- pathways. Their efforts integrating approach that expresses both a tion and muscle atrophy in many biochemistry, microbiology and missing lysosomal enzyme and a disease states and their elucidation chemical biology have revealed phosphotransferase that enables of the role of the proteasome and parasite and human proteins proper lysosomal targeting. cellular peptidases in antigen pre- that are important for pathogen sentation to the immune system. infection. CONTINUED ON PAGE 8

6 ASBMB TODAY MAY 2021 MEMBER UPDATE

American Academy of Microbiology inducts fellows

he American Academy of Microbiology has elected 65 new fellows into its class of 2021. The academy, an honorific leadership group of the American Society for Microbiology, elects microbiologists annually through peer Treview. Five of this year’s AAM fellows are American Society for Biochemistry and Molecular Biology members.

Julie Maupin–Furlow is a of Medicine. Her lab pursues broad-based research professor of microbiology on inflammatory diseases, including studying the and cell science of the Uni- contribution of epigenetic modifications and other versity of Florida’s Institute regulatory genes in inflammation and seeking of Food and Agricultural small-molecule treatments for several types of can- Sciences. She is known cers and cancer immunotherapy. She is a fellow of for her lab’s biochemical the American Association for the Advancement of and proteomic character- Science and has received numerous research awards. ization of archaeal protein turnover through the Mario Feldman proteasome–ubiquitin system. The work, which is a profes- uses extremophiles from environments like the sor of molecular micro- hypersaline Dead Sea, is relevant to bioenergetic biology at Washington research, aiming to generate renewable fuels, as well University in St. Louis, as to astrobiological research. Maupin–Furlow is a where he studies patho- member of the Archaeal Proteome Project, has or- genic Gram-negative ganized Gordon Research Conferences and received bacteria, some of which her university’s UF Research Foundation award in frequently cause hospital- 2010. acquired infections. Feldman’s lab works to develop new antimicrobials by better understanding bacte- Kenneth Marians is a profes- rial secretion systems, virulence factors and outer sor at Memorial Sloan membrane vesicles. Feldman also co-founded a Kettering Cancer Center in biotechnology startup called VaxNewMo in 2016 New York and a leader in and serves as chief scientific officer; the company the field of DNA replica- aims to use glycoengineering to produce vaccines tion. He served as chair that more closely resemble true bacterial antigens. of the molecular biology Sarah Gaffen program for 25 years and is the Gerald was the founding dean of the Louis V. Gerstner Jr. P. Rodnan endowed Graduate School of Biomedical Sciences. He is now professor of rheumatology back in the lab full time. and clinical immunol- ogy at the University Mitzi Nagarkatti is Carolina of Pittsburgh and the distinguished professor director of the Pittsburgh and SmartState endowed Autoimmunity Center of chair of the Cancer Drug Excellence in Rheumatology. Her lab was among Discovery SmartState Cen- the first to study interleukin-17 and continues to ter as well as chair of the study the role of this cytokine, and the T cells that department of pathology, produce it, in host defense from fungal infection microbiology and immu- and also, when unchecked, autoimmune disorders nology at the University of South Carolina School such as psoriasis.

MAY 2021 ASBMB TODAY 7 MEMBER UPDATE

CONTINUED FROM PAGE 6 served on numerous research review in Kornfeld’s lab at WashU in boards for awards and granting the 1980s. As a postdoc, she The scientific board’s chairman agencies. In 2012, characterized mannose-6-phosphate is also the company’s co-founder, he received the receptors that govern lysosomal glycobiologist Stuart Kornfeld, Herbert Tabor enzyme targeting. She has studied a professor at Washington Research Award glycoproteins and their receptors University Medical School in St from the ASBMB. ever since, becoming a leading Louis. Kornfeld, who has taught Board member expert in Fabry disease, a lysosomal at WashU since 1967, has a long Nancy Dahms, a storage disorder caused by buildup history of service to the field. professor at the of a glycosphingolipid when a He served several terms on the DAHMS Medical College certain lysosomal glycan-digesting editorial board of the Journal of of Wisconsin, enzyme is mutated or absent. She Biological Chemistry, including a has studied lysosomal storage is the 2021 president of the Society term as an associate editor, and has diseases since she was a postdoc for Glycobiology.

IN MEMORIAM

Robert Baldwin

Robert Lesh Baldwin, a founding member of Stanford who were moving to Stanford to University’s biochemistry department and a member of the establish a biochemistry depart- ASBMB since 1957, died March 6 at his home in Portola ment. Baldwin began his tenure at Valley, California. He was 93. Stanford as an associate professor “Baldwin devoted his career to studying how proteins, and was promoted to full professor which begin life as linear chains of chemical building in 1964. blocks, quickly assume their characteristic highly complex, In 1965, he married Anne Norris, functional structures,” an article posted on the Stanford a postdoc in the lab of Paul Berg. Medicine news website stated. “His research sped a shift (Another member of the Stanford biochemistry founding group, in many biologists’ attention from organismic biology, the Berg went on to win the 1980 Nobel Prize in chemistry.) Norris study of creatures great and small, to molecular biology, had been offered a faculty position at Harvard that year but which focuses on the individual biochemical reactions that chose to stay in California. underpin all living processes and on the molecules — usually Baldwin served as Stanford’s biochemistry department proteins — responsible for catalyzing those reactions.” chair from 1989 through 1994. He was a member of the Born Sept. 30, 1927, in Madison, Wisconsin, Baldwin National Academy of Sciences and of the American Academy was nicknamed “Buzz” by one of his sisters. He earned a of Arts and Sciences and a fellow of the Biophysical Society. He bachelor’s degree in chemistry at the University of Wiscon- received the Stein and Moore Award of the Protein Society in sin before attending the University of Oxford as a Rhodes 1992 and the Wheland Award in chemistry in 1995. scholar, where he received his D.Phil. in biochemistry. He did He had been an emeritus professor since 1998 and, ac- a postdoc in physical chemistry at the University of Wiscon- cording to Berg, continued to make major theoretical advances sin and then joined that school’s faculty. until the last five years of his life. In 1958, Arthur Kornberg invited Baldwin to join a group In addition to his wife, Baldwin is survived by two sons, of researchers from Washington University in St. Louis David and Eric, and five grandchildren.

8 ASBMB TODAY MAY 2021 RETROSPECTIVE

Remembering Curtiss, former JLR associate editor

By Angela Hopp

for Women in Science and, in the inda Kay Curtiss, a professor 1980s, served on the board of the San at Scripps Research in Califor- Diego chapter. L nia, died Feb. 23 of cancer. She For decades, Curtiss served as an was 77. editorial board member and associate Curtiss studied plasma lipopro- editor for the JLR. teins, inflammation and innate im- Kerry-Anne Rye, who became munity in atherosclerosis. She was a JLR’s co-editor-in-chief in 2020, is former associate editor for the Ameri- a longtime friend and colleague of can Society for Biochemistry and Curtiss. She said that Curtiss was a Molecular Biology’s Journal of Lipid role model for her and other women Research, a champion of women in they rolled the stairs out to meet you in their field. science, and an advocate for robust — the sun hit my eyes, I smelled the “This is a huge loss. I’m going to federal funding for research. ocean, and I immediately thought, miss her a lot, but I fortunately got Curtiss was born in 1943 to Ruby ‘This is where I’m going to stay.’” to see her for the last time during my and Glenn Curtiss in Seattle and Indeed, she did. She won a faculty final pre-COVID trip to the U.S. It raised in Kirkland, Washington. She position at Scripps’ immunology and was just a few days before everything attended and held leadership posi- microbiology department and started was locked down. Talk about impec- tions and participated in sports at her own lab in 1978. cable timing,” Rye said. Lake Washington High School, where Curtiss was a committed volun- She also said that Curtiss’ early love her mother taught biology. She gradu- teer and leader for the American of athletics never faded. ated in 1962. Heart Association, which ultimately “One of the first times I went to Curtiss earned her bachelor’s made her an elected fellow and visit Linda in San Diego, she was degree in zoology at the University of gave her three awards for her body in a great hurry to get to a baseball Washington in 1966 and then earned of work and her service: the Dis- game, so we went straight there from a master’s degree in biology at the tinguished Achievement Award in the airport. I thought we would be University of Colorado Boulder in 2006, the Mentor of Women Award spectators. That was certainly the 1968. in 2004 and the Special Recognition case for me, but she was one of the She spent six months in Europe Award in 2000. players!” Rye said. “Actually, her main and another six in Africa before With the AHA, Curtiss on mul- sporting passion was golf, which she returning to UW for her Ph.D. She tiple occasions visited Capitol Hill played with huge enthusiasm for finished her thesis on immunochem- and talked to lawmakers about her many years.” istry while doing a research fellowship work, federal spending priorities and Curtiss retired from Scripps in at the Mayo Clinic in Minnesota in science policy. 2014 and remained in San Diego. 1974. For most of the 1990s, Curtiss She is survived by her wife of For postdoctoral studies, she held leadership positions on the four decades, Jeanne Niosi, a sister moved to Scripps to work on advisory board for the Deuel Confer- and a brother, and many nieces and plasma lipoproteins in the lab of ence on Lipids. She also served on nephews. Tom Edgington. numerous National Institutes of “I left the Mayo Clinic in a bliz- Health study sections and review Angela Hopp (ahopp@ asbmb.org) is executive zard in 1974,” she said in an interview committees. editor of ASBMB Today and with Scripps’ online weekly back in Curtiss also was committed to communications director for 2007. “I stepped off the plane in San supporting other women in science. the ASBMB. Follow her on Twitter @angelahopp. Diego — those were the days when She was a member of the Association

MAY 2021 ASBMB TODAY 9 FIRST CLASS Meet the inaugural ASBMB FELLOWS Introduction by Judith Bond & Edward Eisenstein

he title of fellow has a long history in academia and professional societies and typically designates distinguished members or partners Twho have contributed significantly to a field or endeavor. Over the past year, the leadership of the American Society for Biochemistry and Molecular Biology established a fellows program to recognize members of our society who have demonstrated exceptional commitment to the ASBMB and made outstanding contributions to advance the molecular life sciences. The Membership Committee took on the responsibility of implementing the program by defining criteria and developing a process for selection of the fellows. The committee decided that fellows should demonstrate exceptional service through active participation and leadership in ASBMB programs and should personify the core values of the ASBMB through scientific achievements, educational endeavors, mentorship, commitment to diversity, and/or service to the society and the scientific community. Our objective was to select fellows who represent the breadth and diversity of the society’s membership and all its missions. A call for nominations for fellows was announced electronically to members in society publications (including ASBMB Today) and on our website. Nominations were accepted from regular, industry and emeritus ASBMB members in good standing. There was an immediate and robust response. It became obvious that our society has a very large number of accomplished members who have served the ASBMB and advanced the life sciences in many ways. A subgroup of the Membership Committee screened and assessed the candidates, the assessments were then discussed with the whole committee, and finally a list of 30 candidates (out of about 100 nominees) was submitted to and approved by the ASBMB Council. The list was announced during the 2021 ASBMB annual meeting in late April. The 2021 fellows are indeed a distinguished group of scientists who have contributed to multiple missions of our society over a sustained period of time and enriched our world through their efforts and accomplishments. It was an honor to be part of the process to recognize this group, and their contributions make us proud to be members of the ASBMB.

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Natalie Ahn, University of Colorado Boulder Teaster Baird Jr., San Francisco State University Natalie Ahn is a distinguished Teaster Baird Jr. is a professor Meet the inaugural professor of biochemistry at the Uni- and chair of the department of versity of Colorado Boulder. Her lab chemistry and biochemistry at San merges proteomics, cell biology and Francisco State University. A dedi- biophysical approaches to investigate cated educator who has led many ASBMB FELLOWS signal-transduction mechanisms, par- initiatives within and beyond his ticularly those implicated in cancer. university to improve science educa- Ahn served as president of the American Society tion, Baird also maintains a research program in serine for Biochemistry and Molecular Biology from 2016 protease enzymology, examining and engineering the to 2018. Before that she was a member of the society’s enzymes to modify their catalytic activity, substrate speci- Council. She was nominated to be an ASBMB fellow by ficity and interactions with macromolecular inhibitors. Ruma Banerjee, who wrote: “Natalie worked tirelessly to Baird has served the ASBMB as the Southwest regional enhance the status of the national meeting and selected a director of Student Chapters for at least six years and new editor-in-chief for (the ASBMB’s) flagship journal, remains the faculty adviser for his university’s Student JBC, which ushered in sweeping and positive changes. Chapter. For 10 years, he served on the steering commit- … Natalie’s scientific record is stellar. … She is most tee that developed concept-driven teaching strategies in deserving of the recognition that would be conferred as biochemistry and molecular biology. an ASBMB fellow.” He was nominated to be an ASBMB fellow by a panel She earned her Ph.D. from the University of Califor- of seven colleagues from SFSU and the ASBMB Student nia, Berkeley, and did postdoctoral work at the University Chapters program, who wrote that “he sees potential, of Washington. provides opportunities, and gives a voice to students and faculty who often are forgotten or overlooked … (and) Karen Allen, Boston University is constantly pushing the boundaries of the way students Karen Allen is a professor and are educated.” chair of the chemistry department Baird earned his Ph.D. from Duke University and was at Boston University. Her lab uses a postdoctoral fellow both at Duke and at the University structural biology techniques to of California, San Francisco. study enzyme evolution and sub- strate specificity, with a longstanding Ruma Banerjee, University of Michigan focus on the haloalkanoate dehaloge- Ruma Banerjee is a professor of nase superfamily. Her lab also has designed inhibitors for biological chemistry at the Univer- several enzymes from pathogens that cause understudied sity of Michigan whose lab studies diseases such as elephantiasis. the enzymes that metabolize and Allen is a former member of the ASBMB Council transform sulfur-containing com- and secretary of the society and a founding member of pounds. Her work focuses especially the Women in Biochemistry and Molecular Biology on coenzymes, notably vitamin Committee. B12, or cobalamin. She was nominated to be an ASBMB fellow by Ann Banerjee was nominated to be an ASBMB fellow by Stock and Tina Iverson, who wrote that Allen “is a superb Tina Iverson, who wrote, “Ruma is a mover and shaker in scientist who has made fundamental contributions to the enzymology … (who) has maintained this field-leading field of enzymology … has her pulse on the leading ques- research program in the context of extensive service to tions of the field and is an investigator with the highest her home institutions and the world at large.” integrity and values.” Among her many service projects, Banerjee has served Allen earned her Ph.D. at Brandeis University and did on the ASBMB Council and Minority Affairs Commit- postdoctoral training at the Massachusetts Institute of tee; is the founding co-PI of the society’s Maximizing Technology. Opportunities for Scientific and Academic Independent

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Careers, or MOSAIC, program; and is an associate editor biology, and he also played a key role in developing the of the Journal of Biological Chemistry. She has been the ASBMB accreditation program. recipient of numerous awards, including, in 2019, the Bell was nominated as an ASBMB fellow by Marilee ASBMB–Merck Award, which recognizes outstanding Benore, who wrote, “Ellis’ gift is his ability to step back contributions to research in biochemistry and molecular and allow faculty to work within the strategic outline to biology. create change, develop professionally and then step into Banerjee earned her Ph.D. at Rensselaer Polytechnic their own leadership roles.” Institute and was a postdoctoral fellow at the University Bell earned his doctorate at Oxford University and did of Michigan. postdoctoral research at Duke University.

Suzanne Barbour, University of North Carolina Squire Booker, Pennsylvania State University at Chapel Hill Squire Booker is a professor and Suzanne Barbour is the dean of distinguished chair at Pennsylvania the graduate school and a professor State University, where his lab studies at the University of North Carolina the catalytic mechanisms of redox at Chapel Hill. enzymes involved in natural product Barbour served on the ASBMB biosynthesis and human health. He Education and Professional Devel- is also a Howard Hughes Medical opment Committee for 12 years. Institute investigator. She is now a member of the Minority Affairs Committee Booker has chaired the ASBMB’s Minority Affairs and the Council. Barbour serves on the Annual Meeting Committee and was the founding principal investiga- Program Planning Committee and organized scientific tor on the ASBMB Interactive Mentoring Activities for sessions for the 2020 annual meeting. She has been on the Grantsmanship Enhancement grant writing workshop. Journal of Lipid Research editorial board for almost 14 He also co-organized the 2016 ASBMB annual years. meeting. He now serves on the Finance and Nominating She was nominated to be an ASBMB fellow by Sterling committees. Bradley, who wrote that Barbour “is a recognized national Booker was nominated to be an ASBMB fellow by advocate for many aspects of career development and Ruma Banerjee, who wrote, “Squire’s work is character- the challenge facing working scientists and the coming ized by its elegance and rigor. … His research productivity generation of scientists.” is all the more impressive given his heavy teaching load Barbour earned her Ph.D. at Johns Hopkins University and service commitments both at Penn State and and did postdoctoral training at the University of Cali- nationally.” fornia, San Diego. She has been a program director at the Booker earned his Ph.D. at the Massachusetts Insti- National Science Foundation and a dean at the University tute of Technology and did postdoctoral research at the of Georgia. Université René Descartes in Paris and the University of Wisconsin. He is an elected member of the American J. Ellis Bell, University of San Diego Academy of Arts and Sciences and the National Academy J. Ellis Bell is a lecturer at the of Sciences. University of San Diego. A dedi- cated educator, Bell has published George Carman, Rutgers University extensive pedagogical research and George Carman is a professor at also pursues structural biology stud- Rutgers University and director of the ies in a lab jointly run with his wife, university’s Center for Lipid Research. USD professor Jessica Bell. He has made seminal contributions Ellis Bell won the 2015 ASBMB Award for Exemplary to the understanding of the regula- Contributions to Education. That award recognized his tion of phospholipid synthesis using service to biochemistry education as a long-serving mem- the yeast Saccharomyces cerevisiae. ber of the Education and Professional Development Com- His group identified the molecular function of the yeast mittee; he led the committee that developed concept- version of mammalian lipins, phosphatidic acid phospha- driven teaching strategies in biochemistry and molecular tase enzymes that are crucial regulators of fat metabolism.

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Carman is a repeat associate editor for the society’s Enrique M. De La Cruz, Yale University Journal of Lipid Research and is a former associate edi- Enrique M. De La Cruz is a tor for its Journal of Biological Chemistry. He won the professor at Yale University, where society’s 2012 Avanti Award in Lipids, which recognizes he leads the molecular biophysics outstanding research contributions in the area of lipids. and biochemistry department and He also has served on and as chair of the society’s Branford College. His lab studies the Meetings Committee and Annual Meeting Program actin cytoskeleton, molecular motor Planning Committee. He also has been a member of the proteins and nucleotide signaling ASBMB Council and Awards Committee and co-orga- enzymes. nized numerous society events. De La Cruz is an associate editor for the Journal of Alfred H. Merrill Jr. at Georgia Tech University Biological Chemistry and an advisory board member for nominated Carman to be an ASBMB fellow. “George the society’s Maximizing Opportunities for Scientific and has made impressive contributions to science through Academic Independent Careers, or MOSAIC, program. both the discoveries of his laboratory and his assistance He previously served on and chaired the society’s Publica- to others through these activities,” he wrote. tions Committee, served on the Meetings Committee, Carman earned his master’s degree from Seton Hall co-organized a 2013 annual meeting thematic session and University before going on to complete his Ph.D. at the co-organized the 2014 annual meeting. University of Massachusetts. He did postdoctoral work Mark Hochstrasser at Yale nominated De La Cruz to at the University of Texas Medical School in Houston. be an ASBMB fellow. “Enrique is an active member of the ASBMB and is an exemplary scientist in his research, Michael Cox, University of Wisconsin–Madison teaching and training, particularly of underrepresented Michael Cox is an endowed scientists. … He has done an enormous amount of professor in the University of work in helping to build diversity both here at Yale and Wisconsin–Madison department elsewhere.” of biochemistry. His lab studies De La Cruz earned his Ph.D. at the Johns Hopkins DNA replication and repair and University School of Medicine and completed postdoc- is best known for contributions to toral training at the University of Pennsylvania. understanding the RecA and Flp recombinases, which have become widely used tools Edward Dennis, University of California, San Diego for biotechnology and developing transgenic model Edward Dennis is a distinguished organisms. professor at the University of Cox served as a member of the ASBMB Council and California, San Diego. He has made an associate editor of the Journal of Biological Chem- important contributions to the study istry; he was a member of the steering committee that of lipid metabolism and cell signaling developed concept-driven teaching strategies in bio- through his research on phospholi- chemistry and molecular biology and continues to advise pase A2 enzymes. Importantly, he his university’s ASBMB Student Chapter. He has served pioneered the lipidomics movement. for many years as a judge in the undergraduate research Dennis has been a member of the ASBMB Council poster competition at the ASBMB annual meeting. and served as the first chair of the ASBMB Annual Meet- UW–Madison colleague Aaron Hoskins, who ing Program Planning Committee, program chair of the nominated Cox as an ASBMB fellow, wrote, “Mike is a 1996 annual meeting, and on the society’s Membership remarkable scientist. … From writing a grant to writing Committee, Education and Professional Development an exam, Mike has been an exceptional scientific role Committee, and Finance Committee. He was a mem- model in every way.” ber of the Publications Committee when the society Cox earned his Ph.D. at Brandeis University and was started the journal Molecular & Cellular Proteomics and a postdoctoral researcher at Stanford University School acquired the Journal of Lipid Research, and he went on of Medicine. to serve as editor-in-chief of the JLR for 15 years. He also served on the editorial board of the Journal of Biological Chemistry. He won the society’s 2000 Avanti Award in Lipids and its 2020/2021 Bert and Natalie Vallee Award

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in Biomedical Science. Dohlman has been an ASBMB member for more than George Carman nominated Dennis to be an ASBMB three decades. He served multiple terms on the editorial fellow. “Numerous investigators have entered the field board of the Journal of Biological Chemistry and today is of phospholipases and signal transduction as well as an associate editor. lipidomics because of the contributions of Dr. Dennis,” Jeremy Thorner, who nominated Dohlman as an Carman wrote. “These investigators do not even include ASBMB fellow, wrote, “Henrik has made numerous the many graduate students and postdoctoral fellows that path-finding contributions about what are now known as Dr. Dennis has mentored at the University of California G-protein coupled receptors. … Moreover, in the process, at San Diego. The fact that many of his past students are he has trained legions of his own Ph.D. students and now leaders in the field in their own right is testimony of postdoctoral trainees.” his outstanding ability to train and motivate people.” He earned his Ph.D. at Duke University and complet- Dennis earned his master’s degree and Ph.D. from ed postdoctoral training at the University of California, Harvard University and completed postdoctoral training Berkeley. at Harvard Medical School. William Dowhan, University of Texas Health Science John Denu, University of Wisconsin–Madison Center at Houston McGovern Medical School John Denu is a professor at the William Dowhan is an endowed University of Wisconsin‒Madison, professor in biochemistry and where his lab studies enzymes re- molecular biology at the University sponsible for adding and removing of Texas Health Sciences Center post-translational modifications. McGovern Medical School, where Recently, his team revealed new his lab studies lipid‒protein interac- regulatory mechanisms that link tions. His lab found that lipids are metabolism and chromatin function, opening up new involved in proper folding of membrane proteins and that insights into diet, gut microbiota and the epigenome. changes to the lipid environment can alter membrane Denu has served as an editorial board member and protein activity. now is an associate editor of the Journal of Biological Dowhan won the ASBMB’s 2005 Avanti Award in Lip- Chemistry. He also serves on the ASBMB Nominating ids, which recognizes outstanding research contributions. Committee. He has organized both scientific sessions and He has served on the society’s Meetings Committee and professional-development events for the ASBMB annual organized a scientific symposium for the annual meeting. meeting. He is a past editorial board member for the Journal of Sharon Dent, who nominated Denu as an ASBMB Biological Chemistry. fellow, wrote, “John’s research is consistently trailblazing. “Dr. Dowhan’s success lies in successfully challenging … John is a highly productive scientist … (who) is also dogma … use of evolving technology and approaches … highly committed to teaching and mentoring.” and generating new concepts,” wrote George Carman, Denu earned his Ph.D. at Texas A&M University who nominated Dowhan as an ASBMB fellow. and completed postdoctoral training at the University of Dowhan earned his Ph.D. at the University of Califor- Michigan. nia, Berkeley, and did postdoctoral research at Harvard Medical School. Henrik Dohlman, University of North Carolina Henrik Dohlman is a professor Catherine Drennan, Massachusetts Institute at the University of North Caro- of Technology lina, Chapel Hill, where he chairs Catherine Drennan is a profes- the pharmacology department and sor at the Massachusetts Institute of studies G protein–coupled recep- Technology and a Howard Hughes tor signaling and desensitization Medical Institute investigator. She in yeast. His lab was the first to studies the structural biology of demonstrate G protein regulation by GTPase-activating metalloenzymes. Her lab’s targets RGS proteins, mono- and poly-ubiquitination, and pro- have included multiple enzymes that ton second messengers. depend on metal cofactors, such as ribonucleotide reduc-

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tase, an early enzyme in DNA biosynthesis. Drennan service to ASBMB and the scientific community. … was once a high school science and drama teacher, and Overall, the products of Dr. Sumter’s mentorship skills she has remained committed to developing teaching have established broad contributions and her widespread best practices and research-based modules for students impacts will continue to influence the next generation ever since. of science education and production of scientists.” As a postdoctoral fellow in 1997, Drennan started Sumter earned her Ph.D. at the University of South the undergraduate poster competition at the ASBMB Carolina and completed a postdoctoral fellowship at the annual meeting. She ran it for the next five years. She Johns Hopkins University School of Medicine. also served on the ASBMB Education and Professional Development Committee during the period when Karen Fleming, Johns Hopkins University the society developed its undergraduate biochemistry Karen Fleming is a professor at curriculum recommendations. She later served on the Johns Hopkins University and a Publications Committee. In 2013, she co-organized pioneer in the study of membrane- a themed session on catalytic mechanisms for the protein folding. Her lab focuses on ASBMB annual meeting, and she is organizing one on beta-barrel proteins of the bacterial enzymology for the 2022 meeting. outer membrane and investigates In her nomination letter, Tina Iverson at Vander- the structural basis of chaperone bilt University noted Drennan’s “deep commitment interactions with unfolded membrane proteins. to education and inclusivity” and her “long service to Fleming is an associate editor of the Journal of Bio- ASBMB, her contributions to training, and her stature logical Chemistry and a past member of the Council. as a world leader in the field.” She has organized multiple meetings in protein biophys- Drennan earned her Ph.D. from the University of ics, including events for the ASBMB, and she has been a Michigan and completed her postdoctoral research at vocal advocate for equity in scientific careers. the California Institute of Technology. Cynthia Wolberger, who nominated Fleming as an ASBMB fellow, wrote, “She has worked extensively Takita Felder Sumter, Winthrop University on issues facing women in STEM … and has recently Takita Felder Sumter is the expanded her efforts to confront issues that face both dean of the College of Arts & Sci- women and men of color.” ences and a professor at Winthrop Fleming earned her Ph.D. at Georgetown University University. and did postdoctoral training at Yale University. She has been deputy chair and later chair of the ASBMB Minor- Lila M. Gierasch, University of Massachusetts Amherst ity Affairs Committee. She was Lila M. Gierasch is a distin- instrumental in creating the society’s Marion B. Sewer guished professor and former Distinguished Scholarship for Undergraduates and department head at the University co-led the Interactive Mentoring Activities for Grants- of Massachusetts Amherst. Her lab manship Enhancement program. She helped organize studies protein folding, investigat- regional workshops and other activities that ultimately ing the mechanisms of molecular led to the creation of two new mechanisms to evalu- chaperones and the effects of ate student learning: the ASBMB degree-accreditation misfolded protein aggregates. program and the ASBMB certification exam. She has been the editor-in-chief of the Journal of She has been a regional director for the society’s Stu- Biological Chemistry since 2016. She was the 2014 dent Chapters program, and she has served for the past recipient of the ASBMB’s Mildred Cohn Award, which decade and a half as a judge for the annual undergradu- honors scientists who have made substantial advances ate poster competition. Sumter is now on the ASBMB in understanding biological chemistry using innovative Council. physical approaches. Heather J. Evans Anderson at Stetson University, Daniel Hebert, who nominated Gierasch as a fellow, who nominated Sumter to be an ASBMB fellow, wrote: wrote that, beyond her many accolades, “What is most “Taken together these efforts exemplify Dr. Sumter’s special about Lila are the so many things she does that exemplary mentorship skills and her commitment to do not show up on a resume. Beyond serving as an

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example of excellence and dedication, she cares deeply Heidi Hamm,Vanderbilt University about her trainees and colleagues.” Heidi Hamm is a professor at Gierasch earned her Ph.D. at Harvard University. Vanderbilt University School of She joined Amherst College as a faculty member im- Medicine Basic Sciences, where she mediately after finishing her Ph.D. and subsequently once led the pharmacology depart- held positions at the University of Delaware and the ment. Her lab is focused on G University of Texas Southwestern Medical Center before proteins’ roles in protease-activated joining UMass Amherst. Gierasch is an elected member receptor signaling in the cardiovas- of the National Academy of Sciences and a fellow of the cular system and regulation of exocytosis at synapses. American Academy of Arts and Sciences. Hamm served as the president of the ASBMB from 2006 to 2008. Before that, she was a member of the F. Peter Guengerich, Vanderbilt University Council and Annual Meeting Program Planning Com- F. Peter Guengerich is a mittee. She also has been an editorial board member for professor at the Vanderbilt the Journal of Biological Chemistry. She won the society’s University School of Medicine 2001 Fritz Lipmann Memorial Lectureship, which recog- Basic Sciences. His lab stud- nizes conceptual advances in biochemistry, bioenergetics ies mechanisms of activation and molecular biology. and detoxification of chemical Tina Iverson, who nominated Hamm to be an ASBMB carcinogens and toxicants and fellow, emphasized Hamm’s commitment to advocating characterizes enzymes involved in these processes. Major for science, writing that “her national contributions to areas of interest include the metabolism of carcinogens science advocacy and her stature as a world leader in the and drugs by cytochrome P450 enzymes, the bioacti- field warrant her inclusion.” vation of halogenated hydrocarbons, and polymerase Hamm earned her Ph.D. at the University of Texas at interactions with carcinogen-modified DNA. Austin and did postdoctoral research at the University of Guengerich has served as an editorial board member, Wisconsin‒Madison. associate editor, interim editor-in-chief and, most recently, deputy editor of the Journal of Biological William Merrick, Case Western Reserve University Chemistry. He also has been a member of the society’s School of Medicine Public Affairs Advisory Committee and the Council. In William Merrick is a professor at 2005, he won the ASBMB William Rose Award, which the Case Western Reserve University recognizes outstanding contributions to biochemical School of Medicine. His lab seeks to and molecular biological research and a demonstrated identify all of the eukaryotic transla- commitment to the training of younger scientists. tion initiation factors and determine Lawrence J. Marnett nominated Guengerich as an their sequential utilization in the ASBMB fellow, writing that his “extraordinary accom- initiation pathway as well as to plishments in scientific research are matched only by characterize how the initiation pathway is regulated and his devotion to the ASBMB.” Marnett added that his the different consequences depending on the exact point inclusion “will go far to distinguish the body of fellows of regulation. as being the very crème de la crème of the august body Merrick has been an ASBMB member for almost 50 of scholars, educators, and public servants represented years. He served on the society’s Public Affairs Advisory by the ASBMB.” Committee and as the PAAC chair. He was a member of Guengerich earned his Ph.D. at Vanderbilt and the society’s Annual Meeting Program Planning Commit- completed postdoctoral training at the University of tee and a symposium chair for the 2006 annual meeting. Michigan. In addition, he has served as the ASBMB representative to the American Association of Medical Colleges. He has been a member of the Journal of Biological Chemistry editorial board, during which time he was a lead reviewer for papers on protein synthesis. He contin- ues to serve as an external reviewer from time to time. Thomas Dever nominated Merrick as an ASBMB

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fellow, writing, “His work has established much of our have focused some attention on the regulation and roles current understanding of the initiation pathway for eu- of these enzymes in the nervous system, particularly the karyotic protein synthesis and the biochemical properties central nervous system. of the translation factors.” Raben has chaired the ASBMB Meetings Commit- Merrick earned his Ph.D. at the University of Georgia tee for the past eight years. He is also on the executive and completed a postdoctoral fellowship at the National committee of the society’s Lipid Research Division, which Institutes of Health. he co-founded. In the past, he chaired the ASBMB Task Force on Graduate and Medical Education and served Alexandra Newton, University of California, San Diego multiple terms on the Journal of Biological Chemistry Alexandra Newton is a distin- editorial board. guished professor at the University Michael Wolfgang, Binks Wattenberg and Jessica of California, San Diego, and co- Ellis nominated Raben as an ASBMB fellow. Wolfgang director of the graduate program’s wrote, “It is hard to imagine another ASBMB member molecular pharmacology track. who has contributed as much service to the society in as Her lab investigates the molecular many capacities over the last 25 years.” Wattenberg wrote, mechanisms of cell signaling and “His extensive, selfless, and underappreciated contribu- how they are deregulated in disease, with particular em- tions to the Society are exemplary,” and Ellis wrote, “His phasis on protein kinase C and the phosphatase PHLPP. leadership skills and passion for the society are extremely Newton has served on the ASBMB Nominating Com- evident.” mittee, the Annual Meeting Program Planning Com- Raben earned his Ph.D. from Washington University mittee and the Council. She has been an editorial board and was a postdoctoral fellow at the University of Califor- member for the Journal of Biological Chemistry and has nia, Irvine. organized numerous ASBMB symposia. She co-chaired the 2004 and 2007 International Union of Biochemistry Kerry-Anne Rye, University of New South Wales and Molecular Biology/ASBMB congresses in Boston. Kerry-Anne Rye is a research She won the ASBMB Avanti Award in Lipids in professor, head of the Lipid Research 2008. She has served as the ASBMB representative to the Group and deputy head of research IUBMB general council and was elected president of the in the University of New South IUBMB, a role she will assume in July. Wales School of Medical Sciences. John D. Scott nominated Newton to be an ASBMB With expertise in high-density fellow, writing, “Alexandra is a thought leader in the field lipoprotein structure, function and of signal transduction, a role model for the next genera- metabolism, she and her team study signal-transduction tion of women biochemists, and a tireless advocate for pathways in multiple cell types to identify new therapeu- ASBMB. … There is no question that ASBMB is a better tic targets for atherosclerosis and diabetes. organization as a result of (her) insights, commitment and Rye is co-editor-in-chief of the Journal of Lipid enthusiasm.” Research. She was nominated as an ASBMB fellow by Newton earned her Ph.D. from Stanford University Nicholas Davidson, her fellow JLR co-editor-in-chief, and did postdoctoral research at the University of Califor- who wrote, “Rye has had a long and distinguished scien- nia, Berkeley. tific career, in which she has advanced the molecular life sciences, through her own research programs as well as Daniel Raben, Johns Hopkins University through her commitment to education and mentorship School of Medicine and as well as her service to the society.” If appointed a Daniel Raben is a professor fellow, he wrote, Rye would doubtless be “an exemplary at the Johns Hopkins University international ambassador for the organization and a School of Medicine. His lab began wonderful role model for successful women scientists by investigating the molecular spe- everywhere.” cies of lipids generated in signal- Rye earned her Ph.D. from Flinders University in ing pathways and now studies the South Australia and did postdoctoral work at the Univer- enzymology, structure, regulation sity of Illinois at Urbana‒Champaign. In 2017, she and function of lipid-metabolizing enzymes. These studies won the American Heart Association Arteriosclerosis,

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Thrombosis, and Vascular Biology Council Mentor of biochemistry and molecular biology to the understand- Women Award. ing of disease. Dana Carroll, who nominated Sundquist as an Sarah Spiegel, Virginia Commonwealth University ASBMB fellow, wrote, “It has been my pleasure to have Sarah Spiegel is a professor at Wes Sundquist as a colleague … and to witness his Virginia Commonwealth University, amazing accomplishments.” where she chairs the biochemistry Sundquist earned his Ph.D. at the Massachusetts and molecular biology department. Institute of Technology and conducted postdoctoral She is also director of the VCU research at the Medical Research Laboratory of Molecu- Massey Cancer Center’s cancer cell lar Biology in the United Kingdom. He is an elected biology program. The Spiegel lab member of the National Academy of Sciences. studies the lipid sphingosine-1-phosphate and discovered its role as a bioactive mediator in cell-growth regulation. Susan Taylor, University of California, San Diego Spiegel has served on the editorial board of the Jour- Susan Taylor is a distinguished nal of Lipid Research for more than a decade and was a professor at the University of member of the Journal of Biological Chemistry editorial California, San Diego, in the board from 2010 to 2018. She won the ASBMB’s 2009 departments of pharmacology and Avanti Award in Lipids. of chemistry and biochemistry. Her Suzanne Barbour, who nominated Spiegel as an lab studies the structure, function ASBMB fellow, said she “is a remarkable scientist whose and dynamics of cAMP-dependent brilliant career has helped to launch and sustain an entire protein kinase using crystallography, kinetics, fluo- field of biochemistry. In the process, she has trained rescence, hydrogen–deuterium exchange, small-angle outstanding scientists and thus has contributed to the X-ray/neutron scattering, cryo-EM and computational development of human resources as well.” tools to define conformational changes, ligand binding Spiegel earned her Ph.D. in biochemistry at the Weiz- sites and sites of protein‒protein interaction. She also mann Institute of Science in Rehovot, Israel, and did uses fluorescence imaging to elucidate isoform specific- postdoctoral work at the National Institute of Neurologi- ity of PKA signaling in tissues. cal Disorders and Stroke. She was named one of Vir- Taylor won the ASBMB’s 2017 Earl and Thressa ginia’s outstanding scientists and industrialists of 2008. Stadtman Distinguished Scientist Award and 2007 William C. Rose Award. She served as the society’s presi- Wesley Sundquist, University of Utah dent and as a member of the Council, the Nominating School of Medicine Committee, the Publications Committee and the edito- Wesley Sundquist is a distin- rial board of the Journal of Biological Chemistry. She guished professor and the bio- planned national meetings and organized workshops chemistry department co-chair at including pseudokinase meetings in 2015 and 2018. the University of Utah School of She was nominated as a fellow by Alexandra Newton, Medicine. His laboratory originally who wrote, “Susan’s service to biochemistry and train- studied HIV protein structure and ing the next generation of biochemists is exceptional. assembly, and his work supported … Her leadership has had a far-reaching impact, from the development of a drug candidate that blocks capsid UCSD to a global level. … Her infectious enthusiasm function, which is now in clinical trials. The lab’s studies for biochemistry is unparalleled.” of interactions between the virus and the host endomem- Taylor earned her Ph.D. from Johns Hopkins brane system have led to a deeper understanding of virus University and completed postdoctoral studies at the budding and cell biology. Medical Research Council Laboratory of Molecular Sundquist is a former member of the ASBMB Coun- Biology in England and at UCSD. She is an elected cil and has served as chair of the Public Affairs Advisory member of the National Academy of Sciences, the Committee. He also won the 2003 ASBMB‒Amgen American Academy of Arts and Sciences, and the Award, which was for new investigators who had National Academy of Inventors. made significant achievements in the application of

18 ASBMB TODAY MAY 2021 ASBMB FELLOWS

Herbert Weissbach, Florida Atlantic University we move forward into the next decade.” Herbert Weissbach is an emeri- Wolfson earned her Ph.D. at Columbia University tus professor at Florida Atlantic and did postdoctoral work at the University of Paris. University. His lab studies how cells She is a fellow of the American Association for the respond to oxidative stress and how Advancement of Science. oxidative damage can be prevented. At previous stages in his 65-year bio- Stephen Young, University of California, Los Angeles chemistry career, Weissbach worked Stephen Young is a distinguished on serotonin and melatonin biosynthesis and metabo- professor of medicine and human lism and discovered and investigated the coenzyme form genetics at UCLA. Working closely of vitamin B12. After the genetic code was cracked, with UCLA colleagues, Young has Weissbach spent years studying the mechanism of pro- investigated mechanisms by which li- tein synthesis. He was a founding member of the Roche poprotein lipase is transported to the Institute of Molecular Biology and a vice president of capillary lumen and how the fatty Hoffmann‒La Roche before returning to academia. acid products of intravascular triglyceride processing Weissbach has been involved with the ASBMB since move across endothelial cells and into vital tissues it was called the American Society of Biological Chem- such as the heart. ists. He has served as an associate editor for the Journal Young is an associate editor of the Journal of Lipid of Biological Chemistry, treasurer of the society, and Research. He is a member of the board that man- member of the Annual Meeting Program Planning, ages the annual ASBMB Deuel Conference on Lipids Nominating and Membership committees. and has served as that meeting’s treasurer. He was the Weissbach earned his Ph.D. from George Washington Havel lecturer at the 2009 Deuel Conference. University while carrying out research at the National He was nominated as an ASBMB fellow by Peter Institutes of Health. He did postdoctoral studies at the Tontonoz, who wrote, “Dr. Young is an international University of California, Berkeley, and then returned to leader in the field of metabolism whose work has the NIH before accepting a position at Hoffmann–La transformed decades-old models of lipid physiology. Roche. He is an elected member of the National Acad- … He has been the force that has kept the Deuel emy of Sciences. meeting financially viable and scientifically vibrant.” Young attended medical school at Washington Uni- Adele Wolfson, Wellesley College versity in St. Louis and completed internal medicine Adele Wolfson is a professor training at UC San Francisco and cardiology training emerita of chemistry and natural at UC San Diego. He did postdoctoral research train- and physical sciences at Wellesley ing in lipid metabolism at UCSD. He is an elected College. She studied proteases and member of the National Academy of Sciences. peptidases with a focus on the en- INTRODUCTORY TEXT ON PAGE 10 BY: zyme thimet oligopeptidase, which terminates the signal of bioactive Judith Bond ([email protected]) is an adjunct pro- peptides. Her recent educational research focuses on fessor of biochemistry and biophysics at the University concept inventories in biochemistry and on under- of North Carolina at Chapel Hill. She is the chair of the standing how students connect learning in science and ASBMB Fellows Program Subcommittee. nonscience courses. Wolfson is a member and former chair of the ASBMB Programmatic Accreditation Committee, and she was nominated as a fellow by 13 current and former mem- Edward Eisenstein ([email protected]) is an investiga- tor at the Institute of Bioscience and Biotechnology Re- bers of that committee, who jointly wrote, “Adele is a search and a faculty member of the Fischell Department role model for committee leadership. … She balances of Bioengineering at the University of Maryland. He is the a focus on rigor and consistency with the recognition chair of the ASBMB Membership Committee. of diversity and promotion of inclusiveness. … She has helped lead this society and helped shape its positions as

MAY 2021 ASBMB TODAY 19 LIPID NEWS Ceramides’ role in liver disease By Eleonora Scorletti & Rotonya M. Carr

lcoholic liver disease, or ALD, is a chronic condi- tion that includes hepatic steatosis, steatohepatitis, Afibrosis and cirrhosis. Nonalcoholic fatty liver dis- ease, or NAFLD, is a chronic condition with histological progression similar to ALD, but its pathogenesis is due in large part to diets high in fat and sugar rather than heavy alcohol consumption. The early stages of both ALD and NAFLD are charac- terized by excessive accumulation of lipid droplets within hepatocytes. Perilipin 2, or PLIN2, is the most abundant hepatocellular lipid droplet protein. In both ALD and NAFLD, PLIN2 is upregulated and is associated with PLIN2 and that prevent mitochondrial fragmentation. hepatic accumulation of ceramides. Moreover, liver-specific induction of lysosomal acid cerami- Ceramides are biologically active sphingolipids that dase through ASAH1 overexpression improves hepatic in- have roles in apoptosis, inflammation and insulin resis- sulin sensitivity and ameliorates alcoholic steatosis through tance, all critical factors in the pathogenesis of both ALD very low-density lipoprotein–mediated and lipophagy-me- and NAFLD. Accumulation of ceramides inhibits insulin diated mechanisms. Finally, tissue-specific and DES1 null signaling and promotes insulin resistance. Ceramides mice fed a high-fat diet have increased levels of dihydrocer- can inhibit protein kinase B activity either through the amides, reduced accumulation of ceramides synthesis (in- activation of protein phosphatase 2A or protein kinase cluding C16:0 ceramides), reduced steatosis and increased c isoform zeta. In addition, ceramides impair fatty acid glucose tolerance. beta-oxidation by promoting mitochondrial fission. An increasing body of evidence supports the view that The liver is a key organ for the production of cerami- reducing hepatic ceramide production improves hepatic des, the synthesis of which takes place by three pathways: lipid accumulation and insulin resistance in ALD and (1) synthesis from simple molecules, which requires NAFLD. However, little is known about therapies that several enzymes, including dihydroceramide desaturase 1, safely lower ceramides in humans and improve patient or DES1, and ceramide synthase, or CerS, enzymes; (2) health. Further studies are needed to better understand sphingomyelin hydrolysis by sphingomyelinases; and (3) how ceramides affect liver function, with the eventual aim lysosomal salvage of complex sphingolipids that requires of developing targeted treatments for ALD, NAFLD and acid ceramidase, an enzyme that deacylates ceramides into insulin resistance. sphingosine and fatty acids and is encoded by the ASAH1 gene. Eleonora Scorletti Recent studies showing that reduction of ceramide ([email protected]) is a synthesis can improve steatosis and insulin resistance have postdoctoral researcher in Rotonya M. Carr’s lab in the division of gastroenterology at the University of elucidated the critical role of ceramide synthetic pathways Pennsylvania. Follow her on Twitter @EScorletti. in ALD and NAFLD. As our lab reported in the FASEB Journal and Philipp Hammerschmidt and colleagues reported in the journal Cell, reduction of synthesis of ceramide C16:0 using both pharmacologic and genetic Rotonya M. Carr models of CerS reduction prevents lipid droplet accumu- ([email protected]) is director of the Liver Metabolism and Fatty Liver Program and an lation and insulin resistance in experimental models of associate professor of medicine in the division of gastro- ALD and NAFLD. enterology at the University of Pennsylvania. Follow her Prevention of steatosis and improvement of insulin on Twitter @RotonyaC. resistance involve mechanisms that are dependent on

20 ASBMB TODAY MAY 2021 JOURNAL NEWS JLR names new junior associate editors By Angela Hopp

he American Society for Biochemistry and Molecular Biol- his residency at Massachusetts General Hospital in 2010 ogy’s Journal of Lipid Research has appointed six junior and then completed a fellowship in gastroenterology Tfaculty members to its editorial leadership team. and hepatology at UT Southwestern in 2014. He joined The journal’s junior associate editor program, now in its the faculty at UTSW after completing his fellowship. second year, was created to achieve two chief goals: demystify Engelking is also an investigator at the UTSW Center the peer-review process and train the next generation of journal for Human Nutrition. During his term at JLR, Engelk- leaders. ing will partner with Associate Editor Jay Horton of UT Southwestern and Editor-in-Chief Nicholas Davidson of Each junior associate editor will serve a two-year term. Washington University in St. Louis.

Michael Airola, Stony Brook University Scott M. Gordon, University of Kentucky Michael Airola is an assistant College of Medicine professor in the biochemistry and Scott M. Gordon is an assistant cell biology department at Stony professor in the physiology depart- Brook University (also known as ment at the University of Kentucky the State University of New York College of Medicine, where his lab at Stony Brook). He runs a lab studies intestinal lipid absorption focused on the structural biology and atherosclerotic cardiovascular of lipid-modifying enzymes. He disease. Gordon earned his Ph.D. at earned his Ph.D. at Cornell University in 2010 and com- the University of Cincinnati College pleted a postdoctoral research fellowship at the Medical of Medicine in 2012 and completed a postdoctoral re- University of South Carolina and Stony Brook Cancer search fellowship at the National Heart, Lung, and Blood Center. He joined the faculty at Stony Brook in 2017. Institute in 2018. He joined the faculty of UK shortly Airola will partner with JLR Associate Editor George Car- thereafter. He will partner with Associate Editor W. Sean man of Rutgers University during his term. Davidson of the University of Cincinnati during his term at JLR. Luke Engelking, University of Texas Southwestern Medical Center at Dallas Rebecca Anne Haeusler, Columbia University Luke Engelking is an associate Rebecca Anne Haeusler is an professor in the internal medicine assistant professor in the pathol- and molecular genetics departments ogy and cell biology department at the University of Texas South- at Columbia University. Her lab western Medical Center at Dallas. studies the mechanisms that link A physician–researcher, Engelking insulin resistance and cardiovascular practices adult gastroenterology disease. She earned her Ph.D. at with a focus on the care of patients the University of Michigan in 2007 with inherited forms of colorectal cancer, such as Lynch and completed a postdoctoral fellowship at Columbia in and FAP syndromes. His lab focuses on the roles that 2011. She worked as an associate research scientist at Co- lipids play in the growth of intestinal cells. He earned his lumbia until 2014, at which time she joined the faculty. M.D.–Ph.D. at UT Southwestern in 2007, completed During her JLR term, Haeusler will partner with Associ-

MAY 2021 ASBMB TODAY 21 JOURNAL NEWS

ate Editor Paul Dawson of the Emory University School Judith Simcox, University of Wisconsin–Madison of Medicine. Judith Simcox is an assistant pro- Renate Schreiber, University of Graz fessor in the biochemistry depart- ment at the University of Wiscon- Renate Schreiber is a senior sin–Madison. Her lab studies the scientist at the University of Graz sources of lipids that fuel brown Faculty of Science in Austria. fat thermogenesis using lipidomics, Schreiber studies lipid-degrading genetics, and cellular and molecular enzymes and their impact on the biology techniques. Simcox earned generation and degradation of her Ph.D. at the University of Utah in 2014 and com- lipid metabolites in health and dis- pleted a postdoctoral fellowship at the University of Utah ease. Schreiber earned her master’s in 2019. She joined the faculty at Madison soon after. degree in 2007 and her Ph.D. in 2011 and then com- During her term at JLR, Simcox will partner with Associ- pleted a postdoctoral fellowship in 2019 at the University ate Editor Alan Attie of Madison. of Graz. She also has held visiting scientist positions at the University of Cambridge, University College London, Angela Hopp ([email protected]) is executive editor of Umeå University in Sweden and Medical University of ASBMB Today and communications director for the ASBMB. Graz. She was named a tenure-track senior scientist at the Follow her on Twitter @angelahopp. University of Graz in 2019. Schreiber will partner with JLR Associate Editor Stephen Young of the University of California, Los Angeles.

Upcoming ASBMB events and deadlines MAY Asian American and Pacific Islander Heritage Month National Stroke Awareness Month Hepatitis Awareness Month 9 National Women’s Health Week 10 National Lipid Day 11, 18 & 25 Protonic bioenergetics and action potential: Latest discoveries and progress in mitochondria,

MAY MAY neurons and other biosystems 15 Dementia Awareness Week 21 Early registration deadline for Teaching science with big data 23 World Melanoma Day 24 Deadline to apply or submit a nomination for ASBMB annual awards 27 Abstract deadline for Extracellular vesicle studies: From benchtop to therapeutics

JUNE 1 Deadline to apply for Marion B. Sewer Distinguished Scholarship for Undergraduates 6 National Higher Education Day 14 World Blood Donor Day 16 Regular registration deadline for Teaching science with big data 19 World Sickle Cell Day 20 World Refugee Day 21 Flux-independent signaling by ionotropic receptors: Unforeseen roles and complexities 25 Early registration deadline for Extracellular vesicle studies: From benchtop to therapeutics

JULY 18 National Ice Cream Day

JUNE JULY 21–23 Extracellular vesicle studies: From benchtop to therapeutics

22 ASBMB TODAY MAY 2021 JOURNAL NEWS Study reveals experimental targets for lymphoma research

By Caleigh Findley NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NATIONAL INSTITUTES OF HEALTH editor for the Journal of Biologi- cal Chemistry. “[In] an interesting ymphocytes, white blood cells twist … mice heterozygous for a null made in the bone marrow, are (complete loss-of-function) Dnmt3b L an essential part of the immune allele developed T-cell malignancies,” system. The two main types of lym- Fearon wrote in an email. “In con- phocytes, T cells and B cells, carry out trast, mice that expressed a Dnmt3b adaptive immune responses. B cells allele encoding a DNMT3b protein target circulating pathogens in the that lacked catalytic activity devel- body, and T cells manage cell response oped B-cell malignancies.” to infection. These findings demonstrate that Mutations that arise during the both the catalytic activity and ac- T lymphocytes like the one pictured manage cell cessory functions of Dnmt3b are production of these immune cells, a response to infection, and mutations that arise important for fighting cancer. process called hematopoiesis, can lead during their production in the bone marrow can The researchers investigated to T-cell or B-cell lymphomas. Dur- lead to lymphomas. ing hematopoiesis, genes are some- molecular mechanisms that could times said to be turned “on” or “off” cancer research as Dnmt3b suppresses explain the link between Dnmt3b through a biological process called tumor development. Loss of Dnmt3b and blood cancer. Genome-wide DNA methylation. This occurs when is linked to human chronic lympho- analysis revealed decreased meth- a methyl group is added to the DNA cytic leukemia, leading researchers to ylation and increased expression of power switch that controls the expres- wonder if loss of Dnmt3b activity is a tumor-promoting genes. The results sion of that gene. A family of enzymes major factor in blood cancer. also showed reduced expression of called DNA methyltransferases, or Katarina Lopusna and colleagues the p53 pathway, known for prevent- Dnmts, carries out this process and is investigated the significance of ing T-cell transformation. an important part of cellular function. Dnmt3b in lymphoma by generat- The researchers’ efforts “highlight A new study in the Journal of ing mice lacking Dnmt3b’s catalytic how careful analysis of mutant alleles Biological Chemistry reports that activity for either one or both of the in mouse models can yield insights one DNA methylation enzyme, genetic alleles and comparing them into the potential non-catalytic Dnmt3, suppresses the development to mice with only one Dnmt3b allele. functions of certain enzymes, such as of lymphomas through its catalytic Knocking out one allele of Dnmt3b Dnmt3b,” Fearon wrote. The study and non-catalytic functions. The decreases all of its functions, including also puts forth potential molecu- authors, researchers at the universities accessory jobs such as recruiting other lar targets that may contribute to of Florida and Nebraska, also provide Dnmts or influencing gene expres- Dnmt3b-related tumor development evidence for a molecular pathway pos- sion (outside of methylation). Taking for future research. sibly involved in lymphoma develop- away the catalytic activity of Dnmt3b, DOI: 10.1016/j.jbc.2021.100285 ment related to mutated Dnmt3. even partially, should hinder DNA Previous research linked lymphoma methylation specifically, reducing Caleigh Findley ([email protected]) is a development with mutations to Dn- production of blood cells and possibly fourth-year Ph.D. candidate in mt3b — alongside other diseases that tumorigenesis. pharmacology and neurosci- impair the immune system. Dnmt3b This study design yielded unexpect- ence at Southern Illinois University School of Medicine. influences the expression or silenc- ed results for lymphoma development, Follow her on Twitter @ ing of genes, an important aspect for according to Eric Fearon, an associate benchtopblog.

MAY 2021 ASBMB TODAY 23 JOURNAL NEWS Researchers target cell membrane for cancer research

By Nivedita Uday Hegdekar Natividad “Robert” Fuentes, a former graduate student in the Chapkin obert Chapkin has spent lab and the first author on the lab’s decades studying the molecular recent paper in the Journal of Lipid Rroles components of nutrition Research, uncovered some ground- play in protein signaling and the breaking molecular insights into this prevention of diseases. His lab’s recent mechanism. Using cell and animal discoveries about lipids and the cell models and a cutting-edge technique membrane could revolutionize trans- called super-resolution microscopy, lational cancer research. he studied the changes to the lipid “Cell membranes are the lipid membrane and EGFR after DHA environment in which many proteins incorporation. function,” said Chapkin, a professor “We found that when DHA is in- A lipid bilayer cell membrane with membrane and of nutrition at Texas A&M Universi- corporated, it alters the localization of intracellular receptors. ty. “It is now appreciated that protein the lipid bilayer with EGFR,” Fuentes and lipids assemble to form distinct said. “It alters the spatial orientation With membrane therapy still in micro- or nanodomains (clusters) that of the protein in the lipid bilayer.” its infancy, Fuentes believes it will facilitate key signaling events.” It turns out that the architecture be applicable in other research areas. Cell membrane composition is of the protein within the lipid bilayer “Membrane therapy holds promise altered in diseases such as cancer of the cell membrane is one of the for any disease states where receptor and obesity. Chapkin believes that factors that drives its function. This clustering within the cell membrane membrane therapy — the modulation might explain why DHA incorpora- is affected,” he said. “For instance, it of cellular membrane lipid composi- tion suppresses EGFR signaling. could be used in diabetes research to tion and organization — might be an Fuentes said he believes such mem- target the insulin receptor and insulin effective therapeutic strategy. brane therapy could synergize with signaling.” “The central idea is that if you alter other cancer treatments. “The fatty Chapkin is eager to explore the the composition of the cell mem- acids that modulate the lipid bilayer more mechanistic nuances and speci- brane, you can potentially alter the are completely innocuous to humans ficity of membrane therapy and study functionality of the proteins within and could potentially be used as adju- other potential players. the membrane and thus the disease vants to suppress the functionality of “We will be researching other overall,” he said. proteins that drive cancer.” preventative components of nutrition Chapkin’s lab discovered that As a postdoc at the University of and target proteins,” he said. “There docosahexaenoic acid, or DHA, a Texas MD Anderson Cancer Center, is so much exciting work to be done well-known dietary omega-3 fatty Fuentes now uses membrane therapy in this field.” acid and chemoprotectant, suppresses in translational pancreatic cancer DOI: 10.1016/j.jlr.2021.100026 the functionality of epidermal growth research. factor receptor, or EGFR, a protein “Pancreatic cancer is resistant to Nivedita Uday Hegdekar ([email protected]) in the cell membrane that drives the many therapies,” he said. “Part of is a graduate student at the formation of many types of cancer, my work is to study how disrupting University of Maryland working including colon cancer. the pancreatic cell membrane might toward a Ph.D. in biochemistry and molecular biology and an But how does DHA suppress improve the efficacy of cancer M.S. in patent law. Follow her on the function of the EGFR protein? therapeutics.” Twitter @NiveditaHegdek1.

24 ASBMB TODAY MAY 2021 JOURNAL NEWS Parasitic secretions create microenvironment for survival By Jaclyn Brennan

aramphistomes, also known as gether, they performed transcriptome ROBINSON LAB / QUEEN’S UNIVERSITY BELFAST rumen or stomach fluke, are analysis of four rumen fluke life-cycle Pflatworm parasites that infect stages and integrated these results sheep and cattle in temperate and with proteomic analysis of secretions tropical regions. In recent years, the from two of these stages. They picked incidence and severity of rumen fluke the juvenile flukes and mature adult infections (specifically the paramphis- stages for the proteomics studies, as tome Calicophoron daubneyi) have these are the key stages responsible for increased sharply in Western Europe. acute and chronic disease, respectively. Heavy infections of immature rumen Juvenile flukes emerge in the small This illustration shows the development of the rumen fluke in the small intestine can lead intestine and eventually migrate along fluke Calicophoron daubneyi. In a recent study, secretome to hemorrhaging and even death, so the digestive tract to the rumen, profiling revealed distinct families of virulence factors early detection and correct diagnosis where they mature into adults. Dur- and immunomodulators associated with acute and chronic infection. are imperative. However, researchers ing each stage, the parasite must adapt still know little about the biology of to drastic changes in the host micro- C. daubneyi and its effects on host environment and counter inevitable which are so important for the para- animals. attacks by the host immune system. site, we may be able to come up with Mark Robinson’s lab at Queen’s According to Robinson’s findings, new treatment options,” he said. University Belfast focuses on parasitic they do so easily. The lab has developed the first worms and how they interact with “The rumen fluid is like a soup of enzyme-linked immunosorbent assay their hosts at the molecular level. bacteria and protozoans which the for C. daubneyi, which they hope He has studied liver fluke for over flukes must live amongst and survive,” can be used by veterinarians, animal 20 years. With the recent emergence Robinson said. producers and farmers for disease of the less-studied rumen fluke in Rumen flukes appear to secrete surveillance and diagnosis. Next, Europe (particularly in Northern certain molecules that help them Robinson wants to perform functional Ireland, where his lab is based), his establish and maintain infection studies to validate certain molecules latest work shifted to understand- within this challenging host environ- as targets for fluke control. As with all ing this unusual parasite and its host ment. Robinson likens the protective the work done in his lab, these efforts interactions. His findings, published properties of these secreted molecules center on improving animal health in the journal Molecular & Cellular to those of the garments worn by as- and welfare, which he says is of benefit Proteomics, show how C. daubneyi tronauts: “Imagine stepping onto the to everyone. regulates expression and secretion of surface of the moon without a space DOI: 10.1074/mcp.RA120.002175 certain molecules to establish infec- suit — you wouldn’t last very long. tion, feed on host tissue and fight off Same goes for flukes within their host the host immune response in rumi- environments without their shield of Jaclyn Brennan (jabrennan@ gwmail.gwu.edu) is a post- nant livestock. secreted molecules.” doctoral researcher at George To begin to investigate the molecu- Robinson believes the host–para- Washington University, where her lar biology of rumen fluke, Robinson’s site interface can be adjusted to fight research focuses on electrophysi- ology of the cardiac conduction group teamed up with other research- off infection. “If we can devise ways system. Follow her on Twitter ers from the United Kingdom. To- of blocking the secreted molecules, @jaclynb_phd

MAY 2021 ASBMB TODAY 25 JOURNAL NEWS

From the journals By Nuala Del Piccolo, Vaishnavi Muralikrishnan, Laurel Oldach & Anand Rao

We offer summaries of papers These findings, published in a Bacteriodes. This improves our under- recently published in the Journal of paper in the Journal of Biological standing of how dietary sphinganine Biological Chemistry, the Journal Chemistry, detail the role of clathrin- is processed in the body and how it in of Lipid Research, and Molecular & mediated endocytosis in viral infectiv- turn affects the gut microbiome. In Cellular Proteomics. ity and may support the development addition, the novel BOSSS technique of new therapies for the treatment of is useful to study the flux of any COVID-19. alkyne-labeled metabolite in diet– Clathrin-coated DOI: 10.1016/j.jbc.2021.100306 microbiome interactions. endosomes encourage DOI:10.1194/jlr.RA120000950 SARS-CoV-2 entry How gut bacteria assimilate dietary lipids Plasmodium mutant Severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, The human intestine is home to promotes parasite survival initiates infection by using its spike trillions of microorganisms known Malaria is a serious and often glycoprotein to engage with the collectively as the gut microbiota. The fatal disease that afflicts over 200 surface of host cells. Previous research type and amount of fat we eat can million people worldwide every year, in cell cultures and animal models has have a significant impact on the gut according to a 2020 World Health shown that when the spike glycopro- microbiome and thus on our metabo- Organization report. It is spread to tein engages with host cell receptors, lism and immunity. Sphingolipids are humans through mosquitoes carrying other coronaviruses, such as MERS- a class of bioactive lipids present in Plasmodium parasites. Five species of CoV and SARS-COV-1, undergo foods such as milk and also produced these parasites cause malaria in hu- endocytosis. However, researchers by gut microbes. However, researchers mans, and Plasmodium falciparum is don’t know yet whether SARS-CoV-2 do not understand yet how the gut responsible for the most common and follows a similar cell entry process microbes use sphingolipids. deadliest form of the disease. Health and, if so, which mechanism facili- Recent research by Min-Ting Lee care providers take a two-pronged tates its entry into the host cell. and colleagues at Cornell University approach to combat malaria around Using purified spike glycoprotein published in the Journal of Lipid Re- the world. One common preven- and a lentiviral model of SARS- search used a novel technique called tion strategy is the use of drugs that CoV-2 infectivity, Armin Bayati, Ra- Bioorthogonal labeling-Sort-Seq-Spec, suppress the blood stages of malaria hul Kumar and colleagues at McGill or BOSSS, to study the assimilation infection, thereby preventing the University showed that SARS-CoV-2 of sphingolipids by gut microbes. The disease through chemoprophylaxis. undergoes rapid endocytosis when it first step in BOSSS, bioorthogonal However, P. falciparum resistance to engages with the host cell surface. The labeling of sphingolipids, involved antimalarials is a recurring problem, researchers found that upon binding labeling without interfering with na- undermining malaria control efforts, with membrane host cell receptors, tive biochemical processes in the body. so scientists continue to search for SARS-CoV-2 is engulfed by vesicles The next step was fluorescence-based new strategies to treat infections. coated in clathrin, a protein criti- sorting of microbes containing the la- The drug ′4 -deaza-1′-aza-2′-deoxy- cal for shaping vesicles and sorting beled sphingolipids. Finally, the sorted 1′-(9-methylene)-immucillin-G, or their cargo. SARS-CoV-2 infectivity microbes were sequenced and analyzed DADMe-ImmG, inhibits the purine was reduced by blocking clathrin- by mass spectrometry to identify nucleoside phosphorylase PfPNP, mediated endocytosis through the products of sphingolipid assimilation. an enzyme that is essential for P. knockdown of clathrin heavy chain, a The researchers found that sphin- falciparum growth. Treatment with component of clathrin necessary for golipids are assimilated primarily DADMe-ImmG clears P. falciparum its function. by a type of gut microbe known as infections in a primate malaria model,

26 ASBMB TODAY MAY 2021 JOURNAL NEWS

but P. falciparum cultured in the presence of DADMe-ImmG develops resistance to the inhibitor. G protein inhibition could help treat In a study published in the Journal uveal melanoma of Biologial Chemistry, Yacoba About 83% of ocular melanoma, a type of eye cancer that develops Minnow and colleagues at the Albert in cells that produce pigment, arises from the uvea, a layer of the eye Einstein College of Medicine beneath the sclera and cornea, according to the American Cancer describe their efforts to determine Society. While rare, uveal melanoma, or UM, is particularly deadly. how PfPNP develops resistance to About 50% of patients with UM develop metastatic disease; with a DADMe-ImmG. Using covalently lack of effective treatment, the long-term prognosis is poor. linked native and mutant PfPNP Guanine–nucleotide binding proteins, or G proteins, use extracel- monomers, the researchers showed lular signals to initiate intracellular signaling cascades. Activating that PfPNP mutants alone are un- point mutations in G proteins are causative factors in several human able to execute the essential function cancers, and recent work suggests that uveal melanoma is driven by of PfPNP due to a loss in catalytic G proteins Gq and G11 that have mutated to become constitutively properties. However, hybrid mol- active. ecules consisting of mutant and native A new paper by Michael Onken and colleagues at Washington subunits give rise to DADMe-ImmG University published in the Journal of Biological Chemistry ex- resistance while also preserving plores the therapeutic potential of FR900359, or FR, an extract from catalytic function. As a result, these the evergreen plant Ardisia crenata that selectively inhibits Gq/11 mixed PfPNP molecules can promote activity. Using cultured UM cell lines and human UM tissue assays, parasite survival despite the presence single-cell RNA-sequencing and animal experiments, the researchers DADMe-ImmG. showed that all constitutively active forms of Gq/11 found in UM are DOI: 10.1016/j.jbc.2021.100342 sensitive to FR. JONATHAN TROBE/UNIVERSITY OF MICHIGAN KELLOGG EYE CENTER The authors Glycosylation of the also found that SARS-CoV-2 spike protein FR arrests UM Severe acute respiratory syndrome cell growth but coronavirus 2, or SARS-CoV-2, the does not kill virus responsible for the ongoing Gq/11-driven COVID-19 pandemic, is known to be UM cell lines glycosylated — that is, infected cells and that it tar- attach sugar molecules to viral proteins gets UM tumor during replication. In the most com- cells from patient mon form of glycosylation, known as biopsies of N-glycosylation, sugars are attached to primary tumors the amino acid asparagine. The loca- with both low tion and composition of these attached and high meta- sugars can obstruct protein–protein static potential. Uveal melanomas, like the one show here in the iris of an eye, interactions, thereby modulating Lastly, the re- are driven by G proteins Gq and G11 that have mutated to processes like infectivity of and human searchers identi- become constitutively active. immune reaction to a virus. fied a therapeutic In a recent article in the journal window in which FR strongly arrested tumor growth without causing Molecular & Cellular Proteomics, major effects on heart rate, liver function or behavior. Yong Zhang, Wanjun Zhao and These findings show new ways that clinicians might be able to use colleagues at Sichuan University Gq/11 inhibitors such as FR for the treatment of UM patients either describe how they characterized N- alone or in conjunction with current standards of care. glycosylation of the SARS-CoV-2 DOI: 10.1016/j.jbc.2021.100403 —Anand Rao spike protein, which mediates viral

MAY 2021 ASBMB TODAY 27 JOURNAL NEWS

entry into human cells. Using mass therapy and vaccine development for which can lead to avoidable dis- spectrometry, the team identified 22 COVID-19. ease progression and death. Fanny sites of N-glycosylation in the virus’ DOI: 10.1074/mcp.RA120.002295 Boyaval of Leiden University and a spike protein. The composition of the team of researchers in the Nether- attached sugars is heterogeneous and Characterizing the glycan lands hypothesized that the N- depends on the host cell, not the gly- glycan signature in tumor tissues can cosylation site: Insect and human cells signature of tumor tissue predict patient outcomes. N-glycans, preferentially attach high-mannose Despite vast improvements in or sugar molecules attached to the and complex sugars, respectively. Giv- cancer diagnosis and care in recent surface of membrane-bound and en the influential role of glycosylation decades, clinicians still struggle to secreted proteins, regulate cancer- on viral infectivity and immunogenic- predict which patients will and will related processes including angio- ity, these findings will inform future not respond to a specific therapy, genesis, immunity, metastasis, tumor

Silver nanoparticles target metabolically unadaptive cancer cells Silver nanoparticles have many applications, includ- Cellular Proteomics, Reetta Holmila and colleagues ing medical uses such as wound dressings and implants, based at Wake Forest School of Medicine’s Center for because of their antimicrobial activity: They disrupt cell Redox Biology and Medicine report on an investigation wall integrity and perforate cell membranes. The particles into silver nanoparticles as a cancer treatment. The team are considered nontoxic to humans, but researchers have used redox proteomics, which detects both the abun- observed that they sometimes cause oxidative stress and dance of proteins and their oxidation at cysteine resi- programmed cell death by disrupting mitochondrial mem- dues, to investigate nanoparticle responses in two cancer branes. These observations raise concern about occupational cell lines from lung epithelia. Previously, the team had exposure to silver nanoparticles — but also suggest they established that one line was sensitive to silver nanopar- might make promising anticancer therapeutics, since cancer ticle treatment, proliferating more slowly or dying after cells tend to be more metabolically active than their healthy exposure, while the second was resistant. counterparts. They recently observed that protein oxidation In a recent article in the journal Molecular & increased in both cell types in the hours after silver nanoparticles were introduced. The resistant cells A transmission electron microscopy image of the silver nanoparticles mounted a robust oxidative stress response through studied as a cancer treatment at the Wake Forest School of Medicine. metabolic adaptation, upregulating protein turnover and COURTESY OF CRISTINA M. FURDUI / WAKE FOREST SCHOOL OF MEDICINE antioxidant synthesis pathways. As a result, they tended to show less protein oxidation after a long treatment with silver particles than after a short one. The more sensitive cell line failed to ramp up antioxidant metabo- lism and mitochondrial protection as strongly, and it maintained high oxidation levels, which was ultimately detrimental to cells. Using microscopy, the researchers observed that the sensitive cell line had started out with mitochondria that were larger and less morphologically defined than their counterparts’. After nanoparticle treatment, mitochon- dria in sensitive cells swelled and sometimes burst. The findings suggest that preexisting mitochondrial abnormality might predispose some cancer cell lines to respond to nanoparticle treatment by dying, while others manage to adapt. DOI: 10.1016/j.mcpro.2021.100073 — Laurel Oldach

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cell invasion and cell–cell signaling. Boyaval and her colleagues Why high HDL is not always good characterized biopsies from stage II colorectal cancer patients using Heart diseases are the leading cause of death in the United States. matrix-assisted laser desorption/ion- Coronary heart disorder, the most common type of heart disease, is ization mass spectrometry imaging, caused by atherosclerosis, or the accumulation of cholesterol in the ar- or MALDI-MSI, a technique that terial walls leading to stiffening and lowered blood flow in the arteries. produces a spatially resolved picture The two types of cholesterol are low-density lipoprotein, or LDL, of N-glycan distribution and com- and high-density lipoprotein, or HDL. While HDL cholesterol often position in a tissue sample. Writing is referred to as “good cholesterol” because of the inverse correlation in the journal Molecular & Cellular between HDL levels and heart disorders, the presence of excess HDL Proteomics, they report that cancer in plasma may be due to reduced plasma clearance of cholesterol. The cells exhibit an increase in sialylated primary receptor for HDL is scavenger receptor class B type I, or SR- and high-mannose glycans and a BI, which promotes clearance of excess cholesterol from the plasma, decrease in fucosylated and highly thus reducing the risk for atherosclerosis. branched glycans, but these changes In a recent study in the Journal of Lipid Research, Sarah May do not correlate with patient survival. and colleagues at the Medical College of Wisconsin characterized a However, the N-glycan signature of rare heterozygous variant of the gene encoding SR-BI that results in tumor-adjacent tissue is similar to the substitution of arginine-174 with cysteine, or R174C, in a patient that of cancer cells and correlates with with high HDL cholesterol levels. They demonstrated that the R174C patient survival. The study shows mutation leads to diminished cholesterol transport, suggesting this that MALDI-MSI can characterize variant does not clear cholesterol from circulation as intended. primary tissue samples and provides The researchers write that the reduced function of this variant could a new technique to classify colorectal be due to disruptions in surface electrostatic charges of SR-BI leading cancer patients. to a decrease in the net-positive charge, which in turn could affect the DOI: 10.1074/mcp.RA120.002215 ability of SR-BI to bind HDL and transport cholesterol from HDL particles. A randomization This study provides insight into the structure and function of SR-BI and emphasizes that measurement of HDL-cholesterol levels may not to measure risk be a sufficient indicator to predict the risk of cardiovascular diseases Variations in certain genes can act accurately. as risk factors for some diseases, and DOI: 10.1016/j.jlr.2021.100045 these risk associations can be studied —Vaishnavi Muralikrishnan

using a technique called Mendelian NIH/FLICKR randomization, or MR. This tech- nique measures variations in genes whose functions are known in order to determine whether the variations can cause specific diseases in humans. In a recent study in the Journal of Lipid Research, David G. Thomas and colleagues at Columbia Uni- versity performed an MR of lipid traits such as levels of low-density lipoprotein, high-density lipoprotein, triglycerides, body mass index, Type 2 diabetes and systolic blood pressure in coronary artery disease, or CAD, A normal artery is shown on the left, and narrowing of the artery due to deposit of in large genomewide association study cholesterol plaque, which represents atherosclerosis, is on the right. data sets.

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A challenging aspect of determin- modification. By knocking down CRD4. The authors then explored ing the effect of risk factors is that Rab11 protein levels in HeLa cells mechanisms of ligand–CRD4 bind- some of these lipid trait variants may and using liquid chromatography– ing by generating and examining be pleiotropic, meaning that a single mass spectrometry, they discovered crystal structures of CRD4, and their gene can influence two or more seem- that a reduction in Rab11 selectively structural analyses highlighted several ingly unrelated phenotypic traits. This enhanced the sialyation of glyco- distinctive aspects of ligand binding study used multivariate MR analysis proteins. They found that the major by the mannose receptor to additional to evaluate the pleiotropic effects alpha-2,3-sialyltransferase ST3GAL4 classes of ligands. of lipid trait genetic variants and to was confined tightly to the trans-Gol- The authors state that the details adjust for these effects in evaluating gi network in the absence of Rab11 revealed in this work could help to ex- the risk for CAD. The researchers versus its more diffuse localization plain differences in the way pathogens reported that the lipid traits they when Rab11 is present. interact with host receptors. studied all are associated indepen- These findings, published in DOI: 10.1016/j.jbc.2021.100368 dently with CAD even after adjusting a recent article in the Journal of for their pleiotropic effects. Biological Chemistry, present a DOI: 10.1194/jlr.P120001000 new mechanism for the regulation of Nuala Del Piccolo glycosylation modification. ([email protected]) is a science writer in the biomedical Rab11 reorganizes DOI: 10.1016/j.jbc.2021.100354 engineering department at the University of California, Davis. sialyltransferases She earned her Ph.D. in materi- Macrophage mannose als science and engineering at Sialylation, or the addition of receptors rely on sugars Johns Hopkins University. sialic acid to glycoproteins, is a modification involved in embryonic The human mannose receptor is Vaishnavi Muralikrishnan development, neurodevelopment, expressed on macrophages and plays ([email protected]) is a doctoral candidate in the cell, molecular oncogenesis and immune responses. a critical role in innate and adaptive and cancer biology program at The enzymes responsible for cata- immunity as well as reducing dam- the Indiana University School of lyzing this modification, known as age after tissue injury. The recep- Medicine. Follow her on Twitter @ Wise_navi. sialyltransferases, primarily reside and tor’s function depends on its C-type function in the endoplasmic reticu- carbohydrate-recognition domain 4, lum, and it is unclear how their local- or CRD4, which contains a site for Laurel Oldach (loldach@ asbmb.org) is a science writer 2+ ization to this region and trafficking Ca -dependent interaction with sug- for the ASBMB. Follow her on to other regions are regulated. ars. However, researchers do not yet Twitter @LaurelOld. In previous work, Masato Kitano know the details surrounding CRD4– at Osaka University and colleagues ligand interactions. identified a connection between In an article published in the Jour- N-glycosylation and Rab11, a small nal of Biological Chemistry, Hadar Anand Rao ([email protected]) GTPase that is a key player in the Feinberg and colleagues at Stanford is an ASBMB science communi- cator. Follow him on Twitter post-Golgi transport that connects University School of Medicine used @AnandRaoPhD. recycling endosomes and other glycan array screening to identify compartments. The authors recently mannose-containing ligands that elaborated on Rab11’s role in glycan are likely to interact strongly with

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30 ASBMB TODAY MAY 2021 VIRTUAL EVENT Flux-independent signaling by ionotropic receptors: Unforeseen roles and complexities

June 21, 2021 | Virtual

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MAY 2021 ASBMB TODAY 31 FEATURE Targeting 20,000proteins by2035

By Laurel Oldach

hen you run a web search for “Target 2035,” most of the results are investment options. Aled Edwards and Cheryl Arrowsmith are hoping that by the time Gen- W eration X has begun to retire, a second meaning will be as common — at least in the chemical biology community. Target 2035 is the name of their effort to inspire the community to develop a probe, or a specific small-molecule modulator, for each of humanity’s 20,000 proteins. The two Canadian structural biologists, among the leaders of the international Structural Genomics Consortium, are the driving force behind Target 2035, which launched in November. “It’s an ambitious project,” said pharmacologist Bryan Roth, who is not part of the consortium but has advised for it, a role he compares to reviewing for a journal. “It’d be great if we had real, useful chemical tools for all the targets in the genome.” Assessing the Human Genome Project Edwards began to consider the whole proteome about a decade after the Human Genome Project was completed in 2001. That project had identified 20,000 protein-coding genes, many of them for the first time. After some fellow researchers in the Structural Genomics Consortium in 2010 urged the cancer research community to explore as-yet-undrugged kinases instead of revisiting ones that already had been chemically validated, Edwards and collaborators conducted a literature review to see how research into other protein families, such as ion channels and nuclear receptors, had progressed. They found that most research had continued to circle historical targets. “This makes no bloody sense!” he said. “If you were a logician and not a scientist, you’d say, ‘Well, that’s kind of dumb.’”

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But science funding agencies and smith said. She became the chief COURTESY OF ALED EDWARDS journal editors tend to reward a more scientific officer of the consortium’s conservative approach. Arrowsmith Toronto location. saw that while serving on a Canadian Edwards and Arrowsmith, who study section recently. “Everybody met as structural biology trainees at else on the panel said, ‘Why (is the Stanford University, already had col- applicant) studying this protein? laborated on large-scale approaches Nobody works on this protein; it to find protein structures as profes- doesn’t do anything important that sors at the University of Toronto be- we know of.’ I was disappointed, but fore getting involved in the nascent it was kind of hard to argue.” project. Aled Edwards is the CEO of the During a recent seminar, Edwards Both said that their working styles Structural Genomics Consortium. said, “It’s so much easier to work complement each other: Edwards, COURTESY OF CHERYL ARROWSMITH where people know about stuff. It’s an energetic speaker whose tangents really hard to develop hypotheses sometimes eclipse his original point, about something that is unknown.” appreciated Arrowsmith’s focus and During their literature review, follow-through. She appreciated his Edwards and his team also noticed big ideas. a few proteins that had bucked the “We kind of feed off each other in trend. Over the 10-period they terms of what can be done and what examined, those molecules had gone should be done,” Arrowsmith said. from obscurity to popularity. In The SGC now supports uni- those cases, Edwards said, almost versity-affiliated scientific teams without fail there was a potent and in six countries and is funded by Cheryl Arrowsmith is the chief specific inhibitor available for the eight multinational pharmaceutical scientific officer of the Structural protein. Having a pharmacological companies, Wellcome and Genome Genomics Consortium in Toronto. approach to perturb a protein’s activ- Canada. ity made it much easier to study. “Initially it was purely a structure- “We thought, OK, then why don’t determination organization,” said we start to proactively make research Susanne Müller–Knapp, a molecular tools for proteins that no one cur- biologist who co-authored the initial rently gives a shit about?” kinase study and today coordinates activities at the Frankfurt arm of the “At some point, we were consortium. wondering, ‘We have these The SGC Structures and inhibitors can The “we” was the Structural be mutually beneficial; knowing a freezers full of proteins; Genomics Consortium. protein’s structure can help in the Founded by the Wellcome Trust, rational design of a small molecule what else can we do with several Canadian research organi- to bind to it, while having a small them?’” zations and molecule that binds to the protein GlaxoSmith- can sometimes stabilize it, making SUSANNE MÜLLER–KNAPP Kline in 2004, crystallization and structural studies the SGC is a easier. nonprofit pub- Over time, the group collected in- lic–private partnership that aims to hibitors of proteins they were study- coordinate and accelerate protein ing and noticed when inhibitors were structure discovery. lacking. Müller–Knapp said, “At “Al was recruited to be the CEO some point, we were wondering, ‘We of SGC, and the first person he have these freezers full of proteins; asked to join him was me,” Arrow- what else can we do with them?’”

MAY 2021 ASBMB TODAY 33 FEATURE

COURTESY OF SUSANNE M That was when the team started to a compound called DZNEP, often work on developing small-molecule reported as an inhibitor of the widely tools to bind to those proteins and studied histone methyltransferase block their activity, with a tight focus EZH2. However, the compound Ü LLER-KNAPP on epigenetic modulators, enzymes actually was developed to disrupt the that modify DNA or histones or de- synthesis of S-adenosylmethionine, tect these modifications, to alter gene the cell’s universal methyl group expression patterns. donor, wreaking havoc on every methyltransferase. Rigorously defining a probe The original report on DZNEP was not strictly wrong, Arrow- Susanne Müller–Knapp is a molecular Although genetic techniques to smith said. “It does inhibit EZH2. biologist who coordinates activities manipulate protein expression are It inhibits everything.” However, at the Frankfurt arm of the Structural well developed, the SGC team is interpreting experimental results Genomics Consortium. not interested in generating 20,000 after DZNEP treatment as specific to knockout mice or cell lines. They EZH2-mediated methylation would argue that removal of a protein be a mistake. Unfortunately, Arrow- through genome editing may have smith added, although this molecule’s wider-reaching effects than blocking drawbacks have been known for some its function with a small molecule and years, many reagent supply companies is harder to translate into potential still offer it as a specific inhibitor of drug development. EZH2. “Even now, I still see papers Instead, the team focuses on small- where people use this DZNEP, which molecule and biological tools, or is a sloppy compound.” probes, to block protein activity. DZNEP is similar to other mol- “Probe is a word that anyone can ecules known in the chemical biology apply to their molecule,” Edwards community as pan-assay interference said during a webinar. But the SGC compounds, or PAINs. They act by a A scientific illustration shows a chemical team applies a stringent definition: variety of mechanisms, but the unit- probe that SGC scientists designed to A probe is a molecular tool that acts ing feature is that they are not specific bind the histone methyltransferase KMT4 selectively, by a known mechanism, to to individual proteins. They tend to (green), which modifies DNA-binding histone modulate protein activity. show up in the literature again and complexes (blue). Unlike a drug, a probe doesn’t need again, particularly after high-through-

D. IVANOCHKO AND S. ACKLOO to make its way put screens, frustrating experienced through an organ- medicinal chemists and leading less ism to its target. experienced ones astray in interpret- Unlike an inhibi- ing their data. tor, a probe doesn’t To be sure that each probe the need to block SGC develops or distributes is selec- enzymatic activity; tive for the target it was designed to it might act, for ex- block, the team collects a standardized ample, by inducing set of assays. They look for data that protein degradation demonstrate a probe binds to its tar- or binding to an get protein and blocks its activity in allosteric site. test tubes and in cells — and ideally In some cases, a can be cocrystallized, giving structural bad chemical tool proof that it binds. They consider a could be worse molecule’s selectivity between closely than no tool at all. related proteins and its stability in so- Arrowsmith cited lution to make sure it will not degrade

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into inactive compounds. Ideally, along with each probe, the SGC also hopes to distribute control compound Chemogenomics: Putting imperfect probes to use that is chemically related but does not affect the same protein target. Two Finding a selective modulator of a protein can be difficult, according to Cheryl expert panels, one from within the Arrowsmith, a structural biologist and co-founder of Target 2035. “Often, one has to SGC and one of external academics, make a compromise with saying, ‘OK, this compound is good enough; let’s publish review each probe to certify it before it and see what we can do with it, warts and all, if you will,’” she said. “The issue is, publishing. everybody should know what the warts are.” Although the team has been Some approaches take the warts into account and work around them. For example, successful in developing probes for adenosine triphosphate mimics tend to block numerous kinases. An approach de- epigenetics, the rigorous development veloped by chemists at the Structural Genomics Consortium and numerous pharma- process takes time. To achieve their ceutical companies involves applying many kinase inhibitors, each of which targets genome-scale ambitions, the SGC a relatively small number of kinases, and using the overlap in results to determine team will need reinforcements. Ed- exactly which kinase target is responsible for an assay result. The approach is called wards said, “We’ve spent considerable chemogenomics. time and effort making 100 probes — and obviously, that won’t scale.” drug-discovery programs where there Pharmaceutical partners are good modulatory molecules. Nor- mally they’d just go sit on the shelf The largest developers of protein and wouldn’t be used anymore. Now “If academics use compounds inhibitors are pharmaceutical and many companies are making these that are not characterized, biotech companies, which routinely available to the community.” bombard protein targets with po- GlaxoSmithKline was one of the they will always ascribe the tential inhibitors and fine-tune the first companies to make samples and results one functional group at a time annotation about its probes openly phenotype to the so-called on the hunt for future drugs. available. In 2014, inspired by SGC ‘specific target’ that the inhibitor “Discovering new medicines is scientists’ work, the company made extremely difficult and also increas- 367 previously published kinase was made for. And so the whole ingly expensive,” said Adrian Carter, inhibitors available to researchers. literature is polluted. the head of discovery research coor- In an article in the journal SLAS ” dination at pharmaceutical company Discovery, a team of medicinal chem- SUSANNE MÜLLER–KNAPP Boehringer Ingleheim, at a recent ists originally from GlaxoSmithKline Target 2035 webinar. “Much of but now affiliated with the SGC that high cost is driven by failure, described the process of publiciz- unfortunately.” ing those probes, which they called The SGC hopes that molecules “extreme open science.” First, the that don’t make it as drug candi- chemists collected the hundreds of dates still might be useful as chemi- inhibitors and screened each molecule cal probes — and that companies for effects on more than 260 human will make them freely available to kinases (see “Chemogenomics” box researchers. This historically has been on this page). Next, an equally daunt- a difficult sell for companies whose ing task, they worked out a process business model depends on proprie- with the company’s legal team to tary molecules. However, Arrowsmith distribute molecules for research use said that thanks to a culture shift in under a simplified materials transfer the pharmaceutical industry, compa- agreement. nies are now more willing to release The kinase inhibitor set broke a molecules from “both past and failed trail for other companies to make

MAY 2021 ASBMB TODAY 35 FEATURE

ascribe the phenotype to the so-called ‘specific target’ that the inhibitor was Machine learning and the future of probe design made for,” she said. “And so the whole In November, the protein folding program AlphaFold made headlines by cor- literature is polluted.” rectly predicting the structures of some two dozen proteins that had been solved By enabling academic research- by researchers but were unpublished. ers to make more discoveries, these “Bingo! Miracle result,” Canadian structural biologist Aled Edwards said. “Only probes (which, after all, already had 50 years in the making.” been rejected as drug candidates) The folding program evolved from a structural biology competition called CASP, could contribute to the pool of or Critical Assessment of Structure Prediction, which organizers always had envi- reliable knowledge about biology sioned as a training ground for new structure prediction tools. Using sequence– that industry researchers draw from structure relationships made public in the Protein Data Bank as a training set, the regularly. competition has challenged participants to extrapolate from a known sequence to Besides, Arrowsmith said, making a new structure. a small molecule available for research A success like AlphaFold’s “was exactly the plan of structural biologists,” use is not the same as giving up the Edwards said. “They’ve spent literally billions and billions of dollars creating the exclusive right to sell it. “If they let foundation so that this could happen.” one of the molecules out there, they Just as the Protein Data Bank collected and organized knowledge about still may be covered by a patent, but protein structure, becoming an integral resource for machine learning, Edwards they’re making it available to the said that the Structural Genomics Consortium, which he co-founded, means to world to use.” organize knowledge about chemical probes and their activities that may be used But it’s not without effort for data mining in the future. for companies. In industry, the Researchers already are beginning to use computational tools to develop new discovery process is aimed at probes. For example, in a Nature paper in 2020, labs at the University of North bringing molecules to market. If a Carolina at Chapel Hill and University of California, San Francisco, used computa- probe does not have a reasonable tional tools to dock 150 million hypothetical compounds to a melatonin receptor, path forward, researchers often stop synthesizing and screening only the most promising. experimentation. This leaves some The approach dramatically expands the speed of screening, said Bryan Roth, molecules incompletely characterized who led the UNC team. “It’s now possible, once you have a structure of a protein, by SGC standards. According to to dock billions of small molecules that don’t actually exist in the physical universe Müller–Knapp, companies that have … then to get them synthesized, and to develop probes that way.” committed to donating a set number of probes have occasionally dropped one and proffered another if the their probes publicly available as original candidate needed too much well. Müller–Knapp led a team that additional wet lab characterization. recruited about 90 more selective molecules from numerous companies Target 2035 in a collection called the donated chemical probes panel, which they an- The SGC has sent out thousands nounced in a paper in eLife in 2018. of samples of the epigenetic probe Each compound had taken medicinal collection its scientists developed, the chemists years to develop, at a cost of Published Kinase Inhibitor Set and up to 2 million euros apiece. the donated chemical probes set, ac- According to Müller–Knapp, cording to Arrowsmith. companies are motivated to release Phil Cole, a pharmacologist at the right to use their compounds in Harvard University who studies epi- part to make the literature they rely genetic modulators and has used some on more reliable and reproducible. of the epigenetic probes, said, “SGC “If academics use compounds that has had enormous impact in produc- are not characterized, they will always ing important protein structures and

36 ASBMB TODAY MAY 2021 FEATURE

small-molecule probes and is one of the great success stories in big science applied in chemical biology.” TAKUMA-SA/WIKIMEDIA COMMONS SGC organizers say they’re not sure whether the consortium will continue to function as a warehouse for the chemical probes they certify. To do so might institutionalize the SGC along- side nonprofits like Addgene, Jackson Labs and the American Type Culture Collection, or ATCC. On the other hand, Arrowsmith said, most SGC investigators are also active researchers and want to focus on using the probes they’ve worked so hard to develop to study biological questions. Target 2035 kicked off with a tional goal and said, ‘Let’s go for it.’” series of webinars in November, and Most other scientists are skeptical organizers have continued to hold about whether 2035 is a realistic end monthly webinars on topics in drug date. But pharmaceutical industry development. commentator Derek Lowe wrote, In the project’s first phase, set to “The good news is that this isn’t one A crystal structure drawing shows the last until 2024, organizers aim to of those efforts that has to make it to epidermal growth factor receptor, or EGFR, which is frequently mutated in cancer, in solicit donations of existing small the end to be really valuable.” complex with the cancer drug gefitinib. molecules and develop processes for Target 2035 overlaps with a major validating the molecules and sharing National Institutes of Health initia- characterization data. In later phases tive called Illuminating the Drug- they will try to use those data mining gable Genome, which targets kinases, and biochemical profiling tools to ion channels and receptors, and a coordinate and speed up probe devel- more recent European effort called opment assays. EUb Open that takes aim at 1,000 “It doesn’t break any laws of Like the improvements in sequenc- proteins. SGC adviser Roth said that physics, right? So it should ing during the Human Genome because of differences in funding Project, Arrowsmith said, she expects streams, “They’re all separate projects, happen. It’s just a matter of the available tools for drug design to sadly. It’d be great if we could all be improve during the project, accelerat- part of one gigantic project.” when. We chose 15 years ing discovery. According to Edwards, bringing as an aspirational goal and How did they settle on the 15-year major international projects, industry target date? “That was Aled,” Arrow- groups and individual academic labs said, ‘Let’s go for it.’” smith said with a chuckle. “He pulled into alignment is precisely the goal ALED EDWARDS that out of a hat somewhere.” of Target 2035. “I’m talking about a To achieve the goal of disrupt- science project,” he said. “But my No. ing every protein in the proteome, 1 and 2 projects are culture.” Edwards explained, “You need to improve the technologies … You Laurel Oldach (loldach@ need to get better at chemistry, faster asbmb.org) is a science writer and more effective. But it doesn’t for the ASBMB. Follow her on break any laws of physics, right? So Twitter @LaurelOld. it should happen. It’s just a matter of when. We chose 15 years as an aspira-

MAY 2021 ASBMB TODAY 37 FEATURE Exploring underappreciated molecules and new cities Meet Journal of Lipid Research associate editor Xianlin Han

By Laurel Oldach COURTESY OF XIANLIN HAN

Xianlin Han presented at the International Symposium on Metabolomics in Shanghai in 2019.

aybe you’ve never heard of sulfatides, sphingolipids that contain a sulfate moi- ety in the head group. That won’t offend Xianlin Han. The genial neurochemist, Ma professor at the University of Texas Health Science Center at San Antonio, is accustomed to explaining his work to people who are unfamiliar with most of his favorite molecules. His lab studies how changes in sulfatides and other lipids may contribute to Alzheimer’s disease, along with other brain lipidomics research. Among his many professional service activities, Han has been an associate editor for the Journal of Lipid Research since 2019. In a wide-ranging conversation with ASBMB Today, Han explained how his interest in instrumentation led him to a lifelong study of lipids and to his penchant for exploration both in his research and in his travels. This interview has been condensed and edited.

Q. How has the pandemic seems very strange.” affected your work life? You have Then Wuhan started to lock a lot of collaborators in China — down, and I thought, “It seems like did you have a sense of the risks it’s not easy to get this virus totally of COVID-19 very early on? controlled; seems like it’s going to be a global problem.” And gradually, it A. I was in Hong Kong, Guangzhou was. and Macau in January 2020. At that I knew it would become a prob- time, people over there were saying, lem, but I didn’t foresee how severe “Something is going on in Wuhan, it it would be here. I asked our lab

38 ASBMB TODAY MAY 2021 FEATURE

manager to order PPE — at that COURTESY OF XIANLIN HAN time it was still available. On March 5, 2020, we had a JLR editorial meeting at La Jolla, in San Diego. I was the only one wearing a face mask in the entire plane. People probably thought, “He’s so strange.” Three weeks later, there was no PPE available anywhere, and we donated some face masks to the hospital. Our lab actually remained open. We are in the medical center, so all the different lab heads could make their own decision. Our lab has a lot Xianlin Han (right) and postdoc Juan Pablo Palavicini enjoy a light moment of animals that we needed to keep while working on the lab’s mass spectrometer. working on. We remained open to keep an eye on them; otherwise, we reduction people had already reported would have lost at least three years’ and linked with oxidative stress. I work. thought, “That seems like it’s not very novel, although it’s interesting.” Q. Tell me about your research. Ceramides were linked to neuro- inflammation, which was also well A. My lab is lipidomics based; most connected to Alzheimer’s disease. So I of our projects are related to how picked the last class of lipids, sulfa- brain lipids connect to some kind tides, and for the last 20 years, we of disease. We use lipidomics to dis- have kept working on this area. Not cover lipid changes, then try to iden- too many people study sulfatides, so tify the molecular mechanisms that we can gradually understand many contribute to the lipid changes and different areas. The bad thing is that find the consequences of these al- not very many people are interested. tered lipids in context of the disease Some have never heard of them. or physiological change. The three The sulfatide reduction turned out keys are discovery, identification and to be very interesting. Using trans- determining the consequences. Our genic and knockout animal models whole lab’s research is based in these obtained from our collaborators, we strategies, which has a fancy name, found that the mechanism is a lipid “functional lipidomics.” change connected with apolipo- We’ve been studying Alzheimer’s protein E. You probably know that disease for almost 20 years now. A ApoE4 is the strongest genetic risk long time ago, when I was at Wash- factor for Alzheimer’s. In the early ington University School of Medi- 2000s, we found that the ApoE4 par- cine, we used a lipidomics platform ticle carries a much higher content of and found that three classes of lipids sulfatide than other ApoE isoforms. changed very significantly in the When ApoE4 is transported, that earliest clinically recognizable stages leads to the brain having much less of Alzheimer’s disease. One kind was sulfatide. called the plasmalogens, the second Later on, we studied the conse- was ceramides and the third was quences. If the sulfatides are lost, sulfatides. what symptoms does that cause in the The plasmalogen change is a brain? We found that loss of sulfatide

MAY 2021 ASBMB TODAY 39 FEATURE

(T)hat’s what we study — the causes A-beta toxicity and hyper- is based on lipid metabolism. Ev- ‘‘ phosporylation of tau, the hallmarks erybody thinks you’re working on connection of sulfatide loss with of Alzheimer’s disease. cholesterol, because ApoE is con- diabetes, traumatic brain injury, Loss of brain sulfatides can cause nected to cholesterol metabolism. other consequences: ventricular So usually I need to take a while to anesthetic toxicity, etc.” enlargement, bladder enlargement, explain what we are studying. glial cell activation, and neurotoxic- People think that lipids are only XIANLIN HAN ity and neuroinflammation. When a readout reflecting some kind of the conditional knockout animals protein activity or gene expression, are about 12 months old, we already or maybe affecting the membrane see cognitive decline. integrity. But actually, the sulfatide People are always thinking Al- appears to behave as a signaling zheimer’s is a multifactorial disease. compound. It senses the environ- We thought, What if many factors mental changes and interacts with could cause sulfatide loss, and once cell receptors. That kind of action the sulfatides are lost then the conse- turns out to be very important. quences are the different hallmarks? So that’s what we study — the Q. What got you interested in connection of sulfatide loss with lipids? diabetes, traumatic brain injury, A. That takes us back 30 years. I anesthetic toxicity, etc. came to the United States in 1985 We also try to understand the and went to Washington Univer- mechanisms of diabetic neuropathy. sity to do my Ph.D. in chemistry. And traumatic brain injuries can I really liked using instruments; also cause sulfatide loss, so we’re my goal was to learn all kinds of trying to understand the mechanism instrumental technologies to study there. Then there are other areas, in- biology. cluding end-stage diabetic neurotox- My mentor, Richard Gross, was icity and other metabolic diseases. studying the calcium-independent Q. So your trainees have a lot of phospholipase A2 and chemical projects to choose from? biology of membranes in health and disease, using a variety of tech- A. Yeah, we have too many projects niques such as high-performance — too many meats on our plate. liquid chromatography, fluores- They can try whatever: pork, beef, cence spectroscopy and nuclear chicken. magnetic resonance. I thought that was cool. When I talked with him, Q. Now must be a good time to he said, “Whatever you want to be an Alzheimer’s researcher use we can make available.” That’s who doesn’t study amyloid beta. how I initially moved into studying Have you noticed a change in lipids. other researchers’ interest in At the time, we were trying to your work? understand how lipids travel on the membrane and interact with A. When I say we are studying different regulatory proteins. How lipids, most people’s first reaction are they transported from the outer is to think we are trying to develop leaflet to the inner leaflet? How do biomarkers for Alzheimer’s disease. they affect ion channel function? Second they think that our study We used HPLC to purify mem-

40 ASBMB TODAY MAY 2021 FEATURE COURTESY OF XIANLIN HAN

Xianlin Han in his lab space at Sanford Burnham Prebys Institute, where he was a professor for several years before moving to Texas in 2018.

brane components and to quantify age, my joints started to get poor. lipids. I had so many headaches. I I grew up in the southern area of really hated all of this HPLC purifica- China. So I moved south, first to tion. You don’t know how much time Sanford Burnham Research Institute I spent late at night, doing months in Florida, then to the UT Health of work to get one data point, not Science Center at San Antonio three knowing whether it’s a good one or a years ago. bad one. UT Health Science Center at San After I graduated, Dr. Gross asked Antonio is relatively small com- me whether I would like to stay in the pared to other centers in the UT lab, so I stayed and became a postdoc. system. But it has faculty with broad At this period, I had the opportunity interests, from cancer to neurode- to apply mass spectrometry to study generation to metabolic diseases. I lipids when Dr. Gross brought an can collaborate on all my projects in electrospray ionization mass spec- such an environment. That’s why it’s trometer to the lab. the right place for me.

Q. Why did you move on? Q. Besides research and teaching, you also do community A. I got a little bit bored after 25 years in St Louis. I was at the same service. What organizations are university from Ph.D. to postdoc and you involved in? as faculty. I thought I’d make some A. I’m on the editorial board for a change. Also, in St. Louis the weather number of journals, mostly related is terrible, and when I hit middle to lipids. Besides lipids, I have

MAY 2021 ASBMB TODAY 41 FEATURE

‘‘Whatever city I’m staying in, COURTESY OF XIANLIN HAN whether at home or traveling to a conference, I like to take time to walk around and see what’s there.”

XIANLIN HAN

Xianlin Han (right) and doctoral mentor Richard Gross look at data in 2009.

done mass spectrometry, so I am 10 miles. The next week we go from involved in the Chinese American there to the next stop, seeing the city Society for Mass Spectrometry; I and exploring. served as president for two years, Whatever city I’m staying in, and I’ve basically been a board whether at home or traveling to a member forever. I also serve as conference, I like to take time to secretary for the International walk around and see what’s there. Lipidomics Society. Since I study And I like to travel. People ask, the brain, I’m also involved in the “Hey, Han, maybe you could come neurochemistry community. join our meeting and give a talk?” I say, “Sure, I’ll come!” Travel not Q. Where do you find the time? only exchanges science and adver- tises your work but also makes new A. I’m usually in the office six days friends. You explore areas you’ve a week, from 9 to 7 every day. Still, never visited. That’s what’s so excit- there are so many things I almost ing. People sometimes say, “Why do cannot finish. I agree to review so you take so much time and expense many papers because I know the to travel?” I say, “It’s fun.” editor, or I know the author or I My third hobby is stamp collect- think the research is interesting. ing. I’ve learned a lot through stamp Having a big network is good and collecting: geography, language, bad. Good is that I’ve made lots of cultures. I used to go fishing at friends. Bad is that I always have stamp shows. Now I do not have something to do — it’s so busy. time anymore; I had to hide all my Q. Do you have any time for albums. hobbies? Laurel Oldach (loldach@ A. I like hiking. San Antonio has asbmb.org) is a science writer a really good hiking system called for the ASBMB. Follow her on Twitter @LaurelOld. the Greenway, which goes around the entire city. Usually my wife and I go hiking once a week, for about

42 ASBMB TODAY MAY 2021 VIRTUAL CONFERENCE Extracellular vesicle studies: From benchtop to therapeutics

July 21–23 | Virtual

Submit your abstract by May 27: asbmb.org/meetings-events/extracellular-vesicle-studies

VIRTUAL CONFERENCE Serine proteases in pericellular proteolysis and signaling

Oct. 28–30, 2021 | Virtual

asbmb.org/meetings-events/serine-proteases-2021

MAY 2021 ASBMB TODAY 43 ESSAYS

Winners of the ‘aha moments’ essay contest To celebrate our three journals going open access, we invited readers to share their moments of discovery in science. Here are our top 10 essays.

FIRST PLACE Finding a common ancestor By Richard F. Ludueña

As a child, I loved science fiction. I always have liked history, and I espe- cially was drawn to stories about time travel, because I loved to imagine looking far back into the past. My aha moment came in 1972 when I was a graduate student in Dow Wood- ward’s laboratory at Stanford determining the first 25 amino acids in the se- quences of alpha- and beta-tubulin from chickens and sea urchins. At that time, very little was known about tubulin sequences. The results came off the sequencer around Christmas Day. I realized that chicken and sea urchin α-tubulin were about 95% identical and that the same was true of the β-tubulins. This meant that I had just learned something very intimate about the common ancestor of vertebrates and echinoderms, an organism whose appearance and morphology were unknown and only could be guessed at. I felt like I was looking perhaps 700 mil- lion years into the past. I had no idea what that animal looked like, but I knew something about its tubulin. I also observed that α- and β-tubulin were themselves about 40% to 45% identical, so I now perhaps was see- ing more than 2 billion years into the past to the time of the first eukaryotes, one-celled organisms that lived on a planet that would be unrecognizable to us. This was one of the most exciting moments of my career as a biochemist and the closest I ever came to real- izing my childish fantasy of time travel. I think a child lives inside every scientist, a child whose curiosity is challenged by mysteries, who wants to make visible the invisible and to magnify the microscopic and who wants to look back into time as far as the origins of everything — of cells, life, the earth and the universe.

Richard F. Ludueña ([email protected]) is a professor emeritus of biochemistry at the University of Texas Health Science Center at San Antonio. He received his Ph.D. in biological sciences from Stanford University in 1973. He spent his professional career investigating tubulin–drug interactions and the functions and expression of tubulin isotypes.

44 ASBMB TODAY MAY 2021 SECOND PLACE Dreaming of Western blots By Mindy Engevik

It was a cold night; the wind was blowing, and the branches of a nearby tree were scratching against the roof of my apartment. I was in bed huddled under a big down ARGYMEG/WIKIMEDIA COMMONS comforter, which enveloped my whole body like an amoeba. I was deep in REM sleep, dreaming of Western blots. Horrible Western blots … the bane of my existence. As a gradu- ate student, I A nitrocellulose membrane stained for protein detection during Western was fascinated blotting. by the beauti- fully orchestrated events of ion transport of the intestine. I gloried over ion transporter mRNA, enjoyed functional assays in tissue cultures, reveled in measuring fecal ion concentrations by flame photometry — but then I encountered the dreaded Western blot. I needed to measure the protein levels of the sodium–hydrogen exchanger isoform 3 and the colonic HK-ATPase in mouse colon by Western blot. Day after day, I had been troubleshooting these Western blots. I had tried optimizing the denaturing steps, removed the denaturing step, changed the blocking buffer, modified the run times … I had tried everything I could think of and everything my helpful colleagues had recommended. But to no avail — the Western blot had won. But that night, in my dreams, I went over the Excel sheet provided by my PI that provided a handy plug-in for calculating the amount of protein to add to the Western blots. I dutifully added my dream concentrations and realized … the math was wrong. I bolted awake, ran to my laptop, checked the Excel sheet and voila — the Excel sheet math equation was incorrect! That morning, I went to the lab, added the correct amount of protein, and this time, the Western blot worked. I felt like a conquering hero. I guess dreams really do come true.

Mindy Engevik ([email protected]) is an assistant professor at the Medical University of South Carolina. She earned her Ph.D. in systems biology and physiology at the University of Cincinnati and did her postdoctoral fellowship at Baylor College of Medicine. She loves mucus, microbes and all things science. Follow her on Twitter at @micromindy.

MAY 2021 ASBMB TODAY 45 ESSAYS

THIRD PLACE Beauty in brown By Kazuhiko Igarashi

The laboratory where I started as a new faculty member, led by Norio Hayashi and Masayuki Yamamoto, focused on erythroid cells: Colleagues were working on the regulation of heme synthesis during erythropoiesis, and I was trying to identify transcription factors that would regulate globin genes by binding to their superenhancers, the locus control region, together with two graduate students. One student, Ken Itoh, got two promising candidate cDNA clones in two hybrid screenings using MafK, one of the subunits of nuclear factor erythroid 2, as a bait. The other student, Tatsuya Oyake, expressed one clone in E. coli for purification. When he came out of the cold room, he was disappointed, thinking that his purification was a total failure. The protein solutions looked brown. We were troubleshooting in front of the cold room, with the tubes in his ice box. Then our lab head, Norio Hayashi, who has a long track record in enzymes of heme synthesis, happened to walk by. It did not take a second before he saw the tubes and suggested carefully, “This may be a heme protein.” A beauty emerged: Heme, which is massively synthesized during erythropoi- esis, would regulate the activity of this transcription factor, BACH1, coordi- nating heme synthesis and globin gene expression. As so many scientists know, the simplicity of a model does not guarantee a simple way forward. For us, it took another two decades to come to a reason- ably correct answer on the function of the heme–BACH1 axis in erythropoi- esis. Various functions of BACH1 and the other clone, BACH2, which also is regulated by heme, have emerged in not only erythropoiesis but also iron and heme metabolism, immune response and cancer progression. If Tatsuya had discarded the tubes out of disappointment or Professor Hayashi had not seen those tubes, what would we be doing today?

Kazuhiko Igarashi ([email protected]) is a professor of biochemistry studying regulation of cell responses and differentiation by transcription factors at Tohoku University in Japan and a member of Science Council of Japan. Follow him on Twitter @kazuigarashi.

46 ASBMB TODAY MAY 2021 HONORABLE MENTIONS

Fringe inspiration mouse until this moment — my aha moment — and to By Miguel A. Contreras Hidalgo understand the pathobiological and translational conse- quences of psychosine accumulation outside the CNS. (In memory of Maria Leticia Sanchez Ortiz, a teacher When I was a junior faculty member, my only and a mentor.) break from research was to have dinner with my family and, from time to time, enjoy a science fiction TV show and then get back to the lab. Miguel A. Contreras Hidalgo ([email protected]) Back in September 2008, I sat down to enjoy the is a program officer at the National Institutes of Health. He earned his Ph.D. in molecular and cellular biology and second episode of a new show called “Fringe.” The show pathobiology at the Medical University of South Carolina. follows the adventures of FBI agent Olivia Dunham (as- This essay was prepared by the author in their personal signed to the bureau’s Fringe Division); junior FBI agent capacity and does not reflect the view of the NIH. and sidekick Astrid Farnsworth; fringe science researcher Dr. Walter Bishop; and his son, Peter. In this particular episode, a pregnant woman deliv- A life filled with aha ers a newborn that ages rapidly in minutes and soon dies, having aged into an 80-year-old man. Olivia and moments her associates are called to investigate. Eventually, Dr. By Danielle Guarracino Bishop makes a connection to the pituitary gland, which controls growth in humans. A life dedicated to science is filled with aha I literally jumped from the couch. For the past three moments. For me, a few noteworthy ones define my years, I had been using the twitcher mouse model to trajectory. study the molecular mechanism of Krabbe disease, an In seventh grade, I had an inspirational female inherited lysosomal disorder in which galactosylsphin- teacher who delved into biology with a memorable gosine (psychosine) accumulates mainly in the central gusto. We did dissections, talked to marine biologists via nervous system. The mouse recapitulates genetic and satellite and had many hands-on activities. I remember enzymatic aspects of the disease and is characterized by one night, when studying, I realized that science offers its small size. It has been a valuable tool to advance our an answer to every “why.” My first aha. understanding of the development/progression of the Later, in high school, when I lost a close friend to disease’s inflammatory process in the CNS. what seemed like a medical mystery, I was empowered to want answers: in science, in medicine, in life. Fast-forward through my doctoral program, where late-night incremental gains celebrated over a few hours of sleep and the whir of the laboratory instruments were punctuated with the aha of innovation. Now I have been a professor for 10 years at a small college and am lucky to see aha moments for a living. Recently, a student, camera not on, stayed after our remote class in need of validation. When I assured her she understood a concept, she switched her camera on, doing a dance in excitement — the aha moment of a connection made. It never had occurred to me before to investigate the As I bridge teaching remotely while caring for my molecular mechanism by which the toxic accumulation toddler, I love introducing my daughter to science. One of psychosine in peripheral organs was responsible for day we stabbed pencils through Ziploc bags filled with the inhibition of the postnatal somatic growth of the water, amazed they did not leak. When I asked her later

MAY 2021 ASBMB TODAY 47 ESSAYS

HONORABLE MENTIONS

DANIELLE GUARRACINO The first to know By Guy Hervé

At 3 o’clock in the morning, locked into the small black room in the basement of the biology building of the deserted Saclay Nuclear Research Centre in Paris, lighted only by a small red lamp, I was waiting for the development of an autoradiograph that was going to tell me if a modified aminoacyl–tRNA that I had deaminat- ed was able to initiate protein biosynthesis by a bacterial ribosomal system, thus indicating that the initiation of protein biosynthesis does not involve the N terminus. In the darkness and solitude of this peculiar environ- ment and atmosphere, I was suddenly assaulted by the strange feeling that, although the result I was expecting was a very small piece of knowledge, I was going to be the first one to know it in the history of the universe. Danielle Guarracino’s daughter enjoys an aha moment, discovering

principles of science first-hand. COURTESY OF GUY HERVÉ

about “science time,” her face lit up as she remembered the pencils — her aha became mine, setting no age limits on science engagement. Perhaps one of the most poignant aha moments in my career came to me unexpectedly this past summer. After muddling through several months of isolating at home, navigating issues with work and home life, I re- ceived an email from a former student who was about to start medical school after years in the service, including several tours in Afghanistan. He wrote to thank me for recommendation letters and for the materials from my class, which he was using to prepare for this new phase of life. I was humbled and proud to know I had played a Guy Hervé gets out of a small submarine during the French–American small part in his path. expedition HOT 96; he dove 2,600 meters to the bottom of the Pacific Some of us are heroes, but others get the unique Ocean to collect tube worms, Riftia pachyptila, which he was studying in opportunity to educate them. For me, that was the aha the lab when he had his aha moment. moment that speaks to me most and that I return to whenever I am in doubt about what I do and who I am. Guy Hervé ([email protected]) is director of research at the French National Centre for Scientific Research and at Sorbonne University in Paris and vice Danielle Guarracino ([email protected]) is a biochem- president of the Biophysical Committee of the French istry professor at the College of New Jersey, studying the Academy of Science. He earned his doctorate in 1965 at folding of short peptides into secondary structures and the University of Paris and was a postdoc at Stanford peptides as inhibitors to protein–protein interactions University. His research concerns molecular and cellular implicated in disease. She earned her Ph.D. in bioorganic enzymology, aspartate transcarbamylase, allosteric chemistry and chemical biology at Yale University. Follow regulation, extremophile and deep-sea-vent organisms, her on Facebook or Instagram @daguarracino. and high-pressure studies.

48 ASBMB TODAY MAY 2021 HONORABLE MENTIONS

The right experiment tion of proPC2 and permits it to retain an activatable By Iris Lindberg form. Finally, I realized that instead of facilitating a positive process, such as enzyme activation, 7B2 blocked a nega- There are only very few moments in experimental tive event: spontaneous misfolding. This is very unusual science when one realizes that all of the parts to the within the secretory pathway, where misfolded proteins puzzle have fallen neatly into place. One tests hypoth- generally are degraded rather than efficiently secreted. esis after hypothesis — but nothing clicks. It is as if But once the right experiment was done, the pieces fell into place.

Iris Lindberg ([email protected]) is a professor of anatomy and neurobiology whose lab at the University of Maryland–Baltimore studies both proprotein convertase cell biology and neuronally expressed chaper- ones in neurodegenerative disease. Follow them on Twitter @lindberglab or visit thelindberglab.com.

Prepared mind leads phenomena occur by magic rather than by any orderly process. to life-saving medical I knew that overexpression of the enzyme precursor proPC1/3 in CHO cells resulted in the robust secretion advice of active enzyme, but expression of the related enzyme By Rona R. Ramsay precursor proPC2 resulted only in the secretion of cata- lytically dead enzyme — even at the pH known to cause The neural activity ahead of an aha moment intramolecular autoactivation. was evident in a hypothesis from the psychiatrist Ken I did know that proPC2 had a binding protein, 7B2, Gillman regarding the nature of the potentially fatal and bound cofactor proteins can be key to activating drug interaction called serotonin toxicity, which had enzyme precursors. But time after time, no matter how caused unexplained deaths over the previous decades. many conditions were tried, adding recombinant 7B2 His understanding of pharmacology and intellectual to secreted dead proPC2 did nothing to generate active curiosity about serotonin toxicity mechanisms prepared enzyme. his mind with an understanding of how drugs affecting The only way we could obtain any active PC2 at the monoamine system of the brain interacted. This in- all was to immunoprecipitate it from the conditioned cluded the interactions and effects, both clinical and ex- medium of a pancreatic cell line. perimental, of monoamine oxidase, or MAO, inhibitors Finally, I decided to look at the problem as the cell on serotonin levels in the brain. An anomalous report of would: by co-expressing 7B2 in our proPC2-overex- serotonin toxicity after surgery where methylene blue, or pressing cell line. The next day, a short enzyme assay MB, was used led him to suppose that MB had unrecog- resulted in the rare eureka: I saw abundant PC2 enzyme nised monoamine oxidase inhibitory properties. activity in medium from proPC2 cells co-expressing To substantiate a biochemical cause–effect relation- 7B2! ship, Ken contacted me in November 2006 and made a The aha moment: I suddenly realized that proPC2, case for testing his theory. I found literature indicating while still being efficiently secreted, must undergo a a Ki value of 5 millimolar for MB against the MAO-B denaturing event during transport through the cell. It found in glial cells and serotonin neurons, but nothing turned out that binding 7B2 blocks the deadly aggrega- on the serotonin-metabolizing enzyme MAO-A found

MAY 2021 ASBMB TODAY 49 ESSAYS

HONORABLE MENTIONS PROTEIN DATA BANK a moment of silence followed that storm instead of the other way around. Two amused faces were looking over my shoulder at a figure on my laptop screen. “You are making a Hulk, right, Mom?” one asked. I looked to check how serious they were and then looked back at the figure to connect some dots. It was a microscopic image of green fluorescent cells. I realized the connection with the green pulsing cells in the open- ing sequence of the 2003 Hulk movie. A moment of desperation led me to say “Yes!” and continue explain- Methylene blue (center) in the active site of monoamine oxidase close to ing that this was indeed my thesis project. the flavin–adenine dinucleotide (right). In the years that followed, I enjoyed support most student parents can only dream of. My only worry was in all the other neurons as well as glial cells. to be sure my boys didn’t perceive me as David Ban- My student tested it and quickly found that MB was ner’s evil scientist character. And I had to give routine

indeed a tight-binding inhibitor of MAO-A with a Ki COURTESY OF MONA AL–MOGOTIR value of 27 nanomolar. Furthermore, spectral experi- ments showed that MB could both donate and accept electrons from MAO-A, indicating a close active-site association. Subsequent drug discovery work by others found that many common compounds sharing the structure had additional influences in the brain. After our joint publication in 2007 and Ken’s efforts to spread the word via publications, website and net- working, medical advice on the use of MB was changed to avoid its use in patients on antidepressants to prevent the elevation of brain serotonin to toxic levels.

Rona R. Ramsay ([email protected]) is a biochem- ist who studied mitochondrial enzymes over 45 years at the University of Cambridge, University of California, San Francisco, and University of St. Andrews. Highlights LEFT: The author’s sons gave her these original specific aims for the include the carnitine carrier, neurotoxins and electron transport, and monoamine oxidase and drug design. superheroes project during her first year in graduate school. The older one, Ayman, wrote on behalf of his little brother, Ibraheem, as noted in the bottom “brother side.” Ayman’s payback for doing the writing was the freedom to allocate more powers to himself. He even crossed out Superhero science the request for magic for his brother. This sheet went through one edit By Mona Al–Mogotir by Ayman several months later as shown by the different pen colors and addition and omission of certain powers. Normally, life throws things at us, leading to some RIGHT: Mona Al–Mogotir, Ayman and Ibraheem five years later, after her aha moments. In my case, my kids were doing the graduation ceremony in May 2018. throwing part on behalf of life. I started my Ph.D. with two superhero-aspiring boys, updates of my progress over the dinner table, prob- ages 6 and 3. One day, as I was reading and dodging fly- ably more often than I did with my Ph.D. committee ing toys and shoes generated by superheroic excitement, members.

50 ASBMB TODAY MAY 2021 HONORABLE MENTIONS

Eventually, I was handed a paper with a list of su- perpowers to work on, which looked very much like a specific aim page. With time, speculations were raised, and I had just the right response to obliterate them, a green EGFP-tagged protein in solution. At the end of my defense presentation in April 2018, I decided to come clean about my real project during my acknowledgments. My two superheroes-in-waiting were among the audience. Since then, the story lives as a joyous memory at home and work.

Mona Al–Mogotir ([email protected]) is an analytical chemist at GlaxoSmithKline. She earned her doctorate in biochemistry and molecular biology from the University of Nebraska Medical Center and continued her postdoctoral training in Gloria Borgstahl’s lab for three years before moving into her current position.

Not quite out of the box By Najla Arshad

It was way back during my master’s program that I had this epiphany of sorts. One of our laboratory classes seemed on the verge of being canceled due to the absence of clean glass mea- suring cylinders. Or was it pipettes? I don’t remember the afternoon off, and I took the time to reflect on that detail now. The bottom line was that we needed to this with two of my friends. They thought it was a measure a specific volume of a liquid reagent and didn’t pretty smart idea. They even thought that the profes- have the necessary apparatus. sors were impressed. While the prospect of a free afternoon lit up my Then why didn’t we do it? Because, when an out- classmates’ faces, something in the back of my mind of-the-box idea meets the set ways of human nature, lit up as well. An abstract idea, a definition memorized the latter often wins. and an equation used to answer quiz questions sud- Recognizing this was an aha moment reminded me denly made perfect practical sense. to be open to taking risks and creative suggestions, “But we don’t need to measure the volume,” I piped trying new things, and applying old ideas in new up. ways. How well has that worked out for me so far? While some wondered where I was going with this, That’s a different story! I added, “We know the density. We can calculate the weight for the volume we need and just weigh it out.” Najla Arshad ([email protected]) is an associate I looked around for a response. research scientist in the laboratory of Peter Cresswell at “Well done!” Yale University, where she studies how ER chaperones “What an idea!” regulate immune responses. She received her Ph.D. from the Indian Institute of Science. Follow her on Twitter “Let’s do it!” @arshad_najla. That was just in my head. In reality, we were given

MAY 2021 ASBMB TODAY 51 QFive Questions “I could be happy doing other things” By Laurel Oldach

hen Alanna Mitsopoulos do because the state labs had shut decided that her aspiration down; with the backlog of evidence, Wto become a forensic scientist they were trying to reduce false was not practical for financial reasons, positives and avoid sending some- it spurred a lot of exploration — and thing out for secondary analysis she found that there were many jobs that would come back without any to consider. DNA. There wasn’t a lot of (compar- Mitsopoulos told ASBMB Today ative) research, so I dug really deep about her career path and her current to find information on how the tests role at the nonprofit AddGene, which work so that after I left they could catalogues and distributes plasmids decide whether to switch. for research. This interview has been condensed and edited. Alanna Mitsopoulos First job after college? CURRENT POSITION Viral vector senior technician, To pursue forensic science, I Tell me about your scientific 3 Addgene would have needed to go to grad training? CAREER PATH school, and I didn’t have the money I’ve been interested in science since Bachelor’s degree, biochemistry 1 to do that right away. In exploring and forensic science middle school, when I did a women other careers, I realized that I could FIRST JOB OUTSIDE OF ACADEMIA in science and engineering program. be happy doing other things; that’s In college I earned a biochemistry Embryologist when I found embryology. I spent FAVORITE MOLECULE OR PROTEIN degree with a forensic science con- four years in an in vitro fertilization centration. My senior year, I did an p30, a prostate-specific antigen used clinic, doing everything from egg to detect semen at crime scenes internship with the Boston Police De- retrieval to inseminating, assessing partment crime lab, right at the time the embryos, and freezing or trans- of all the scandals with the Massachu- ferring them. setts state labs. (Editor’s note: In 2011 Advice for younger and 2013, two state forensic scientists scientists? Now you’re at Addgene. were accused and later convicted of Internships are the best way to falsifying evidence in criminal cases What do you do there? 5get experience. But when that’s not and stealing confiscated drugs, re- possible — because internships are I’m part of the viral vector team; spectively.) They actually just made a 4 hard to get, especially now — make we produce readymade virus aliquots Netflix documentary on it. I’m watch- yourself stand out in some way. Have to make it easier for researchers. My ing it and thinking, “I remember this your professors review your resume average day involves culturing cells conversation happening!” and your cover letter. And always look — those are always being taken care into the company that you’re hoping of — and following my virus prep to be a part of. Wow. So what was through till the end: harvesting, pu- rifying and concentrating the virus. your role? Laurel Oldach (loldach@ Our team takes turns to do quality asbmb.org) is a science writer 2The crime lab was considering control checks; we’re very proud of for the ASBMB. Follow her on switching to a different preliminary the way we handle quality control Twitter @LaurelOld. test to look for semen for sexual as- to confirm that we’re sending the sault cases. They had a lot more to customer exactly what we say we are.

52 ASBMB TODAY MAY 2021 QFive Questions classifieds Marketing Manager Sr. Scientist, Assay Development American Society for Biochemistry and Molecular Biology Astellas (ASBMB)

The American Society for The Astellas Institute of Biochemistry and Molecular Regenerative Medicine (AIRM) Biology (ASBMB) is an international is a wholly-owned subsidiary nonprofit, scientific and educational of Astellas Pharma and organization. With over 11,000 members, made up of students, focused on the development and commercialization of stem cell researchers, educators and industry professionals, the ASBMB is and regenerative medicine therapies. Astellas is an R&D-driven one of the largest molecular life science societies in the world. global pharmaceutical company whose philosophy is to contribute to the improvement of people’s heath around the world through ASBMB is seeking a full-time Marketing Manager to work in the provision of innovative and reliable pharmaceutical products. conjunction with the Director of Marketing & Member Engagement and the Website Content Manager, to develop and execute Astellas is announcing a Sr. Scientist, Assay Development multichannel marketing strategies and campaigns for all programs opportunity at their Astellas Institute of Regenerative Medicine and departments. Also working with the Director of Marketing (AIRM) site in Westborough, MA. & Member Engagement, to develop and execute membership https://careers.asbmb.org/job/sr-scientist-assay- recruitment, retention, and engagement strategies, including development/56727081/ analyzing reports. https://careers.asbmb.org/job/marketing-manager/56726540/

Assistant or Associate Professor of Oral AssociateApplied BioMath, Editor, Science LLC Signaling Biology AAASSenior Scientist, Mathematical Modeler University of Manitoba

Applicants must have a PhD (AAAS) and Science Signaling or DMD/DDS and MSc or are seeking a full-time Associate higher. Applicants should have Editor to join our editorial post-doctoral training and demonstrated evidence of research team. Science Signaling is experience (with peer-reviewed publications) in alignment an interdisciplinary journal, which covers cellular signaling with current research strengths in the department, including and regulation in a range of fields focusing on mechanisms cellular, molecular, or developmental biology. Preference given underlying physiology and disease. We are looking for a scientist to individuals demonstrating strong research and teaching with research experience and interest in cell biology, molecular expertise in areas related to immunology/inflammation of oral biology, biochemistry, immunology, physiology, or another life tissues in health and disease. The applicant should be fluent in science with an emphasis on studying mechanisms of signal English. Rank and salary will be commensurate with qualifications transduction. and experience. The appointment will commence on July 1, https://careers.asbmb.org/job/associate-editor-science- 2021 or as soon thereafter as possible. signaling/55760722/ https://careers.asbmb.org/job/assistant-or-associate- professor-of-oral-biology/56726938/

To see a full list of jobs, please visit careers.asbmb.org 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