Vol. 19 / No. 2 / February 2020

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY

A matter of degree We ask experts what steers so many black scientists toward earning a master’s before a Ph.D. Don’t wait a lifetime for a decision.

C. elegans daf-2 mutants can live up to 40 days. JBC takes only 17 days on average to reach a fi rst decision about your paper.

Learn more about fast, rigorous review at jbc.org.

www.jbc.org NEWS FEATURES PERSPECTIVES 2 24 52 EDITOR’S NOTE A MATTER OF DEGREE A BEGINNER’S GUIDE TO MINORITY Picking up the slack What steers so many black scientists toward PROFESSOR HIRES 3 earning a master’s before a Ph.D.? NEWS FROM THE HILL 34 Acting to protect research integrity MEYERHOFF SCHOLARS A model for increasing diversity in STEM ANNUAL 4 MEETING MEMBER UPDATE 36 INCLUSIVE EXCELLENCE 7 36 A goal of lasting change NEWS 39 Program at Northeastern aims to fix the Honoring undergrads who promote diversity institution 8 40 RETROSPECTIVE FOR VULNERABLE POPULATIONS, Kensal E. van Holde (1928 – 2019) THE THORNY ETHICS OF GENETIC DATA COLLECTION 10 44 RESEARCH SPOTLIGHT JBC/TABOR AWARDS Understanding how arsenic changes 44 chromatin and causes cancer Award winners to speak at annual 13 24 meeting 45 NEWS Lavrsen finds endless possibilities Don’t wait a lifetime for a decision. Nan-Shan Chang has made WWOX in PTMs his life’s work 46 Varghese roams from forests to C. elegans daf-2 mutants can live up to 40 days. 15 enzymes JBC takes only 17 days on average to reach a fi rst LIPID NEWS 47 A cyclooxygenase inhibition hotspot Yang follows the science where it decision about your paper. takes her Learn more about fast, rigorous review at jbc.org. 16 48 JOURNAL NEWS Selenium led Zhao from icy hometown to German hospitality 16 Early immune response may improve cancer immunotherapies 49 17 The proteome of the cave bear Dagar dissects a prostate cancer driver 18 Quantifying bacteria-borne bile 19 From the journals 50 ATTENDING A CONFERENCE WHEN YOU DON’T HAVE 52 THE BUDGET www.jbc.org FEBRUARY 2020 ASBMB TODAY 1 EDITOR’S NOTE

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Picking up the slack OFFICERS COUNCIL MEMBERS Gerald Hart Suzanne Barbour By Comfort Dorn President Joan Broderick Matt Gentry Toni M. Antalis Blake Hill President-elect Audrey Lamb came to work at the American Wei Yang James M. Ntambi Society for Biochemistry and Mo- Secretary Takita Felder Sumter Kelly Ten–Hagen Ilecular Biology about 16 months Joan Conaway JoAnn Trejo Treasurer after Marion Sewer died. When I ASBMB TODAY EDITORIAL first heard her name, in connection EX-OFFICIO MEMBERS ADVISORY BOARD with an undergraduate scholarship Robert S. Haltiwanger Rajini Rao program, I assumed she was a long- Carla Koehler Chair Co-chairs, 2020 Annual Ana Maria Barral gone figure in the society’s history. Meeting Program Committee Natasha Brooks She came into focus when I was Kelly Chacón Cheryl Bailey putting together an article about the Chair, Education and Beronda Montgomery Professional Development Bill Sullivan winners of that scholarship and I first Committee Melissa Vaught Marion Sewer Binks Wattenberg saw the photo of her smiling in front Daniel Raben of a shelf of heavy books. The photo Chair, Meetings Committee ASBMB TODAY Sonia Flores accompanied Squire Booker’s re- in desperate need of role models to Angela Hopp Chair, Minority Affairs Executive Editor membrance of Sewer, which is where affirm that their dreams and aspira- Committee [email protected] I learned that she died suddenly, so tions are indeed achievable.” Nicole Woitowich Comfort Dorn suddenly that her last article for this Sewer was a black woman in sci- Chair, Science Outreach and Managing Editor Communication Committee [email protected] magazine was published days after ence. In an essay about imposter syn- Terri Goss Kinzy Lisa Schnabel her death, and that she was only 43 drome, she wrote about teachers and Chair, Public Affairs Graphic Designer Advisory Committee when she died. She remains forever mentors disparaging her accomplish- [email protected] Ed Eisenstein John Arnst that unlined face with the broad, ments, causing her to doubt herself. Chair, Membership Committee Science Writer arresting smile. I didn’t know her, so I can’t speak to Susan Baserga [email protected] Sewer crammed more into her her motivations, but I imagine her Chair, Women in Biochemistry Laurel Oldach and Molecular Biology Science Writter life than most of us can hope to do work on behalf of minority students Committee [email protected] in twice the time. She was a profes- was inspired by a desire to counter Sandra Weller Ed Marklin Chair, Publications Web Editor sor at the Skaggs School of Phar- such experiences. Committee [email protected] macy and Pharmaceutical Sciences Members of underrepresented Lila M. Gierasch Allison Frick Editor-in-chief, JBC Multimedia and Social Media at the University of California, San minority groups are often at the A. L. Burlingame Content Manager Diego. She published more than 44 helm of efforts to level the playing [email protected] Editor, MCP papers and reviews, 30 of those as field. Their experiences inspire them Barbara Gordon Nicholas O. Davidson Executive Director an independent investigator, on her to this work, but these responsibili- Editor-in-chief, JLR [email protected] work in lipid metabolism and steroid ties are piled on top of the need to, Kerry-Anne Rye Editor-in-chief, JLR hormone biosynthesis. as Sewer wrote, “work twice as hard” Sewer worked hard at her sci- as their non-URM colleagues. For information on advertising, contact Pharmaceutical Media Inc. at 212-904-0374 or [email protected]. ence, but she found time to advocate That’s a heavy load. I’ll leave it for a diverse workforce, most notably at that. (to us) as a leader of the ASBMB Minority Affairs Committee. She

led research projects in increasing Comfort Dorn www.asbmb.org/asbmbtoday participation among underrepresent- ([email protected]) is the PRINT ISSN 2372-0409 managing editor of ASBMB ed minorities and furthering student Today. Follow her on Twitter @cdorn56. Articles published in ASBMB Today reflect solely the authors’ views and not training. She was, as Booker wrote, the official positions of the American Society for Biochemistry and Molecular “a mover and a shaker and a champi- Biology or the institutions with which the authors are affiliated. Mentions of products or services are not endorsements. on of those young scientists who are

2 ASBMB TODAY FEBRUARY 2020 NEWS FROM THE HILL

Acting to protect research integrity By Benjamin Corb

he U.S. House of Representatives Science and Tech- since the Scientific Revolution has there been a more im- nology Committee approved the Scientific Research portant moment to stand for the basic ideas that inquiry TIntegrity Act in October with an overwhelmingly must be free and facts and evidence matter.” bipartisan vote. The American Society for Bio- If you get most of your information chemistry and Molecular Biology from television news or newspapers, you Public Affairs Advisory Committee might not have heard about this. You applauds Tonko for this important might think Congress did little in the legislation, which would create bar- final quarter of 2019 beyond debating riers to political pressure on federal the impeachment of President Donald scientists and the politicization of Trump and passing federal spending scientific findings. We are encouraged bills. My job is monitoring Congress, to see that the legislation has biparti- and sometimes even those of us who do san support. The majority of ASBMB this for a living have trouble finding re- members are not federal scientists, porting — outside our science policy-fo- but some are — and we think they cused news sources — about any activity should be trusted to serve as reliable unrelated to impeachment on Capitol and unbiased experts in the scientific Hill. My job is monitoring enterprise. That said, here is an example of what Congress, and sometimes This legislation is not likely to Congress is doing. Introduced by Rep. become federal law. Some of our Paul Tonko, D-N.Y., the Scientific Re- even those of us who analytical tools, supplied by the search Integrity Act, or H.R. 1709, aims do this for a living have media company Politico, estimate a to codify protections for federally funded less than 5% chance of enactment. science and federally funded scientific trouble finding reporting In the past 10 Congresses, or 20 researchers and to put the brakes on pol- — outside our science years, an average of only 3.1% of bills icymakers’ and administration officials’ introduced have been enacted into efforts to politicize science funding. policy-focused news law. While passage of the bill may Specifically, the bill allows federal sources — about any not be likely, it is not uncommon for agencies and government-employed popular, noncontroversial proposals activity unrelated to scientists to review data for technical in legislation to be included in other accuracy and provides a mechanism for impeachment on related bills that are on track for scientists to review and revise official Capitol Hill. passage. statements about their findings. Further, We will continue to support it allows federal scientists to present passage of this bill, and we findings at scientific conferences, sit on will encourage our partners on councils and participate in peer review Capitol Hill to view this legislation (subject to conflict-of-interest review). Under as an important way to support the scientific the proposal, federal scientists would be authorized to enterprise. talk to the news media about their science without prior Benjamin Corb ([email protected]) is director of approval from the administration or the agency they public affairs at the ASBMB. Follow him on Twitter work for. @bwcorb. When Tonko introduced this legislation, he said of government scientists, “More and more, their research has become the subject of one political agenda or another. Not

FEBRUARY 2020 ASBMB TODAY 3 MEMBER UPDATE CREDIT: MARYMOUNT MANHATTAN COLLEGE STUDENT CHAPTER MANHATTAN MARYMOUNT CREDIT:

Keeping abreast with student outreach The Marymount Manhattan College ASBMB Student Chapter used an American Society for Biochemistry and Molecular Biology Student Chapters Outreach Grant to host its second annual “I Heart Boobies!” event in October for Breast Cancer Awareness Month. Chapter officers, from left, Simran Sahansra (campus coordinator), Elena Markovitz (treasurer), Jordan Barnett (vice president), Julia Furnari (president) and Elizabeth Scott (secretary) pose at their display table. Read more at asbmb.org/asbmbtoday.

Baharvand, Chen among Agarwal leads nephrology society new TWAS fellows Anupam Agarwal, a physician– Hossein Baharvand and Ye-Guang scientist who directs the division of Chen are among the 36 fellows new- nephrology and serves as the executive ly elected to the World Academy of vice dean at the University of Alabama Science. at Birmingham’s medical school, took Baharvand is the director of the Roy- office in January as the president of the an Institute for Cell Biology and Tech- Agarwal American Society of Nephrology. Baharvand nology in Tehran. Throughout his career, Agarwal, who also directs the he has contributed to the understanding O’Brien Center for Acute Kidney Injury Research at of how mouse and human embryonic UAB, is known for research into acute kidney injury and stem cells establish and maintain plurip- its transition to chronic kidney disease. His laboratory otency and differentiation over genera- studies heme oxygenase-1, or HO-1, an enzyme involved tions. He was the first scientist to induce in the breakdown of heme to biliverdin, carbon monoxide pluripotent stem cells in Iran. and ferrous iron. The conversion removes heme, a strong Chen Chen is a professor and Cheung oxidant, from the kidney and replaces it with cytoprotec- Kong scholar at Tsinghua University in tive products. Agarwal’s laboratory has provided import- Beijing. There, he has researched cell-fate determination ant insights into the mechanisms for the protective effects and tumorigenesis by investigating the mechanisms of of this enzyme system and is exploring this pathway as a TGF-beta signaling specificity, discovered the regulation promising therapeutic target in acute kidney injury. of Wnt signaling by autophagy, and showed the essential The ASN is an organization of some 20,000 phy- role of bone morphogenetic protein signaling in intestinal sicians in 131 countries. It publishes three journals, stem cells. supports continuing medical education and advocates for Established in 1983 under the leadership of the Paki- kidney science. stani physicist and Nobel laureate Abdus Salam, TWAS recognizes, supports and promotes excellence in scientific research in the developing world.

4 ASBMB TODAY FEBRUARY 2020 MEMBER UPDATE

Dahms honored for achievements in glycobiology Nancy Dahms, a professor of biochemistry at the Medical College of

Wisconsin, received the 2019 Rosalind NYC CHRISTOPHER LEARY, Kornfeld Award for Lifetime Achieve- ment from the Society for Glycobiology. Mannose-6-phosphate is a tag Dahms added in the Golgi during posttrans- lational processing to direct lysosomal enzymes to the lysosome. Dahms is best known for her work on this trafficking pathway; over her career, she has isolated and characterized several lectins that act as Reyes–Soffer named Irving scholar mannose-6-phosphate binding receptors. Her lab cur- Gissette Reyes–-Soffer, an assistant professor of rently studies an endoplasmic enzyme called glucosidase medicine at Columbia University Medical Center, II, which regulates glycoprotein folding in the ER, and a has won recognition from the Herbert and Florence lysosomal storage disease called Fabry disease caused by Irving Scholars Program. mutations to another glycan-trimming enzyme, alpha-ga- As an Irving fellow, Reyes–Soffer will receive lactosidase A. $60,000 a year for three years for her research project Dahms has served on the editorial board of the Jour- titled “Unraveling the complexities of lipoprotein (a) nal of Biological Chemistry and other journals, is on the in humans through stable isotope metabolic studies, board of directors of the Society for Glycobiology, and has proteomics, and particle characterization.” She also won numerous teaching and service awards at the Medical will hold a named professorship. College of Wisconsin. Reyes–Soffer is a junior associate editor for the American Society for Biochemistry and Molecular Bassler among first Genius of NJ awardees Biology’s Journal of Lipid Research. Bonnie Bassler, chair of the depart- ment of molecular biology at Prince- ton University and a Howard Hughes other pathogenic behaviors. Bassler holds 19 patents on Medical Institute investigator, is among various strategies to antagonize quorum sensing. the first class of recipients of the Genius Bassler has received numerous awards, including a of New Jersey awards. MacArthur “Genius Grant.” This latest award was con- Bassler Bassler is a leader in the field of ferred in December during a gala fundraiser at the Liberty quorum sensing, the mechanism by Science Center, a science museum in Jersey City. which bacteria communicate with chemicals, detect the number of neighboring cells present and, as collectives, Agre joins Aeromics board change their behaviors. Such intercellular signaling among Peter Agre has joined the board of single-celled organisms, once considered outlandish, is Aeromics Inc., a pharmaceutical compa- now known to govern behaviors from bioluminescence to ny developing a drug candidate to reduce virulence to biofilm formation. complications of stroke. Quorum-sensing bacteria release small molecules Agre, a distinguished professor at called autoinducers. When the molecules accumulate the Johns Hopkins Bloomberg School of to a critical threshold level, they bind to receptors that Agre Public Health and director of its Malaria drive the activation and transcription of quorum-sensing Research Institute, is best known for genes to effect changes in group behaviors. Autoinducers, his discovery of aquaporins, membrane channel proteins many of which Bassler discovered or co-discovered, have that allow water to cross the hydrophobic cell membrane. exotic forms: cyclic oligopeptides, lactones, fatty acids and In 2003, Agre shared the Nobel Prize in chemistry with sugar derivatives containing boron. Researchers hope that potassium channel biologist Roderick MacKinnon. He interrupting quorum sensing could suppress infection and also served as president of the American Association for

FEBRUARY 2020 ASBMB TODAY 5 MEMBER UPDATE

IN MEMORIAM Larry Rudel Jane Park

Lawrence Lee Rudel, Jane Park, who professor emeritus at served as treasurer for Wake Forest University, the American Society died in Winston–Salem, for Biochemistry and North Carolina, on Aug. Molecular Biology in the 29. He was 77. 1970s, died Aug. 19 in Rudel was born in Nashville, Tennessee. Salt Lake City in 1941. She was 94. He attended Colorado Park was a professor State University, receiv- and researcher at Van- ing a bachelor’s degree in physical sciences in derbilt University for six decades. She used nuclear 1963, and then the University of Arkansas Medical magnetic resonance spectroscopy and magnetic Center, where he earned a Ph.D. in biochemistry in resonance imaging to study muscle function in 1969. After completing his postdoctoral training at a variety of muscle diseases, including muscular the Banting and Best Institute in Toronto and the dystrophy. University of California, San Francisco, he joined Born in St. Louis in 1925, Park did her under- the faculty at the Wake Forest School of Medicine, graduate and Ph.D. studies at Washington Univer- then named the Bowman Gray School of Medicine, sity in St. Louis, where she worked with the noted in 1973. embryologist Victor Hamburger. She did postdoctor- During his decades at Wake Forest, Rudel, al work at New York University with Severo Ochoa, who served on the editorial board for the Journal of who won a Nobel Prize a few years later. In 1953, Lipid Research for 36 years, focused on cholesterol she married Charles “Rollo” Park, then the newly metabolism and cardiovascular disease. He trained appointed chair of the department of physiology at and mentored graduate students and postdoctoral Vanderbilt. fellows and published the results of his research As a professor of molecular physiology and extensively. His many awards included the Estab- biophysics at Vanderbilt, Park initially focused her lished Investigator Award in basic sciences in 2001 research on glyceraldehyde-3-phosphate dehy- for his outstanding research achievements. He drogenase and became nationally known for her retired in 2018. mechanistic studies of this enzyme. She began He is survived by his wife, Katherine Bouwman studying muscular dystrophy in the mid-1970s, us- Rudel; three sons, Brian (Sheri) Rudel, John (Cin- ing a hereditary model of the disease in chickens. dee) Rudel and David Rudel; five grandchildren; She became professor emerita in 2014. and a niece. In addition to serving as the ASBMB treasurer from 1976 to 1979, she chaired the Board of Sci- entific Counselors of the National Institute on Aging. the Advancement of Science from 2009 to 2010. The lead compound in development by Aeromics, which was founded by physiologists Marc Pelletier and New members The American Society for Biochemistry and Walter Boron, is an aquaporin-4 inhibitor. Aquaporin-4 Molecular Biology welcomed more than 1,300 new is expressed in the blood–brain barrier, and the compa- members in November from all over the United ny hopes that blocking its water permeability may be a States and beyond. To find out who they are, go to successful drug target for edema, or swelling, of the brain, asbmb.org/asbmbtoday. which is often a complication of stroke. The company ex- pects to begin phase 2 clinical studies of the drug this year.

6 ASBMB TODAY FEBRUARY 2020 NEWS

Honoring undergrads who promote diversity

By Stephanie Paxson

he American Society for Bio- participation among underrepresent- Student Chapters Steering Commit- chemistry and Molecular Biolo- ed minorities and furthering student tee select up to five undergraduate T gy’s Minority Affairs Committee training. Within the ASBMB, she students to receive up to $2,000 created the Marion B. Sewer Distin- organized the MAC’s Interactive toward tuition. The 2019 Sewer guished Scholarship for Undergradu- Mentoring Activities for Grants- scholarship recipients are Diego ates in 2016 to support students who manship Enhancement workshop Rodriguez, Oregon State Universi- excel academically and are dedicated program for postdoctoral fellows ty; Ifechukwu Okeke, University of to enhancing diversity in science. The and early-career scientists, known as California, Berkeley; Olivia Drake, award was named to honor Marion IMAGE, which addresses the dis- Juniata College; Selena Vanapruks, B. Sewer, who was an ASBMB mem- parity in underrepresented minority Colgate University; and Shellaina ber and past chair of the Minority scientists’ ability to secure federal Gordon, Northeastern University. Affairs Committee when she died in research grants. She also wrote about Read more about them at asbmb.org/ January 2016 at age 43. issues that URM scientists face, such asbmbtoday. As well as being an internation- as impostor syndrome. Sewer’s work al authority on the regulation of reflected her commitment to diversity Stephanie Paxson cytochrome P450 enzymes and on and inclusivity of underrepresented ([email protected]) is the ASBMB’s diversity and the biosynthesis of steroid hormones, minorities in science, technology, undergraduate coordinator. Sewer was a principal investigator engineering and math. Follow her on Twitter on projects devoted to increasing Each year, the MAC and the @stephaniepaxson.

Pictured above: Diego Rodriguez, Ifechukwu Okeke, Olivia Drake, Selena Vanapruks and Shellaina Gordon.

ABOUT THE SEWER SCHOLARSHIP

The Marion B. Sewer Distinguished Scholarship for ground adds to the diversity of the biomedical work- Undergraduates provides up to $2,000 toward tuition force or who show commitment to enhancing academic to students who demonstrate an interest in the fields of success of underrepresented students. biochemistry and molecular biology and who enhance Applicants must describe how they uphold diversity the diversity of science. on their campus or in the science community, how All undergraduate members of the American Soci- the scholarship will help their career goals, and any ety for Biochemistry and Molecular Biology are eligible hardships they have experienced while pursuing their to apply for the scholarship, which aims to support own educations. students whose social, educational or economic back- Apply at asbmb.org/diversity by June 1.

FEBRUARY 2020 ASBMB TODAY 7 RETROSPECTIVE

Kensal E. van Holde (1928 – 2019) JBC By Christopher K. Mathews

ensal van Holde, one of the somehow coated fibers of supercoiled courses per year) so long as I prom- world’s premier physical bio- DNA. Measurements of electric ised not to put him on any com- K chemists and a longtime associ- dichroism of calf thymus chromatin mittees. To say that I was delighted ate editor of the Journal of Biological carried out in Ken’s lab by Randy would be an understatement. I didn’t Chemistry, died peacefully at home Rill ruled that out but didn’t solve realize at that embryonic stage of our on Nov. 11 following a brief illness. the structure. relationship that Ken was as devoted He was 91. Randy and Ken turned to the to teaching as to research. In the Perhaps the best way to appreci- ultracentrifuge. Limited digestion of summers, he regularly decamped ate Ken’s scientific career is to read chromatin with micrococcal nuclease to Massachusetts, where he taught his own words. In a 2008 Reflec- yielded a preparation containing and served as instructor-in-chief of tions article in JBC, he describes a both DNA and the core histones, the famed physiology course of the scientific odyssey that began in the which displayed a ladder when ana- Marine Biological Laboratory at 1950s with a focus on the ultra- lyzed in the ultracentrifuge or by gel Woods Hole. centrifuge. Together with Robert electrophoresis. Analysis by precipi- I learned more about Ken’s devo- “Buzz” Baldwin at the University of tation and resolubilization suggested tion to teaching when he suggested Wisconsin, he developed a method that the DNA in chromatin was that we teach a course together. for rapid approach to sedimentation present in two forms, one of which We called the course DNA-Protein equilibrium and its use to analyze was particulate. Physical analysis of Interactions and graded each student the size and shape of protein mole- the particulate fraction indicated not by exams but by preparation cules. This led to a faculty position that DNA was on the outside of of an original research proposal — in the department of chemistry at the particle, in disagreement with just like the National Institutes of the University of Illinois, where he the prevailing model. Chintamin Health, but we assigned grades, not designed improvements in light scat- Sahasrabuddhe and others analyzed priority scores. Ken was a spellbind- tering and circular dichroism, as well these particles, showing them to be ing lecturer, and I learned a great as ultracentrifugation. He continued spherical, with the DNA wrapped deal during the several times that we to explore protein structure and around the outside. taught the course together. function, with emphasis on inverte- Ken’s laboratory had described Members of Ken’s research brate respiratory proteins. the nucleosome core particle. Others group were devoted to him to a As Ken’s interests evolved, he took notice, and Ken’s group was greater extent than I have seen with sought an environment where he then in a race to define chromatin other professors. They worshipped could focus his biophysical strengths that continued until 1997, when him. Their unusual esprit de corps on problems in biology. In 1967, X-ray crystallography confirmed the was evident on Friday afternoons. he moved his laboratory to Oregon van Holde model. Ken’s laboratory included a small State University, joining the newly I met Ken in 1977, when I was a room in the building’s inner core formed department of biochemistry candidate for the chairmanship of his dubbed the Cave. There, members and biophysics. There he met Irvin department at OSU. Ken had recent- of his group and others gathered Isenberg, who introduced him to ly been awarded an American Cancer to drink beer and talk science. As chromatin. Society research professorship, and department chair, I had to tell them Irv and Ken noted that four of this relieved him of all departmental liquor was forbidden on campus and the five histones in chromatin were duties. I asked how he wanted to that the Cave would close if anyone present in equimolar quantities. The contribute, and he said he would complained. Eventually, someone prevailing view was that histones maintain a full teaching load (three complained, and the OSU president

8 ASBMB TODAY FEBRUARY 2020 JBC

Members of Ken’s research group were devoted to him to a greater extent than I have seen with other professors. They worshipped him.

This photo portrait accompanied a 2010 article, “Chromatin Structure and the Nucleus: The Work of Kensal E. van Holde,” in the Journal of Biological Chemistry.

visited my office to admonish me for Stockholm, where I was on sabbati- lis, Woods Hole and their mountain permitting Cave parties even though cal, Ken’s enthusiasm was palpable. retreat in the Oregon Cascades. Some they were the occasions for some We pushed ahead, and “Biochemis- years after Barb’s death in 2010, Ken excellent science. try” was published in four editions, reconnected with a widowed OSU Ken was a gifted writer as was sometimes with co-authors, in a faculty wife, Myrna Shepper, and shown in his two research mono- competitive market. they were married in 2015. graphs, “Chromatin” and “Oxygen After his formal retirement In recognition of his work, Ken and the Evolution of Life” as well as in 1993, Ken continued to write was elected to the National Academy of in “Principles of Physical Biochem- books—now with his former asso- Science in 1989 and to the American istry,” co-authored in the second ciate, Jordanka Zlatanova. In 2015, Academy of Arts and Sciences in 1996. edition with Shing Ho and Curtis they published “Molecular Biology,” Johnson. I should not have been a textbook, and in 2018, barely a year surprised at Ken’s excitement when I before Ken’s death, “The Evolution

approached him about co-authoring of Molecular Biology,” a historical Christopher K. Mathews a general biochemistry textbook. By account. Both books display Ken’s (Christopher.Mathews@ the time we had written a prospectus, biophysical expertise and his gift for oregonstate.edu) is a distinguished outline and two sample chapters (one clear writing. professor emeritus each), I feared this was a bigger job Ken enjoyed a rich family life. in the department of biochemistry and than we could handle. However, in With his wife Barbara and their four biophysics at Oregon State a phone call between Corvallis and children, he shuttled between Corval- University.

FEBRUARY 2020 ASBMB TODAY 9 RESEARCH SPOTLIGHT

Understanding how arsenic changes chromatin and causes cancer By Kerri Beth Boggs

vonne Fondufe–Mittendorf took “I didn’t think I could be a PI, a winding path from the Repub- and I wasn’t sure of myself,” she said. Ylic of Cameroon to the bluegrass Widom helped her overcome this of Kentucky. self-doubt by convincing her that she “I call myself an academic tour- was already asking the right questions ist,” she said. UNIVERSITY OF KENTUCKY to pursue an academic research career. Inspired by her older sisters who “He said, ‘I think you can do it,’ studied science, Fondufe–Mittendorf so he pushed me towards that,” she moved from Cameroon to Nigeria to said. “He believed in me.” earn bachelor’s and master’s degrees from the University of Ibadan. Finding a niche While she was at the university, After completing her postdoc, a visiting researcher from Germany Fondufe–Mittendorf took a position told the students about his uni- at the University of Kentucky in the versity’s doctorate program. Eager department of molecular and cellular to continue her academic journey, biochemistry to study the epigenetics Fondufe–Mittendorf applied to the of cancer. With her transition from program at the Georg-August Univer- postdoc to principal investigator, she sitaet in Göttingen. She was accepted On her winding journey from Cameroon to the faced a new set of challenges. and moved to Germany to pursue a U.S., Yvonne Fondufe–Mittendorf learned doctorate in molecular genetics. the importance of asking for help in science. Her time in Germany was a “When I face roadblocks in my research,” she ABOUT THE RESEARCH learning experience. She had never said, “I reach out to fellow colleagues and other SPOTLIGHT seen a micropipette before. Neither scientists in my field for help. I’m not afraid to had she experienced a snowy winter. say ‘I don’t know.’” “I remember the first winter I The American Society for Bio- came outside, and everything was molecular biology,” she said, “and I was chemistry and Molecular Biolo- white,” she said. always hesitant to trust my results.” gy’s Research Spotlight highlights She excitedly put on her new During her doctoral training, distinguished biomolecular winter boots and hurried to the bus Fondufe–Mittendorf attended a and biomedical scientists from stop to catch a ride to the university. seminar on epigenetics. “Scientists had diverse backgrounds as a way to However, her excitement turned to just started understanding that not inspire up-and-coming scientists surprise when her boots lost traction every disease is caused by mutations to pursue careers in the molecu- in the wintery mix. Her dash to the and how chromatin packaging could lar life sciences. Eligible candi- bus stop came to a crashing halt as be dysregulated,” she said, “and that dates include Ph.D. students, she slipped and fell. actually intrigued me.” postdoctoral fellows, and new or That first snowfall in Germany Her interest in epigenetics led her established faculty and research- reflected her experience as a young to a postdoc at Northwestern Universi- ers. To nominate a colleague for scientist stepping into unknown ty, where her mentor, the late Jonathan this feature, send an email to territory. Widom, dramatically influenced the [email protected]. “I had never done that much course of her career.

10 ASBMB TODAY FEBRUARY 2020 RESEARCH SPOTLIGHT UNIVERSITY OF KENTUCKY

Yvonne Fondufe–Mittendorf, pictured with Meredith Eckstein in the lab at the University of Kentucky, analyzes the effects of toxicants on chromatin biology.

“I wrote two or three grants and taminates drinking water sources. in cancer. By studying these effects they were all triaged,” she said. “I Residents of Eastern Kentucky and on chromatin regulation, she aims realized that names count, and I was other coal-mining areas face a greater to understand the connection playing with the big guys. Fortu- risk of arsenic contamination, and between arsenic exposure and disease nately, I kept searching and found these regions often have higher cancer pathology. a different perspective that I could rates. The lab also studies chromatin to bring to the competition.” Fondufe–Mittendorf’s research understand how it is involved in basic Although Fondufe–Mittendorf suggests that arsenic may displace cellular processes such as transcrip- never had studied toxicology, she zinc in proteins that regulate tion, DNA repair and alternative found her niche analyzing the effects chromatin structure for gene splicing. of toxicants on chromatin biology. expression, leading to changes in Along her journey from Camer- The impact of arsenic exposure protein-DNA binding that alter the oon to the U.S., Fondufe–Mittendorf on gene regulation became one focus wiring of the genome. Work from learned the importance of asking for of her research. Arsenic is a natural- her lab also focuses on the effects of help in science. ly occurring element and a known arsenic exposure on the incorporation “When I face roadblocks in my carcinogen that poses a significant of histone variants into the chromatin research,” she said, “I reach out to risk to human health when it con- since the variants are upregulated fellow colleagues and other scientists

FEBRUARY 2020 ASBMB TODAY 11 RESEARCH SPOTLIGHT COURTESY OF YVONNE FONDUFE–MITTENDORF COURTESY

Yvonne Fondufe–Mittendorf, second from right, poses with members of her lab at the University of Kentucky during an outing in summer 2019.

in my field for help. I’m not afraid to discuss science and life in general.” es herself with fashion. Instead of say ‘I don’t know.’” Fondufe–Mittendorf knows that conforming to norms among science emotional and mental health play a faculty, she proudly wears clothing, Just be yourself key role in student success. She sets shoes and jewelry that complement Fondufe–Mittendorf encourages an example for her students by main- her personality. her students to talk about their re- taining a balance among her work, “Work is hard enough without search struggles, and she offers them family and hobbies. Outside of work, trying to be like someone else,” she wisdom from her own story. “If I she enjoys watching movies with her said, “so you should do whatever could do it despite my long journey two daughters, exploring different makes you comfortable and happy. from a different place where I hadn’t parts of the world and shopping. Just be yourself.” done molecular biology, then I think Although fashion and science Fondufe–Mittendorf said her late you can do it too,” she said. don’t usually go together, Fondufe– father always let his girls know that Wesley Saitilnord, an interna- Mittendorf embraces both. Her nothing could stand in their path to tional Ph.D. student from Haiti, interest in fashion started at a young success. She gratefully relies on the reflected on why he chose to join age when her older sisters dressed her support of her daughters, husband, Fondufe–Mittendorf’s lab at the in different outfits. Though unwilling mother, brothers and sisters to University of Kentucky. at first, she grew to love trying on achieve her goals. “Choosing a lab for graduate clothes. Today, fashion helps her deal school is an important decision that with the stress of grant writing. can define your career,” he said. “I “If I’m stressed while writing a Kerri Beth Boggs (kerri. joined Dr. Fondufe-Mittendorf’s lab grant, I go to the mall. I just walk [email protected]) is a graduate student in the because she’s built a welcoming and around,” she said. “It’s like I’m not biochemistry department supportive lab environment. She really thinking, I’m just walking. By at the University of Kentucky. Follow her on makes sure I feel that I belong, and doing that, I think I’m at peace.” Twitter @KB_Boggs. she makes herself readily available to Fondufe–Mittendorf also express-

12 ASBMB TODAY FEBRUARY 2020 NEWS

Nan-Shan Chang has made WWOX his life’s work

By Nuala Del Piccolo

he National Institute on Aging neurodegeneration. Chang is thrilled While working as associate sci- announced last year that a study about the publicity around WWOX entist and lab director at the Guthrie T of more than 94,000 people and neurodegeneration and said he Research Institute in Pennsylvania, had identified five new risk genes for hopes the “announcement encourages Chang became interested in the sensi- Alzheimer’s disease. One of the five momentum, competition, collabora- tivity of cancer cells to tumor necrosis was the WW domain-containing tions, and new directions in WWOX factor, or TNF. At the time, scien- oxidoreductase, or WWOX, gene, research.” tists around the world were in what which codes for the cytoplasmic When Chang was ready to start Chang described as a “crazy hot race WWOX protein, a tumor suppressor college, his older brother told him to understand how WWOX works in involved in apoptosis. that he’d make more money with a cancer suppression,” which was fueled The importance of WWOX to degree in food science, but Chang by the WWOX gene’s localization on Alzheimer’s disease wasn’t news to chose to follow his interests and a common chromosomal fragile site. Nan-Shan Chang, a biochemist and study biology at the National Taiwan Though Chang’s lab frequently immunologist at the National Cheng Normal University. He then earned a numbered fewer than five people, his Kung University in Taiwan. Chang Ph.D. in immunology at the Medical team was one of three to report inde- was involved in the initial cloning University of South Carolina and pendently the cloning of WWOX in of the WWOX gene in the 1990s completed his postdoctoral work in the Journal of Biological Chemistry and since then has been studying the immunobiology at the Samuel Rob- in 2001. He described his research role of WWOX in both cancer and erts Noble Foundation in Oklahoma. journey in a recent interview: “I was

Nan-Shan Chang, an American Society for Biochemistry and Molecular Biology member for almost 20 years, has mentored many students and postdocs.

COURTESY OF NAN-SHAN CHANG COURTESY Pictured in this 2009 photo are, from left, postdoc Dudekula Subhan, technicians Ming-Hui Esti Lee and Sing-Ru Lin, master student Jean-Yun Chang and Nan-Shan Chang. Chang’s mentees Li-Jin Hsu, Jean-Yun Chang, Annie Su, Yongda Sie and Charlene Kuo won travel awards to the 2005, 2009, 2012, 2015 and 2017 ASBMB annual meetings, respectively; Kuo also gave an invited talk at an ASBMB mini- symposium in 2017. Another mentee, Tsung-Yun Tom Liu, will give an invited talk at Experimental Biology 2020.

FEBRUARY 2020 ASBMB TODAY 13 NEWS

Nan-Shan Chang (center) discovered the connection between WWOX and neurodegeneration through collaboration with two college classmates, neuroscientists

COURTESY OF NAN-SHAN CHANG COURTESY Shur-Tzu (Su) Chen (not pictured), who died in 2015, and Chun-I Sze (left). Yu-Min Kuo (right) collaborates with Chang on a project studying the role of Zfra in Alzheimer’s disease.

interested in understanding why cer- might play a role in neurons. The WWOX in immunology, dermatol- tain cancer cells resist TNF cytotoxic- team looked for WWOX in devel- ogy and cancer, and Chang remains ity. I noticed that cancer cells secrete oping and adult mice and found committed to his craft, frequently large amounts of hyaluronan and that the protein was expressed. They logging 16-hour days in the lab. hyaluronidase in order to metastasize. characterized WWOX expression in The Chang lab now studies Hyaluronidase increases the expres- postmortem healthy and diseased WWOX and Zfra, another small sion of tumor suppressor WWOX human brain tissue and found that protein involved in the TNF in cancer cells, thereby rendering it was significantly downregulated signaling pathway. The team them sensitive to TNF toxicity. By in Alzheimer’s. To follow up on this examines how WWOX and functional cloning, we caught the fish observation, the research team used Zfra expression, trafficking and — WWOX. It took us five years.” siRNA technology to knock down phosphorylation influence cancer and Chang’s paper explored how hyal- WWOX expression in cells; to their neurodegeneration. Both proteins uronidase contributes to the cytotox- amazement, this treatment led to the have proven particularly challenging icity of TNF; it linked hyaluronidase phosphorylation of the tau protein, a to isolate, clone and characterize, but exposure to increased expression of state implicated in the formation of Chang hopes that hard work and a small protein dubbed WWOX. Alzheimer’s signature neurofibrillary time will overcome these obstacles The paper reported the isolation of tangles. These studies produced an- to elucidating a more complete WWOX and established that the pro- other Journal of Biological Chemistry understanding of the role of WWOX tein mediates the cytotoxicity of TNF article in 2004. This early work on in cancer and neurodegeneration. by upregulating the tumor protein the role of WWOX in Alzheimer’s p53 and downregulating mitochon- was cited in the Nature Genetics drial proteins that block apoptosis. paper highlighted in the National Nuala Del Piccolo Chang discovered the connection Institute on Aging’s announcement (ndelpiccolo@ucdavis. between WWOX and neurodegen- about the five new Alzheimer’s risk edu) is a postdoctoral scholar in the eration through collaboration with factors. biomedical engineering two classmates and friends from In November 2006, Chang department at the his undergraduate days in Taiwan, moved his laboratory to National University of California, Davis. She earned neuroscientists Chun-I Sze and Shur- Chang Kung University in Tainan, her Ph.D. in materials Tzu (Su) Chen. They had heard the Taiwan, so he could care for his ailing science and engineering at Johns Hopkins hype about WWOX and wondered father. His move prompted new University. Follow her on whether the small but potent protein collaborations with groups studying Twitter @nualadp.

14 ASBMB TODAY FEBRUARY 2020 LIPID NEWS

A cyclooxygenase inhibition­ hotspot

By Michael Malkowski

rostaglandins, or PGs, are critical the enzymes function as heterodimers, different region of the active site criti- for such physiological functions such that only one subunit is catalyti- cal for aspirin and Celebrex to inhibit Pas the regulation of renal water cally active at a time. COX-2. They showed rotation of the and sodium metabolism, blood clot- Structurally, COX-1 and COX-2 side chain of the residue Leu-531, ting, parturition and stomach acid are virtually identical. However, subtle opposite the side pocket, as a way to secretion. These lipid signaling mol- differences drive isoform-specific expand the volume of the cycloox- ecules derive from the oxygenation substrate specificity and inhibition. ygenase channel. Crystal structures of arachidonic acid by prostaglandin Among these are the substitutions of of COX-2 have provided evidence endoperoxide H synthases 1 and 2, cyclooxygenase channel residues Ile- for the existence of alternate rotamer commonly called cyclooxygenase-1 434, His-513 and Ile-523 in COX-1 conformations for this side chain and -2, or COX-1 and COX-2. for Val-434, Arg-513 and Val-523 in when different ligands are bound. Abnormal changes in PG produc- COX-2, which result in the formation To evaluate the importance of the tion contribute to disease pathologies of a unique side pocket and increased conformational flexibility of the side including inflammation and cancer, volume of the cyclooxygenase active chain of Leu-531, our research group so researchers view COX-1 and site in COX-2. This side pocket, with generated L531F and L531N muta- COX-2 as pharmacological targets. Arg-513 at its base, has been exploited tions and showed that these substitu- Indeed, nonselective nonsteroidal in the design of coxibs aimed at re- tions reduced aspirin and Celebrex’s anti-inflammatory drugs, or NSAIDs, ducing the gastrointestinal side effects inhibition of COX-2. Thus, expan- such as ibuprofen, inhibit both iso- caused by conventional NSAIDs. sion of the active site volume via the forms, while coxibs such as Celebrex Researchers work to to identify flexibility associated with the side selectively inhibit COX-2. the changes in COX-2 that drive the chain of Leu-531 allows Celebrex to COX enzymes are sequence transitions between the kinetically achieve a high-affinity binding state homodimers; each subunit consists observable inhibitor binding states. and facilitates formation of the initial of physically distinct cyclooxygenase These studies originally focused on the noncovalent complex in the case of and peroxidase active sites linked by COX-2 side pocket, but recent molec- aspirin acetylation. a bridging heme moiety. In solution, ular dynamics simulations identified a Deciphering the protein confor- mational motions associated with COX catalysis and inhibition is the next frontier in studying this enzyme. If we understand how the binding of substrates, allosteric activators and

MICHAEL MALKOWSKI inhibitors induce conformational motions to modulate COX activity, we will be closer to developing and repurposing drugs for maximum efficacy with minimal risks.

Michael G. Malkowski ([email protected]) is a professor and chair of the department of structural Each COX monomer comprises three domains and is bound by heme (red). Arachidonic acid (yellow) biology in the Jacobs binds within the cyclooxygenase active site in an L-shaped conformation. The side chain of Leu-531 School of Medicine and Biomedical Sciences at rotates from a closed conformation (blue) to an open conformation (gold) and in conjunction with Arg- the State University of New 513 serves as a critical determinant for the inhibition of COX-2 by aspirin and Celebrex. York at Buffalo.

FEBRUARY 2020 ASBMB TODAY 15 JOURNAL NEWS

Early immune response may improve cancer immunotherapies

By Natasha Wadlington

iruses, bacteria and cancer have many ways to replicate and survive in our bodies. Viruses V BOUVIER LAB CREDIT: and bacteria invade a cell directly to avoid detection. Cancer cells have the advantage of being native in the body. However, the body has safe- guards against such sneaky tactics. In a paper published in the Journal of Biological Chemistry, University of Illinois at Chicago researchers and colleagues report a new mechanism for detecting for- An X-ray crystallography-generated image of a long foreign peptide (purple) being partially held eign material during early immune inside MHC I protein’s surface groove (gray). responses. “There are proteins in the cell that await the presence of foreign X-ray crystallography (a method to peptides to be labeled as ‘foreign’ — material,” said Marlene Bouvier, see structures on an atomic level) and allowing the cancer cells to replicate senior author and UIC professor mass spectrometry (used to identify and grow. But if you have a way to of microbiology and immunology peptide length by mass) to show that manipulate how ERAP1 generates at the college of medicine. “One ERAP1 can cut extra-long peptides cancer peptides, then you can hope- protein, called endoplasmic reticu- even after they have bound to MHC I. fully skew the peptide repertoire that lum aminopeptidase 1, or ERAP1, “X-ray crystallography allowed is presented on the cell surface in our is programmed to find foreign mate- us to determine three-dimensional favor. This is the most translational rial, like viral and bacterial proteins, structures to see how these longer application of our research.” and break it into smaller parts, also peptides bound to the MHC I Lenong Li and Mansoor Batliwa- known as peptides. Another protein groove with high resolution,” Bouvi- la from the department of microbi- — major histocompatibility complex er said. “Using an ERAP1 enzymatic ology and immunology in the UIC class I, or MHC I — is programmed assay with mass spectrometry gave us College of Medicine are co-authors to attach itself to a foreign peptide the ability to show, for the first time, on the paper. and move it to the cell’s surface. that ERAP1 can trim peptides bound DOI: 10.1074/jbc.RA119.010102 With the foreign peptide outside the to MHC I. These tools allowed us to This article originally was pub- cell, immune cells can recognize and develop a model of this new immune lished by the University of Illinois destroy the infected cell.” response mechanism.” at Chicago. It has been edited for This is an example of a normal Bouvier said this new informa- ASBMB Today. process, Bouvier said, but sometimes tion may help researchers leverage

a foreign peptide, once bound to ERAP1 to fight infections and Natasha Wadlington MHC I, remains in the cell. This cancer. is a freelance science writer. She has a Ph.D. happens when the foreign material is “This research can have major in neurobiology from the not broken down to a small enough implications for immunotherapies,” University of Chicago. Follow her on Twitter size or is too long. she said. “For example, cancer @Natwadlington. Bouvier and colleagues used cells do not always present enough

16 ASBMB TODAY FEBRUARY 2020 JOURNAL NEWS

The proteome of the cave bear New metric helps researchers unlock strange samples

By Laurel Oldach

s a rule, it takes a genome to interpret a proteome. A A genome database gives the range of possible proteins that a sam- ple is expected to contain, allowing a computer program to match short peptide fragments from the raw data to the full-length proteins they came from. The genome is like a picture showing how a jigsaw puzzle will look when it’s finished — and each peptide is a single tiny piece of the puzzle. Among the exotic samples used in Richard Johnson’s study was glacial meltwater. Richard Johnson, a staff scientist at the University of Washington’s department of genome sciences, has researchers solve this problem by to study the makeup of electrosensory spent nearly three decades working sequencing as much DNA as they organs in electric fish. with no picture. Before genomes were can from a sample and using the re- A third potential application assembled and available, he became sult, a metagenome, to guide protein is for analysis of very old but not an expert in de novo peptide sequenc- identification. fossilized tissues — those that come ing, piecing together the overlapping But even with a metagenome, from extinct species, such as a vial of puzzle pieces from mass spectra to sometimes the proteins observed in powdered cave bear bone that John- determine the amino acid sequence of a proteomics experiment just don’t son’s team obtained. Extinct species proteins. match the given reference database. very rarely have a genome assembled, That ability has been coming in “I came up with a metric that can tell and the close-cousin conundrum is handy recently since Johnson started you whether the protein sequence compounded by slow biochemical seeing more requests for environmental database is any good for interpret- changes to proteins that happen over proteomics and other exotic analyses. ing your mass spectrometry data,” thousands of years. “I sit next to an oceanographer, Johnson said. But the approach doesn’t solve and she does these proteomics The technique, which Johnson every problem. Johnson said, “Using analyses on strange samples, like and colleagues recently published in this quality metric tells you how good glacial meltwater and seawater,” he Molecular & Cellular Proteomics, or bad a sequence database is. But it said. “Those are cases where it’s really can be used to solve related problems, won’t tell you what to do about it if difficult to decide what database to such as proteomic analysis of an it’s bad.” even search.” animal whose genome has not been se- DOI: mcp.TIR119.001752 To annotate a sample from a quenced. “You typically use a sequence human, a researcher can use a human database from a closely related species Laurel Oldach (loldach@ genome database. But a tablespoon of and hope that the sequences did not asbmb.org) is a science ocean water or glacial runoff is likely diverge too much,” Johnson said. writer for the ASBMB. Follow her on Twitter to contain a complex community of “Sometimes that hope is warranted, @LaurelOld. microbes. So which genome databases and other times it’s not.” should the researcher survey? Usually, Johnson has used this approach

FEBRUARY 2020 ASBMB TODAY 17 JOURNAL NEWS

Quantifying bacteria-borne bile By John Arnst

eyond breaking down food, obtained from a study of people with the steroid bile acids produced Type 2 diabetes. Bboth by our livers and by our Nemet was intrigued to find that intestinal inhabitants have a range of bacteria played a role in regulating

functions, from helping absorb lipids WELLCOME COLLECTION the production of a number of pri- and fat-soluble vitamins to acting mary bile acids that were thought to as signaling molecules for myriad be produced exclusively by the liver. pathways. “The circulating levels of three When gut microbes use amino primary bile acids are completely acids to conjugate metabolites or dependent on microbial activity,” she primary bile acids created by the said. “That’s really interesting for me, liver, secondary bile acids are formed. because usually people say primary These secondary acids are linked to an bile acids are host-derived, but … if increased risk of metabolic diseases, we put humans or mice on antibiot- but their physiochemical properties ics, these levels go down. That means make it difficult to puzzle out which the majority of these bile acids are bile acids are being produced by which coming from microbial contribu- gut bacteria. To rectify this, research- tion, even though we’re calling them ers in Stanley L. Hazen’s laboratory primary.” at the Cleveland Clinic’s Center for The liver, pictured here in a Chinese woodcut Nemet and Hazen plan to use the Microbiome and Human Health have from the Ming period, is responsible for the bile panel to test samples from larger developed a new stable isotope dilu- production of primary bile acids. clinical studies before homing in on tion liquid chromatography-tandem the specific mechanisms by which mass spectrometry method to quantify bile acids increase the risk of Type 2 bile acids in mice and humans. They meat, spurs gut bacteria to produce diabetes, which potentially could be described their method in the Journal the bile acid trimethylamine N-oxide, disrupted by small-molecule drugs. of Lipid Research. or TMAO, Hazen and colleagues “This is our start in looking into Ima Nemet is a senior scientist reported in 2018. TMAO can cause the contribution of bile acids in de- in Hazen’s lab and the corresponding plaque to accumulate in arteries and veloping metabolic diseases,” Nemet author on the paper. “We know that is a predictor of heart attacks. They said. “There are now a plethora of so many bile acids have been known reported in 2015 that TMAO derived experiments where we can look and and studied for a long time, but we from dietary sources of choline was see whether these metabolites are wanted to have some very robust elevated in cases of chronic kidney just associations or whether they are methods that can be very easily used diseases. driving Type 2 diabetes.” for large clinical studies,” Nemet said. To validate their new analyti- DOI: 10.1194/jlr.RA119000311 “When we run these large cohorts, cal method, a bile acid panel, the we use multiple instruments that researchers examined circulating

are sometimes even from different levels of more than 50 primary and John Arnst (jarnst@ vendors. So we wanted to have some- secondary bile acids in serum and asbmb.org) is an ASBMB Today science thing that’s ‘clickable’ on all different fecal samples from mice and humans. writer. Follow him on types of machines.” They used the panel to identify a Twitter @arnstjohn. Eating foods containing high handful of circulating bile acids amounts of choline, notably red associated with diabetes in samples

18 ASBMB TODAY FEBRUARY 2020 JOURNAL NEWS

From the journals

By Isha Dey, Anand Rao & Tori Zirul

Trimming peptides mirror the function of the producer metabolism in the brain an import- down to size cells. Exosomes of varying tissue ant topic of research. However, the An important step for activating types look and behave differently, existing method to study DHA turn- the immune system in response to and these distinctions can be used as over requires infusing stable isotope potential threats is the processing biomarkers for diseases. Fluids such tracer-labeled fatty acid followed and presentation of peptides by as blood and semen are conduits for by tracing its metabolism kinetics. major histocompatibility complex, infection of many viruses, but little Not only is this approach expensive or MHC, molecules. To accomplish is known about the function and and complicated, but its limitations this, a mechanism for handling pep- composition of their exosomes. include inaccurate measurement of tides of various lengths is necessary. Hussein Kaddour and a team of steady-state kinetics. The processes underpinning these researchers led by Chioma Okeoma R. J. Scott Lacombe and a team alterations are not fully understood. at Stony Brook University were at the University of Toronto devised Answers might lie in studying the first to compare the proteomes a tracer-free way to study DHA turn- endoplasmic reticulum aminopepti- of autologous blood and semen over by measuring the ratio of natural dases, or ERAPs, enzymes essential exosomes from HIV-infected and 13C to 12C of DHA with high-pre- for the presentation of peptides non-HIV-infected individuals. cision gas chromatography combus- by MHC I molecules. In a paper Their findings were published in tion isotope ratio mass spectrometry. published in the Journal of Bio- the journal Molecular & Cellular They fed mice with either alpha-lino- logical Chemistry, Lenong Li and Proteomics. They identified lenic acid or DHA for six weeks and colleagues at the University of Illinois discrepancies within and between then switched the fatty acids in their shed new light on how peptide trim- exosome samples from blood and diets, followed by analyzing 13C ming by ERAP1 shapes the MHC semen of infected and noninfected to 12C DHA for six months. Their I immunopeptidome and provide individuals using systematic results, published in the Journal of detailed structural and biochemical multifactorial proteomic profiling Lipid Research, correlate to findings evidence demonstrating how peptides detection methods. Proteins unique using isotope tracers. of noncanonical lengths interact to blood or semen were identified DOI: 10.1194/jlr.D119000518 with MHC I. Their results provide along with their role in reproduction new fundamental knowledge about and HIV pathogenesis. Synthesis versus salvage the processing and presentation of DOI: 10.1074/mcp.RA119.001594 in parasite species unconventional peptides by MHC I. The large phylum of apicom- DOI: 10.1074/jbc.RA119.010102 A novel method to detect plexans includes parasites such as brain DHA turnover Toxoplasma gondii, which causes Profiling autologous body Docosahexaenoic acid, or DHA, the infectious disease toxoplasmosis, fluid exosomes is essential for brain development and the malaria-causing Plasmodium The saying goes, it’s what’s on the in infants and normal function- falciparum. These parasitic intruders inside that counts, but some studies ing of adult brain. The brain can can acquire metabolites from their require researchers to look at a cell’s produce only a limited quantity of hosts in addition to using their own surroundings as well as its internal this polyunsaturated fatty acid, so it metabolic reactions to thrive in the processes. In tissue, where cells are in depends on a supply from circulating hosts they’ve hijacked. close contact, exosomes — bioactive blood to replenish the metabolized In a review published in the RNA and proteins encased in a fatty DHA. Decreased DHA levels in the Journal of Biological Chemistry, bilayer — are released into the body brain are associated with the onset Dominique Soldati–Favre, recipient to communicate with other cells and of Alzheimer’s disease, making DHA of the ASBMB’s 2019 Alice and C.

FEBRUARY 2020 ASBMB TODAY 19 JOURNAL NEWS

Gut feeling: the endocannabinoidome and intestinal microbe connection

The endocannabinoidome is a complex signaling the basal endocannabinoidome lipid mediator levels as well pathway consisting of several G protein–coupled receptors, as receptor expression, so the authors used liquid chro- metabolic enzymes and 20-plus lipid mediators. Recent matography–mass spectrometry lipidomics to analyze the research links this pathway to intestinal health. With the different endocannabinoidome lipid mediators and found discovery of endocannabinoid receptors in the gut, mech- that their levels were altered substantially in the intestines of anisms underlying crosstalk between such receptors and both kinds of mice. The levels of some of these molecules the gut microbiota are being investigated. Scientists have were significantly different under germ-free conditions and speculated that a dysregulated endocannabinoid system sensitive to the introduction of fecal matter from conven- may lead to inflammatory bowel disease and colon cancer. tionally raised mice. Thus, germ-free and conventionally To take a deep dive into the interactions of the endo- housed mice had differing global gene expression of endo- cannabinoid pathway with the gut microbiome, Claudia cannabinoidome. Manca and researchers from Canada, Belgium and Italy The research shows that lack of gut microbiota sig- investigated alterations in the endocannabinoidome in nificantly altered the levels of endocannabinoid receptors germ-free and conventionally housed mice, both juveniles as well their effector molecules at the transcriptome level and adults. Using transcriptomic analysis, they found that in the small and large intestines of mice. Published in the expression of several endocannabinoid receptors was Journal of Lipid Research, this study provides evidence reduced in the germ-free mice compared to convention- of direct interaction of the endocannabinoidome with gut ally housed ones. However, when fecal matter containing microbiota and opens new avenues to investigate the patho- natural bacteria from healthy mice was transferred to the physiological role of endocannabinoid signaling. germ-free mice, this receptor expression was restored. En- DOI: 10.1194/jlr.RA119000424 docannabinoidome signaling tone can also be affected by —Isha Dey

Commensal bacteria (red) reside among the mucus (green) and epithelial cells (blue) of a mouse small intestine. THE UNIVERSITY OF CHICAGO / NIH FLICK

20 ASBMB TODAY FEBRUARY 2020 JOURNAL NEWS

C. Wang Award in Molecular Parasi- proteins responsible for transporting identified their important role in tology, and colleagues at the Uni- oxygen in a variety of arthropods and melanoma. The study was published versity of Geneva discuss the salvage mollusks. Mollusk hemocyanins are in the journal Molecular & Cellu- and synthesis pathways that provide used widely as carriers, adjuvants and lar Proteomics. The research used a vitamins to these species, with an eye nonspecific immunostimulants in can- proximity-dependent biotinylation toward new therapeutic targets. cer treatments due to their ability to technique called BioID and mass DOI: 10.1074/jbc.AW119.008150 promote Th1 immunity. In a collabo- spectrometry to identify RSK cellular rative study published in the Journal partners and protein interactions. Of Treating insulin resistance: of Biological Chemistry, Michelle L. the identified proteins, p120-catenin, To err on the side of caution Salazar and researchers in Chile sought or p120ctn, is noteworthy, as it is In the pathological condition to reveal how mollusk hemocyanins essential to the cell adhesion charac- known as insulin resistance, cells fail — specifically from Concholepas teristic of cancer formation. When to respond to insulin, resulting in concholepas, Fissurella latimarginata RSK activity is inhibited, cellular increased blood glucose levels. This and Megathura crenulata — modulate adhesion is increased. The study also can result in increased risk of Type the immune system. Using an enzyme showed Ser320 as a novel active site 2 diabetes, heart attacks, strokes and to remove sugar entities from hemocy- of p120ctn for activity of the MAPK cancer. An underlying cause of this anins, they found that sugar residues pathway. These results indicate that condition is an excess of circulating are important for their structure and RSK might be used as a therapeutic fatty acids, which promotes the immunogenic effects. The changes to target against cancer, and the work oxidation of fat over glucose. Thus, glycan content altered the interaction contributes to the overall understand- inhibition of fatty acid oxidation, of hemocyanins with immune cells. ing of RSK behavior. or FAOX, has been suggested as a Their findings elucidate aspects of DOI: 10.1074/mcp.RA119.001811 treatment for insulin resistance. hemocyanin immunological activities Anne-Marie Lundsgaard and a and have significant implications for A link between enzyme team from Germany and Denmark the biomedical application of these mutation and cerebellar ataxia did a collaborative study to under- proteins. Spinocerebellar autosomal re- stand the consequences of inhibiting DOI: 10.1074/jbc.RA119.009525 cessive type 16, known as SCAR16, FAOX on overall metabolism. They is a fatal neurodegenerative disease used etomoxir to inhibit FAOX Finding the RSK in melanoma characterized by difficulties with swal- in mice, which in the short term protein interactions lowing, eye movement, speech and resulted in increased glucose oxi- According to the Centers for coordinated voluntary movements. dation and lowered blood glucose Disease Control and Prevention, skin SCAR16 is a monogenetic disorder as expected. However, within days, cancer is the most common form of dependent upon coding mutations in they saw triglyceride accumulation cancer in the U.S., and, of the various a single gene called STUB1, which in the heart and liver. In fact, when skin cancer types, melanoma is the encodes the versatile enzyme C ter- etomoxir was administered to mice most aggressive. Historically, dereg- minus of HSC70-interacting protein, over a prolonged period, it resulted ulation of the Ras/mitogen-activated or CHIP. In a study published in the in hepatic steatosis or fatty liver protein kinase, or MAPK, pathway Journal of Biological Chemistry, disease and glucose intolerance. Their has been known to result in cancer. Sabrina Madrigal and colleagues at the findings, published in the Journal The MAPK pathway activates a University of North Carolina School of Lipid Research, shed light on the protein enzyme known as ribosomal of Medicine examined the relation- long-term consequences of FAOX s6 kinase, or RSK, a necessary com- ships between clinical phenotypes of inhibition for treating insulin resis- ponent for growth and proliferation SCAR16 patients and the biophysical, tance, which could move researchers of melanoma. Little is known about biochemical and functional properties to rethink such treatment strategies. behavior and cellular interactions in of CHIP variants. The researchers DOI: 10.1194/jlr.RA119000177 the relationship between RSK activity provide linear models that suggest that and melanoma progression. inhibition of mutant CHIP lessens How mollusk proteins Antoine Méant and colleagues at disease severity, a finding that may be modulate the immune system the Université de Montréal studied useful for clinical therapies. Hemocyanins are respiratory the RSK interacting proteins and DOI: 10.1074/jbc.RA119.011173

FEBRUARY 2020 ASBMB TODAY 21 JOURNAL NEWS

Untangling Alzheimer’s and the spread of misfolded proteins

In 1906, seeking to understand the symptoms of a de- Francisco, used CRISPR interference, a genetic tool ceased patient who had been plagued by confusion, mood that allows specific genes to be turned off, to identify swings and disturbed sleep, Alois Alzheimer arranged for a cellular components involved in the spread of patholog- brain autopsy. He found alterations to proteins in her brain ical tau. cells, later called amyloid plaques and tau tangles. These In a paper published in the Journal of Biological are the hallmarks of what we now call Alzheimer’s disease, Chemistry, John Chen and colleagues reported that which affects more that 5 million Americans aged 65 years knocking down components of the endosomal sorting or older. It remains incurable, with only symptomatic relief complexes required for transport, or ESCRT, machin- available. ery using CRISPR interference accelerated the spread In the past decade, Alzheimer’s drug development of tau buildup in cells. Specifically, the researchers largely has focused on the elimination of amyloid plaques, discovered that the individual knockdown of charged with little success. Recently, tau, a protein that modu- multivesicular body protein 6, known as CHMP6, or lates cellular support elements called microtubules, has co-knockdown of CHMP2A and CHMP2B (a gene as- emerged as a therapeutic target. Researchers now believe sociated with familial frontotemporal dementia) caused the buildup and tangling of the protein tau may be at the the ESCRT pathway to become leaky and accelerated heart of disease severity. Mounting evidence suggests that tau buildup. These results increase our understanding tau aggregates spread via prionlike propagation. of how pathological tau spreads across brain cells and To understand how misfolded tau spreads across brain identify potential therapeutic targets. cells, researchers from the University of California, San DOI: 10.1074/jbc.RA119.009432 — Anand Rao

This photomicrograph shows nerve cell bodies TULEMO/WIKIMEDIA COMMONS (indicated by the arrow) and their processes (indicated by the arrowhead) in the neocortex of a patient who died with Alzheimer’s disease. Tau protein is stained brown using immunohistochemistry.

22 ASBMB TODAY FEBRUARY 2020

PACAPturing a link between chronic migraines and opioid-induced sensitivity

Hundreds of millions of people suffer from debilitating possible solution. The results will be useful for developing migraines, and opioid-based medications regularly are treatment options with less risk of addiction and depen- prescribed to manage migraine pain. These treatments are dence than that associated with opioid-based therapeutics. effective at first but can lead to the progression of migraines DOI: 10.1074/mcp.RA119.001767 from occasional to chronic, and continued use can lead to ­— Tori Zirul addiction and dependence on opioids. Regular opioid use also can lead to a lower pain threshold and higher opioid tolerance, a condition known as opioid-induced hyperalge- sia, or OIH. Researchers lack a complete mechanistic understand- ing of OIH and the exacerbating effect it has on migraines, making the development of alternative treatments a chal- lenge. Krishna Anapindi and colleagues at the University of Illinois at Urbana–Champaign and the University of Illinois at Chicago studied neurological proteins to find mechanis- tic links between chronic migraines and OIH. The results of this study were published in the journal Molecular & Cellular Proteomics. The team used liquid chromatography–mass spectrom- etry to identify and measure neuropeptide dysregulation similarities between the brains of mice engineered to have DOROTHY LOUDERMILK/UIUC SCHOOL OF CHEMICAL SCIENCES GRAPHIC SERVICES OIH and those engineered to have chronic migraines. Of the more than 1,500 neuropeptides they studied, the results showed 16 in common between the two disorders. Of those 16 peptides, pituitary adenylate cyclase-activating polypeptide, or PACAP, shows the most promise for further study, as it bridges the mechanistic gap between OIH and chronic migraines. PACAP, when working properly, dilates blood vessels, but if the signaling values increase, this vasodilation could lead to both disorders. When the researchers blocked Mouse models were used to examine changes in brain peptides associated the PACAP receptor, PAC1, for both groups of mice, the with opioid-induced hyperalgesia and chronic migraines. A large-scale blocked receptor prevented hyperalgesia in both models. liquid chromatography–mass spectrometry screen of several brain regions This is the first study to identify PACAP as an aggrava- revealed PACAP as a peptide that could bridge the mechanistic gap tor of OIH and chronic migraines and blocking PAC1 as a between chronic opioid use and chronic migraines.

Isha Dey (ishaadey@gmail. Anand Rao (arao@ Tori Zirul (tezirul@gmail. com) is a scientist at asbmb.org) is a science com) studied molecular Thermo Fisher Scientific communicator for the virology at Montclair State in India. ASBMB. Follow him on University and is passionate Twitter @AnandRaoPhD. about communication, advocacy and education of the sciences.

FEBRUARY 2020 ASBMB TODAY 23 FEATURE

What steers so many A matter black scientists toward earning a master’s of degree before a Ph.D.? By Laurel Oldach

rowing up in Sicily Island, Louisiana, doctoral programs. Among students who Zerick Dunbar loved his high school identify as black or African American, that math and biology courses. He went proportion is significantly higher: closer to to Tulane University, some 200 miles 45%. A master’s degree can be an important Gfrom home, to study biomedical en- intermediate step for students who at first gineering and landed a job after college that are not competitive for admission to doctoral was in a lab — he worked in quality assur- programs. At the same time, it can be costly, ance at a petroleum company — but didn’t and a bad experience could derail promising fit his interest in biology. So he returned to researchers at an early stage. Tulane after a few years to seek a master’s de- Knowledge of this disparity varied gree, hoping to find work at a medical device among experts on diversity and inclusion company. in science interviewed for this story. Some As he worked in the lab alongside Ph.D. consider it common knowledge. Others students, Dunbar said, his ideas about what expressed surprise and even skepticism. could be done with his degree changed. Now Kenneth Gibbs, a program officer who he’s a third-year doctoral student at Meharry directs training programs at the National Zerick Dunbar School of Medicine in Alabama studying Institute for General Medical Sciences, or variations between natural killer cells across NIGMS, said, “We need more research. tissues. He has become interested in entre- That’s not just a pat answer; we really need preneurship and hopes to pursue a career in to understand better why individuals make biotechnology, eventually launching his own the choices they do leading up to entering a ventures after graduation. Ph.D. program. About 30% of Americans who earned “A master’s is not a bad degree. A master’s a Ph.D. in the biological and biomedical en route to a Ph.D. is not a bad thing. It sciences in 2017 had, like Dunbar, earned a becomes a bad thing if there is some dif- Kenneth Gibbs master’s degree before they enrolled in their ferential, systemic issue that is causing this

24 ASBMB TODAY FEBRUARY 2020 different outcome — that is, if admissions on his own. committees require more from black candi- Compared with many fields, including dates than others.” Dunbar’s undergraduate major of engineer- Does such a systemic issue exist? Policy- ing, biology is unusual in that students don’t makers don’t know for sure, but they point to need to earn a master’s degree before applying several well-documented educational dispar- to doctoral programs. Students who don’t ities that may make it likely for black Ph.D. have a family member or mentor with insider recipients to enter graduate school knowledge may not realize that. with more education on their CVs than Alyssa Cobbs, who finished her Ph.D. their peers. at Morehouse School of Medicine in 2019, started considering a research career as a First in the family senior in college, rethinking her original “Black scientists live as black people, and interest in pharmacy school. While attending black people in America have different lived the Annual Biomedical Research Conference experiences than other groups,” Gibbs said. for Minority Students, widely known as One part of that mosaic is a legacy of limited ABRCMS, she learned that she could apply access to education, meaning that many for a funded Ph.D. program even without students of color are the first in their families a master’s degree in hand. The conference to pursue college or postgraduate degrees. happened in November; Cobbs rushed to Alyssa Cobbs Zerick Dunbar is an example. “No take the GRE graduate school entrance exam one from where I’m from has ever gotten a and wrote as many applications as she could Ph.D.,” he said. “Maybe one guy back in the finish before the December deadlines. ’50s or ’60s.” As a consequence, his path According to Cobbs, throughout gradu- to graduate school was his to determine ate school, younger students would ask about

The proportion of life scientists who are black drops off over the stages of a traditional academic career path.

15

30% 12 12.3%

of all U.S. biomedical 9

Ph.D.s earned a master’s 7.6% degree first. Among 6 7.1%

4.2% black biomedical Ph.D.s, 3 3.0% 2.9% the proportion is Percent of population that is Black/African American 2.1% 0 significantly higher at All U.S. Bachelor’s Master’s Ph.D. Postdoctoral TT faculty Tenured residents recipients recipients recipients fellows faculty In life sciences

45% Source: NSF/NCSES, Women, Minorities and Persons with Disabilities in Science & Engineering (2019) and Science and Engineering Indicators (2018) Source: National Science Foundation/National Center for Science and Engineering Statistics (NSF/NCSES), Survey of Earned Doctorates (2017)

FEBRUARY 2020 ASBMB TODAY 25 FEATURE

“A master’s is not a bad degree. A master’s en route to a Ph.D. is not a bad thing. It becomes a bad thing if there is some differential, systemic issue that is causing this different outcome.” — Kenneth Gibbs

where she earned her master’s degree and were surprised when she said she didn’t have one. Now her younger brothers and sisters are expressing interest in becoming scien- tists, and she looks forward to talking them through the process. “You know what you see,” Cobbs said. “If you’re never exposed to it, you don’t know how to go about it.” Plenty of students are never exposed to the particulars of biomedical higher educa- Taylor Carmon

tion. According to Avery August, a Howard Hughes Medical Institute professor of immu- majority-white institutions. nology and vice provost for academic affairs “I decided that maybe I should look at LINDSAY FRANCE/ LINDSAY at Cornell University, some of the undergrad- HBCUs to get some diversity in my educa- uate students he counsels are “quite surprised tion. Just in case I didn’t get tuition assis- that you can, so to speak, skip the master’s tance, I decided to stay in Alabama.” That degree. … The other really interesting thing narrowed the selection down to two pro- CORNELL UNIVERSITY PHOTOGRAPHY is that many students still don’t appreciate grams, one of which he eventually joined. Avery August that during the process of getting a Ph.D., The decision worked out for his scientific you are supported financially.” education. “My current adviser just picked me out of the crowd to start talking to me Paying out of pocket about molecular genetics,” he said. “He got The overwhelming majority of Ph.D. me interested in his research area by bring- students in biological and biomedical sciences, ing me into the lab, talking to me about the some 95%, are supported by grants that cover different genes involved in lipid synthesis and both tuition and living expenses. In contrast, how characterizing those genes could help paying for a master’s degree in the field most people better understand certain diseases.” often falls on students. While about one-third Almost three years later, Carmon has of students join a funded program or land re- traveled to conferences to present research search or teaching assistantships, the majority he did as a master’s student and is building of master’s degrees in biomedical sciences are on that work as he pursues a Ph.D. in his financed by loans or out of pocket. adviser’s lab. Taylor Carmon took out student loans But the master’s, which was not funded, to finance his master’s degree in food science was costly; even for an Alabama resident, at Alabama A&M University, a historically tuition for a year in the program is about black university in Huntsville. He developed $9,000, excluding living expenses. Across an interest in nutrition while reading up on academic fields, according to the National diabetes and high cholesterol to help some Center for Education Statistics’ Postsecond- relatives manage their diagnoses. That interest ary Student Aid Survey, 81% of black M.S. evolved into a college major and, eventually, graduates carry debt related to their master’s a master’s program. degrees, compared with 56% of all M.S. Carmon said he chose Alabama A&M graduates. Master’s recipients who are black strategically. All of his prior education was in carry, on average, almost twice as much debt

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as students in general. Time in the lab Even now, neither Carmon’s adviser nor When Natasha Brooks was an under- his department is able to provide a stipend graduate at Penn State with an interest in — or cover his tuition as a doctoral student biochemistry in the early 2000s, she initially researcher. imagined a job in forensic science. A fan of “That’s the downfall of choosing an the television show “CSI,” she wanted to use HBCU; they may not have the funding to her lab skills to solve crimes. pay for your education,” Carmon said. “I After her goal shifted to biomedical know it’s a disadvantage to me, because right research, Brooks said, applying for a mas- now, I’m paying out of pocket. I chose to ter’s program seemed like the logical next stay here over leaving … because I know the step. She mentioned the plan to her research Natasha Brooks research in the lab, I know what’s going on, adviser, who told her, “‘No, you need to just I’m independent. I don’t have to start over apply to Ph.D. programs.’ He didn’t feel that from scratch.” I needed to take the intermediate step.” Carmon expects to graduate in three or Brooks had worked in the lab every sum- four years. He said he and other students at mer since her freshman year, so the adviser Alabama A&M hope their department will was confident that she would be a strong land a grant sometime soon to cover tuition. graduate researcher. And he was right; Brooks In the meantime, he’s racking up debt. was accepted to the University of Texas

In biological sciences, master’s students are more likely than Ph.D. students to pay out of pocket. The average debt burden is higher for black M.S. recipients in all fields than for their peers. Master’s students 67% self- supported

Black M.S. recipients $42,009

All M.S. recipients $24,446 Ph.D. students 5% self- supported

0 $10,000 $20,000 $30,000 $40,000 $50,000 Average debt per student Self-supporting Received other funding Source: U.S Department of Education, National Postsecondary Student Aid Survey (2016) Source: NSF/NCSES, Graduate Students and Postdoctorates in Science and Engineering Survey (2018)

FEBRUARY 2020 ASBMB TODAY 27 FEATURE

Medical Branch at Galveston for a Ph.D. in have smaller research programs and graduate biochemistry and molecular biology, which populations. she defended in 2012. She now works as a “HBCUs are wonderful institutions and medical writer. are doing great work in terms of giving stu- “The people who seemed to be more suc- dents the skills or the confidence they need to cessful in the lab weren’t the people who had want to pursue graduate education,” Griffin the highest GPA and GRE scores,” Brooks said. But “they may not have the lab facilities said about her fellow graduate students. that would allow students to get the depth of “They were the people who actually had lab experience doing lab-based science that other experience. I think that’s a good predictor of students might have.” the outcomes.” For students whose degrees are from Kimberly Griffin, an associate professor schools with less robust research activity, a of student affairs at the University of Mary- master’s degree may be a substitute for under- land, confirmed this impression. Admissions graduate research experience. committees, she said, “think quite critically Kenneth Gibbs at the NIGMS thinks about research experience and who you’ve about it in terms of his own educational path. had the opportunity to work with prior to “If you’re at Stanford, you have different entering your Ph.D. program.” levels of research available to you than at (the All five of the top institutions where University of Maryland, Baltimore County). Ph.D. recipients earned their bachelor’s Those are two places that I went to school. I Kimberly Griffin degrees are classified as R1 universities by the took advantage of what was available to me Carnegie Commission on Higher Education, — but sometimes, at Stanford, Ph.D. appli- meaning that they have very high research cants were judged by the Stanford standard.” activity. In contrast, the historically black Admissions committees, he said, would colleges and universities that educated the do well to consider how much access an most black students who later earned Ph.D.s applicant has had to research labs.

Top five baccalaureate institutions of all Ph.D. recipients in science The NSF keeps track of where Institution Historically black Carnegie classification Ph.D. recipients first earn college and university their undergraduate degrees. Whereas the top five alma University of California-Berkeley No Doctoral – very high re- search activity (VHRA) maters of those who go on to earn Ph.D.s are all R1 Cornell University No Doctoral – VHRA universities, most of the top University of Wisconsin-Madison No Doctoral – VHRA alma maters of black Ph.D. recipients are HBCUs, with University of Michigan-Ann Arbor No Doctoral – VHRA lower research activity but University of California-Los Angeles No Doctoral – VHRA stronger support systems. Source: NSF/NCSES, Women, Minorities and Persons with Disabilities in Science & Engineering (2019)

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“Students have been figuring out on their own that where they initially can’t get access to a Ph.D. program, a master’s program can be a stepping stone.” — Keivan Stassun

Gibbs often speaks to trainees — at var- graduate research conferences for minority ious academic stages — whom he considers students. ready for a next career step by most metrics. “It wasn’t an academic deficit,” he empha- Sometimes he finds that they don’t feel sized. “It was ‘I’m just not ready yet … I want ready. He suspects that the hypercompetitive to get more experience in research so I feel like culture of academia affects different groups to I know what I’m getting myself in for.’” different degrees. For students he has worked with, McGee “As a professional black person, it’s not said, taking time to be sure of the decision uncommon to hear you have to be twice as to pursue a Ph.D. often has been positive. good to get the same results as people from Whether the intermediate step is a master’s majority backgrounds,” Gibbs said. That, degree or another training model, “Your con- he said, might motivate students to rack up fidence, your self-image, your self-efficacy; extra credentials before applying to start a all this stuff is going to be bolstered at each Ph.D. step along the way (as) you get more data In 1996, Richard McGee, a professor to counter the narrative that ‘I don’t belong Richard McGee of medical education and associate dean of here.’” professional development at Northwest- ern University’s medical school, started a The GRE postbaccalaureate program for students who Along with research experience, recom- want to spend more time in the lab before mendation letters and undergraduate grades, committing to a doctoral degree. The model the GRE is an important factor in graduate has caught on and been adopted as the Post- admissions. According to Keivan Stassun, baccalaureate Research Education Program a physics professor at Vanderbilt University at campuses across the country. McGee says who has written extensively on equitable he was motivated by having variations on the access to graduate education, “Doctoral pro- same conversation over and over at under- grams have put and continue to put outsize Keivan Stassun

Top five baccalaureate institutions of black Ph.D. recipients in science

Institution Historically black Carnegie classification college and university

Howard University Yes Doctoral – higher research activity

Spelman College Yes Baccalaureate colleges – arts & science focus

Florida A&M University Yes Doctoral – higher research activity

University of Maryland No Doctoral – high research activity Baltimore County

Hampton University Yes Master’s colleges & universities – Source: U.S. Department of Education, National Postsecondary Aid Survey (2016)medium programs

FEBRUARY 2020 ASBMB TODAY 29 FEATURE

influence on GRE scores. As soon as you and her team described an intervention to realize that, all of these other patterns become reduce the disproportionately high triage understandable.” of applicants from underrepresented back- GRE scores have been known for decades grounds. Once, a GRE score or GPA below Critics say that to correlate with race and gender. The Educa- a threshold got an application set aside right the GRE is a tional Testing Service, which administers the away, and only an intervention from interest- GRE and other standardized tests, has taken ed faculty could rescue an applicant. In the biased test. steps to reduce that bias; though the gap is redesigned admissions process, applications Black test-takers shrinking, it remains at greater than 10% of with weaker scores are reviewed by a second interested in the possible score. That can be a problem at committee; if the reviewers think a student biology score the triage stage of admissions, when commit- has potential, they forward the application tees decide which applications to review in to the main admission committee, which is lower on both depth and which are unlikely to be successful. blinded to applicants’ triage status. halves of the “If you sort your applicants by their GRE test, on average, scores … because of the massive disparities The safest bet than their white in GRE scores that correlate with race and According to Wilson–Pham, now an gender, your diverse applicants are going to associate dean at Rush University in Chicago, peers. Their mean end up being sorted to the bottom of the when admissions committees meet to discuss combined score spreadsheet,” Stassun said. Once those candi- applicants who have cleared the triage hurdle, is about dates are there, he added, even if diversity in subtle bias may creep into their assessment of admissions is a priority, the ranked list predis- qualitative factors. poses the committee to think of more diverse “People fall into this lull,” Wilson–Pham 10 candidates as less qualified. said. “They like to see candidates who remind points lower Qualitative research suggests that triage them of who they once were. … If I have to based on GRE score is common across bet on which person is going to succeed, it’s on an scientific fields because the average commit- this person that looks just like me — because tee must assess so many applications. But I succeeded.” as research has begun to show that, while This type of bias, known to social scien- 80 predictive of first-year grades, GRE scores tists as homophily, isn’t only about race, eth- point are not correlated strongly with measures nicity and gender. It can apply to any feature total scale. like publication rate and completion time in that a student and an admissions committee graduate school, an increasingly large move- member shares, such as where they went to Source: Educational Testing Service, ment, cheekily dubbed GRExit, is demand- college or whether the applicant’s recommen- Snapshot of the individuals who took ing that admissions committees drop their dation letter comes from a professor whose the GRE general test (2017). GRE requirement. reputation the admissions committee knows. Another approach is to reduce the At MD Anderson, where she both earned committee’s focus on GRE scores while still her Ph.D. and got her start in academic ad- gleaning some information from the test. ministration, Wilson–Pham used the Socratic That’s the route Marenda Wilson–Pham method when she sensed reviewers saw some took when she was assistant dean of diversity applicants as safe bets and others as risky. “It’s and alumni affairs at MD Anderson Cancer almost like a research seminar,” she said. “The Center. In an article last year in the journal way I’d get people to reflect on their behavior CBE-Life Sciences Education, Wilson-Pham was to ask a bunch of questions. ‘Tell me why

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you feel this way about this applicant. Well, While Ph.D. students outnumber then let’s go back to this applicant that we master’s students in the biomedical reviewed an hour ago and this is what was sciences overall, there are more black said.’ … My job was to make sure that, for students pursuing master’s than every applicant, the criteria were equal.” doctoral degrees. Aware that a program’s future funding All students in biomedical sciences (2017) depends on student success, a committee 50,000 with doubts about an applicant’s ability to 40,000 succeed may hedge its bets by suggesting 51,291 Marenda Wilson–Pham Ph.D. students that student consider a master’s degree in the 30,000 same department, generally with funding. 20,000 33,926 Both Wilson–Pham and LaRuth McAfee, M.S. students the senior assistant dean at the University of 10,000

Delaware’s graduate college, mentioned this 5,000 when discussing the preponderance of mas- ter’s degrees among black Ph.D. recipients. 0 “Maybe the student knows they want a Ph.D., but the program wants them to prove White students LaRuth McAfee themselves,” McAfee said. “If they do well in 30,000 the master’s program, they can stick around 25,000 for the Ph.D.” 25,056 Ph.D. students Anecdotally, both deans said that these 20,000 offers are more commonly extended to 15,000 16,894 students from minority-serving institutions. M.S. students “It’s not that they’re saying, ‘We don’t think 10,000 someone from this institution can cut it,’” 500 McAfee said. “It’s more like, ‘We’re con- 0 cerned that we’re putting ourselves at risk — and even concerned that we might be hurting Black students the student by admitting them to a program 3,000 in which, if they’re not successful, they’ll have fewer options when they leave than when 2,500 2,702 M.S. students they came in.’” 2,000

Some students seize the opportunity to 1,970 attend their school of interest on any terms. 1,500 Ph.D. students

Others recoil. When Zerick Dunbar was 1,000 finishing his master’s degree and applying for Ph.D. programs, he received one counter- 500 offer of acceptance into a master’s program 0 instead. “I was like, ‘Uh, I already have a Source: NSF/NCSES, Graduate Students and master’s?’ Getting another would be a waste Postdoctorates in Science and Engineering Survey of my time.” (2018)

FEBRUARY 2020 ASBMB TODAY 31 FEATURE

Recruitment and retention American Society for Biochemistry and Mo- The National Science Foundation’s Grad- lecular Biology’s Minority Affairs Committee. uate Student Survey indicates that, across the She put the master’s-before-Ph.D. phenome- many disciplines of biology and biomedicine, non in the wider context of academia’s inhos- about three people are pursuing doctoral pitability to underrepresented scientists. degrees for every two pursuing master’s “Any time there’s a stopping point in the degrees. This ratio is about the same for white pipeline, there’s a potential that you get lost,” students. But it’s inverted for black students; she said. “Students may get the master’s and there are three black Ph.D. students for every be satisfied with it. Or, due to the things that Suzanne Barbour four black master’s students. Advancing fur- happened to them during the master’s, (they ther through academic career stages, the un- may) say, ‘The last thing in the world I want derrepresentation of black scientists becomes to do is go for a Ph.D.! I haven’t been treated more and more pronounced. well in academia.’ “Students are making — I think in “A lot of things have been done in the some cases justifiable — choices to do other last two generations. There are all kinds of things,” August said. “At the same time, I pipeline-building programs, (but) everything think we’re losing an opportunity to diversify tends to focus on recruitment, recruitment, faculty, because of the culture we have in the recruitment.” academy.” In Barbour’s opinion, it is time for the Suzanne Barbour is the dean of the gradu- focus to shift to retention of underrepresent- ate school at the University of North Carolina ed students and to increasing diversity and at Chapel Hill and a longtime member of the inclusion in more senior roles.

Historically black colleges and universities

The college experience can wasn’t a community that I felt could foster my growth in be- govern a student’s interest in, and ing a scientist and continuing to be myself. When I went to preparedness for, further education. Fisk, I was at an HBCU and I was able to be in a communi- A disproportionate number of black ty where it was OK to be a black young woman in STEM.” Ph.D. students attended a historically The time she spent in the program boosted her black college or university as under- confidence in her ability as a scientist and also her ability graduates. to compete in the admissions process. When she chose “Those are institutions that have a doctoral program, she selected universities with equally Briana Whitehead really mastered what it means to strong underrepresented communities. have cultures of inclusion and to Students from prominent HBCUs are courted by many provide support structures that ensure graduate programs. However, some faculty at research students come out armed to succeed in whatever they do,” universities lack knowledge of these institutions. When Keivan Stassun, a physics professor at Vanderbilt Univer- Kenneth Gibbs, a program officer at the National Institute sity, said about HBCUs. “Many of our R1 institutions who for General Medical Sciences, was a graduate student have been working harder to increase the diversity of their at Stanford, he served on an admissions committee; one student bodies still have a lot to learn from minority-serving applicant was a senior at Morehouse College, and some institutions.” faculty “hadn’t heard of Morehouse and didn’t know how to For Briana Whitehead, a first-year biophysics Ph.D. assess (the student’s) potential contributions or his ability student at Johns Hopkins who earned a master’s through to excel in the program.” a bridge program at Fisk University in Tennessee, the dif- Gibbs said his answer was, “Well, have you heard of ference between her undergrad and her master’s program Martin Luther King Jr.? Because that’s where he went to was stark. When she was an undergraduate, she said, “it school.”

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Outlook underrepresented graduate students) … the “People in science are still people in hard part is the ‘why.’” science,” Gibbs said. “Even though our ideals Experts say determining and redressing are universal, science happens in a social envi- the causes of underrepresentation are as much ronment. The biases that exist in the world a strategic priority as an ethical imperative. shape how we do science and the experience “There was a time when people thought that people from different backgrounds have of this as an issue of just plain diversity,” Bar- in science.” bour said. “But now, I think we have to start Many scholars have worked for years to thinking about it in terms of the workforce unravel the way that those biases directly and and the leadership that the country needs to indirectly steer young black scientists toward continue to be the global leader in research extra years of schooling or away from science and development in the life sciences.” altogether. For some of them, such as Mi- chelle Jones–London, chief of the workforce diversity office at NINDS, students’ research experience prior to graduate school is coming Laurel Oldach (loldach@asbmb. into focus as a research topic of its own. org) is a science writer for the “We recognize that this needs more of ASBMB. Follow her on Twitter a careful look,” Jones–London said. “We’ve @LaurelOld. seen what we think could be a potential difference (between well-represented and

Bridge to doctorate programs

According to Keivan Stassun, a physics professor at capabilities are.” Vanderbilt University, “Students have been figuring out Avery August, who ran a Bridges to the Doctorate on their own that where they initially can’t get access to program as a professor at Penn State in partnership with a Ph.D. program, a master’s program can be a stepping Alcorn State in Mississippi, saw some applications from stone.” undergraduates who were already well prepared to enter a Launched in 1992, the Bridges to the Doctorate Ph.D. program. He said, “We specifically counseled those funding mechanism at the National Institutes of Health is students to apply directly to Ph.D. programs.” designed to offer that stepping stone but with funding to Sometimes, he added, those students were reduce the financial burden on students. It pairs minori- disappointed not to be accepted into the supportive ty-serving institutions that offer a terminal master’s degree community of the bridges program, so the program staff with predominantly white institutions that offer doctoral took steps to expand the extra mentoring and other programs. When a student successfully completes the activities to underrepresented students who didn’t need master’s, they receive admission to the Ph.D. program. the transitional master’s step. Stassun launched Vanderbilt’s Master’s to Ph.D. Bridge When a panel met to review the NIH funding mech- program in collaboration with Fisk University in Nashville in anism in 2018, they concluded that it was unevenly suc- 2003. (The program is independent of the NIH program.) cessful: Some universities’ programs were very effective, “Almost without exception, these are students who have while others had limited success in funneling underrepre- applied to doctoral programs and been denied admission sented students into Ph.D.s and later faculty positions. The to every one of them,” he said. The program “provides a committee added that a lack of longitudinal data on student way for these students to demonstrate on site what their outcomes made it difficult to assess accurately.

FEBRUARY 2020 ASBMB TODAY 33 FEATURE

THE MEYERHOFF SCHOLARS PROGRAM MEYERHOFF SCHOLARS PROGRAM A model for increasing diversity in STEM

By Nathalie Gerassimov

n the late 1980s, Robert Meyerhoff, an MIT-trained explains why MPS embraced this change. “If we want to engineer turned Baltimore businessman and philanthro- change the narrative and landscape — we need everyone pist, turned his attention to changing negative narratives at the table to understand the issues and do part of the Iabout black men and increasing their participation in work,” he said. the science, technology, engineering and mathematics The MSP experience begins, before a student starts fields. their first year, with the six-week residential Summer Meyerhoff joined forces with a black university ad- Bridge program. Members of the new class live together in ministrator, Freeman A. Hrabowski III, who would go on one building and take two credited classes: a math course to become the president of the University of Maryland at and Race, Science and Society, a course designed and Baltimore County. Together, they initiated a bold one-year taught since 2013 by psychology professor Shawn Bediako experiment: to reproduce the supportive environment to examine critically how these three constructs inform Hrabowski had experienced at Hampton Institute, now and influence one another. Hampton University, a private historically black university, “All students — regardless of their background — live at the predominantly white UMBC. in a social context that basically tells them the same thing Some three decades later, the resulting Meyerhoff about power, who has power and who should have power,” Scholars Program, or MSP, is a national model for how to Bediako said. “They process these messages differently, increase diversity in science. however. Some students have internalized these messages The MSP has tracked outcomes for its more than and are motivated by a desire to prove themselves and 1,200 graduates since 1993. A student who accepts an their worth. Some students have externalized these mes- invitation to join the program is five times more likely to sages and are motivated by a desire to change the system attend or graduate from a STEM Ph.D. or M.D.–Ph.D. so that it is more equitable. program than a student who is invited to join the MSP “My goal for this class is to give students the vocabu- but chooses another undergraduate program. As of 2019, lary to speak about systems of inequity and reflect on how the program’s alumni had earned 319 Ph.D.s, including those systems show up in society — particularly through 59 M.D.–Ph.D.s and 147 M.D. or D.O. degrees, as well the process and practice of science.” as 280 master’s degrees, primarily in STEM fields. Most As part of the Summer Bridge program, Harmon of these degrees are from prestigious institutions such as said, students also attend seminars and talks designed to Harvard, Stanford and Yale. prepare them for the academic rigor and collaborative The first MSP class, referred to as M1, was 19 black learning at UMBC by introducing them to best practices men from Maryland. Meyerhoff financed their tuition, for undergraduate success, including learning styles, time fees, room and board, and books. He also took a great management and networking. interest in them, their college experience, and their back- “We help the students and the parents understand the grounds and personal circumstances. That first year con- sacrifices and the dedication it takes to be successful in vinced him to continue his support of the program. Black STEM,” Harmon said. “We set high standards for them, women were admitted into the MSP starting with M2. but we will not expect any less than we resource them for.” In the late 1990s, following the Supreme Court’s de- Mitsue Wiggs, the MSP assistant director and Sum- cision to uphold a federal appeals court ruling that struck mer Bridge coordinator, emphasizes that, in addition to down a scholarship program limited to high-achieving academic excellence and undergraduate research, commu- black students, the MSP was opened to people of all races nity service and civic engagement are core values of the and backgrounds who are interested in increasing diversity program. As part of a for-credit class called the First Year in science. Experience, incoming students engage in a semester-long Keith Harmon, director of the program since 2012, service-learning project with one of more than 100 non-

34 ASBMB TODAY FEBRUARY 2020 FEATURE MEYERHOFF SCHOLARS PROGRAM

Program founder Robert E. Meyerhoff and Freeman A. Hrabowski III, president of the University of Maryland at Baltimore County, sit center stage surrounded by program graduates and staff at the 30th anniversary celebration of the Meyerhoff Scholars Program.

profit organizations in the Baltimore area. done undergraduate research without MSP,” he said. Once “It has been really successful for us to have them at UMBC, he followed the MSP’s recommendation and engaged early in their process and to really start to under- did undergraduate research for three years with Howard stand the responsibility and the benefits of serving their Hughes Medical Institute investigator Michael Summers community,” Wiggs said. and this past summer at Dana–Farber Cancer Institute Nicole Attram, an MSP first-year student majoring at Harvard Medical School. Gilchrist is now applying in mechanical engineering, volunteered with a program to M.D.–Ph.D. programs and has interview offers from called Reading Partners. She tutored elementary students New York University, Columbia University, the University who were behind grade level in reading to help improve of Maryland and the University of Texas Southwestern their skills. “I chose this volunteer site because I had a dif- Medical Center. ficult time learning to read when I was younger,” she said, “MSP community is like a family, which I really en- “and I thought it was only right for me to help someone as joyed,” Gilchrist said. “I thrived with the support from the I was helped.” staff and the other MSP students and alumni who helped The institutional commitment of senior administra- me through my struggles, helped plan my next steps and tion and UMBC faculty is the secret sauce to MSP suc- shared my good news with me. I have no doubt that I am cess, Harmon said. “We would not have the success we’ve more successful today because of MSP.” had, had it not been for the commitment of our faculty, especially the STEM faculty who take students into their labs and train them and teach them to think critically and Nathalie Gerassimov (nathalie.gerassimov@ gmail.com) is a postdoctoral researcher at the deeply about the challenging problems within STEM.” Carnegie Institution of Washington department Darin Gilchrist, a senior majoring in biochemistry of embryology. and molecular biology, recalls that prior to becoming part of the MSP, he was interested in science but really didn’t know what research was. “I don’t know if I would have

FEBRUARY 2020 ASBMB TODAY 35 FEATURE

INCLUSIVE EXCELLENCE A goal of lasting change

By Courtney Chandler

he scientific community now inadequate.” recognizes that diversity is im- This is partially due to a long- portant, yet historical exclusion standing focus on students without a T of certain groups from the sci- corresponding focus on the learning FETTERS PAUL ences hinders inclusivity and growth. environment in which the students This limits the range of perspectives find themselves, Asai said. Many pro- within the community, which then grams provide tutoring, mentoring loses this benefit of diversity. and research experiences for specific Funding agencies have developed groups of students without altering programs to increase diversity in sci- the academic structures in their ence. But David Asai, senior director schools or universities. of science education for the Howard “While these ‘fix the student’ Hughes Medical Institute, thinks interventions might help the students more needs to be done. who participate, they generally do not “These efforts have had a result in lasting change,” Asai said. positive effect,” Asai said, “but our “When the grant ends, the activities overall progress has been appallingly end, and the system goes back to David Asai

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where it was before.” generation in their families to attend American Colleges and Universities To overcome these limitations, college. Instead of a student-centric to enact these changes. The second the HHMI conceived a new ap- approach, the Inclusive Excellence round of awards went to 33 schools proach to increase diversity in the initiative is focused on the institution in 2018, and the application process sciences: the Inclusive Excellence itself. is under way for the next round, initiative. Launched in 2015, this “This approach emphasizes the called IE3. initiative provides grants to colleges building of significant and lasting Specific programs and implemen- and universities that are working changes in the institution’s capacity tation plans vary among institutions to achieve significant and sustained for inclusion,” Asai said. based on their needs and goals, and a increases in their inclusivity of all Colleges and universities can ap- single school may have multiple ini- students. ply to be a part of the initiative, and tiatives. For example, several schools, Each participating school is asked Asai said interest is high. In 2017, including the University of Wiscon- to think about the populations of stu- the 24 schools in the first cohort were sin–Madison, Framingham State and dents that may be excluded at their awarded $1 million each in grant the University of Utah, are working institution. These may include stu- funding over five years to support with nearby community colleges to dents from racial and ethnic groups institutional-level changes that create align their curricula and advising so historically excluded from science, an inclusive culture for all students. that students transferring into four- students transferring from communi- The schools work in collaboration year universities can be successful in ty colleges and those who are the first with HHMI and the Association of science, technology, engineering and

FEBRUARY 2020 ASBMB TODAY 37 FEATURE

DRIVING CHANGE

The Howard Hughes Medical Institute launched a new initiative, Driving Change, in 2019 to promote a com- prehensive approach to diversity and inclusion at research universities. Each Driving Change university is expected to achieve three objectives: 1. Learn about the Meyerhoff Scholars Program at the University of Maryland, Baltimore County, and design their own student-centered program that will honor the underlying values of and achieve the outcomes of the Meyerhoff Program. 2. Design, implement and assess programs aimed at creating a significantly more inclusive learning envi- ronment for all students, especially with an eye toward closing the disparity gaps between students from excluded and nonexcluded groups. 3. Become an active participant in a learning community comprising other Driving Change universities in which the schools will share their ideas, efforts and outcomes. Each school applying for a Driving Change grant will conduct a self-study to identify how it can create a more inclusive STEM learning environment. Letters of intent for the first round of grants are due Feb. 7.

mathematics studies. “Working toward inclusive announced Driving Change program. Kenyon College and others excellence is a never- For the learning community to connect inclusive behaviors in the improve as a whole, Asai said, its ending process, and the ways faculty do their jobs, such as the members need to reflect on and share way they teach and advise, to faculty process is dynamic,” their experiences. For example, each rewards systems, including tenure, Asai said. grantee institution is part of a small to provide incentives for conscious peer implementation cluster, typically inclusive efforts. Still other schools up to 30 will be awarded grants. composed of four schools, that meets are revising their introductory science The Inclusive Excellence initiative regularly. During these sessions, curriculums to include course-based is relatively new, but Asai said HHMI groups of faculty and staff from each research experiences for beginning staff members already have gained Inclusive Excellence school share with science students, as is the case at Tow- insight about what it takes to create one another what they are learning son University and Norfolk State. meaningful culture change in an and how they can improve further. Inclusive Excellence allows schools to institution. As an increasing number of schools be creative and individualized with “Working toward inclusive become involved in the Inclusive their approaches as long as they are excellence is a never-ending process, Excellence learning community, this striving for increased inclusivity and and the process is dynamic,” Asai mutual support will help promote lasting change. said. “The institutional context lasting and meaningful change. Institutions submit proposals that changes all the time, often are reviewed by HHMI staff as well as unexpectedly, and scientists and educators who provide the work toward inclusive excellence Courtney Chandler is a advice to the HHMI review panel must navigate these changes.” postdoctoral researcher at Johns Hopkins during the application process. Pre- The lessons of the first two University and columnist proposals for the IE3 cycle were due rounds will help the HHMI improve for the ASBMB Careers Column focusing on Jan. 14, and more than 400 schools the program and other inclusivity industry. Follow her on indicated that they intended to apply; efforts including their recently twitter @CourtneyEChan.

38 ASBMB TODAY FEBRUARY 2020 FEATURE

PROGRAM AT NORTHEASTERN AIMS TO FIX THE INSTITUTION

By Leia Dwyer As a woman studying physical chemistry n the higher education-dense Boston region, Northeastern with few female mentors and a member of University always has stood out for its rich tradition of the Mohawk Nation, Mary Jo Ondrechen says Iexperiential learning. So it comes as no surprise that Mary she felt invisible when she was a student but Jo Ondrechen has employed this concept in launching the always did her best to push ahead.

Inclusive Excellence program at Northeastern, with a focus JO ONDRECHEN OF MARY COURTESY on flipped classrooms and encouraging faculty to share with each other best practices for diversity and inclusion. Though she speaks in an unassuming way about her Ondrechen employs the flipped classroom approach initiatives at Northeastern, Ondrechen herself navigated in her own teaching, reversing the traditional split of higher education at a time when few resources supported homework versus lecture and putting more emphasis on diversity and inclusion, so she has a deep personal connec- active, team-based problem solving in the classroom as tion to these efforts. As both a woman studying physical opposed to instructor lectures. Research shows that while chemistry with very few female faculty mentors and a this flipped approach is good for all students, it offers the member of the Mohawk Nation, she says she felt invisible greatest benefits to women and minorities, she said. She but always did her best to push ahead despite challenges. was happy to eliminate individual quizzes in her quantum Ondrechen and Wendy Smith, professors of chemistry chemistry and spectroscopy class in favor of team-based and biology, respectively, heard the call for preproposals quizzes, she said; students can solve harder problems for the first round of the Inclusive Excellence competition together through discussion and collaboration than they back in 2015. After their full proposal was selected by the would be able to tackle individually. Howard Hughes Medical Institute for funding, the project As part of Northeastern’s Inclusive Excellence pro- launched at Northeastern during the 2017 fall semester gram, workshops educate faculty on basic principles of and has continued for two years. diversity and inclusion in the classroom. Ondrechen said The goal of Inclusive Excellence is to make the science attendance at some of these workshops has exceeded her majors more welcoming to diverse students, Ondrechen expectations. The workshops are followed by teaching said, including first-generation college students. circles where about a dozen faculty members gather to “We don’t need to fix the students,” Ondrechen said. discuss their practices and open tough conversations about “We need to fix the institution.” bias and inclusion that faculty then carry with them back A professional evaluator measures the Northeastern to their own classrooms. program’s success with both students and faculty and is Ondrechen emphasizes the advantages of these just starting to acquire early data. Students and faculty peer-to-peer discussions and notes that the small, easily associated with the program take before-and-after surveys, implemented changes often have the greatest impact. One and the change in number of students graduating with of her favorite examples is eliminating implicit bias in call- science, technology, engineering and math degrees will be ing on students in the classroom by using a stack of index a key metric of success. cards with students’ names and drawing at random. Ondrechen doesn’t mince words about traditional And the best measure of success in an interactive class- academia. Research shows that lecturing is “just about room? “The noise level.” the worst way to teach,” she said. However, most fac- ulty learned by this method, so they employ it in their classrooms today. She aims to educate her colleagues on Leia Dwyer ([email protected]) is a senior business analyst at Lifescience Dynamics. the benefits of interactive classrooms where students drive their own, often collaborative, learning — classrooms where they feel more engaged and, as a result, more included.

FEBRUARY 2020 ASBMB TODAY 39 FEATURE

For vulnerable populations, the thorny ethics of genetic data collection

By Adrian Pecotic

To be n 2009, researchers collected DNA from and complex diseases, we’re getting a biased equitable, four elderly men in Namibia, each from snapshot,” said Alicia Martin, a geneticist at one of the many San indigenous com- the Massachusetts General Hospital and the genetics munities scattered across southern Africa. Broad Institute, a biomedical and genomics research IA year later, analyses of the men’s DNA research center affiliated with Harvard and the were published in the journal Nature — Massachusetts Institute of Technology. needs more alongside that of South African human rights Research to capture these snapshots, called diverse activist Desmond Tutu. The intention, in genome-wide association studies, can only part, was to increase the visibility of south- draw conclusions about the data that’s been samples. But ern, indigenous Africans in genetic-based collected. Without studies that look at each collecting medical research. Soon after, a nongovern- underrepresented population, genetic tests mental organization representing indigenous and therapies can’t be tailored to everyone. that data minorities in Southern Africa took issue with Still, projects intended as correctives, like All could the consent procedures used to gather the of Us and the International HapMap Project, data and wrote to Nature’s editors accusing face an ethical conundrum: Collecting that present the paper’s authors of “absolute arrogance, data could exploit the very people the pro- ethical ignorance, and cultural myopia.” grams intend to help. issues. The San case highlights the thorny ethics Researchers with All of Us have collected of collecting genetic data. Yet today, to make data from about 1,600 Native Americans, medicine more equitable, scientists see the some of whom live in cities outside of sover- importance of sampling DNA from more di- eign lands, where tribal approval is not neces- verse populations. Most genetic research uses sary for genetic research, according to Krystal DNA from descendants of Europeans, which Tsosie, a geneticist at Vanderbilt University means the related medical applications — who is co-leading a study in collaboration such as genetic tests to see the likelihood of with a tribal community in North Dakota. developing a certain disease, called polygenic “Obviously there’s an interest in mone- risk assessments — can only benefit those tizing biomarkers collected from diverse pop- populations. In 2018 in the United States, ulations and underrepresented populations,” for example, the National Institutes of Health Tsoise said, so without adequate protections, launched All of Us, a research program “the concern becomes about exploitation.” that aims to collect DNA, electronic health records, and other data, from about one mil- Shifting gears lion Americans with emphasis on including Medical genetic research generally works many different groups of people. like this: Geneticists use powerful computers “When we do genetic studies, trying to to compare the genomes of people affected understand the genetic basis of common by a particular disease to healthy controls.

40 ASBMB TODAY FEBRUARY 2020 FEATURE

Researchers mark genetic patterns that are common in people with, say, diabetes, but not the controls, as “associated” with the dis- ease. The more samples geneticists feed to the algorithms, the more likely that the findings reflect reality. But studies restricted to descendants of COMMONS STAEHLER/WIKIMEDIA Europeans will only find associations between diseases and “variants that are common in European ancestry populations,” said Martin — if those variants are common enough to be found. Scientists use the results to develop polygenic risk scores, which count the risky variants on someone’s genome to estimate their susceptibility to a disease. But if studies don’t use the genomes of non-white popula- tions, the tests won’t pick up on the prob- lematic variants in different groups of people. One 2019 Nature Genetics study, on which Martin was an author, determined that these blind spots reduce the accuracy of polygenic A San woman drills a hole in a slice of ostrich egg and adds it to a jewelry chain. After tests by approximately two and five times in researchers published an analysis of DNA from four San men in Namibia, an organization South or East Asian, and black populations, representing indigenous minorities took issue with the consent procedures used to collect respectively. the samples. In many cases, the groups whose DNA is missing have worse health care outcomes than their white counterparts; genetic medi- of genome diversity within the human fam- cine could worsen these disparities. “I think ily” by collecting DNA samples from about there’s a huge responsibility,” said Martin. “If 500 distinct groups, with an emphasis on we look at the history of the field, over the indigenous peoples that might soon “vanish.” past decade we’ve gone from participants in Indigenous-rights organizations criticized genetic studies being 96 percent European the project, taking issue with being treated as ancestry to about 80 percent. We’ve shifted mere objects of scientific interest and poten- gears a little bit, but not nearly enough to be tial for commercialization. All of Us, more able to serve minority populations.” recently, has run into similar objections from Jantina De Vries, a bioethicist at the the National Congress of American Indians. University of Cape Town, agreed that “rep- resentation in genomics research can bring Collective consent health benefits,” particularly if it is paired The concerns are linked to the long with measures to build research capacity so history of exploitative encounters between that, eventually, “there are researchers at every researchers and vulnerable populations. level” within the groups themselves. The Tuskegee Study — in which the U.S. Collecting broader genetic samples poses Public Health Service withheld treatment a host of challenges. Efforts to collect and from African American men with syphilis study the genomes of indigenous peoples, — lasted from 1932 until 1972, ending less for example, have been controversial since than 20 years before the HGDP proposal. the early ‘90s. The first such project, called And in 1989, researchers from Arizona State the Human Genome Diversity Project, or University collected DNA samples from HGDP, was meant “to explore the full range the Havasupai Tribe and reused the data for

FEBRUARY 2020 ASBMB TODAY 41 FEATURE

research to which the participants hadn’t talk to?” she added. The Yoruba are an ethic consented: on schizophrenia, inbreeding, and group of more than 20 million individuals, migration history. Tsosie said this context most of whom live in Nigeria, with smaller has created a “climate in which we’ve seen populations in Benin, Togo, and across sev- tribes deciding to disengage from biomedical eral diaspora communities. De Vries believes research completely.” the onus lies on researchers to “think in terms

IAN BEATTY/WIKIMEDIA COMMONS IAN BEATTY/WIKIMEDIA All the geneticists and ethicists this of respecting communities,” rather than in author spoke with agreed that community terms of collective consent. engagement is crucial to establish trust. Gaining collective consent involves But they didn’t agree on the degree of the logistical hurdles, especially for large-scale engagement. Some believed that gaining projects. The NIH’s All of Us program, the consent of communities is necessary for example, wasn’t able to get input from for ethical research, while others said it was each of the 573 federally-recognized tribes. enough to have respect and open dialogue According to Tsosie, during the planning between researchers and the people they’d stages, “there was talk of gaining tribal input, like to study. but that plan seemed to be abandoned But both approaches are difficult in the early on.” The All of Us website does have a context of collecting and analyzing genet- section on tribal engagement, but only offers ic data, since geneticists take DNA from “formal consultation and listening sessions” individuals to make conclusions about entire for ongoing projects, not guidance on how to populations. For instance, the San paper in approach these issues before a project starts. Nature extrapolated findings regarding in- Among non-indigenous policymakers dividual genomes to discuss the genomes of and scientists, Tsosie noted, there’s a “magical the broader communities. “One’s genome is notion” that stakeholders from every tribe not their own specifically; one’s genome is in- can be brought together in one room “when, formed by their recent ancestry, their family in reality, that is not how we make consensus structures, and their more distant ancestry,” decisions for ourselves.” said Tsosie. Geneticists are never “talking A San tribesman in Namibia. about an individual that’s siloed.” Respecting groups The gap between individual and col- Even more difficult than logistics may be lective consent is partly responsible for the conceptualizing the genetic studies to begin continued friction between genetic science with — for example, deciding which people and indigenous peoples. Collective consent, belong in which groups. “One of the greatest said Tsosie, who is herself Navajo, is “more political acts, acts of power, that we perform culturally consistent with how tribal groups as human beings is dividing ourselves up govern themselves.” for the purpose of knowing and governing In 2017, Andries Steenkamp, a San lead- ourselves,” said Jenny Reardon, a sociologist er, and Roger Chennells, a lawyer, wrote that who specializes in genomics at the University the Nature study failed in this regard by only of California, Santa Cruz. getting “informed consent from the indige- Globally, indigenous peoples are so nous individuals who participated.” culturally distinct from one another that a Not everyone agrees that collective single understanding of a community won’t consent can or should be a requirement for resonate with everyone. Finding a method all genetic studies. For instance, de Vries for data collection “that crosses all indigenous said, “it depends what sort of community groups is going to be really hard,” said Vanes- we’re talking about,” drawing a contrast sa Hayes, a geneticist at the Garvan Institute between small, rural, communities and larger of Medical Research and the University of populations spread across several cities or Sydney in Australia who conducts fieldwork countries. “If we’re talking about the entire in South Africa. “Because, straightaway, that’s Yoruba population, who would you even assuming all indigenous people are the same.”

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Without common ground, scientists must do the hard work of understanding each unique community. As Hayes put it, “every group that you work with, you have to respect that group, and take the time to understand what is important in that group.”

Hayes was one of the authors of the COMMONS STAEHLER/WIKIMEDIA 2010 Nature study on the San, and she was responsible for obtaining consent, gathering samples, and discussing the results with the community. While Steenkamp and Chen- nells suggested the researchers were hasty in their data collection and ignored governance structures, Hayes countered that, at the time of the study, she’d already been working in these communities for more than a decade and they were working directly with govern- ment agencies. She’d been in contact with the A San man in Namibia adds finished giraffe bone to the arrow shaft made of hard grass. Working Group of Indigenous Minorities in Southern Africa, or WIMSA — the NGO entists have the necessary time and resources. which would eventually criticize the study There is no easy way to choose which — before it began. But, she said, “when I organizations to deal with, especially when went back to the community and asked if there are internal disagreements about repre- they knew who WIMSA was, they said ‘no.’ I sentation. Or, as Reardon put it: “The folks asked them if they wanted WIMSA to repre- that are trying to democratize the science are sent them, and they said, ‘Hell no.’” going to have the same problem as the people (As an organization, WIMSA is current- who were attempting to treat it as ‘We’re just ly being restructured. The South African going to go out and get these groups, and San Council, which now represents the San study them from a scientific perspective.’” communities of South Africa, declined an Although the repeated controversies interview, citing a requirement for financial surrounding research and indigenous groups compensation and a signed contract.) may have slowed their inclusion in genetic Hayes followed the principles of collec- science, the researchers this author spoke tive consent, she said, just at a lower level with said ensuring these concerns are heard than formal institutions like WIMSA or the and addressed is a vital part of the work. San Council: “Their decision was made as a Indigenous groups are demanding a greater group. They are the group, they are the band, say in research that concerns them, whether they are the family.” She added, “No one can under the All of Us program or conducted represent them that is not them.” by individual researchers in Africa. Resolving The difficulties in defining a group make the ethical ambiguities is no easy task, but, as collective consent even more challenging. Hayes asked: “Why should it be easy?” In the clearest of circumstances, where This article was originally published on an established organization exists, approval undark.org. processes can be difficult to navigate and can take months. But within some indigenous Adrian Pecotic (adrianpecotic@zoho. and minority groups, issues of representation com) is a freelance writer based in remain controversial. Often, a scientist will Sarajevo. He’s written for the TLS, have to invest a lot of time interacting with Foreign Policy, and NBC Think. He also blogs for Psychology Today. potential subjects in order to judge what consent procedures are appropriate. Few sci-

FEBRUARY 2020 ASBMB TODAY 43 ANNUAL MEETING

JBC/Tabor award winners to speak at annual meeting

By George N. DeMartino

inners of the 2020 Journal of Biological Chem- istry/Herbert Tabor Early Career Investigator WAwards will give talks on April 5 at the American Society for Biochemistry and Molecular Biology Annual Meeting in San Diego. The awards, named for Herb Tabor, who served as JBC’s editor-in-chief from 1971 to 2012, recognize ear- ly-career first authors of standout JBC papers published the previous year for their creativity and scientific excel- Kirstine Lavrsen Febin Varghese Cindy Yang lence. After carefully reviewing nominations from JBC readership, consulting experts in the field and evaluating the quantitative impact of the papers, a committee of JBC associate editors selected six award-winning first authors. “We are very pleased to celebrate these early-career investigators who have authored top-notch papers in JBC that report exciting and significant research,” said Lila Wenchao Zao Manisha Dagar Gierasch, distinguished professor at the University of Massachusetts Amherst and editor-in-chief of JBC. “These awardees are outstanding representatives of the future leaders of biological chemistry.” n Wenchao Zhao, a graduate student at the Institute At the ASBMB annual meeting, five of the six award Rheinische Friedrich-Wilhelms-Universität Bonn, winners will give talks about their research findings, which developed animal models to reveal how missense mu- span a diverse array of topics within biological chemistry. tations of a protein result in pathology. Read more about the five 2020 speakers in the following n Manisha Dagar, a graduate student at Amity Univer- pages. sity Haryana, India, discovered that phosphorylation of HSP90 by protein kinase A is essential for the The JBC/Tabor award winners nuclear translocation of androgen receptor. n Kirstine Lavrsen, a postdoctoral researcher with the n Ayumi Nagashima-Kasahara was a postdoctoral Danish Cancer Society in Copenhagen, identified an scientist at the University of Tokyo when she identified enzyme that converts normal colon into cancerous a transcriptional co-repressor that plays a key role in tissue by attaching sugar to certain cellular proteins. sensing and mediating volatile organic compound sig- n Febin Varghese was a graduate student at Imperial nals in plant cells. Nagashima-Kasahara is on materni- College London when he discovered the molecular ty leave and will present her work at the 2021 ASBMB mechanism by which a bacterial oxidase functions via annual meeting in Indianapolis. its interaction with another enzyme. n Yue (Cindy) Yang was a graduate student at Weill George N. DeMartino (George.DeMartino@ Cornell Medical School when she discovered that dihy- UTSouthwestern.edu) is a professor of physiology at dronicotinamide riboside is a critical regulator of the the University of Texas Southwestern Medical Center and a JBC associate editor. cellular concentration of NAD+.

44 ASBMB TODAY FEBRUARY 2020 JBC/TABOR AWARD Lavrsen finds endless possibilities in PTMs

By Nivedita Uday Hegdekar

hen she was an undergraduate at the University of Co- Sugar-adding enzyme makes Wpenhagen, Kirstine Lavrsen colonic cells cancerous became fascinated by the impact of posttranslational modifications, or Epithelial cancers are char- PTMs, on cellular function. She was acterized by aberrant expression working with Hans Wandall’s group of O-glycans sugar molecules in at the university’s glycomics center, cancerous cells. Addition of these researching the role of glycosylation sugar molecules is mediated by a in cancer and how cancer-associated post-translational modification — changes in O-glycans could be used O-glycosylation — through a large Kirstine Lavrsen to target solid tumors. “So many family of GalNAc transferases, or protein glycosylations are modified GalNAc-Ts. in cancer,” she said. “The research Analyzing transcriptomic and immunohistochemistry data, Hans Wan- possibilities were endless.” dall’s research group found that GalNAc-T6 was the only GalNAc-T that A native of Denmark, Lavrsen was highly expressed in colon cancer and was absent from healthy colon earned her bachelor’s and master’s tissue. To investigate the specific role of GalNAc-T6 in the development degrees in molecular biomedicine of colon cancer, the group used CRISPR/Cas9 to develop isogenic colon from the University of Copenha- cancer cell lines with a knockout/rescue system for GALNT6. GalNAc-T6 gen. Pursuing a Ph.D. in cellular expression was associated with a cancerlike dysplastic growth pattern, and genetic medicine seemed like whereas GALNT6 knockout cells showed a more normal differentiation the natural and best next step, she and phenotype. Mass spectroscopy identified that GalNAc-T6 targeted a said, and she continued her doctoral subset of proteins involved in cell-cell adhesion. research in Wandall’s laboratory. This study highlights the importance of a post-translational modifica- For her Ph.D., Lavrsen re- tion in cancer development, and its publication in the Journal of Biologi- searched the role of O-glycosylation cal Chemistry earned Kirstine Lavrsen a Journal of Biological Chemistry/ in colorectal carcinogenesis. She Herbert Tabor Early Career Investigator Award. identified an important role for a PTM enzyme, GalNAc-T6, in con- version of normal colon tissue into of PTMs in cancer cells will lead to spending time with her young cancerous tissue through its ability improved early diagnostic tools, tar- children. to O-glycosylate a small subset of geted drugs and immunotherapies. This is an exciting time in cancer proteins. She then used antibodies PTMs continue to fascinate research, she said, and she is optimistic targeting cancer-specific O-glycans Lavrsen. She now works as a post- about where the research will take her. to distinguish between cancerous and doctoral researcher in Marin Barisic’s normal tissue and to induce can- lab at the Danish Cancer Society, in- Nivedita Hegdekar (nivedita. cer-specific cell death. vestigating the role of another PTM, hegdekar@umaryland. “Recent findings show that detyrosination of tubulin, during edu) is a graduate student at the University of Maryland PTMs have been playing a bigger cancer development. working toward a Ph.D. in role in cancer development than Lavrsen appreciates the analytic biochemistry and molecular biology and an M.S. in earlier thought,” Lavrsen said. She and creative blend of research work. patent law. Follow her on hopes that further understanding When not in the lab, she enjoys Twitter @NiveditaHegdek1.

FEBRUARY 2020 ASBMB TODAY 45 ANNUAL MEETING

JBC/TABOR AWARD Varghese roams from forests to enzymes

By Guananí Gómez–Van Cortright

hen Febin Varghese is not puzzling out enzyme struc- Protecting nitrogenase Wtures in the lab, there’s a good chance he’s out on the trail. Nitrogen is abundant in the “When I was really young, I used atmosphere yet scarce in the to watch a lot of documentaries on biosphere; only prokaryotes are National Geographic and Discovery equipped with the enzymes nec- Science and such,” Varghese said. essary to fix atmospheric nitrogen “We would watch as a family, and I into bioavailable forms. To subvert think that’s where it all started.” this limitation and boost crop pro- This early interest in the natural duction, researchers are studying Febin Varghese world sparked Varghese’s lifelong nitrogen-fixing enzymes with the study of biology both out in the goal of genetically engineering crop plants that can express nitrogenase of forest and deep inside molecular their own. structures. “I love being in the lab, Iron-only nitrogenase, encoded by fewer genes than other nitro- but I try my best to take breaks,” gen-fixing enzymes, is a promising candidate for this endeavor. However, he said. “Something about being in it becomes inactive in the presence of oxygen; this barrier must be over- the mountain air, up in the clouds, come for it to be expressed functionally in crops. stepping away to clear your head, is To explore how the structure of iron-only nitrogenase responds to really refreshing.” oxygen, Varghese and colleagues at the James W. Murray lab at the After earning a doctorate at department of life sciences at the Imperial College of London investigated Cambridge University, Varghese em- the structure and oxygen-reducing role of Anf3, a protein associated with barked on a 15-month backpacking nitrogenase function. journey throughout Southeast Asia, By characterizing the crystal structure of Anf3 at atomic resolution, Australia and New Zealand. the team saw that its heme and flavin adenine dinucleotide cofactors were He then returned to the world unexpectedly close to each other. of metalloenzymes as a postdoc at “The structure itself was a surprise,” Varghese said. “We knew (Anf3) the Imperial College of London, had a heme and an FAD cofactor, but that they were so close together where researchers in his lab peered and that there was a cooperative effect was unexpected.” into the mystery of how associated Further experiments suggested that electron transfer between the two proteins protect nitrogen fixation in cofactors contributes to Anf3’s ability to reduce oxygen, thus protecting the presence of oxygen. The project iron-only nitrogenase from being inactivated. Anf3 protein is a promising combined Varghese’s interest in ener- candidate for enhancing functional nitrogenase in aerobic environments. gy-conserving metalloenzymes with the potential for long-term environ- mental applications — an excellent fit. For his contribution to the study expecting it at all,” he said of the Guananí Gómez–Van as first author on the paper published award. “It’s an honor to be recog- Cortright (guananigvc@ gmail.com) is a recent in the Journal of Biological Chemis- nized, but a lot of people’s work Reed College graduate, try, Varghese won a 2020 JBC/Tabor went into this paper. Collaboration is outdoor educator and science teacher. Award. everything in science.” “I was very surprised, I wasn’t

46 ASBMB TODAY FEBRUARY 2020 JBC/TABOR AWARD Yang follows the science where it takes her

By Elizabeth Stivison

ue (Cindy) Yang grew up in a university environment in her A new pathway to increase Yhome country of China, and cellular NAD+ from a young age she pictured herself as a professor at a university. Her Cindy Yang finds the work in father is a mechanical engineering Anthony Sauve’s lab incredibly excit- professor and her mother is a dentist, ing. The innovative and collaborative and both helped inspire her to seek a environment in the lab allows her life of science, though her inspiration to dive deep into the NAD+ field is also internal. with all its nuance and potential to “I’ve always loved science,” Yang improve human health. Cindy Yang said, “especially biology.” The job of NAD+ is to transfer a After earning a bachelor’s degree hydrogen from one molecule to another. This central activity means that from the Chinese University in NAD+ is a cofactor for over 500 enzymatic reactions in the cell and is Hong Kong, Yang wasted no time in essential to life. Researchers now see that modulating cellular NAD+ lev- continuing her education and moved els can have wide-ranging effects in the cell and in the whole body, such to the U.S. to get her master’s. She as preventing metabolic syndrome and neurodegeneration; it may even chose the University of Nebraska so slow aging in general. This has inspired many clinical trials and patents, she could study with Ji-Young Lee in but with typical compounds that increase NAD+ in the cell, the dosage the nutritional sciences department. required to see any effect is extremely high. Yang was drawn to the lab’s astax- Yang and her colleagues discovered that a new compound, dihydron- anthin work, and she enjoyed Lee’s icotinamide riboside, or NRH, increases NAD+ levels in cultured cells to mentorship so much that when Lee an unprecedented level with a lower dose and in as little as an hour. NRH moved to the University of Con- also appears to act as a precursor to NAD+ through a novel pathway. necticut, Yang followed, joining the While a novel pathway means a lot of work must be done to find out Ph.D. program there and continuing what exactly is happening in the cells, this new work is opening the door her work in the lab. to increasing our understanding of NAD+ metabolism and its effects on During her Ph.D., Yang studied human health and may lead to efficient modulation of NAD+ in the clinic. the health effects of astaxanthin, an antioxidant carotenoid compound found in algae. She thrived in the lab, loving the freedom to follow the science. “Sometimes you go into a lab and everything is established, and postdoctoral fellowship at Weill you just follow and do what every- Cornell Medicine, where she studies Elizabeth Stivison (elizabeth. [email protected]) is one has been doing,” she said. “But NAD+ metabolism in Anthony a postdoc at Columbia when I was in Dr. Lee’s lab, we’d Sauve’s lab and recently was pro- University studying mechanisms of DNA repair have to find what the next step is and moted to instructor. That young girl and a careers columnist for decide for ourselves what to do. It who always saw herself as a professor the ASBMB. was a great experience.” seems to be well on her way, follow- She took these skills into her ing where the science takes her.

FEBRUARY 2020 ASBMB TODAY 47 ANNUAL MEETING

JBC/TABOR AWARD Selenium led Zhao from icy hometown to German hospitality

By Nathalie Gerassimov

enchao Zhao is fascinated by selenium or, more accurate- Tissue-specific stability of key Wly, what happens when it is regulator of selenoprotein lacking. synthesis A trace element in soil, selenium is an essential nutrient for many spe- Selenoproteins, characterized by cies, including humans. Its deficiency the presence of selenocysteine, the is associated with Keshan disease, a 21st amino acid containing seleni- cardiomyopathy first identified in um in its sidechain, are essential to the Keshan county of Heilongjiang human health. Their main roles are province in northeastern China, in the antioxidative response and Wenchao Zhao bordering Russia. Zhao’s hometown thyroid function. Not surprisingly, is Harbin, the capital of that prov- selenoprotein deficiency is associated with cancers, heart disease and ince, a city of more than five million neurodegeneration. people known for cold weather and The biosynthesis of selenoproteins relies on selenocysteine insertion the world’s biggest ice festival. sequence-binding protein 2, or SECISBP2. Human mutations in SE- Keshan disease used to be CISBP2 associate with clinical phenotypes of variable severity. Wenchao widespread in China, especially Zhao’s research, published in the Journal of Biological Chemistry and in Heilongjiang province, before selected for the JBC/Herbert Tabor Early Career Investigator Award, inves- the government started a selenium tigated the effect of two human mutations using mice. supplementation program in the Zhao and his colleagues found that while one mutation behaves like 1970s. Research into the mechanism a null allele, the other shows a different phenotype in the liver and the of selenium action in physiology brain. Specifically, the R543Q mutant of the SECISBP2 protein is unstable remains important, not least because and undetectable in liver but retains residual function in brain. a form of thyroid disease is caused by Zhao’s research contributes to our understanding of why so many dis- mutations in the selenium pathway. eases of ubiquitous proteins affect specific organs, he said. “A mutation Zhao decided to study the may not be equally detrimental in every cellular context, since cellular effect of selenium deficiency using context can affect the stability of that protein.” chickens when he was doing master’s degree research in his hometown. This descriptive research prompted him to seek laboratories studying the to his unfamiliar German life. When playing basketball or soccer with his molecular mechanism of selenium Zhao couldn’t find an apartment friends, Zhao is learning German. action. Ulrich Schweizer’s lab at the right away, he lived at Schweizer’s His favorite and most-used phrase is University of Bonn’s Institute of house for his first month in Bonn. “Alles gut” — all is well. Biology and Molecular Biology was a Zhao is now writing his Ph.D. perfect fit, although Zhao spoke no dissertation and hopes to finish his Nathalie Gerassimov German. degree this spring. He doesn’t have (nathalie.gerassimov@ gmail.com) is a Zhao describes himself as “super firm post-graduation plans; learning postdoctoral researcher lucky” to have Schweizer as his to manipulate sequencing data from at the Carnegie Institution of Washington mentor. In addition to tutoring him his research is a short-term goal. Department of in the lab, Schweizer helps him adapt When not working in the lab or Embryology.

48 ASBMB TODAY FEBRUARY 2020 JBC/TABOR AWARD Dagar dissects a prostate cancer driver

By Alyson Smith

any cancer treatments block hormones that drive tumor cell Targeting molecular chaperones Mdivision and metastasis. These to stop prostate cancer therapies only shrink tumors tem- porarily, however, as cancer cells can Testosterone and related use alternative signaling pathways to androgen hormones act through reduce their hormone dependence. the androgen receptor, which is Drugs that target these pathways stabilized in the cytoplasm by the may halt tumor growth and extend molecular chaperone HSP90. When patient survival. the receptor binds an androgen, Manisha Dagar has uncovered it releases HSP90 and enters the Manisha Dagar the details of a signaling pathway nucleus to regulate gene expression. that drives advanced prostate cancer. Androgens thus direct the development and maintenance of the prostate Dagar has always been interested gland but also drive prostate cancer. in science, especially biology. Her Manisha Dagar and her colleagues knocked down protein kinase A to mother encouraged her to pursue learn how this enzyme affects androgen receptor nuclear entry. They dis- higher education and a research covered that protein kinase A phosphorylates HSP90, causing it to release career. She earned an undergradu- the androgen receptor. The receptor then binds HSP27, a different mo- ate degree in biotechnology, and a lecular chaperone, which helps it enter the nucleus. Once in the nucleus, summer internship at the National the receptor can bind certain DNA regions to turn on genes. Centre for Disease Control in New Blocking protein kinase A activity blocked testosterone-induced Delhi gave her the lab experience she HSP90 phosphorylation, androgen receptor-HSP90 dissociation, andro- needed to pursue a Ph.D. at Amity gen receptor-HSP27 binding, androgen receptor nuclear entry, changes Institute of Biotechnology, Amity in gene expression and increase in proliferation of prostate cancer cells. University in Haryana, India. “By targeting HSP90 phosphorylation by protein kinase A, androgen At Amity University, Dagar de- signaling in prostate cancer cells can be blocked,” Dagar said. “This can cided to study the molecular biology be used as a therapeutic target for treatment of prostate cancer.” of cancer. She joined Gargi Bagchi’s As first author on the paper reporting this research, Dagar received lab where she studies androgens, the a 2020 Journal of Biological Chemistry/Herbert Tabor Early Career male sex hormones, in prostate can- Investigator Award. cer. Previous research revealed that protein kinase A, which phosphor- ylates proteins to change their func- tions, can activate androgen signaling levels in these cells, Dagar could ing cell signaling. Outside the lab, in the absence of hormones. Dagar track how blocking protein kinase she enjoys reading and traveling. and colleagues in the lab discovered A phosphorylation activity changed how this aberrant activity contributes androgen signaling. Her work has Alyson Smith to prostate cancer progression. revealed new drug targets that could (alysonscsmith@gmail. com) is a recent Ph.D. Dagar studied protein kinase A treat advanced prostate cancer. graduate from Scripps function in a cell line derived from Dagar successfully defended her Research in La Jolla, California. Follow her on a prostate cancer patient. After opti- Ph.D. thesis in January. She hopes to Twitter @cellbionerd. mizing protocols to measure protein pursue postdoctoral research study-

FEBRUARY 2020 ASBMB TODAY 49 ANNUAL MEETING

Attending a conference when you don’t have the budget By Bonnie L. Hall, Rebecca Roberts, Julia Koeppe & Paul A. Craig

ttending the American Society closer to the conference center than Pay attention to the vendors. for Biochemistry and Molec- the conference hotel at the same price Sometimes they host workshops that Aular Biology Annual Meeting as a hotel a mile away. If you’re trav- include meals. or any professional conference can eling with a group from your campus Pay attention to workshops that be rewarding but expensive. Here or company, several of you could are part of the meeting. If they start are a few ideas to manage costs, to share the space. at noon, trays of sandwiches or fruit help those professional development Have a roommate (or if you rent might be included. dollars go as far as possible. It might a house, multiple roommates) at the Get out of the conference center be too late to take some of these conference. Some conferences provide for breakfast and/or lunch. Picking steps for the ASBMB meeting in roommate matching services if you up coffee or a sandwich on your way San Diego this April, but keep them are attending alone. to or from the meeting is often sub- in mind for other meetings and for Consider staying with a friend or stantially less expensive than on-site ASBMB 2021 in Indianapolis. relative who lives in the city. food options. Walk a couple of blocks Connect with people from other away to find cheaper restaurants with Registration and other meeting labs or institutions; attendees from shorter wait times (lots of conference costs: multiple groups can stay together to attendees will go to the place across Register by the early-bird dead- reduce costs. the street). line. If you’re not a member of the If you stay at a hotel, ask about host society, consider joining; the Meals: a concierge level for your stay. This reduction in registration costs is often Attend the opening ceremony. might cost a bit more, but it often more than the cost of membership. Often, it includes a buffet of some includes breakfast, snacks, beverages Volunteer. If you help to put on sort. It’s not gourmet food, but it’s and evening hors d’oeuvres. So meal the conference, you might get a par- not bad. Sometimes, there’s even free costs are almost zero. tial or full waiver of your conference beer and wine. Bring a refillable water bottle and fee and maybe some free meals. Look for free food breaks. At hit the water fountain (both in the Apply for travel awards from the many conferences, finger foods or airport and at the convention center). host society. These often have early snacks are served in the midmorning Fill your own reusable coffee mug at deadlines, so pay attention. or midafternoon. the meeting coffee/tea breaks. If you’re traveling with infants or Stay somewhere with a refrigera- If you have dinner out with children, ask about free childcare on tor and microwave; stock up at a local colleagues, don’t be shy about asking site (slots are often first-come first- grocery store, then carry your lunch. for a take-home bag for leftovers and served, so plan ahead). You can have fresh fruits, beverages avoiding pricey drinks. Politely ask and sandwiches for less than half of for a separate check (use the excuse of Lodging: what you would pay at a restaurant. institutional reimbursement rules) to Pick a hotel a mile from the con- Remember to bring reusable utensils avoid the dreaded “let’s split the bill.” ference center that includes breakfast. and a plate or bowl to make this If you’ve brought children with The nightly rate will be less because option less frustrating. you, look for restaurants with kids- of the distance, and you won’t have Grocery stores often have hot eat-free options. to pay for one meal each day. buffets where you can get an inex- Consider finding lodgings on pensive dinner plus a few meals to Airfare and transportation: Airbnb, VRBO or HomeAway. You reheat in your room later if you have Purchase your plane ticket well in might find a room or an apartment a microwave. advance. This is especially advisable if

50 ASBMB TODAY FEBRUARY 2020 ASBMB

Bonnie L. Hall (bhall@ grandview.edu) is an associate professor of chemistry and the director of faculty advising at Grand View University, Des Moines, Iowa. Follow her on Twitter @ BonnieHallGV. you’re flying on Southwest Airlines. people with poster tubes at the lug- Rebecca Roberts (rroberts@ You also can use Google Flights to gage carousel — they often are going ursinus.edu) is an associate professor of biology and of track ticket prices. to the same conference and can share biochemistry and molecular Bring good walking shoes and en- ride costs. biology at Ursinus College, Collegeville, Pennsylvania. joy the chance to move while walking If your funding is limited, these Follow her on Twitter @ to the conference site. ideas should help make attending a ProfRRoberts. Look for a hotel on a bus or trol- conference more accessible. We hope ley line or one with a free shuttle. this means we’ll meet you at a confer- Julia Koeppe (julia. If you’ve been invited to speak at ence social or in the airport luggage [email protected]) a nearby university, try to schedule claim area. is an assistant professor of chemistry at the State the visit around the conference time University of New York to combine travel costs. Note: The authors are all mem- Oswego. Research how to get from your bers of the BASIL Consortium home to the airport: catch a ride, (https://basilbiochem.github.io/basil/) use public transportation or find less at various points in our careers as ed- Paul A. Craig (paul.craig@ rit.edu) is a professor of expensive off-site airport parking. ucators and researchers. We are located biochemistry and head of Find out how to get from the on small and large campuses, public the School of Chemistry airport to the hotel; public transpor- and private institutions, primarily un- and Materials Science at the Rochester Institute of tation or a hotel shuttle service will dergraduate institutions as well as those Technology. He won the be the least expensive. Coordinate with M.S. and Ph.D. programs. 2018 ASBMB Award for Exemplary Contributions sharing taxi rides with others to to Education. Follow him reduce costs. Introduce yourself to on Twitter @PaulCraigRIT.

FEBRUARY 2020 ASBMB TODAY 51 PERSPECTIVES

A beginner’s guide to minority professor hires By Michael D. L. Johnson

hat makes a good principal investigator? What change in the percentage of URM biomedical professors at makes a great one? Often, there is a certain mold research-intensive universities. The best solution is to hire W that hiring committees look for in applicants. more URMs, but no unilateral solutions to do so exist or By and large, the first two cutoffs are funding and great they would have been implemented already. Given this in- papers. However, most of us in the professoriate do more formation, here are some things I propose that might help than acquire grants and submit papers. We advise stu- faculty searches increase their URM faculty candidates: dents, sit on committees and teach — all things that are n Recognize and evaluate the intangibles of prospective essential to being a successful professor because they show professors. that you can juggle more than just science. l Talk with and seek advice from minority profes- Many underrepresented minorities, or URMs, take on sors at your institution and ask them what their a lot of those intangible items, not only because people ask background was, how they got recruited and what us to serve in a multitude of areas for the sake of having made them feel more welcome at one place over representation, but because we also want to be that rep- another. Let this be the start of the conversation, resentation. As a postdoctoral fellow looking to be hired not the end. as an assistant professor, I performed service, mentoring, n Identify URM individuals and encourage them to teaching and more. Doing some of these intangible activi- apply for open positions at your university. A selection ties can make it hard to measure current and future success of databases to look through includes: as a principal investigator, and thus, may be a major l Awardees of the Hannah Gray Award from the problem facing URMs looking to join a research-intensive Howard Hughes Medical Institute professoriate. l Awardees of the National Institutes of How are these Health Blueprint Diversity Specialized Predoctoral We advise students, intangible activities to Postdoctoral Advancement sit on committees and scored during a l Awardees of the Ford Postdoctoral Fellowship teach — all things that faculty application l Awardees of the Burroughs Wellcome Fund Post- are essential to being review? When in doctoral Enrichment Program the process are l MinorityPostdoc.org a successful professor they scored? Are l Diversify Microbiology because they show that they scored? l Diversify EEB (Ecologist and Evolutionary Biolo- you can juggle more The argument gists) than just science. against looking l Diversify Immunology deeper into the l Diversify Chemistry pool of applicants n Share job openings within groups and communities is that it takes time, money and lots of effort. Hundreds of that commonly self-identify on social media, applications have to be distilled down to five or so people such as #BLACKandSTEM, LatinxandSTEM and to interview in person. Practicality has to be valued, espe- #diversityinSTEM. cially given the juggling act of being a professor with so n Create university initiatives to encourage or facilitate many things to do. How does an institution that wants to minority hires, such as having a designated slot to hire add more URM faculty do so? a URM faculty. Add to the prestige by naming it after The increasing number of URM doctorates hasn’t been a donor. reflected in URM faculty hires. Despite a 930% increase n Align your department/institution as a place that in URM Ph.D.s since 1985, there has been no significant values diversity by making public statements on your

52 ASBMB TODAY FEBRUARY 2020 PERSPECTIVES JOSE ALJOVIN/UNSPLASH

webpage about diversity. spend money and time for these efforts because, n Require new hires to submit a diversity statement after all, commitment without currency is counterfeit. with their application and make it a part of the de- This article first appeared on the American Society for cision-making process. It helps to surround yourself Microbiology’s website, asm.org with people who value diversity. n Re-evaluate what kind of candidate you are looking for Michael D. L. Johnson (mdljohnson@email. and see if it excluded the people you talked to in the arizona.edu) is an assistant professor in the first bullet point. department of immunobiology and BIO5 Institute at the University of Arizona. n Provide URMs with a platform to present their re- search by inviting them to a research seminar. Overall, as an institution, you must be willing to

VIRTUAL ISSUE Cancer jbc.org/site/vi/cancer/

FEBRUARY 2020 ASBMB TODAY 53 Upcoming ASBMB events and deadlines

14 Deadline for ASBMB Outstanding Chapter Award applications 19 Deadline for ASBMB–Deuel Conference on Lipids registration 29 Rare Disease Day

FEBRUARY

National Colorectal Cancer Awareness Month 1 Deadline for Student Chapters Outreach Grant

MARCH 3–6 ASBMB–Deuel Conference on Lipids meeting

World Parkinson’s Awareness Month 4–7 2020 ASBMB Annual Meeting held in conjunction with

APRIL Experimental Biology 25 World Malaria Day

PROMOTING RESEARCH OPPORTUNITIES FOR LATIN AMERICAN BIOCHEMISTS

The Promoting Research Opportunities for Latin American Biochemists (PROLAB) program allows Latin American graduate students and postdoctoral fellows to spend up to six months in U.S. or Canadian laboratories.

Apply at asbmb.org/pabmb

54 ASBMB TODAY FEBRUARY 2020 www.mcponline.org

Your technological advances belong here.

Molecular & Cellular Proteomics is the home for papers describing new, impactful technologies that make substantial contributions to the understanding of proteomics. The editors of MCP are eager to publish papers about automation of sample preparation protocols, micro-scaling approaches, targeted protein identification and quantitation methods, and other technological advances. Get your work noticed by publishing with MCP.

FEBRUARY 2020 ASBMB TODAY 55 56 ASBMB TODAY FEBRUARY 2020 CLASSIFIEDS

Tenure Track Faculty Positions Postdoctoral Fellow Vanderbilt University, Yale, New Haven, Tennessee, United States Connecticut, United States

The Department of Molecular Physiology & Biophysics (MPB) Postdoctoral positions are available in the Ben Mamoun at Vanderbilt University invites applications for a tenure-track Laboratory at Yale to study the agents of human malaria and faculty appointment. MPB has a long and distinguished scientific babesiosis and their interactions with their mammalian hosts history and currently has 23 primary faculty members with active and arthropod vectors. Ph.D., M.D./Ph.D. and MD candidates research programs studying biophysics, gene regulation, genetics, with strong experience in the fields of cellular, molecular membrane transport, metabolic/endocrine disorders, neuro- biology, genetics and biochemistry are encouraged to apply. science, signal transduction, single-cell biology, and structural Yale University offers a competitive postdoctoral salary, a biology. Applicants must have a Ph.D. and/or M.D. degree and an comprehensive benefits package, and an excellent work outstanding record of scholarly achievement that demonstrates environment. the potential to establish a highly productive and innovative re- https://careers.asbmb.org/jobs/view/postdoctoral- search program. A generous start-up package will be provided to fellow/52892325/ facilitate cutting-edge investigations into fundamentally sig- nificant biomedical research questions. https://careers.asbmb.org/jobs/view/tenure-track-faculty- positions/52487077/

Biology Tenure Track Faculty Postdoctoral Research Fellow IUPUI, Department of Biology, University of Connecticut, Indiana, United States Farmington, Connecticut, United States

The Department of Biology at Indiana University–Purdue Univer- An NIH funded postdoctoral research position is available imme- sity Indianapolis (IUPUI) invites applications for a tenure-track diately in the Weller lab in the Department of Molecular Biology faculty position at the assistant professor level, but appointment and Biophysics at the University of Connecticut School of Medicine at a more senior level is possible for applicants with suitable in Farmington CT. The Weller lab uses biochemical, biophysical experience to begin August 1, 2020. Competitive salary and start- and molecular genetic approaches to study the mechanisms up funds are available. A Ph.D. and postdoctoral experience are and enzymology of DNA replication in Herpes Simplex Virus. HSV required. Applicants must demonstrate the ability to initiate and infects almost 70% of the world’s population, and we have discov- sustain an externally funded program of research, dedication to ered that this important viral pathogen has evolved an unusual effective student mentoring and the ability to teach courses at replication strategy that uses recombination-dependent replica- the graduate and undergraduate levels. Applicants at a senior tion to produce progeny genomes. Our newly funded R01 focuses level must have an established record of research excellence and on a virally-encoded ssDNA binding protein that plays many roles external funding, and a demonstrated commitment to mentoring during viral DNA replication, participating protein-protein inter- students. Candidates able to contribute to teaching in microbiolo- actions necessary for the initiation of DNA synthesis, the cooper- gy and biochemistry are particularly welcome. Research strengths ative binding to ssDNA, filament formation and the annealing of in the department span a range of topics in cellular, molecular, complementary ssDNA. developmental and neuro- biology. https://careers.asbmb.org/job/postdoctoral-research- https://careers.asbmb.org/jobs/view/biology-tenure-track- fellow/52783956/ faculty/52487080/

To see a full list of jobs, please visit asbmb.org/careers ANNUAL MEETING SAN DIEGO | APRIL 4-7, 2020

Community Binds Us Take your place among a diverse network at the 2020 ASBMB Annual Meeting. Attend high-caliber lectures, participate in hands-on workshops and team up with the best minds in your fi eld to strengthen your life’s most important work. Discover your common bond.

Advance registration deadline: March 13