CONTENTS

NEWS FEATURES PERSPECTIVES

2 20 35 EDITOR’S NOTE SIX QUESTIONS MEETINGS Reclaim inspiration FOR THREE PRESIDENTS ASBMB to host symposium on transcriptional regulation 3 26 NEWS FROM THE HILL ADDRESSING THE TANGLED ROOTS 36 The NIH is cruising — WHEN SCIENCE MEETS SICKNESS OF HEALTH DISPARITIES now let’s boost the NSF From a personal disease to a personal research project 4 20 NEWS Three college 38 Member update and university presidents from ESSAY underrepresented Raising a rainbow of scientists groups talk about 10 how a background LIPID NEWS in science serves 42 Back to the (poly)basics — them at the helm. RESEARCH SPOTLIGHT lipin enzyme phosphoregulation From back-porch evolution 12 to learning slang at the bench JOURNAL NEWS 26 12 New insights into treating 38 amoebic keratitis 13 When mitochondria make B cells go bad 14 Sugary secrets of a cancer-related protein 15 Scientists find cellular backup plan for keeping iron levels just right 16 From the journals 13

16 36 WHEN SCIENCE MEETS SICKNESS

FEBRUARY 2018 ASBMB TODAY 1 EDITOR’S NOTE

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Reclaim inspiration By Comfort Dorn OFFICERS COUNCIL MEMBERS Natalie Ahn Squire J. Booker President Victoria J. DeRose Wayne Fairbrother ack when Juliette Bell was a dential tweet. And I have to admit Gerald Hart Rachel Green President Elect Blake Hill chemistry professor, she shared that Coates is right. It’s a perilous her concerns about a lack of thing to be an American of color. Jennifer DuBois Susan Marqusee B Secretary Celia A. Shiffer research support with the new presi- You wouldn’t know that talking to Takita Felder Sumter dent of her university. “That president Juliette Bell and Ashley Oyirifi and Toni M. Antalis JoAnn Trejo Treasurer told me that if I wanted things to the other African American scientists ASBMB TODAY EDITORIAL change, I had to be willing to take a and educators featured in this issue. EX-OFFICIO MEMBERS ADVISORY BOARD leadership role and not just stand by As we enter Black History Month Jin Zhang Rajini Rao and complain,” she said. And Bell Wilfred van der Donk Chair in this most peculiar era, we need to Co-chairs, 2018 Annual Charles Brenner did just that. She became an interim balance all the awfulness of the last Meeting Program Past Chair dean, a dean and then a provost. Now year with some inspiration. So in this Committee Ana Maria Barral she is president of the University of issue, we question three college and Cheryl Bailey Floyd “Ski” Chilton Maryland Eastern Shore. Chair, Education and Henrik Dohlman university presidents about how their Professional Development Peter J. Kennelly After earning an undergraduate lives as black Americans and scientists Committee Beronda Montgomery degree and working in analytical have shaped the way they administer Daniel Raben A. Maureen Rouhi chemistry for a few years, Ashley Chair, Meetings Committee Melissa Vaught institutions of higher learning. That’s Binks W. Wattenberg Warfield Oyirifi realized it was time quite the crucible for leadership, yet Sonia Flores to face the distance and detachment Chair, Minority Affairs they wear their legacy and respon- ASBMB TODAY Committee she felt as a black woman in the field sibility with grace and humility. “I Angela Hopp Susannna Greer of biochemistry. She wrestled with Executive Editor, learned by making a lot of mistakes,” Chair, Public Outreach [email protected] this question in graduate school and Committee says Roy Wilson of Wayne State Uni- Comfort Dorn began to find answers in, of all places, versity, “and learning from mistakes.” Matthew S. Gentry Managing Editor, an elective anthropology class. She is Chair, Public Affairs [email protected] We also talk to experts tackling Advisory Committee now a passionate advocate for scien- John Arnst the tough issues of health dispari- Amnon Kohen Science Writer, tific investigation situated in a larger ties among people of color in this Chair, Publications [email protected] societal context. country, asking them about the role Committee Valery Masterson I recently heard the writer Ta- Designer, of basic researchers in what seems to Lila M. Gierasch Nehisi Coates say in a podcast that, Editor-in-chief, JBC [email protected] be overwhelmingly an issue of poverty Ed Marklin no matter what they say, no white A. L. Burlingame and inequality in the delivery of Web Editor, person would ever really want to be Editor, MCP [email protected] health care. black. I thought back a decade to Edward A. Dennis Allison Frick And we bring you Oyirifi’s imagi- Editor-in-chief, JLR Media Specialist, when Barack Obama was on his way [email protected] native and inspiring essay on diversi- William L. Smith to becoming president and Michele Barbara Gordon fying educational content to attract Editor-in-chief, JLR Obama said she was proud of her Executive Director, and keep more underrepresented [email protected] country for the first time. Though I knew that was a harsh and problem- minorities in scientific research. This piece was submitted to us back in For information on advertising, contact Pharmaceutical atic thing to say, it made sense. I was Media Inc. at 212-904-0374 or [email protected]. proud too, but I wished I could share August, and I’ve been itching to share the pride that was in her heart. At it since then. I’d love to hear your that moment, I thought, it must feel responses. And it may sound corny, so good to be a black American. but please — keep the faith. Now it’s 2018 and Donald Trump www.asbmb.org/asbmbtoday is in the White House, and it feels Comfort Dorn PRINT ISSN 2372-0409 like all the progress that’s been made ([email protected]) is managing in my lifetime and the century that Articles published in ASBMB Today reflect solely the authors’ views and not editor of ASBMB Today. Follow her the official positions of the American Society for Biochemistry and Molecular preceded my birth is in danger of on Twitter @cdorn56. Biology or the institutions with which the authors are affiliated. Mentions of products or services are not endorsements. imploding with each morning’s presi-

2 ASBMB TODAY FEBRUARY 2018 NEWS FROM THE HILL The NIH is cruising — now let’s boost the NSF By Benjamin Corb

ince fiscal 2015, the National from $7.3 billion to $7.4 billion, a 4 the ASBMB’s public affairs staff and Institutes of Health budget percent increase. It is a mistake not to take part in meetings with congressio- S has increased 13 percent, from fund the two agencies proportionally. nal representatives to talk about the $30.3 billion to $34.1 billion. We are Partnerships between the NIH importance of robust federal invest- thrilled to see NIH funding on the and the NSF include the BRAIN ments in science. This year’s Hill Day rise, especially after nearly a decade of Initiative and the Precision Medicine will be April 12. We are accepting flat budgets that, when adjusted for Initiative. Many NIH-funded investi- applications for participants at asbmb. inflation, eroded the NIH’s purchas- gators have received grants by build- org/advocacy/HillDay. ing power by 25 percent. Current ing off NSF-funded basic research. proposals for fiscal 2018 will likely For example, the CRISPR-Cas9 gene Advocacy opportunities lead to another 3 percent increase, editing technology that is breaking As we prepare for the release of so we are cautiously optimistic that ground in the life sciences has its President Trump’s fiscal 2019 budget, members of Congress from both par- roots in NSF-funded research. the Public Affairs Advisory Commit- ties recognize the need for robust and As Congress receives the fiscal tee is launching our first 2018 grass- sustained investment in the NIH. 2019 budget from President Donald roots advocacy campaign. In February Sometimes, though, we wonder Trump and begins its appropriations and March, we ask our members if Congress realizes how the research process, the ASBMB will host a Capi- to take to social media to tell your enterprise works. While the NIH tol Hill briefing to educate lawmak- elected representatives how the presi- wins support, other critically impor- ers on the NSF’s important role in dent’s budget proposal would affect tant science agencies in the govern- supporting and advancing life science your science and your lab. In addi- ment don’t receive the same attention research. This is part of our ongoing work to influence the funding process tion to tweets and Facebook posts, and are in need of funding increases. we’ll create and circulate a petition The National Science Foundation to benefit all our members. In advocating for the NSF, the calling on Congress and the president funds basic biological research, work to provide the scientific community that often builds a foundation for the ASBMB remains committed to fight- ing for a diverse, sustainable and suc- with the investments we need to keep groundbreaking, lifesaving discoveries cessful American research enterprise. the United States the global leader in made at the NIH. The NSF is also the biomedical research and innovation. second highest funder of our mem- Details are at policy.asbmb.org. bers (after the NIH) according to Hill Day recent surveys of the American Soci- It’s that time of year again. The ety for Biochemistry and Molecular Public Affairs Advisory Committee is Benjamin Corb Biology membership. And while the preparing for its annual day of Capi- ([email protected]) is director of NIH budget has grown significantly, tol Hill visits, when scientists from public affairs at the ASBMB. Fol- the NSF budget has not. Since fiscal across the country come to Washing- low him on Twitter @bwcorb. 2015, the NSF budget only has risen ton, D.C., to receive training from

FEBRUARY 2018 ASBMB TODAY 3 NEWS Member update By Erik Chaulk

Three members named Breakthrough Prize winners Don W. Cleveland, Kazutoshi Don W. Cleveland, professor of cellular and molecu- Mori and Peter Walter are among the lar medicine at the Ludwig Institute for Cancer research, winners of the 2018 Breakthrough is being recognized “for elucidating the molecular Prize in Life Sciences. pathogenesis of a type of inherited ALS (amyotrophic The prize was established by a lateral sclerosis), including the role of glia in neurode- CLEVELAND group of technology entrepreneurs, including Google co-founder Sergey generation, and for establishing antisense oligonucle- Brin and Facebook co-founder Mark otide therapy in animal models of ALS and Huntington Zuckerberg, to honor outstanding disease.” scientific achievement in the life Kazutoshi Mori, professor at Kyoto University, and sciences, fundamental physics and Peter Walter, professor in the department of biochem- mathematics. istry and biophysics at the University of California, San MORI The Breakthrough Prize in Life Francisco, both are being honored “for elucidating the Sciences has been awarded since 2013 unfolded protein response, a cellular quality-control and honors contributions to under- system that detects disease-causing unfolded proteins standing living systems and extending and directs cells to take corrective measures.” human life, including one prize that specifically acknowledges research on Each of the winners will receive a $3 million prize, WALTER neurological diseases. the largest individual monetary award in science.

Oppenheimer wins found in many organisms, regulates federal research funding and members the assembly of structural proteins of FASEB societies, including the FASEB BioArt prize that form a cell’s cytoskeleton. American Society for Biochemistry David Oppen- Through the BioArt competition, and Molecular Biology. heimer is a winner FASEB aims to share the beauty and Oppenheimer’s video and the other in the 2017 BioArt breadth of biological research with the winning BioArt entries can be seen at contest, sponsored public. Contestants include investi- faseb.org. by the Federation gators, contractors or trainees with OPPENHEIMER of American Societ- Kinzy now VP for research ies for Experimen- tal Biology. Oppenheimer’s winning at Western Michigan entry is a video showing the protein Terri Goss profilin twisting and wiggling. Kinzy has been Oppenheimer, a cell biologist and appointed as the geneticist, is an associate professor new vice president in the department of biology at the for research at University of Florida. He is also a KINZY Western Michigan creator of the Undergrad in the Lab University. blog, where he writes in his biogra- Kinzy was most recently vice presi- phy, “My current research interests are dent for research at Rutgers, where focused on the proteins that control she oversaw the offices responsible for COURTESY OF FASEB cytoskeleton dynamics, and how this David Oppenheimer’s winning video shows the research and sponsored programs. In influences plant cell shape.” Profilin, protein profilin twisting and wiggling. her new role, she will help main-

4 ASBMB TODAY FEBRUARY 2018 In memoriam: Milton M. Weiser Milton M. Weiser, former chair of the gastroenterology department at Buffalo General Medical Center, passed away in December at age 87. He had Parkinson’s disease. Weiser was born in Detroit, the son of eastern European immigrants. He earned his undergraduate degree in chemistry from Wayne State University before attending the University of Michigan Medical School, where he met his wife, Helen Freedman. Weiser completed a fellowship in molecular biology at Albert Einstein College of Medicine. He then worked at Massachusetts General Hospital in Boston and led the Harvard-Massachusetts Institute of Technology Health Sciences Program. In 1978, Weiser joined the University of Buffalo as a professor of medicine and biochemistry. He also served as head of research at Buffalo General. A talented artist, Weiser became one of the first tenants in the Buffalo

COURTESY OF THE BUFFALO ARTS STUDIO Arts Studio after he retired in 1998. An artist as well as a scientist, Milton M. Weiser Weiser is survived by his wife, two sons, a daughter, a brother and five painted this self-portrait. grandchildren. tain and develop WMU’s research as well as served as mentors to other Born Dec. 6, 1916, in Kidder- initiatives. women in science. Winners receive an minster, England, Smith moved In 1995, Kinzy joined the faculty honorarium, and Maquat will deliver to Canada after World War I. He at Rutgers, where she was a profes- a lecture and be a mentor to Vander- attended the University of British sor of biochemistry and molecular bilt Prize Scholars. Columbia, obtaining his undergradu- biology and pediatrics. Her research Maquat is highly regarded for ate degree in 1939 and his gradu- her research on RNA metabolism in specializes in the areas of gene expres- ate degree in 1941. In 1950, Smith sion, protein synthesis and drug human disease. She is the founding earned his Ph.D. in biochemistry development. director of the Center for RNA Biol- from the University of Toronto. Kinzy is a member of the American ogy at the University of Rochester. Society for Biochemistry and Molecu- In 2003, Maquat founded and has Smith worked at Defense Indus- lar Biology’s political affairs advisory since served as chair of the Graduate tries Limited from 1941 to 1945. He committee. Women in Science program, which later served as a lecturer in the depart- She assumes her new role at WMU provides professional aid and develop- ment of chemical engineering at the in the spring 2018 semester. ment for all graduate women at the University of Toronto and worked at university. Canada’s National Research Council. Rochester’s Maquat wins Maquat will be honored in In 1966, Smith joined the Univer- November and will speak as part of sity of Western Ontario as a professor the Flexner Discovery Lecture Series. Vanderbilt Prize in the biochemistry department. He Lynne Maquat, remained at the university until retir- professor of bio- In memoriam: ing in 1982 as a professor emeritus. chemistry and bio- David Burrad Smith Smith spent much of his career physics at the Uni- studying proteins, including sig- David Burrad versity of Rochester nificant research on the structure of MAQUAT Smith, a former School of Medicine hemoglobin. and Dentistry, has professor in the Smith and his wife, Dorothy West- received the 2017 Vanderbilt Prize in department of lake, were married for nearly 64 years biomedical science. biochemistry at Established in 2006, the Vanderbilt SMITH the University of before she passed away in 2005. They Prize recognizes female scientists who Western Ontario, passed away in July had three children, Stephanie, Janet have contributed significant research at the age of 100. and Duncan.

FEBRUARY 2018 ASBMB TODAY 5 In memoriam: doctoral degree from the Ohio State initiatives. He oversaw the univer- University. sity’s contract to manage Oak Ridge David Millhorn Millhorn was a professor in the National Laboratory and helped plan David Millhorn, department of physiology at the Uni- and develop the UT Cherokee Farm senior vice presi- versity of North Carolina at Chapel Innovation Campus. Hill and then served as director of dent emeritus at He is survived by his wife, Sherry, the Genome Research Institute at the University of and his three daughters, Amy, Emily the University of Cincinnati before Tennessee, passed and Lauren. returning to the University of Tennes- MILLHORN away in December. see in 2005. He was 72. Millhorn joined UT as vice presi- A native of Chattanooga, Mill- Erik Chaulk ([email protected]) dent for research and later assumed horn received his bachelor’s degree is a peer-review coordinator and the additional role of executive vice digital publications web specialist from the University of Tennessee at president; he was instrumental in at the ASBMB. Chattanooga. He later earned his developing the university’s research

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Rodger de Miranda, San Jose State University Thomas Niehaus, University of Florida Xiaojun Wang, Chinese Academy of Agricultural Sciences Jinsu An, Korea University of Science and Technology Pragyan Rath, Jawaharlal Nehru University Brandon Hannay, Université de Moncton Rebecca Hayes, Trinity University Salimeh Mohammadi, National University of Malaysia Saumitra Pitake, North Carolina State University Lisa Yoder, Allegheny College Mohamed Moustafa, Alexandria University Maria Petrillo, National Institute of Environmental Dandan Liu, Georgia State University Health Services Po-Yuan Chang, National Taiwan University College Robert Van Sciver, Eastern Virginia Medical School of Medicine Neill Kim, Texas Tech University Viplendra Shakya, University of Utah Christopher Chang, Taipei American School Gage Rowden, Texas Tech University Vroniqa Faustino, Mount Saint Mary's University Khushboo Bafna, University of Tennessee, Knoxville Jordan Munroe, Boise State University Maria Newhardt, Oklahoma Medical Research Robert Elliott, University of New England Rachel Lent, Towson University Foundation Marissa St. George, James Madison University Sofia Brunet, University of Gothenburg Yap Ching Chew, Zymo Research Corporation Jillian Baker, Towson University Aya Mizuike, University of Tokyo Ashley Scott, Mayo Clinic Anthony Sperber, Texas A&M University Blanca Quiñones-Díaz, University of Puerto Rico, Fahed Elian, University of Alberta Medical Sciences Campus Kamel Alkhatib, University of Arkansas Elizabeth Dreskin, Bio-Rad Laboratories Kendra Oliver, Vanderbilt University Medical Center Jesica Jones, La Sierra University Vihas Vasu, Maharaja Sayajirao University of Baroda Miosotis Alicea-Delgado, University of Puerto Rico, Linkang Zhou, Tsinghua University Sanjay Dey, University of Delhi South Campus Río Piedras John Frangos, La Jolla Bioengineering Institute Xikai Cui, Georgia State University Auston Larratta, Saint Leo University Lishann Ingram, University of Georgia Oluchukwu Okonkwo, University of Pennsylvania Jackson Thompson, Virginia Polytechnic Institute Bing Liu, University of Minnesota Natalie Minkovsky, Community College of Baltimore and State University County , Puerto Rico IDeA Network of Gabriela Asencio Bryan Cobo, University of Puerto Rico, Río Piedras Biomedical Research Excellence Matthew Eddy, The Scripps Research Institute Melanie Wehmöller, Heinrich Heine Universität Andres Lopez-Rivas, University of Puerto Rico, Río Bidyadhar Das, North-Eastern Hill University Piedras Roberto Adachi, University of Texas MD Anderson Eleanor Vane, University of Washington Cancer Center Brian (Byounghoon) Hwang, Promega Corporation

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Ryan Lumpkin, University of California, San Diego Elena Posse de Chaves, University of Alberta Wondong Kim, Massachusetts General Hospital and , University of Colorado Boulder Stony Brook University Harvard Medical School Adrian Ramirez Alexander Spirov, Samantha Cohen, San Diego State University Linda Omer, University of Louisville Yiling Bi, University of Utah Brittney Wyatt, Marquette University Alexander Jones Kaushik Ragunathan, University of Michigan Meredith Haverly, Providence College Ana Zambrana, University of the Republic (Uruguay) Kasia Smolinski, University of Arizona Abhinav Adhikari, Southern Illinois University, Cyril Anyetei-Anum, College of William & Mary Brenda Medellin, University of Texas at Austin Carbondale Chandrima Ghosh, University of Wisconsin– Qian Wang, University of Alberta Suhas Rao, Stanford University Milwaukee Walter Drake, University of Delaware Jason Yun, University of California, Santa Barbara Rheem Medh, California State University, Northridge James Yurkovich, University of California San Diego Surendra Reddy Punganuru, Texas Tech University Mohammad Anwar Hossain, Texas Tech University Viviana Sarmiento, Universidad Autónoma de Baja Health Sciences Center , University of California, San Diego California Norman Huang Shogo Nakano, University of Shizuoka Jett Ballou-Crawford, Southern Methodist University Soumyadip Sahu, National Institute of Environmental Stephanie Cabarcas-Petroski, Pennsylvania State Health Sciences Rebecca Moore, San Jose State University University, Beaver Keri Ngo, Boston University Suzannah Miller, University of Colorado Erin Gorrell, Kent State University Vanessa Torres Gutierrez, University of Puerto Rico Shreya Mukhopadhyay, North Dakota State Jillian Breault, James Madison University University Kasi Holcomb-Webb, Southern Methodist University Sreemoyee Chakraborti, Centre of Biomedical Shaun Gaskin, La Trobe Institute for Molecular Mette Soendergaard, Western Illinois University Research Science Jason Geohring, University of Colorado Anschutz Jie ning Li, National Cheng Kung University , AgResearch Medical Campus Wayne Young Zhiyuan Lou, University of Maryland, College Park Thomas Whitlow, Marshall University Terrin Manes, University of Colorado Anschutz Carla Quinones, University of Puerto Rico, Río Medical Campus Emma Borgeson, University of Gothenburg Piedras Adam MacNeil, Brock University Boris Zinshteyn, Johns Hopkins/Howard Hughes Payel Mondal, University of Illinois at Urbana– Medical Institute Yolanda Huang, Harvard University Champaign Priscilla Salcedo, California State University, Swathi Dantuluri, University of Florida Anmol Singh, Barrow Neurological Institute Northridge Michael Yousef, Brock University Yetunde Adegbite, University of Liverpool Xzaviar Solone, Kennesaw State University Lawrence Kazak, McGill University Gursev Dhaunsi, Kuwait University Rekha Srinivasan, Case Western Reserve University Laura Miller Conrad, San Jose State University Alexander 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University of Puerto Rico Mostafa Waly, Sultan Qaboos University Ekamol Tantisattamo, University of California, Irvine School of Medicine Michael Freeman, University of Minnesota John Ladbury, University of Leeds Abimbola Aro, University of Pretoria Steven Guard, University of Colorado Boulder Ayatun Nesa, Dhaka University Daniel Goldman, Johns Hopkins School of Medicine Beverley Rabbitts, National Heart, Lung, and Blood Jason Tucker, North Central State College Kellie Lemoine, University of California, San Diego Institute Deena Small, University of New England Lee Limbird, Fisk University Roushu Zhang, University of Maryland, College Park Vincent Shaw, Michigan State University Seema Irani, University of Texas at Austin Soumi Ghosh, University of Michigan, Ann Arbor Erin Seifert, Thomas Jefferson University Palanikumar Manoharan, University of Cincinnati Alexandra Peterson, Augustana University Zachary Steinhart, University of Toronto Balaji Nagarajan, Virginia Commonwealth University Erica Bien, Augustana University John Patton, Des Moines University Victoria Haak, Austriaco Research Lab Davina Sin, California State University, East Bay Avery Selberg, Augustana University Nadia Ayala-Lopez, Yale University Brandon Tran, Southern Methodist University Robert Levenson, University of California, Santa Christena Cadieux, U.S. Army Medical Research Sydney Kreutzmann, Augustana University Barbara Institute of Chemical Defense Kembra Albracht-Schulte, Texas Tech University Tyler Eck, Montclair State University Kelly Culhane, Yale University Rashid Riboul, California State University, East Bay Carrie Olson-Manning, Augustana University Pamela Garcia, Florida International University Mallika Asar, Western Illinois University

FEBRUARY 2018 ASBMB TODAY 7 WELCOME, NEW ASBMB MEMBERS

Tamana Yousof, McMaster University Shashi Singh, Jawaharlal Nehru University Qi Ye, Northeastern University Stephane Angers, University of Toronto Rishu Tiwari, Indian Institute of Technology Bombay Aaron Roberts, Marshall University Xin Zhang, Pennsylvania State University Christopher Sue, University of California, Los Nicholas Saba, University of Connecticut Health Angeles Center Colin Johnson, Oregon State University Joshua McDonald, Ohio State University Jessa Kack, Augustana University Adebowale Bamidele, Mayo Clinic Nathan Lewis, University of California, San Diego Tori Leean, Augustana University Janelle Hayes, University of Massachusetts Medical School Shi Yan, University of Veterinary Medicine, Vienna Hirra Arain, Hofstra University Beau Bequeaith, Southern Methodist University Gilles Robichaud, Université de Moncton Henrike Niederholtmeyer, University of California, San Diego Amy Hotchkiss, Northeastern University Siaumin Fung, Vanguard University Swetha Ramadesikan, Purdue University Martina Wallace, University of California, San Diego Ken Liu, Emory University Tahmina Ahmed, Virginia Polytechnic Institute and Ming Fan, University of Guelph Ngoc-Anh Le, Atlanta Research and Education State University Foundation Jennifer Giles, Des Moines University Clinita Randolph, Thomas Jefferson University YU LIU, Pennsylvania State University Eric Eichelberger, Ithaca College Allison Woods, St. Mary's University Rani Menon, Texas A&M University Elisa Palladino, Saint Louis University Noor Kazim, Southern Illinois University, Carbondale Gentry Cork, Washburn University Adrian Franke, University of Hawaii Cancer Center Emily Nakada, University of Vermont Annabella Pauley, Marshall University Charles Richardson, University of Virginia Amber Bakkum, Medical College of Wisconsin Michael Dores, Hofstra University Maryam Raeeszadeh-Sarmazdeh, Mayo Clinic Jonelle White, University of California, Los Angeles Stephen Burley, Rutgers Center for Integrative Emily Taylor, Baylor University Proteomics Research Charles Barlowe, Dartmouth University Suratna Hazra, Biovision Inc. Riley St. Clair, University of Vermont Alicia Dubinski, University of Waterloo Matthew DeMars, University of Michigan Serge Hardy, McGill University Emily Wiseman, Florida Institute of Technology Ginam Cho, Brigham and Women's Hospital Lalage Katunga, Saint Louis University Boontharick Sopontammarak, Texas Tech University Ronald Gary, University of Nevada, Las Vegas Jonathan Weldrick, University of Ottawa Isabel Conde Del Moral, University of Puerto Rico, Bryan Murillo, University of Colorado Boulder Río Piedras Xinru Wang, Brown University Emily Haynes, Purdue University Leandrew Dailey, Fort Lewis College Nina Pipalia, Weill Cornell Medicine Vidyani Suryadevara, University of Illinois at Chicago Karina Luiza Dias Teixeira, University of Virginia Mateusz Stochelski, Purdue University Derek van Pel, University of British Columbia Clinton Taylor, University of Texas Southwestern Loretta Yang, Lectenz Bio Medical Center Shantá Hinton, College of William & Mary Crystal Archer, University of Texas Health Science Austin Reuter, University of Wisconsin–Madison Garrett McCormick, Marshall University Center at San Antonio Kristen Johansen, Iowa State University Alyson Miller, Texas A&M International University Surbhi Verma, University of Utah Supriyo Ray, University of Texas at El Paso Aidan McKenzie, University of Wisconsin–Madison Stacey Wardenfelt, Stevenson University Madhu Dhar, University of Tennessee Victoria Reyes, Texas A&M International University Lauren Ebersol, Pennsylvania State University Caleb Trujillo, Michigan State University Peter Fung, NanoTemper Technologies Brian Nguyen, Northeastern University Asif Shajahan, University of Georgia Guang Song, Johns Hopkins School of Medicine Christopher Parker, The Scripps Research Institute Xin Zhou, University of California, San Diego Jenifer Winters, Northeastern University Zahra Ghalamkari, Humboldt Universität zu Berlin Opher Kornfeld, Stanford University Shaima Patangia, Northeastern Illinois University Megan Showalter, University of California, Davis Abhisek Mukherjee, University of Texas Health Kamariah Ibrahim, University of Malaya Alexey Silakov, Pennsylvania State University Science Center at Houston Nairuti Patel, California State University, Long Beach Brady Goulden, University of Pittsburgh Siavash Mashayekh, University of Delaware Cornelius Funk, John Brown University Giovanna Ghirlanda, Arizona State University Blanca Rodriguez, Duke University Paula Lemons, University of Georgia Matthew Escobar, California State University, San Zachary Wilson, University of Colorado Boulder Marcos Jessica Hill, Tennessee Technological University Elfrieda Ayaydin-Fodor, Biological Research Centre Jianqiang Wu, Chinese Academy of Medical Sciences, of the Hungarian Academy of Sciences Attia Mohamed, Radford University Peking Union Medical College , Rhode Island College Jacob Weber, Kansas State University William Holmes Jacob Crow, Boise State University , Eastern Illinois University Maria Sosa Ponce, University of Calgary Shankar Gurung Aindriu Maguire, Brock University Jason Ear, University of California, San Diego Rachel Massalee, Towson University Anne Ojo, St. Mary's University Aditi Makhija, University of Delaware Sarah Hurst, University of Arizona Anna Schmoker, University of Vermont Matthew Vore, Sonoma State University Shaik Rahaman, University of Maryland Lauren Bates, Florida Institute of Technology Katherine Davis, Princeton University Jeffrey Cameron, University of Colorado Boulder Ramya Sridharan, Weill Cornell Medical Cory Root, University of California, San Diego Marcello Manfredi, Università degli Studi del Piemonte Orientale Fatima Mossolem, St. John's University Judy Kim, University of California, San Diego

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Andraous Hani Saba, University of Puerto Rico, Río Daniela Du Quesne, Florida International University Joyonna Gamble-George, University of Florida Piedras Mingming Sun, University of Wyoming TC Stevenson Keller, University of Virginia Matthew Tillman, Emory University Latifa Elantak, Centre National de la Recherche Madison Clark, University of Gothenburg Nicole Roy, AgResearch Scientifique Benjamin Zalisko, University of Chicago Jhumku Kohtz, Northwestern University Jiangting Hu, Medical University of South Carolina Steven Matzner, Augustana University Kevin Schneider, University of California, Irvine Liyang Zhao, University of North Carolina at Chapel Emerald Ellis, Montana State University Hill Charlotte Phillips, University of Missouri Kelly Li, Mary Baldwin University Lizette Vargas, Smith College Yuanyou Wang, Texas A&M University Justin Duran, University of Texas Río Grande Valley Daniel Lee, Indiana University School of Medicine Jian-Huan Chen, Wuxi School of Medicine, Jiangnan Guilherme Guimaraes, Hampden-Sydney College University Alessandro Senes, University of Wisconsin–Madison Jan Schwarz, Ibidi GmbH Deepali Bhandari, California State University Long Sarath Pathuri, University of California, Santa Beach Barbara Shraddha Rane, University of Manchester Jennifer Bridwell-Rabb, University of Michigan Prerna Sharma, Arizona State University Benita Sjogren, Purdue University Matthew Sazinsky, Pomona College Ellen Sidransky, National Human Genome Research Siddharth Prabhu, Santa Cruz Biotechnology Institute Elizabeth Kolar, Boston University Lorraine Davis, Seattle University Qian Chu, Salk Institute for Biological Studies Chandi de Silva, University of Arizona Jianke Li, Chinese Academy of Agricultural Science Shrikant Barot, St. Johns University Michael Winslow, University of San Francisco Elliot Shelton, Virginia Polytechnic Institute Wesley Kao, California Polytechnic State University, Jun Yin, Georgia State University Manely Rashedan, Los Angeles Department of Water San Luis Obispo and Power Harry Davis, University of Hawaii Andrea Rivera, University of Puerto Rico at Mayagüez XinXiang Lim, National University of Singapore Kambiz Hamadani, California State University San Xin Liu, Johns Hopkins University Marcos Linqi Zhang, Tsinghua University School of Medicine Patrick Chen, San Francisco State University Curtis Thorne, University of Arizona Jaime Jensen, Vanderbilt University Medical Center Kwangbeom Hyun, Korea Advanced Institute of Thirumalai Selvi Ulaganathan, University of , Keck School of Medicine of the Science and Technology Karly Nisson Saskatchewan University of Southern California Behzad Varamini, Biola University Sunil Surapaneni, National Institute of Joshua Lykins, University of Kentucky Pharmaceutical Education and Research Shaquanna Young, Kennesaw State University David Antonetti, University of Michigan Rebecca Parr, Stephen F. Austin State University Ramon Sun, University of Kentucky Ina Mishra, University of North Texas Health Science Kerald Gonzales, Northeastern Illinois University Mariana Acuna, Weill Cornell Medical College Center Nicole DiPietrantonio, Elon University Adaugo Ohandjo, Morehouse School of Medicine Pei-Ju Liu, State University of New York Upstate Medical University Pascal Bernatchez, University of British Columbia Evan Powers, The Scripps Research Institute Joe Lutkenhaus, University of Kansas Medical Center Erin Morgan, University of California, Santa Barbara Barbara Walenkiewicz, College of St. Scholastica Hong Wang, North Carolina State University Diana Castaneda, California State University, Los Bryan Gibson, University of Texas Southwestern Angeles Medical Center Saruar Alam, University of Dhaka Rabiatul S M N Mydin, Universiti Malaysia Sabah Sai Santosh Babu Komakula, Rutgers University Tajreen Islam, University of Dhaka Joseph Genereux, University of California, Riverside George Bloom, University of Virginia Md. Hasan, University of Dhaka Rebekah Napier-Jameson, Stephen F. Austin State Anne Robinson, Washington University in St. Louis Xiuli Zhang, University of Chicago University Pedro Pozo, University of North Carolina at Chapel Ping Song, Georgia State University Weihan Li, University of California, San Francisco Hill Sarah Fritz, National Heart, Lung, and Blood Huong Nguyen, University of California, San Diego Juan Fuxman Bass, Boston University Institute Alexander Petrenko, Shemyakin-Ovchinnikov Robert Muterspaugh, Eastern Michigan University John Whitney, McMaster University Institute of Bioorganic Chemistry Alejandro Oviedo, Texas State University Soumaya El Herry, National Institute of Applied Hashim Aljohani, University of Cincinnati Sciences and Technology Rubina Tuladhar, University of Texas Southwestern Heribert Hirt, King Abdullah University of Science Medical Center Ryan Bockoven, Texas A&M University and Technology Rajendra Prasad, Amith University Haryana Subramaniam Pennathur, University of Michigan Shere Byrd, Fort Lewis College Oaklee Abernathy, Fort Hays State University Ameen Homayoon, Brown University Atoosa Samani, University of Utah Mihwa Lee, La Trobe University Rei Narikawa, Shizuoka Sara Biela, Sullivan College of Pharmacy Zachary Maben, University of Massachusetts Hannah Wolf, Texas Tech University Health Sciences Chao Xu, University of Science and Technology of Medical School Center School Of Pharmacy China Erin Jackson, University of Delaware Roseata Zonouzi, Islamic Azad University Linpei Zhang, Beijing Normal University Aaron Snoberger, West Virginia University David Andreu, Pompeu Fabra University Tianeaka McClendon, University of North Texas Leonardo Tanaka, University of São Paulo Dania Saleh, Kent State University Kaushalya Amunugama, St. Louis University Inamul Haque, University of Kansas Medical Center Shiva Shankar Reddy Nimmala, Osmania University

FEBRUARY 2018 ASBMB TODAY 9 LIPID NEWS Back to the (poly)basics — lipin enzyme phosphoregulation By Salome Boroda & Thurl Harris

lycerolipid synthesis occurs episodes of fever and inflammation in the ability of lipin 1 to associate with, largely in the endoplasmic the bones and skin. At the molecular and act against, dianionic PA (2). G reticulum, or ER. Almost all level, a series of studies has demon- However, the activities of lipins 2 and the enzymes involved in making strated a complex regulation of the 3 are not affected by their phosphory- glycerolipids are embedded in the lipin family that is tied intimately to lation state (3, 4). Why such a stark membranes of the ER. The exception their phosphorylation state and the difference in molecular regulation of is a family of enzymes called lipins, chemical properties of PA (1-4). enzymes that catalyze the same reac- which dephosphorylate phosphatidic The substrate of lipins can exist tion? Perhaps the answer lies within acid, or PA, to generate diacylglycerol in two electrostatic forms: it is either lipins themselves. in the penultimate step of glycerolipid monoanionic (-1 charged) or dian- All lipins contain a polybasic synthesis. ionic (-2 charged) (5). When the domain, or PBD, a short nine-amino Lipins are soluble proteins that membrane pH rises or when PA is in acid sequence composed of lysines can be found in the cell cytosol but proximity to hydrogen bond donors and arginines that is responsible for can move to the ER membrane to — such as phosphatidylethanol- lipin association with PA (6). The pre- perform their function. This family amine (PE) — it exists as a dianionic cise sequence and number of lysines of enzymes consists of three members compound. All lipin family members versus arginines varies between the known as lipins 1-3. Genetic studies preferentially associate with dian- lipins. Recent work has revealed that have shown that increased levels of ionic PA; this can be observed as an the unique PBD of lipin 1 may be the lipin 1 in the fat tissue of transgenic increase in lipin activity and associa- reason it is subject to regulation by mice can improve glucose homeosta- tion with PA in the presence of PE its phosphorylation (phosphoregula- sis, and genetic mutations in human (2-5). And while it has been known tion) (4). The evidence for this came lipins 1 and 2 have been associated that the lipins are highly phosphory- from studies where the lipin 1 PBD with diseases such as rhabdomyolysis, lated, it is now becoming clear how was replaced with the PBD from lipin a rapid destruction of skeletal muscle phosphorylation might affect lipin 3. When the activity of this mutant cells, and Majeed syndrome, a rare enzymatic activity (2-4). Specifically, lipin was measured, it was found condition characterized by recurrent phosphorylation negatively regulates that the presence of the lipin 3 PBD

COURTESY OF SALOME BORODA/UNIVERSITY OF VIRGINIA A schematic of lipin polybasic domain exchange mutants.

10 ASBMB TODAY FEBRUARY 2018 eliminated the phosphoregulation of the lipin 1 enzyme. Conversely, the specific activity of the lipin 3 mutant containing the lipin 1 PBD showed Upcoming ASBMB events potent inhibition by phosphorylation. While it is possible that the mutant and deadlines lipin proteins became dysregulated, phosphoproteomic analysis found no significant changes compared to their wild-type counterparts. 5: Art of Science Communication course To date, there is no structural FEB information available for lipins. As begins such, the mechanisms whereby lipin 12: Outreach poster deadline for ASBMB 1 phosphorylation interferes with the annual meeting ability of the lipin 1 PBD to recognize dianionic PA are a matter of specula- 16: Outstanding Student Chapter Award tion. However, the variation in the deadline for ASBMB annual meeting molecular regulation of lipins suggests that each has a unique role in specific 16: PROLAB application deadline cellular stimuli and physiological con- 27: Late-breaking abstract-submission deadline ditions, and perhaps the field is just for ASBMB annual meeting beginning to elucidate the true com- plexity behind the function of these 27: ASBMB annual meeting early registration enzymes. Further work is needed deadline to probe exactly how these enzymes may be regulated post-translationally. In particular, the exact residues and 6 – 9: ASBMB-Deuel Conference on Lipids molecular pathways involved in the MAR 15: Accreditation application deadline negative phosphoregulation of lipin 1 are still unknown and could provide insight into its physiological role. 12: Hill Day

APR 13: IMAGE grant writing workshop REFERENCES 1. Harris, T.E. et al. J. Biol. Chem. 282, 277- nomination deadline 286 (2007). 16: Outreach Student Chapters grant deadline 2. Eaton, J.M. et al. J. Biol. Chem. 288, 9933- 9945 (2013). 21–25: ASBMB annual meeting, San Diego 3. Eaton, J.M. et al. J. Biol. Chem. 289, 18055- 18066 (2014). 30: Spring Art of Communication course 4. Boroda, S. et al. J. Biol. Chem. 292, 20481- applications open 20493 (2017). 5. Shin, J.J. & Loewen, C.J. BMC Biol. 9, 85-7007-9-85 (2011). 6. Ren, H., et al. Mol. Biol. Cell. 21, 3171-3181 (2010).

Salome Boroda (sb9jq@virginia. edu) is a research associate for clinical studies at the University of Virginia School of Medicine, in the department of anesthesiology. Thurl Harris (teh3c@virginia. edu) is an associate professor of pharmacology at the University of Virginia.

FEBRUARY 2018 ASBMB TODAY 11 JOURNAL NEWS New insights into treating amoebic keratitis By Isha Dey

The human body to the enzyme, stopped provides a hospitable the growth of tropho- environment for many zoites but had no effect micro-organisms that are on normal cholesterol essential to our survival. biosynthesis in human At the same time, it also cells. So this approach attracts a host of para- could treat specifically sites that, if not treated Acanthamoeba infections properly or eradicated, without harming us. This can be extremely harm- is the highlight of Nes’ ful to our health. One published work. such class of parasite is The work has been the infective amoeba, quite challenging, espe- cially because differences which causes rare and COURTESY OF THE W. DAVID NES LABORATORY in sterol biochemistry and sometimes fatal diseases Electron micrographs show the two stages in the life cycle of Acanthamoeba castellani. life-cycle events among in humans. The Acan- amoeba species make it thamoeba species, found the Acanthamoeba to cycle between hard to identify common worldwide, mostly in water and soil, stages and help the infective tro- drug targets. Moreover, Nes’ group causes amoebic keratitis, or AK — an phozoites survive and proliferate required an extensive collaboration to eye infection of the cornea that can in humans. Thus, targeting these integrate a multidisciplinary approach result in permanent blindness. In the specific pathways could prove to be an so as to provide “the most effective USA, 85 percent of AK cases occur efficient strategy to treat Acantham- drugs, which would escape mecha- in soft contact lens users. Although oeba infections. W. David Nes and nisms that otherwise could compro- AK is potentially life-threatening, its his group at Texas Tech University mise their therapeutic longevity,” treatment is not yet promising, owing have investigated such pathways and Nes said. to drug resistance and the absence of reported sterol C24-methyltransfer- Having used keratitis-causing species-specific drugs. Hence, we need ases, or SMTs, synthesized only in Acanthamoeba castellanii as the to identify specific drug targets to bet- amoebae, as novel druggable targets. model system in their published ter fight these parasites. study, Nes and his group now want Their findings were published in the Designing species-specific drugs to test their hypothesis in mouse Journal of Lipid Research. requires an understanding of the models. They also plan to extend Sterols are amphipathic molecules unique evolutionary differences their inhibitor studies to Naegleria that, by virtue of their lipid-based among species, especially with respect fowlerii, a “brain-eating amoeba” properties, act as membrane inserts to to biochemical pathways responsible that can cross the blood-brain barrier control overall growth and develop- for the survival of the parasite within and destroy brain tissue, resulting ment. Ergosterol biosynthesis has in a disease called primary amoe- the host. The Acanthamoeba life cycle been established as essential for the has two stages — cyst and trophozo- bic meningoencephalitis, or PAM. survival of many amoebae in humans, Further down the road, they hope to ite. The trophozoite is the active form and SMTs are critical enzymes in that infects humans, while the cyst develop high-throughput screening the ergosterol biosynthesis pathway. techniques to repurpose existing drugs is the dormant form that can survive SMTs catalyze a crucial step in the harsh conditions such as stress and as novel SMT catalysis inhibitors to ergosterol pathway that maintains tro- cure amoebic infections. lack of nutrients. When conditions phozoite growth. Interestingly, SMTs become favorable, the cyst transforms are absent in humans. Thus, the to a trophozoite via a process called researchers found that inhibiting these excystment. Both forms can enter Isha Dey ([email protected]) enzymes with transition-state analogs is a graduate student at Rosalind the human body through wounds, that blocked the catalytic site on the Franklin University of Medicine nostrils or contact with water. enzyme, or with suicide substrates and Science. Certain metabolic pathways cause that irreversibly bound covalently

12 ASBMB TODAY FEBRUARY 2018 JOURNAL NEWS When mitochondria make B cells go bad By John Arnst

B-cell chronic lymphocytic leukemia, or B-CLL, is the most common type of leukemia in adults and primarily affects elderly patients. The disease results from a patient’s bone marrow overproducing imma- ture lymphocytes, a form of white blood cells that fight infections less effectively than their healthy coun- terparts but survive longer, ultimately overwhelming them and spreading unchecked. Unlike acute leukemia, B-CLL can take several years to cause problems for a patient, but it is less responsive to chemotherapy. While novel treatments have been developed in recent years, they only target the B cells once they’ve mutated to an immature, cancerous state. To develop treatments for B-CLL that might prevent B cells from becoming cancerous in the first place, research- ers led by Christopher Gerner at the University of Vienna and Vienna Metabolomics Center have performed a comprehensive proteomics analysis of B-CLL cells and mature B cells in young and elderly patients. They described their work in a paper in the journal Molecular & Cellular Proteomics. COURTESY OF TORSTEN WITTMANN, UNIVERSITY OF SAN FRANCISCO “It could be nice to not only target When mitochondria, highlighted here in cow cells, suffer age-related oxidative damage, they can give rise to the cancer cells, but those cells prone chronic lymphocytic leukemia. to becoming cancer cells,” Gerner said. “What we actually saw when we tive species, which are carcinogenic numbers of healthy elderly people compared the young and the elderly and cause damage to cells, were being and B-CLL patients to ultimatelybe donors was a very clear signature of upregulated, Gerner said, which able to test when mitochondria have mitochondrial stress and metabolic would explain why the incidence become predisposed for the disease. stress.” of mutations that lead to B-CLL “The pressure on those cells was Gerner and colleagues found that increases with age. The researchers simply different … and this pressure B-CLL cells have an increased expres- hope that the alterations in regula- is something I would like to detect sion of stem cell-associated molecules tion also may provide a proteomic and measure in patients,” Gerner said. and a reduced expression of tumor- signature for immunosenescence, the “That would be the ultimate aim.” suppressing molecules and stress- immune system’s natural weakening related serotonin transporters as well with age. John Arnst ([email protected]) is as an observed increase in glutamine Gerner and his fellow research- ASBMB Today’s science writer. consumption and beta-oxidation of ers plan to continue this research by Follow him on Twitter at twitter. fatty acid. performing their proteomic analysis com/arnstjohn. This indicated that reactive oxida- on blood samples taken from greater

FEBRUARY 2018 ASBMB TODAY 13 JOURNAL NEWS

Sugary secrets of a cancer-related protein By Sasha Mushegian

The proteins in human cells are to its final destination in the cell extensively decorated with different membrane. When the researchers types of sugars, a phenomenon called knocked out POFUT1 or POGLUT1 glycosylation. These modifications in cell cultures using CRISPR/Cas greatly increase the diversity of pro- technology, cells displayed much less tein structure and function, affecting Notch on the cell surface. When both how proteins fold, how they behave, enzymes were knocked out, Notch and where they go in cells. New was almost completely absent. Using research published in the Journal of additional biochemical methods, the Biological Chemistry (1) demon- researchers found that POFUT1 and strates that a rare type of glycosylation POGLUT1 attached glucose and profoundly affects the function of a fucose to portions of Notch only after protein that is important for human they fold in a specific way. “It’s like a stamp of approval,” development and cancer progression. Haltiwanger said. “This part’s folded? Protein glycosylation is either Boom, you put a fucose on it. And called N-linked or O-linked, depend- somehow that tells the cell: Don’t ing on whether the sugar is attached mess with this anymore. Leave it to nitrogen- or oxygen-containing COURTESY OF ROBERT HALTIWANGER, UNIVERSITY OF GEORGIA alone. If you don’t add the sugar, [the sites, respectively. O-linked modi- Sugars fill the “notches” in the Notch receptor. The glycan stabilizes the Notch EGF repeats and thereby Notch proteins] get stuck inside the fications typically involve the regulates Notch trafficking in cells. endoplasmic reticulum, get degraded, sugar N-acetylgalactosamine being and don’t get secreted.” attached to the amino acids serine Haltiwanger said. “So we’ve been Knowing that these sugars are or threonine, called “mucin-type” curious about how these sugars affect essential for Notch activity makes the glycosylation because they are com- [Notch’s] stability and activity.” enzymes that control them, POFUT1 monly found in proteins in mucus The enzymes responsible for modi- and POGLUT1, potential targets membranes; together with N-linked fying Notch with glucose and fucose for cancer treatments. Depending on sugars, these “canonical” modifica- are called POFUT1 and POGLUT1. whether Notch is overactive or insuf- tions modify thousands of types of Haltiwanger’s team, led by Hideyuki ficiently active in a particular cancer, proteins. Takeuchi, wanted to know exactly manipulating the sugars that are For over 20 years, Robert Halti- why POFUT1 and POGLUT1 were added to Notch could help correct the wanger’s research group, now at the attaching glucose and fucose to Notch dysregulation. Haltiwanger’s team is University of Georgia, has studied a in cells. working on finding chemical com- rarer type of O-linked modification: If you genetically engineer a fly pounds that would inhibit POFUT1 attachment of the sugars glucose or or mouse without POFUT1 or and POGLUT1, thus stopping Notch fucose to serine or threonine, a modi- POGLUT1, Haltiwanger said, “you from embedding in the cell mem- fication that affects just a few hundred get a dead fly or a dead mouse. You brane and carrying out its signaling types of proteins. One of these completely disrupt the Notch path- functions. They’re also attempting to proteins is Notch, a signaling receptor way; Notch is not functional if you unravel how the glucose and fucose that is essential for cell development don’t add those sugars. There’s been a modifications work together to fine- and differentiation and is dysregulated lot of work over the years on: Why is tune Notch activity. in cancers such as leukemia, breast that? What is [the sugar] doing?” “That’ll keep us busy,” Haltiwanger cancer, and prostate cancer. Haltiwanger’s new work shows said. “The fact that we found these sug- that the fucose and glucose modifica- ars on Notch was intriguing because tions serve as quality-control markers Sasha Mushegian (amushegian@ Notch is a very important molecule,” that allow Notch to be transported asbmb.org) is scientific communi- cator for the Journal of Biological REFERENCES Chemistry. 1. Takeuchi, H. et al. J Biol Chem. 292:38, 15964-15973 (2017).

14 ASBMB TODAY FEBRUARY 2018 JOURNAL NEWS

Scientists find cellular backup plan for keeping iron levels just right By Sasha Mushegian

Iron is essential for cell function, but excess iron can damage cells, so cells have sophisticated molecular mechanisms to sense and adjust iron levels. Disorders of cellular iron metabolism may affect more than a third of the world’s population. In addition disorders like anemia, caused by overall insufficient iron levels, iron deficiency can impair brain COURTESY OF CARYN OUTTEN, UNIVERSITY OF SOUTH CAROLINA CIA, FBXL5, IRP1 and IRP2 coordinate in control of iron metabolism. Protein degradation and iron-sulfur cluster function in the young and reduce production can suppress the activity of iron regulatory proteins, maintaining the correct iron levels in the cell. muscle strength in adults. Iron may be dysregulated at the cellular level in neurological disorders such as Par- When there is sufficient iron in the degradation was a backup mechanism kinson’s disease, and disordered iron cell, an iron-sulfur cluster is inserted that reduced IRP-1 action in cells metabolism contributes to congenital into IRP-1, inactivating it. Thus, the with high iron. conditions such as Friedrich’s ataxia. activation or suppression of IRP-1 The results have implications for Researchers in the nutritional relates to how much iron is available understanding how iron is sensed, sciences department at the Univer- to produce iron-sulfur clusters. used and regulated in tissues. Dif- sity of Wisconsin have uncovered a However, there was some evidence ferent tissues have different levels of connection in the network of checks of another method by which IRP-1 oxygen, but the iron-sulfur cluster and balances underlying cellular iron could be stopped when it was not production system functions best at regulation. Their research was pub- needed: namely, that a protein called low oxygen whereas FBXL5 functions lished in the Journal of Biological FBXL5 could add molecular tags to best at high oxygen. Therefore, these Chemistry (1). IRP-1 to tell the cell to degrade the two systems may trade off taking the When iron levels in mammalian protein altogether. lead in controlling IRP-1 in different cells are low, iron regulatory proteins, “The idea that IRP1 is also parts of the body. Because iron- or IRPs, spring into action. IRPs pre- regulated by protein degradation sulfur clusters and FBXL5 play many vent iron that enters cells from being was controversial when it was first important roles in cell growth, this improperly stored, allowing the cell to discovered by others,” Eisenstein said. balance between these functions could help different types of cells control produce essential iron-containing pro- “There’s been a belief that IRP-1 was how they use iron. teins. When there is excess iron, IRPs really regulated by this iron-sulfur “Diseases of iron metabolism are inactive, leading to increased iron cluster mechanism, and that the pro- caused by diet or by genetic perturba- storage, lowering potential toxicity tein degradation mechanism wasn’t so tions are major public health issues,” and reserving it for when iron avail- important.” Eisenstein said. “To combat such ability is reduced. Too much or too To test whether this was the case, diseases and develop effective treat- little IRP activity can endanger cells. Eisenstein’s team suppressed the Richard Eisenstein’s research group ments for those afflicted with them, it production of iron-sulfur clusters. is essential to understand iron-sensing at Wisconsin studies what controls Even when this production was and iron-regulatory pathways.” IRP activity. Scientists have long reduced, IRP-1 activity could still be thought the main method by which suppressed. The team confirmed that IRP-1 is inactivated involves essential this was due to the activity of FBXL5. Sasha Mushegian (amushegian@ compounds called iron-sulfur clusters. This supported the idea that protein asbmb.org) is scientific communi- cator for the Journal of Biological REFERENCES Chemistry. 1. Johnson, N.B. et al. J Biol Chem. 292:38, 15976-15989 (2017).

FEBRUARY 2018 ASBMB TODAY 15 JOURNAL NEWS From the journals By Sasha Mushegian, Angela Hopp & Saddiq Zahari

We offer a selection of recent to profile the aortas of atherosclerotic motivated a new study published in papers on a variety of topics from the mice over the development of the dis- the Journal of Lipid Research. A Journal of Biological Chemistry, ease. The researchers quantified 5,117 research team led by Robert Fürst of the Journal of Lipid Research and proteins from this profiling strategy Goethe University found that, in fact, Molecular & Cellular Proteomics. and found that 182 of them changed ACC regulates endothelial cell migra- significantly in response to vessel tion. The study also underscored that Metabolites predict maturation and plaque development. manipulating ACC may be a worth- These include novel factors that were while avenue for treating cell migra- insulin resistance not known to be involved in athero- tion-related diseases. The researchers Insulin resistance leading to high sclerosis, including matrilin-2, peroxi- used human umbilical vein endothe- blood sugar, a hallmark of pre-diabe- dasin and MAM domain-containing lial cells and human microvascular tes, is a complex condition with many 2. The study, published in Molecular endothelial cells for the study. They genetic and environmental determi- & Cellular Proteomics, provides the interfered with ACC activities by nants. Jacqueline Stöckli and col- vascular disease research community administering a compound known as leagues from the University of Sydney with a valuable resource of time- and soraphen A. Originally isolated from carried out a comprehensive machine compartment-resolved proteomic slime bacteria, soraphen A has been learning-enabled metabolomic analy- changes during atherogenesis. used by scientists as an ACC inhibitor sis of three mouse strains fed high-fat doi:10.1074/mcp.RA117.000315 for some time. In this case, soraphen or standard diets. The analysis showed A’s inhibition of ACC changed the that, despite individual environmental Fatty acid metabolism lipid composition of the endothelial and genetic variation, a combina- cell membranes and had other effects tion of three unrelated metabolites and the migration that ultimately prevented the cells (C22:1-CoA, C2-carnitine and of endothelial cells from migrating as usual. C16-ceramide) together formed an Endothelial cells lining blood ves- “Our findings show for the first accurate signature for predicting insu- time that (the enzyme) regulates sels help keep what belongs in and lin resistance. The study, published in endothelial filopodia formation and, what doesn’t belong out. These cells the Journal of Biological Chemistry, most importantly, endothelial cell move around as needed — during, is a step forward in creating preci- migration by rearranging the cells’ for example, development and wound sion medicine approaches to diabetes phospholipid composition,” the healing. Abnormal endothelial cell prevention and treatment. authors report. “The present study migration is seen in various diseases, doi: 10.1074/jbc.M117.818351 fills a gap in the literature by show- including rheumatoid arthritis, cancer ing the relationship between the fatty and macular degeneration. Research- acid metabolism and the migration Unclogging the plaques ers suspect that manipulation of vas- of endothelial cells.” In addition, the Heart disease kills 18 million cular endothelial cell migration could team noted that soraphen A could be people in the world every year. The be a useful therapeutic approach a useful chemical tool for studying underlying pathophysiology of heart for those and other conditions. The fatty acid metabolism in endothelial disease is often atherosclerosis, a enzyme known as ACC, meanwhile, cells. progressive buildup of plaques within catalyzes the first and rate-limiting doi: 10.1194/jlr.M080101 the arteries. While some compo- step in the biosynthesis of fatty acids. nents of the atherosclerotic plaques This enzyme, formally acetyl-CoA have been studied, a comprehensive carboxylase, is of interest to research- Trypsin trips up picture of the changes that occur ers developing therapies for metabolic Alternative splicing has been during development of the plaques is diseases such as obesity and diabetes shown to occur in up to 94 percent of still lacking. Investigators at the Max and for certain cancers in which ACC human genes, resulting in expression Planck Institute of Biochemistry led is upregulated. of different splice forms for each gene. by Matthias Mann aimed to capture So what do vascular endothelial While this phenomenon is known to this picture by using a sensitive and cells and ACC have to do with one increase complexity at the transcrip- in-depth mass spectrometry approach another? That’s the question that CONTINUED ON PAGE 18

16 ASBMB TODAY FEBRUARY 2018 Two amino acids determine cells’ response to warming As the climate changes, we will have to adjust at presence of unsaturated fatty acids and that this deg- many levels. In fruit flies, an enzyme called DESAT1, radation is enabled by a diproline motif at DESAT1’s a delta-9-desaturase, is a key player in responses to N-terminus. temperature changes at both the cellular level, where it “It was surprising that it is regulated by only two influences membrane fluidity by synthesizing monoun- amino acids,” Umeda said. “A very small portion is saturated fatty acids, and at the whole-organism level, responsible for expression of the protein.” where it controls temperature-influenced behaviors like Now, the team is going back a step further in the mating. pathway leading to DESAT1 degradation, trying to Delta-9-desaturases are found in all organisms, from understand how temperature changes are sensed inside bacteria to humans. DESAT1 in fruit flies is transcribed the cell to lead to changes in fatty acid composition and at a constant rate, but the rate at which the protein consequent effects on the whole organism. degrades determines its overall expression level. Masato “Our ongoing project aims to elucidate how cells Umeda’s research team at Kyoto University was inter- recognize temperature or cellular events caused by the ested in understanding how the degradation of DESAT1 temperature changes and control the expression of is regulated in the fruit fly Drosophila melanogaster in DESAT1 to adapt the cellular processes and behaviors,” order to better understand thermal regulation in diverse Umeda said. “We hope our study will lead to an alterna- organisms. The results of their research were reported in tive approach that could potentially circumvent the the Journal of Biological Chemistry. biological crisis due to global warming.” The team discovered that DESAT1 is degraded by doi: 10.1074/jbc.M117.80193 calpains, calcium-dependent cysteine proteases, in the — Sasha Mushegian

COURTESY OF MUHAMMAD MAHDI KARIM/WIKIMEDIA COMMONS Drosophila, photographed in Dar es Salaam, Tanzania.

FEBRUARY 2018 ASBMB TODAY 17 CONTINUED FROM PAGE 16 How nicotine affects receptor localization tome level, the effect of alternative splicing on the complexity at the pro- Nicotinic acetylcholine receptors, or nAChRs, are the main receptors teomic level remains controversial. In in neuromuscular junctions. Observations suggest that nicotine exposure a recent study in Molecular & Cellu- affects the ratio of these receptors on the surface versus those in the endo- lar Proteomics, researchers at Baylor plasmic reticulum of the cell and thus the cells’ sensitivity to these recep- College of Medicine and Vanderbilt tors’ natural ligands. To understand how nicotine affects nAChR localiza- University led by Bing Zhang showed tion, Ashley M. Fox–Loe and colleagues at the University of Kentucky why there has been a lack of evidence developed sensitive, organelle-specific single-molecule imaging methods of exon–exon junction-spanning to quantify precisely changes in the stoichiometry of nicotinic receptors. peptides in published proteomic Publishing the research in the Journal of Biological Chemistry, the team data sets. They found that the ends concluded that nicotine exposure affects receptor distribution through of exons in the genome are enriched combined effects on both receptor assembly and trafficking, which eventu- with codons coding for lysine and ally could help explain the effects of drugs like nicotine on neuromuscular arginine amino acids. This occurrence functioning. could have hindered the detection doi: 10.1074/jbc.M117.801431 of junction-spanning peptides, since most mass spectrometry experiments involve digesting proteins with the enzyme trypsin, which cuts peptide chains exclusively after arginine and lysine residues. The researchers further showed that combining chymo- trypsin and trypsin during sample preparation increased the detection of junction-spanning peptides by 37 percent. The study demonstrates the importance of using complementary digestion schemes in research where identifying different splice forms of proteins is a priority. COURTESY OF ATALY/WIKIMEDIA COMMONS doi:10.1074/mcp.RA117.000155 This illustration shows two views of a nicotinic acetylcholine receptor. Mitochondrial signals tive oxygen species production, an accompany gastrointestinal disease apoptotic signal and oxidative stress or manifest alone, causes chronic through micro-RNAs response, and miR-663 induced the diarrhea. Primary bile acid diar- Communication between the expression of nuclear-encoded mito- rhea, or BAD, in humans has been nucleus and mitochondria is required chondrial respiratory chain subunits. shown to be related to the hormone for cells to function. While signaling Correlative and experimental obser- known as fibroblast growth factor 19. from the nucleus to the mitochondria vations of breast cancer tumors also FGF19 is secreted in the intestine is most obvious, signals from the suggested that miR-663 has a tumor- and downregulates the synthesis of mitochondria to the nucleus are also suppressive effect. These observations, bile acids in the liver. Researchers at crucial. In particular, mitochondrial- published in the Journal of Biologi- the David Geffen School of Medi- nuclear signaling regulates metabolic cal Chemistry, suggest that micro- cine at the University of California, stress responses, and misregulation of RNAs could be important players in Los Angeles, recently reported in the this signaling has been observed in mitochondrial-nuclear signaling in Journal of Lipid Research that they breast cancers. Trevor Carden and col- normal and cancerous cells. have identified a gene variant that leagues at the University of Alabama doi: 10.1074/jbc.M117.797001 affects FGF19 secretion and thus may showed the first evidence of a micro- affect bile acid metabolism in both RNA’s role in mitochondrial-nuclear Investigating the genetic sickness and health. Led by Karen signaling and tumor suppression. The Reue, the research team first used a expression of micro-RNA miR-663 basis of bile acid diarrhea mouse model that they had identi- was induced by mitochondrial reac- Bile acid malabsorption, which can fied previously as having a spontane-

18 ASBMB TODAY FEBRUARY 2018 ous deletion in the Diet1 gene. A tions or additional common variants the researchers’ species of choice, and deficiency in Diet1 results in reduced contribute to variations in bile acid ATP. This simplified system then was FGF15 (the mouse equivalent of metabolism. used to assemble chromatin with FGF19). The team characterized the doi: 10.1194/jlr.M078279 desired DNA sequences and proteins effects of the gene deletion and found from diverse organisms. The research- that the mice had symptoms simi- Do-it-yourself ers hope that this method, published lar to those experienced by patients in the Journal of Biological Chemis- with BAD. Next, they looked at how custom chromatin try, becomes a user-friendly approach Diet1 expression in more than six In the nucleus, DNA is packaged for a variety of chromatin-related dozen mouse strains correlates with with proteins in a form called chro- experiments. the expression of FGFF15 and bile matin. Chromatin’s complex structure doi: 10.1074/jbc.M117.815365 acid levels. Finally, they zeroed in on a regulates gene expression, DNA repair variant in the DIET1 gene in humans and epigenetic inheritance. Building that influences FGF19 secretion customized chromatin for molecular Sasha Mushegian studies remains a challenge because of ([email protected]) is from cultured cells and is associated scientific communicator for the with FGF19 levels in BAD cases. its multidimensionality. Mai T. Khu- Journal of Biological Chemistry. ong and colleagues at the University “Our findings raise the possibility Angela Hopp (ahopp@asbmb. that the (variant) could contribute of California, San Diego, developed org) is executive editor of ASBMB to the seven-fold variation in plasma a method to synthesize chromatin in Today and communications direc- FGF19 levels that have been observed vitro using histone chaperone pro- tor at the ASBMB. in healthy individuals,” the authors teins and an adenosine triphosphate- Saddiq Zahari (szahari@asbmb. driven motor protein derived by a org) is the editor for manuscript wrote. “Resequencing DIET1 in integrity at Molecular & Cellular additional subjects will be required to simple purification from Drosophila, Proteomics. reveal whether DIET1 rare muta- template DNA and histones from

FEBRUARY 2018 ASBMB TODAY 19 FEATURE

College and university leaders from underrepresented groups talk about how a background in science serves them at the academic helm By Takita F. Sumter, Adela Cota-Gomez & Kayunta Johnson-Winters

COURTESY OF KENYON COLLEGE Sean Decatur, president of Kenyon College in Ohio, and students gathered around his dining room table in spring 2016 for a seminar, “Case Studies in Protein Structure, Dynamics and Function.” He plans to teach another seminar, on bioluminescence, this year.

20 ASBMB TODAY FEBRUARY 2018 ll life scientists navigate aca- BELL: I have a B.A. in chemistry demia, at least in the early stages from Talladega College and a Ph.D. A of their careers. These encoun- in chemistry with a biochemistry ters evolve in commitment and com- concentration from Atlanta Uni- plexity depending on whether they versity. I also completed three and occur as undergraduates, graduate a half years as a postdoctoral fellow students, postdoctoral fellows, faculty in biochemistry at the University of or — for a few — administrators. North Carolina at Chapel Hill. I am Life sciences faculty at times currently president of the University assume leadership positions in aca- of Maryland Eastern Shore, an 1890 demia that make good use of their land-grant historically black univer- background and skills as they face sity with a strong focus on science, such issues as enrollment challenges, technology, engineering and math- funding and the need to diversify ematics, or STEM, as well as agri- certain disciplines. These adminis- culture and the health sciences. My trative roles allow scientists to have science background was a great match a positive impact on the future of for the priority on STEM at UMES, education, particularly training young the University System of Maryland, biochemists and molecular biologists and the state of Maryland. I convey who ultimately will work to advance COURTESY OF KENYON COLLEGE my passion for science and research Sean Decatur, president of Kenyon College, started science and improve human health. by actively and personally participat- out as an assistant professor of chemistry at Mount Biochemists and molecular biolo- ing in and supporting undergraduate, Holyoke College, then was dean of the College of Arts gists who move from the bench to and Sciences at Oberlin College. graduate and faculty research activi- college and university presidencies ties. I also mentor students, work do so from a variety of backgrounds. Here, we present the views of three with professional organizations and such presidents who are also from work to strengthen the infrastructure underrepresented groups: Juliette Bell for the sciences on my campus. of the University of Maryland Eastern Shore, Sean Decatur of Kenyon DECATUR: I majored in chem- College in Ohio and Roy Wilson of istry (with a minor in biology) as Wayne State University of Michigan. an undergraduate at Swarthmore Their schools and their academic College; then I went on to complete backgrounds vary, but these three a Ph.D. at Stanford University in share certain key traits, including biophysical chemistry. My interests adaptability, a knack for picking up since graduate school have focused on multiple skills and a unique ability spectroscopic approaches to studying to serve as role models for the next protein structure, dynamics and fold- generation of scientists. ing, and for about 20 years (until I became president at Kenyon College), Describe your science my research was supported by the National Science Foundation (includ- background and discuss ing a CAREER award), National how it benefited you Institutes of Health and private on your path. In your foundations. In my current role, I value the current role, how do you opportunities I have to teach and convey your passion advise students (I am teaching a semi- nar in spring 2018, and I regularly for biochemistry and advise students at Kenyon). In addi- molecular biology or the tion, I am pleased to support efforts scientific enterprise to of my faculty colleagues in the natural sciences to expand opportunities for burgeoning scientists? research to students underrepresented

FEBRUARY 2018 ASBMB TODAY 21 in the sciences and to make the peda- my career as an assistant professor at gogical approaches more inclusive. Mount Holyoke College. Soon after I am very proud of Kenyon’s suc- I received tenure, I became chair of cesses in this area over the past year, my department, and after that I took including an initiative funded by the on responsibility for a number of Howard Hughes Medical Institute’s institutional grant projects, becoming inclusive excellence program, an NSF an associate dean of faculty. I moved Scholarships in STEM program and from Mount Holyoke to Oberlin Col- a Clare Booth Luce grant to support lege, where I took on the role of dean undergraduate women to pursue of the College of Arts and Sciences, research. the chief academic officer for the college. WILSON: I have a bachelor’s In this way, my career has been a degree in biology and pursued extra gradual rise in administrative respon- training in epidemiology/biostatics sibilities. But my administrative work while I was in medical school. Later, has roots in my scientific work. It was when I was a faculty member, I pur- in my research program that I learned sued a Master of Science in epidemi- how to manage a budget, set out a ology. I have collaborated extensively plan for work and supervise a staff, all COURTESY OF THE UNIVERSITY OF MARYLAND EASTERN SHORE with trainees and junior colleagues in of which have served me well in my Juliette Bell, president of the University of Maryland Eastern Shore, previously served as a director of research work leading to publications. later work. biomedical research, dean of the college of science, and provost/vice president/chancellor at three What additional experience WILSON: I came up through institutions. a traditional academic system by qualified you for the first becoming a department chair position of president in ophthalmology and then dean of (for example, were you the medical school (Charles Drew University of Medicine and Science), a department chair or then dean of another medical school dean)? How did those and vice president for health sciences (Creighton University), then presi- experiences help prepare dent of a free-standing health science you to be president? enterprise (Texas Tech University of Medicine and Science), then chan- cellor of the University of Colorado BELL: Before becoming president, Denver (consisting of the general I served as director of biomedical academic and health science campus). research, dean of the college of science I then did a short stint at the NIH and as provost and vice president/ before coming to Wayne State. chancellor at three institutions. These experiences taught me leadership and management skills, which are essential Part of leadership is in the presidential role. I also learned being able to bring people financial management, fundraising/ together and to resolve friend raising, government relations, athletics and other areas essential to conflict. What experiences the presidency. Serving as a faculty do you have that enable member and in these various roles also increased my credibility with you to do this effectively? faculty, since I could relate firsthand to the challenges faculty face. BELL: As president, one must respond to many constituents. These DECATUR: I rose up through the include students, parents, faculty, traditional faculty ranks, beginning staff, boards, legislators, partners, col-

22 ASBMB TODAY FEBRUARY 2018 leagues, accrediting bodies, business passion to encourage and support and community leaders, funders, and other underrepresented minorities in the list goes on. One must be a good achieving their dreams. This is what listener, a good communicator and a led me to devote my career to teach- consensus builder. It is also essential ing, research and service at historically that you have good analytical skills black institutions. Leading an HBCU and the ability to solve problems. is the ultimate opportunity for service These are skills well-suited to scien- to my community. tists and researchers. I often say that I use the scientific method every day DECATUR: I am the first African- as president. Learning how to arrive American, and first person of color, to at win-win solutions to problems lead Kenyon College. While the work and conflicts is an ongoing learning of building a diverse and inclusive process. community should not (and does not) fall exclusively to leaders who are also DECATUR: Managing people members of underrepresented groups, and relationships was an important I do feel that it is important that I component of running a research keep issues of diversity and inclusion as key institutional priorities. COURTESY OF WAYNE STATE UNIVERSITY program, and the skills I learned in Before he was named president of Wayne State that work formed a valuable founda- University, Roy Wilson earned an M.D., was dean of tion for managing larger teams and WILSON: I experienced a lot of two medical schools, held administrative positions at what minority students experience two universities and worked at the National Institutes eventually for my work as president. of Health. In all of this, listening is probably the in higher education today, so I can most important skill I have needed to identify with their challenges and practice and hone; often what is most struggles. I believe these experiences important for resolving conflict is to have made me empathetic, and I try to influence policy that will positively make sure that all voices are heard impact all students. and respected.

WILSON: No specific experiences Most aspiring young come to mind. I learned by making biochemists/molecular a lot of mistakes and learning from biologists do not plan a mistakes. path toward leadership, How did being an and many do not pursue underrepresented minority a high-ranking leadership help to shape your position. Did any specific experiences and how you experience(s) lead you serve your institution? toward that goal?

BELL: As an African-American BELL: For the first 12 years of female biochemist, I was often my academic career, I was content characterized as a “double minority” teaching, conducting my research in many of the professional environ- and serving as the director of several ments I worked in prior to entering training programs. I increasingly academia. Having overcome many became dissatisfied with the level of challenges in achieving my goal of support for research at my university. a career in science and research, I I had the opportunity to share my chose to use my experience, skills and concerns and suggestions for change

FEBRUARY 2018 ASBMB TODAY 23 with a new president. That president my students. This has sparked discus- told me that if I wanted things to sions and social and political action change, I had to be willing to take a among UMES students. leadership role and not just stand by and complain. I took her up on that DECATUR: Our nation has been advice and accepted an interim dean’s burdened with deep-rooted legacies of position. I subsequently applied for racism for a long time, and the events and won the dean’s job, then provost, of the past few years (not just 2017 and the rest is history. but dating back to the tragic deaths of Trayvon Martin in 2013 and Michael DECATUR: I have always been Brown in 2014) have made the strug- interested in educational leadership, gle for racial justice more visible and since I was an undergraduate (my more urgent. College campuses are Ph.D. adviser recently reminded me places where the nature and impact that I mentioned this in my graduate of discrimination can be examined school application). But, over time, with rigor and are often on the front my view on how I could influence the lines of positive change. At Kenyon, educational experience of students the events of the past few years have gradually expanded from a focus on provoked important discussion, led a specific classroom experience to the to reflection about our own practices departmental level to the institutional as an institution and catalyzed the level. process of change.

WILSON WILSON: I did not have an “aha” : Like many other moment. I was thrown into leadership universities, we’ve had to confront roles from the very beginning of my a number of problematic issues this past year, including the immigra- career, and I performed other faculty tion ban, overt racism, the assault on roles, such as teaching and research, science, etc. We’ve tried to be true to concurrently. I knew there was no our mission and our values during turning back when I became dean of these times. We’ve communicated medicine at Creighton. frequently with our entire university community and have sponsored many How have the events of the discussion sessions where people can past year (demonstrations express their feelings and concerns. in Charlottesville and by NFL players, actions Takita F. Sumter (sumtert@ by President Trump and winthrop.edu) is a professor of biochemistry and interim dean of congressional leaders) the College of Arts and Sciences been reflected on your at Winthrop University. Adela Cota-Gomez (adela. campus? [email protected]) is an associate professor of medicine in the division of pulmonary sciences BELL: As HBCU students, my and critical care at the University students are very aware of issues of Colorado Denver–Anschutz impacting diversity and inclusion, Medical Campus. equity and social justice. The events Kayunta Johnson-Winters ( [email protected]) is an associ- of the past year have further increased ate professor in the department of awareness, especially as it relates to chemistry and biochemistry at the events in Baltimore, home to many of University of Texas-Arlington.

24 ASBMB TODAY FEBRUARY 2018 FEBRUARY 2018 ASBMB TODAY 25 FEATURE Addressing the tangled roots of health disparities Life scientists forge collaborations to rethink old questions, train young researchers and engage diverse communities By John Arnst

26 ASBMB TODAY FEBRUARY 2018 n the United States, black babies generations. For a small number of die during birth at more than diseases — including prostate cancer, I twice the rate of white babies. triple-negative breast cancer and As adults, black men and women pre-eclampsia — biological predispo- die from strokes and heart disease at sitions (such as an elevated number higher rates than Americans of other of disease-associated alleles) may play races and ethnicities. roles. While advances in breast can- Clayton Yates, professor of biology cer screening and treatments have and director of Tuskegee University’s reduced the death rate for all Center for Biomedical Research, women in the U.S., the death rate studies the biological mechanisms has decreased more slowly for black responsible for the increased mortality women than for white women, rate of prostate cancer in black men. resulting in a significant disparity. “If we’re not understanding the dis- For example, from 1999 to 2013, the parities and the different mechanisms most recent period for which there are that are occurring at a biochemical data, black women in Houston were level in different populations, it’s no 72 percent more likely to die from wonder that a large percent of our breast cancer than white women. drugs that get to market are failing COURTESY OF CHRISTOPHER RENEGAR The study of health disparities, in a general population,” he said, Clayton Yates has been a faculty member at which includes any condition dispro- “because we’re not even considering Tuskegee University for 11 years. portionately affecting one racial, eth- that in the discovery process.” nic or gender group, is a burgeoning, In 2017, Yates and his colleagues relatively young research field. The received a five-year NIHMD grant National Institutes of Health estab- of nearly $8.5 million to help train lished the National Center on Minor- minority scientists involved in health ity Health and Health Disparities in disparities research. The grant is one just 2000 and then redesignated it of seven that the NIMHD announced as the National Institute on Minor- last year for research centers in ity Health and Health Disparities in minority institutions, or RCMIs, in 2010 as part of the Patient Protection Alabama, Florida, Tennessee, North and Affordable Care Act. Carolina, Arizona, Puerto Rico A product primarily of poverty and and Hawaii. The NIMHD plans unequal access to health care, health to disburse $122 million over five disparities are a staggering challenge. years for the institutions to train The problem is as entrenched as the early-career investigators involved in wealth gap — due to the strong cor- health disparities and minority health relation of income and life expectancy research and to improve research in the U.S., the richest 1 percent of infrastructure. American women and men live an In addition, last year the NIMHD average of 10 and 15 years longer, announced it would direct $82 respectively, than the poorest 1 million in funding over five years percent. to 12 Centers of Excellence focused However, the problem goes deeper on multidisciplinary research and than income. The chronic stress community-engagement activities. caused by economic insecurity, dis- Together, these grants made up crimination and systematic racism is around 15 percent of the NIMHD’s understood to have negative effects on $281 million budget for 2017. the health of millions. Additionally, In addition to advocating for the a growing body of evidence suggests elimination of policies that give rise the cellular stress caused by systemic to social inequality, health disparities trauma can have epigenetic-based experts say basic researchers can help detriments to the health of future address health disparities by question-

FEBRUARY 2018 ASBMB TODAY 27 focused on health disparities; and Jesus Ramirez-Valles, a chair of the Division of Community Health Sciences at the university’s School of Public Health, was established last year after the university received a $6.75 million five-year grant from the NIMHD to develop a center of excel- lence on minority health and health disparities. “We want to strengthen health- equity scholars and produce research activities that can expand the under- standing of structural inequality in order to identify the differential risks and vulnerabilities of racial, ethnic, and sexual minority groups,” said Watson, who is also director of com- munity engaged research and imple- mentation science at the university’s cancer center. The team has three projects that investigate health and structural violence. One examines the factors COURTESY OF BRUCE WETZEL AND HARRY SCHAEFER, NATIONAL associated with disparities in men- CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH ing the established canon of biomedi- tal health among Asian immigrant A breast cancer cell, photographed by a scanning cal research, building interdisciplinary populations. Another examines the electron microscope. The disparity between breast collaborations, training scientists cancer survival rates in black and white women has relationship between cardiovascular widened in recent years, despite decreases for both from underrepresented communities disease outcomes in Latino families groups. and enhancing community involve- and stress due to racial discrimina- ment through participatory research. tion. The third examines colorectal cancer and the epigenetic impacts New frameworks that structural violence has on black for questions populations in Chicago. “When you think of colorectal How does inequity affect people disparities on the south side of Chi- at the molecular level? And how do cago, you think about that as an issue those effects influence, for example, that spans translational research,” the rate of colorectal cancer in black said Winn, who is also the associate men in Chicago? These are the types vice chancellor for community-based of questions being asked by research- practice at the university. “That ers at the Chicago Center for Health issue starts at the cellular-molecular Equity Research, or CHER. level, with the actual testing and the There, Robert Winn and Karriem understanding that biologists have of Watson are part of a multidisciplinary the pathology of colorectal cancer and team of investigators from the Uni- diagnosis of colorectal cancer, all the versity of Illinois at Chicago aiming way to the community uptake of that to minimize disparities by examining screening.” the effects that continual violence The colorectal cancer project and harassment have on the health employs a mouse model that the of minority populations. The center, researchers established with the help which is led jointly by Winn; Martha of Paul Grippo, an associate profes- Daviglus, a cardiovascular researcher sor specializing in animal models of

28 ASBMB TODAY FEBRUARY 2018 gastroenterology. They can use the that we see when we compare black model to simulate food insecurity and men and white men and Hispanic stressful situations perpetuated by men.” aspects of structural violence, such as While the overall death rates for social isolation, stress and trauma. cancer in black men and women have “We can mimic those situations fallen by more than 34 and 19 per- in animal models to demonstrate cent, respectively, over the past two how certain biochemical markers, decades, they are still higher than the such as cortisol, may be elevated in rates for the white population. Black those animals and that may also be men in the United States still have elevated in our human population,” nearly twice the lifetime probability which may illustrate environmentally of dying from prostate cancer as white induced epigenetic changes that cause men. an elevated risk of colorectal cancer, “We’ve identified across all popula- Winn said. tions a region on chromosome 8 that “That’s just an example, to me, increases risk (for prostate cancer),” of where we now have tools that we Kittles said. “The interesting thing is didn’t have (before) to study these that the frequency of these risk alleles, really big issues of our society that these risk variants, are much greater COURTESY OF THE UNIVERSITY OF ILLINOIS AT CHICAGO actually do have a component that in African-descent populations. When At the University of Illinois Cancer Center, Karriem needs to be answered at the bench to we do the math, because of the higher Watson has helped create community-based be able to make any inroads,” Winn frequency, they can account for the programs for screening, preventiing and navigating said. higher frequency we see in prostate breast, colorectal, cervical, prostate and lung cancer. cancer in African-descent popula- Disparities in cancer tions.” While health disparities are pri- marily a consequence of economic The next generation inequity and unequal access to health At the University of Hawaii at care, certain types of cancers — Manoa, Dean Jerris Hedges, Noreen prostate cancer in black men and Mokuau, Marla Berry and their col- triple-negative breast cancer in black leagues are mentoring new and early- women are two examples — are stage scientists to investigate health believed to occur disproportionately disparities in native Hawaiian and due to higher frequencies of predis- Filipino communities on the islands. posed alleles. “We feel that if we can improve At City of Hope Cancer Center the health in those who have a gap in Duarte, California, Rick Kittles is in their overall lifespan and general exploring the link between ancestry- wellness, then we can raise the health informative genetic markers and dis- of all of the population,” said Hedges. ease risk and outcomes, with a special “We’ve been doing this in a transla- emphasis on prostate cancer. tional manner, trying to do bench-to- “The bulk of health disparities bedside-to-community (work).” really doesn’t have any strong sort of Hedges and Mokuau’s team biological component to it, it’s more received an RCMI grant from the social, cultural, behavioral differences NIMHD for nearly $5 million in its across populations that are contribut- first year to facilitate research on the ing to disparities,” said Kittles, the causes of and most effective interven- founding director of the Division tions for health disparities on the of Health Equities at City of Hope. islands related to diabetes, cancer, “But, there’s a subset — for instance, glucose metabolism, cardiovascular COURTESY OF THE UNIVERSITY OF ILLINOIS AT CHICAGO prostate cancer — which has a strong disease and strokes. “There are ele- In addition to his role at Chicago Center for Health Equity Research, Robert Winn is the primary investi- genetic component to it that might ments of the current grant that focus gator in a lab at the University of Illinois at Chicago account for some of the differences not only on community, behavioral that explores signaling pathways in lung cancer.

FEBRUARY 2018 ASBMB TODAY 29 and public health aspects, but also are Lovell Jones is a retired molecular looking at the epigenetics that may endocrinologist who has received affect certain populations to a greater numerous awards for his leader- extent than others,” Hedges said. ship in minority health disparities, Part of the program focuses on including the American Society for introducing young scientists to Biochemistry and Molecular Biol- experts in adjacent fields. ogy’s Ruth Kirchstein Diversity in “(Each young investigator) has a Science Award. Jones said he believes partner or a collaborator or a mentor, that these types of interdisciplinary or both, from a different discipline,” partnerships are key to ensuring that Berry said. These pairings tend to the progress made in the laboratory include basic research scientists part- ultimately has an effect outside of it. nered with clinical or community- “It’s not that (basic researchers) based researchers or cross-disciplinary have to become experts in psychol- pairings such as biologists and ogy or experts in sociology, experts engineers. in urban planning, but they need At Tuskegee University’s Center for to have an array of colleagues that Biomedical Research, Yates is using can advise them in terms of direc- COURTESY OF JI-XIN CHENG, PURDUE UNIVERSITY CENTER FOR the NIMHD grant to train minority tion,” said Jones. “What has been CANCER RESEARCH, NATIONAL CANCER INSTITUTE biomedical scientists who are examin- asked before? What hasn’t been asked Altered lipid metabolism, shown in yellow, may be a key signature of prostate cancer. ing disparities in HIV, obesity and before? What has it done?” prostate cancer. These partnerships are particu- “This grant has been a culmina- larly important at the University of tion of over 10 years of work through Hawaii, where the nearest major multiple other discoveries and papers, academic institution is more than where we’ve identified that there are 2,500 miles away, Berry said. “The molecular and genetic differences, university plays a unique role in particularly in cell-signaling pathways training local scientists to address that are associated with an aggressive health disparities within their own (prostate cancer) tumor in an African- communities,” she said, “which makes American patient versus a European- developing these junior investigators descended patient,” Yates said. particularly crucial.” The funding will allow Yates and colleagues to expand the center’s Community-based research capacity by developing new laboratories and furnishing them with research cutting-edge equipment. The program Helping train minority scientists will operate adjacently with the to study disparities in their own com- center’s pre-existing National Cancer munities is an approach that Kittles Institute-funded mentoring programs. and his colleagues at City of Hope Tuskegee’s program pairs senior also favor. health disparities experts with new “One of the goals, obviously, is to faculty members. The mentorship increase not only disparities research helps prepare the young investiga- but also diversity among the research- tors to answer disparities questions in ers,” Kittles said. “For the most part, their careers, Yates said. scientists study themselves, and so the They’re asking these questions, he more scientists of color we have, the said: “How do you address this popu- more questions and opportunities to lation? How do you transform what really explore this issue of disparity in COURTESY OF TINA SHELTON you are currently doing to address a the scientific community.” Prior to his current role at the University of Hawaii specific population that you see has a In Belcourt, North Dakota, Native at Manoa, Jerris Hedges served as professor and department chair in emergency medicine at Oregon disproportionate outcome or inci- American geneticist Krystal Tsosie is Health & Science University’s School of Medicine. dence of disease?” working simultaneously as a co-inves-

30 ASBMB TODAY FEBRUARY 2018 tigator for a study involving genetic that may affect pre-eclampsia rates. determinants of pregnancy-related “In studies of diverse populations, high blood pressure, or pre-eclampsia, Native Americans in the U.S. are very in the Turtle Mountain band of Chip- much ignored,” Tsosie said. “Part pewa Indians and wrapping up her of it is, the population is so small Ph.D. in genomics and health dispari- to begin with. Another challenge is ties at Vanderbilt University. having an informed process that not “I find that people within these only educates American Indians about interdisciplinary fields tend to come the potential benefits of engaging in from their communities of interest, so genomics research, but then having researchers have their own firsthand the cultural competency of researchers experience with what it’s like to grow to engage a community to have more up in these diverse, underrepresented equitable research.” communities,” Tsosie said. “Being a Tsosie and colleagues have had a Native American scientist, particularly variety of research questions about a Native American geneticist, you the tribes’ saliva and blood samples have to wear many hats, and, because and have kept tribe members abreast there are so few of us, our expertise of the results that come from their gets called upon collectively and samples through newsletters or radio COURTESY OF JESTON MORRIS individually at earlier stages in our programs. Additionally, they train At Vanderbilt University, Krystal Tsosie used the training than maybe other traditional tribal students in the lab and work BioVU database to longitudinally examine whether students.” with a Tribal Institutional Review genetic determinants contributed to black women’s risk of developing uterine fibroids. Prior to her work in Belcourt, Board, which reviews and approves Tsosie was using Vanderbilt’s BioVU their projects. database of more than 225,000 de- This community-based participa- identified genetic samples to study tory research, which involves com- genetic determinants of uterine munity engagement at every step of fibroids in black women. the scientific process, is how most of The pre-eclampsia project at Turtle the genomics research within Native Mountain Community College American communities has trended involves a research cohort of local since a 2004 lawsuit in which the residents who have been working Havasupai Tribe, in a remote part of with the institution for more than 15 the Grand Canyon, sued the Arizona years. Board of Regents and researchers at Pre-eclampsia occurs in about 6 Arizona State University for misusing percent of pregnancies and can result their DNA samples. in premature birth and death for “We’re really hoping that encour- either, or both, the mother and child. aging community-engaged research, Tsosie’s co-investigator, Lyle Best, is in not just Native American commu- a family practitioner who has worked nities but in all diverse ethnic popula- with the Indian Health Service in the tions, as a broad agenda, will not only Belcourt area since 1977. change how researchers interact with While no genetic determinants potential participants but also make have been found yet for pre-eclamp- research more equitable for all diverse sia, risk factors including mutations and nondiverse populations,” Tsosie in DNA have been identified. By said. incorporating clinical data from elec- At Tuskegee University, Yates and tronic health records at the Belcourt- colleagues are involved in outreach area Indian Health Service clinic, programs led by campus investigators the researchers are able to examine in venues such as town hall forums, COURTESY OF THE UNIVERSITY OF CHICAGO potential environmental and sociocul- where the researchers can tell com- Rick Kittles has been researching ancestry-informa- tive genetic markers and how they can be utilizes in tural factors specific to women of the munity members about the elevated genomic studies on disease risk and outcomes for Turtle Mountain Chippewa Nation risk for prostate and breast cancers more than 20 years.

FEBRUARY 2018 ASBMB TODAY 31 32 ASBMB TODAY FEBRUARY 2018 and how best to communicate that $281 million, making up less than 1 COURTESY OF DEBORAH MANOG information with their doctors. The percent of the NIH’s total budget for One project funded by the University of Hawaii’s researchers partner with the South- the year. At $33.1 billion, the NIH’s NIMHD grant is an aquaponics pilot project at the Waimãnalo Learning Center to promote healthy diets. ern Christian Leadership network, budget is just 3 percent of the federal a long-established presence in the government’s $1.07 trillion budget for community, to help disseminate this discretionary spending. information and hold conferences Jones, who was the founding across the state. director of the Health Disparities, It can make a difference, for exam- Education, Awareness, Research and ple, if community members know Training Consortium, is bullish on that tumors may be more aggressive addressing health disparities on a societal level. in certain populations. “(That affects) “Yes, the stock market is going up. how they have that conversation with Yes, unemployment rates are going the physician (and) how they stay on down. But how long is that going top of the clinical management and to last when the population of your care of their own cancer tumors,” nation becomes less healthy as the Yates said. demographics change and you do not address this population with these ‘A national concern’ demographic health issues?” Jones As the demographic makeup of the said. “Ten, 20 years ago, it was a com- country changes each year, disparities munity concern. It was a population affect a larger percent of the popu- concern. But today it’s a national lation, which both the health care concern.” system and the researchers who make treatments possible need to reckon John Arnst ([email protected]) is with. ASBMB Today’s science writer. COURTESY OF LOVELL JONES In 2017, the NIMHD’s annual Follow him on Twitter at twitter. Lovell Jones is the founding co-chair of the Intercul- budget came in 22nd out of the com/arnstjohn. tural Cancer Council, the nation’s largest multicul- NIH’s 27 institutes and centers at tural health policy group focused on minorities.

FEBRUARY 2018 ASBMB TODAY 33 34 ASBMB TODAY FEBRUARY 2018 MEETINGS ASBMB to host symposium on transcriptional regulation

he RNA polymerase II enzyme merase II regulation, including the II transcriptional apparatus. transcribes all protein-coding contributions of noncoding RNAs, Students and postdoctoral fellows T genes and many noncoding chromatin structure and post-transla- are encouraged to attend and will be RNAs in eukaryotic genomes. Regula- tional modifications, and other factors eligible for poster awards; the winners tion of RNA polymerase II activity that regulate gene expression. Dr. Eva will be given an opportunity to pres- requires a host of protein and nucleic Nogales of the University of Califor- ent their work as a short talk toward acid factors, including genomic nia, Berkeley, will present the keynote the end of the meeting. We look for- DNA itself, which is assembled into address on her work on the structure ward to seeing you in Snowbird for an chromatin. Precise regulation of RNA and function of the RNA polymerase exciting and enlightening symposium. polymerase II function, including processing of its RNA transcripts, is essential for cell differentiation and Transcriptional Regulation: development, and defects in these Chromatin and RNA Polymerase II regulatory mechanisms underlie many Dates: Oct. 4–8 human diseases. Recent advances Location: Snowbird Ski and Summer Resort, Snowbird, Utah in biochemical, cellular and bio- physical methods have allowed for unprecedented insights about RNA Organizers: polymerase II transcription and its regulation by chromatin and other factors. Given the importance of RNA polymerase II in biology and human health, the American Society for Biochemistry and Molecular Biology has hosted a biennial symposium on chromatin and RNA polymerase II since 2004. The 2018 symposium, titled “Transcriptional Regulation: ARNDT REESE TAATJES Chromatin and RNA Polymerase II,” will be held in early October at the Karen Arndt, University of Pittsburgh Snowbird Ski and Summer Resort, Joseph Reese, Pennsylvania State University about 35 minutes from the Salt Lake Dylan Taatjes, University of Colorado–Boulder City International Airport. The beau- tiful and intimate setting of the resort Deadlines and the conference facilities provide extensive opportunities for scientific Abstracts for platform presentations: March 16 discussions and networking. Abstract submission for short oral presentations: July 19 Attendance at the symposium will Discounted registration: Aug. 14 be capped at 200 participants, which Poster abstract submission: Aug. 30 will include principal investigators, Symposium registration: Sept. 12 postdoctoral fellows, students, and scientists from the pharmaceutical The status of all submitted abstracts will be posted on the Meetings page at and biotech industries. Sessions will asbmb.org. cover recent findings in RNA poly-

FEBRUARY 2018 ASBMB TODAY 35 WHEN SCIENCE MEETS SICKNESS From a personal disease to a personal research project By Eleftherios P. Diamandis

n 1964, I was an energetic to remove one of the cysts, which 12-year-old living in my home- had partially ruptured and caused the I land, the island of Cyprus. Every anaphylactic reaction. The surgery August, our village filled with workers included removal of some ribs and from other parts of the island who part of the lung. The same operation helped collect carobs, then the most was repeated on the other lung a year valuable agricultural product of the later. These big operations hampered island. My family owned thousands my physical development and my of trees, and I worked alongside my athletic performance. People at the parents and our hired workers at least beach were curious about big scars 12 hours a day for about a month. on my chest, but I did not look back. Tough labor, but well taken by a The EG chapter seemed closed. healthy young boy. I went to the University of Illinois One evening, after one of those at Urbana-Champaign in 1981 for days of hard work, I woke up a brief postdoc training. The com- abruptly in the middle of the night, pulsory medical screen included vomiting hard. I became very ill with chest and abdominal X-rays. I was a high fever and chills. My parents a bit worried when the university

suspected a bad flu or food poison- COURTESY OF ELEFTHERIOS P. DIAMANDIS medical officer asked to discuss my ing. The next day I went to the family Eleftherios P. Diamandis researched the effects of a results. They had found a big, calci- doctor, who found nothing and also parasitic infection he suffered during his boyhood. fied mass in the liver and thought thought it was a flu. But the malaise, stool or through direct contact. After it was a tumor. I reassured them it fever and chills did not subside, and infection, the parasites form cysts was another Echinococcus cyst that after a week there was no diagnosis containing larvae, usually in the liver I knew about. My doctors suggested or improvement. I was desperate, and it should not be removed since the and lungs of humans. Patients may be my parents thought I was going to larvae, after all these years, were likely asymptomatic for years but get sick die. I was admitted to the local hos- dead. As they put it, it was a garbage when a cyst ruptures or mechanically pital, where chest X-rays revealed two basket in my liver that was better left interferes with the organs. This disease 10-centimeter symmetric masses, one alone. was endemic in Cyprus in the 1960s in each lung lobe. There was calcifica- I did not think much about my tion around them, and the specialist and ’70s, largely because household disease for 40 years, but about five made the diagnosis of Echinococcus sheep were sacrificed in unauthor- years ago, the emergence of immuno- granulosus, or EG infection, with ised places and their EG-infected therapy for cancer gave me the idea cysts in the lungs. organs, such as lungs and livers, were of examining the possible relationship EG is a parasite that infects and thrown to stray dogs, which were then between EG infection and cancer. lives in the gut of its definitive host, infected. This is the EG cycle: from Based on existing literature, the usually a dog or other carnivore. sheep to dogs to humans. Cyprus expectation was that a chronic infec- Intermediate hosts include farm eradicated the disease in the 1980s by tion could protect against cancer due animals, such as sheep and goats. eliminating stray dogs and mandating to the intensified immune surveil- Humans and sheep are infected animals be sacrificed only in govern- lance. In published examples, some through ingestion of unwashed vege- ment-controlled slaughterhouses. parasitic and other infectious diseases tables or other products contaminated Instead of going back to school confer protection against cancer with eggs of the parasite from dogs’ that September, I had an operation development. Also, a Turkish group

36 ASBMB TODAY FEBRUARY 2018 had hinted that patients who have surgery for EG are never found to have concomitant cancer. I chose to do this research for the following reasons: I was curious whether my old infection was increasing or decreasing my cancer risk. This information could be useful to others and lead to some practical benefits, such as vaccina- tion against EG antigens to reduce cancer risk. COURTESY OF ELEFTHERIOS P. DIAMANDIS It was a good The author, second from left, looking at the camera, grew up on the island of Cyprus, where at age 12 he contracted a parasitic infection time to do the that caused large cysts to develop in his lungs and liver. Cyprus eradicated the disease in the 1980s. study; 40 years had elapsed since I won’t detail all the difficulties we to do an underpowered study than my infection (enough for cancer encountered, but some lessons are to start a study and then realize that development) and, as mentioned, the listed below. All in all, this study was recruitment is much smaller than infection became extinct in Cyprus a logistical and financial nightmare. expected. after 1980. After three years of hard work, we • There may be a myriad of hidden I found a retired collaborator in ended up recruiting 249 patients and biases with such studies, which could Cyprus who worked with the Min- 753 controls (we hoped for a lot more lead to wrong conclusions. istry of Health in the 1960s and had but could not find them). Our study In the end, I learned that I should records on who developed EG infec- was underpowered, especially when stick to what I do best and leave the tion between 1960 and 1980, along we broke down the cancers according epidemiological studies to the experts. with their contact info. At that time, to organs affected. Our results were Our results showed the exact oppo- there were no electronic records or equivocal, and we ended up publish- site of my original hypothesis. My e-mails, Tweeter or Facebook, or even ing them in a small journal as prelimi- dream of finding a condition (such personal phones. nary evidence. The reviewers killed us as EG infection) that prevents cancer My plan included placing a post- with criticisms, mostly justified. Our development was shattered, and my doc in Cyprus who was responsible overall finding was an approximate 25 anxiety about developing cancer in for the whole project. The postdoc percent increase in cancer risk in EG- the future not only did not decrease recruited 6 to 8 volunteers to help infected patients. but increased by about 25 percent. with the interviews. Each patient had This exercise taught me some I paid dearly for my sentimentally to be located and interviewed at his tough (but obvious to the specialist) motivated mistake. or her home to verify the EG infec- lessons: tion and the patient’s current state of • Sentimentally motivated projects health, including diagnosis of cancer. based on subjective criteria may cost a Eleftherios P. Diamandis (eleftherios.diamandis@ At the same time, we recruited con- lot and carry increased risks of failure. sinaihealthsystem.ca) is the chair in prostate trol subjects (age and gender-matched • Epidemiological studies link- cancer biomarkers and head of clinical biochem- istry, Mount Sinai Hospital, and head of the divi- siblings or neighbors) for comparison. ing diseases with candidate causative sion of clinical biochemistry in the department of Many of the patients were dead, and factors need to be planned carefully laboratory medicine and pathobiology, University we had to interview their relatives. and powered appropriately. Better not of Toronto.

FEBRUARY 2018 ASBMB TODAY 37 ESSAY Raising a rainbow of scientists Situating biochemistry and molecular biology in their social context to retain students of color By Ashley Warfield–Oyirifi

studied biochemistry as an istry students of color often want to money.” He paused to think. “Will undergraduate at the University take our university learning home to graduate school make this mean I of Missouri. As a freshman, I such talented yet disenfranchised rela- more? Will I be able to do more was immediately interested in the tives in a meaningful way. To do so, meaningful stuff?” chemical processes that make biol- biochemistry must matter not just in ogy go. However, as one of the only a cell, organism or clinic but also at a An answer in anthropology black students among more than 200 dinner table and in life. I could not answer Jeremy’s ques- biochemistry undergrads, I found the Although an understanding of how tion. Graduate school helped me find culture within this major to be isolat- my biochemistry studies mattered more meaning in biochemistry, but ing. The concepts and applications around the dinner table eluded me, indirectly. I found the answer in an presented never seemed to touch my the work remained intriguing, and I elective course taught by an anthro- person or my experience, and I failed completed my undergraduate studies pologist where we faced the ques- to understand how a discipline that I in biochemistry. Like many in my tion, “Is race a biological reality or a found so profound and intriguing also cohort, I easily secured employment socially constructed phenomenon?” felt distant and detaching. I perceived after graduation, working in ana- My classmates were students of many an excitement and sense of fulfillment lytical chemistry. The work was well disciplines, from archeology to educa- among my white biochemistry peers paid and interesting, and this career tion. I was the resident life-scientist. that was paralleled in black peers only seemed like a mark of success. How- As such, I was impelled to contribute if they were enrolled in majors like ever, I soon found myself pondering a biochemical rationale to the class social work, psychology or sometimes whether my career had any meaning. inquiry. In my reflection, I shared: “If business. It had to matter beyond investigating we want to utilize an approach where Of course, I cannot assert that molecular structures of compounds we compare biopolymers and small none of my white biochemistry peers and active sites of proteins and help- molecules to elucidate differences longed for more meaning from their ing my company generate revenue. between human populations, then a coursework or that all the biochem- Of what societal utility was the work robust method would be to compare istry students of color sensed a gap I was doing? “Maybe, I’ll find the the full set of molecules that mediate between our academic and real lives. answer in graduate school,” I thought. DNA expression and are mediated However, I can mention anecdotally I didn’t know it then, but I was not by DNA expression. This means that most black students feel respon- alone. Jeremy, another MU biochem- conducting a comparative analysis sibility and satisfaction in connecting istry graduate, recently said, after of not only the genome, as has been their higher education to their loved working five years in oil and polymer done in previous attempts to study ones or communities. Some of our science industries, “I look around differences among races. We must relatives discuss academic topics, but and think ‘Does anybody care about comprehensively profile the transcrip- many of us have living grandparents this (work) beyond the economic tome, proteome, and metabolome. who, despite academic prowess, could value?’ … When I see things around Of the 99.9 percent similarity among not lawfully or reasonably attend the me, I try to consider it at the molecu- genomes of varying races, how much institutions we graduated from. Black lar level. I don’t think other people similarity and difference exists in and other underrepresented biochem- are doing that. We are just making genome expression and why?”

38 ASBMB TODAY FEBRUARY 2018 My thinking was drawn from a previous semester’s graduate biochemistry course in which I studied and pre- sented research findings on initiation complex assembly. The research suggested that euchromatic regions of DNA were coding regions, based on the researchers’ observa- tion of initiation complex assembly throughout those regions. I noted one major limitation: The researchers did not demonstrate gene expression. Why stop at the assembly of the complex? Similarly, for compara- tive analysis of genomes to determine racial difference, it seemed necessary to look beyond the code toward COURTESY OF ASHLEY WARFIELD-OYIRIFI Ashley Warfield-Oyirifi does lab work at the University of Illinois, Urbana–Champaign, where she is studying how dietary global expression patterns compounds influence the expression, activation and signaling of molecules that regulate cancer metastasis. and their environmental influences. After I shared tion. “Why have I not been prompted 2016 story “African-Americans over- this input in class, my classmates and or challenged to understand lived represented among low-paying college professor in the course made valu- experiences through biochemistry majors,” the common practice of able contributions through the lenses before?” I wondered. teaching science, technology, engi- of their disciplines, completing the neering and mathematics, or STEM, discussion. Seemingly, they would not subjects without regard for social have considered suggesting a more Redefining diversity implications ultimately snowballs to comprehensive strategy for investi- Why do U.S. approaches to educa- the displacement of students of color tion imbue us with artificial notions gating racial difference. Similarly, I from sciences and often into lower of a dichotomy between laboratory could not have begun to unpack, as paid service-oriented careers. science and lived experiences? I began my peers did, the implications that How do we undo this? A true and spending late nights and long days lie within concluding that biological systematic commitment to diversity pondering this question. This false differences existed or failed to exist in biochemistry and molecular biol- dichotomy is perplexing, because among races. ogy means recognizing the insepa- the array of biomedical, psychosocial For the first time, primary litera- rable relationship between molecular and sociopolitical dimensions that ture in biochemistry mattered to me interactions and lived experiences. mediate (or are mediated by) life and beyond the methods and molecular To accomplish meaningful diversity physical sciences is immense and can findings. Beyond the potential for in biochemistry, we will need to serve as rich educational material. I clinical applications. The literature redefine diversity and understand it as call it pedagogical capital. This capital spoke to my lived experience, my exis- a variation in the types and applica- often remains untapped in conven- tence. My identity and all our identi- tions of content offered to students tional university-level instruction of ties as humans. It was interesting. It rather than varying shades of students the hard sciences. As a result, many was challenging. It was engaging to in lecture halls. We must extend students with capacities and goals consider the societal implications of the reach of course content beyond to be adept scientists accede to an molecules. But it was not long before applications of the scientific moment, illusion of choice between studies and the celebration of how biochemis- such as the current preoccupation careers that are socially engaging and try and molecular biology could be with precision medicine, rather than those that are scientifically rigorous. used to chime in on questions about relying on admissions offices’ special- As pbs.org reported in the February culture and society turned to lamenta- interest recruitment strategies. It is up

FEBRUARY 2018 ASBMB TODAY 39 to university educators to train diverse A similar unbalanced commitment from their societal status each time students to contemplate diverse (yet to concepts and theories exists in they enter a biochemistry class. Com- robust and sustainable) solutions to a biochemistry education and calls us to mit space in a syllabus for students to diverse and limitless set of biochemis- reposition praxis as a central value. To choose how they apply and explore try and molecular biology questions. introduce variation in biochemistry class content. Some may choose content, we must stop using lectures medical applications and others Steps to take solely to present biochemical equa- socioeconomic issues. Be an advocate tions, concepts and theories. This and model for accurately exploring Here are four steps to attract, serve approach tends to be misaligned with the biochemistry of anything. Be care- and retain heterogeneous populations ful. This advocacy may force you to of students through your instruction. best practices suggested by scholars of instructional design and educational rethink your own research questions 1. Become a learner. Seek out scholarly psychology, which evidences contex- and the interests they serve. reading on societal implications of tual, connected, active learning as Strategies: Assign students to evaluate the biochemistry of cur- molecules. highly effective. A 2014 article in the Proceedings of the National Academy rent events. Or, in the interest of Literature from the history and of Sciences, “Active learning increases time and scale, prepare a five-minute philosophy of science and medicine is student performance in science, engi- weekly segment discussing informa- a stimulating place to start looking for neering, and mathematics,” calls for tion you’ve read from step 1 (above) methodically gathered and recorded the use of active learning to increase and how it intersects with molecular information about scientific knowl- STEM undergraduate degree comple- concepts. edge production. You can gain great tion. Interrogating social applications insight for courses by understanding 4. Be patient and careful of biochemistry provides invaluable the intellectual and social history that and anticipate the benefits led to the modes of scientific inves- content for the type of synthesis, Recentering thinking and teaching tigation we practice. You’ll find sug- analysis and evaluation that defines easily could become a life’s work. It is gested reading at the end of this essay. active learning. In a 2014 article in a slow and imperfect journey. Patience Strategies: When reading, do not the International Journal of Science is key to the cycles of adjusting course make scientist status or scientism Education, Derek Hodson points out strategies, responding to feedback, a condition for deep engagement. the risk of conflating learning science and adapting to social moments and Zoom out and think about how to with learning to address socio-scien- cohorts of students. This kind of integrate information into a problem tific issues. This distinction helps to teaching requires extra time and lacks set or favorite course lecture rather emphasize that we want to integrate than looking for sophisticated expla- social inquiries of molecules into documentability (for tenure promo- nations or appreciation for technical current material rather than make tion), but immense rewards come details. substitutions. at no expense to student learning or Strategies: Revamp a syllabus to course rigor. Look for the following 2. Recenter instruction to include inquiry include one social situation for every benefits and adjust until you notice and application alongside 3 to 5 lecture topics. Ask yourself, them. concepts and theories. “Can a student extrapolate why this Rewards: Students develop as thinkers and problem-solvers rather A groundbreaking text for my rigorous course might be important thinking was political anthro- to a grandparent, general citizen or than learners who know discrete pologist Faye Harrison’s “Outsider legislator?” Read about adult-learning biochemical concepts with no guaran- Within: Reworking Anthropology theories and audit a course in science teed ability to apply them. Professors in the Global Age.” This book and education to retrain yourself as a mul- develop their instructional practices, its approaches serve as a model for timodal, thought-provoking educator. develop a relevant and responsible reconstructing disciplines to extend pedagogy, and challenge many types the reach of inquiries, methods and 3. Share what you’ve learned. Regularly of learners. There is great potential for findings. In chapter 2, “Unburying discuss how molecular events a lifelong sense of professional fulfill- . theory, repositioning practice,” Har- have societal implications ment from coupling biochemistry rison examines how her discipline Scientific spaces at universities instruction with civic engagement to celebrates theoretical knowledge at can serve as a vacuum, separating increase learners’ critical abilities. Fur- the expense of acknowledging how academic content from lived realities. ther satisfaction is likely from seeing practice can inform theory, create Classroom practices must eliminate the outcomes of these new thinkers’ knowledge and advance the discipline. this dialysis effect that filters students work and the impact of recruiting

40 ASBMB TODAY FEBRUARY 2018 Reading list Share your story Have you worked to diver- Thomas Kuhn, “The Structure of Scientific Revolutions,” University of Chicago sify classroom content and find Press (1962). social meaning in basic science? “Kuhn challenged the then prevailing view of progress in ‘normal science’. If so, we want to share your Normal scientific progress was viewed as ‘development-by-accumulation’ story. Please send us examples of of accepted facts and theories. Kuhn argued for an episodic model in ways that you situate biochem- which periods of such conceptual continuity in normal science were inter- istry and molecular biology in a rupted by periods of revolutionary science. The discovery of ‘anomalies’ social context. Send an email to during revolutions in science leads to new paradigms.” [email protected]. — en.wikipedia.org/wiki/The_Structure_of_Scientific_Revolutions away’s term “situated knowledges”) — investigations of molecular events P. Freire, “Pedagogy of the Oppressed,” Herder and Herder Press (1970). coupled with the experiences and cul- “Freire outlines a theory of oppression and the source of liberation. In ture where these events occur or are Freire’s view, the key to liberation is the awakening of critical awareness promoted. I am completing my Ph.D. and the thinking process in the individual.” studies in an applied field, nutrition, — bookrags.com where I am studying how dietary compounds influence the expression, Alondra Nelson, “The Social Life of DNA: Race, Reparations, and Reconciliation activation and signaling of molecules after the Genome,” Beacon Press (2016). that regulate cancer metastasis. From my findings, I am prepared to coordi- “We know DNA is a master key that unlocks medical and forensic secrets, nate a community-based curriculum but its genealogical life is both revelatory and endlessly fascinating … that will determine if awareness of the Nelson incisively shows that DNA is a portal to the past that yields insight biochemistry behind eating can influ- for the present and future, shining a light on social traumas and historical ence chemoprotective dietary habits injustices that still resonate today.” in cancer survivors. Together, these — beacon.org/The-Social-Life-of-DNA-P1140.aspx studies can speak to health disparity in cancer mortality by highlight- Anthony Ryan Hatch, “Blood Sugar: Racial Pharmacology and Food Justice in ing options other than sometimes Black America,” University of Minnesota Press (2016). inaccessible clinic-based preventative “How contemporary biomedicine has shaped race and racism as America’s care. I appreciate the combined social health disparities increase … Hatch argues that the advent of metabolic relevance and scientific rigor of this syndrome … (repackages) race within biomedical and genomic research.” nutrition-based project. — upress.umn.edu/book-division/books/blood-sugar However, I envision a day when students of biochemistry are not driven to declare an alternative course Author’s note: of study to connect their biochemi- Kuhn and Freire are universal texts. The other two suggestions are geared cal investigation to its societal value. toward interests at the intersections of medicine, race, food and science. I believe that with a commitment to However, whatever your research interests, there are texts explaining how diversifying content rather than only your discipline may play out in society or how it evolved into its current students, that day will come. form. These texts can inform and inspire teaching strategies, course mate- rial and students’ thinking. and retaining students with varying Ashley Warfield–Oyirifi (warfild2@ My approach illinois.edu) is a Ph.D. student at backgrounds, interests and goals. Although I have not personally rec- the University of Illinois, Urbana- Let’s reimagine a biochemistry that Champaign. Having navigated onciled the disjunction between bio- attracts and retains the best students the cultures of life and physical chemistry and life science instruction, science, blackness and wellness, of all backgrounds, without a system- she is passionate about conducting scientific atic exclusion of those interested in I have found satisfaction in situated investigations that are situated in a larger panning beyond the protein. science (adapted from Donna Har- societal context.

FEBRUARY 2018 ASBMB TODAY 41 RESEARCH SPOTLIGHT From back-porch evolution to learning slang at the bench

hantá D. Hinton is an associ- lina at Chapel Hill, and a ate professor of biology at the historically black college S College of William and Mary or university, or HBCU, in Williamsburg, Virginia. Here she Howard University, as well describes an early conversation with as serving as faculty at both her grandfather about snakes and an HBCU and a PMI, frogs that inspired her interest in provided opportunities science, explains how she turns her to develop strengths that failures into motivation, and shares allowed me to reach my the values that have served her well as current position. If pressed a mentee and now a mentor. to point out a key decision and experience that allowed Tell us about your current me to obtain tenure at the College of William and career position. Mary, it would be choosing After a year-long sabbatical, I my postdoctoral position recently returned to the biology at Cold Spring Harbor department at the College of William Laboratory. This experience and Mary, a primarily undergraduate challenged me and shaped research university that offers students my career in the best way. the best of both worlds. It blends the I trained as a cell and

one-on-one faculty contact and men- developmental biologist as COURTESY OF SHANTÁ D. HINTON toring associated with a small school a doctoral student; I was Shantá D. Hinton, an associate professor at the College of William with the faculty expertise and research thrust into a hardcore bio- and Mary, says her postdoctoral position in a “hardcore biochemical chemical lab as a postdoc- lab” at Cold Spring Harbor Laboratory challenged her and shaped opportunities typical of research- her career. intensive institutions. It also offers toral fellow. And the most me the best of both worlds: to be a important thing happened scholar at the bench while engaging to me during a lab meeting. or working in the garden with my cousin and me when we were chil- novices in research experiences that My PI said, “This is my standard for dren, he explained the concept of evo- often produce educated scientists. a journal publication, nothing below lution of frogs and snakes. In particu- My research investigates the role of a this. Each of you should aim for this lar, I was fascinated with the concept particular protein we initially thought or higher to publish from this lab.” I smiled inside because for the first that snakes had legs but supposedly was just a “dead” enzyme as a regula- time expectations for me (beyond my lost them through evolution. Because tor in signal transduction cascades family) at a PMI were the same as for I am afraid of snakes and would not (cellular communication). any other gender, nationality, ethnic- touch them (except helping a late ity, etc. No excuses. It was time to dear friend who was a herpetologist), What key experiences and complete the task and soar. time or books would have to prove decisions helped you reach grandpa’s story. Of course, I was abso- How did you first become lutely delighted by the 2015 article this position? in Science, “A four-legged snake from This is a complicated question for interested in science? the Early Cretaceous of Gondwana.” me. My matriculation as a student at My first interest in science came Grandpa, who completed the 10th a primarily majority institution, or through my late maternal grandfather, grade, had great wisdom; his story PMI, the University at North Caro- Jesse Hinton Sr. Sitting on the steps was confirmed, and it brought back

42 ASBMB TODAY FEBRUARY 2018 memories of my introduction to the boundless wonders of science. “After my initial failure, I learned to read and study, to synthesize information to formulate new questions Were there times when you and/or hypotheses — which is so critical as a scientist. I failed at something you felt also learned that failing is a necessary part of the journey was critical to your path? to success.” If so, how did you regroup and get back on track? One critical failure happened in This is challenging, but it is my rule, What are your hobbies? the social sciences. I failed my very so I have to work through it. Lastly, my family taught me at a young age I am an avid CrossFitter, which first oral exam in my 10th-grade helps with stress. In addition, I love history course. That class still ranks that the best way to defeat failure or an enemy is to be successful, which to attend comedy shows and plays, as the most terrifying, engaging and especially on Broadway. Laughter and invigorating experience in all my means you have to move forward and progress. I am the sole person respon- music always heal my soul and help academic matriculation. For the first me cope with a failure. five minutes each day, the teacher sible for my actions. was a drill sergeant, orally quiz- What was the last book zing students on previously taught What advice would you material, with only 15 seconds to give to young persons you read? understand and address the ques- “Hidden Figures” by Margot Lee tion. The timer buzzed, and I heard, from underrepresented Shetterly. Coincidentally, I stopped “Hinton, you’re out. Your grade is a backgrounds who want to reading “Something Must Be Done 50.” No one likes to be embarrassed. pursue a career in science About Prince Edward County: A So I spent hours learning the material Family, a Virginia Town, a Civil and creating questions that I might similar to yours? Rights Battle” by Kristin Green to be asked to ensure the buzz was never Believe in yourself beyond your read “Hidden Figures” for an event at associated with my name again. All knowledge and skills; envision your- my institution. Therefore, I appreci- my fellow students did the same, ated when “Hidden Figures” referred self beyond your present status. There creating such an enjoyable class that to events in Prince Edward County. will be moments where you are the we ran from the cafeteria to attend it. We competed for the best time in only one who believes in you. Pursue Do you have any heroes, answering a question. After my initial science because of a genuine inter- failure, I learned to read and study, to est, while being very careful of the heroines, mentors or role synthesize information to formulate appearance that it is a benefit or an models? If so, describe new questions and/or hypotheses — advantage for someone like you in the how they influenced you. which is so critical as a scientist. I sciences. Align yourself with men- also learned that failing is a necessary tors who will tell you the truth, even My parents (Larry D. Petway and part of the journey to success. Now, if it may alter (hopefully, only for a Mamie L. Hinton) and maternal grandparents (the late Jesse Hinton whenever I experience failure, the brief moment) the relationship. Learn Sr. and the late Mamie R. Hinton). next day I start executing an action your weaknesses; do not be afraid As a first-generation college student, plan to develop the failure into a to share with your mentors, and ask it was important for me to have love success. When this is not possible, I their help to change these weaknesses release the failure and move forward. and structure. These heroes provided into strengths. Understand that pay- In essence, I use my failures as a plat- more than that; they made important ing it forward doesn’t mean you are form to set and achieve higher goals. sacrifices and preached the value of obligated to carry everything on your I am sure this is a relief to those who an education. They made a conscious endured the venting about my early back or alone. Also, don’t be afraid to decision (along with my aunts and failures, including my family, best evolve. Lastly, stay focused on your uncles, who decided not to attend friend and mentors. In addition, I goals while being flexible, constantly college) to invest in me becoming the have a rule never to take a failure as a reminding yourself why you like sci- first in the family to graduate from personal assault, even when it may be. ence, and enjoy the scientific process. college. Although they didn’t under-

FEBRUARY 2018 ASBMB TODAY 43 stand the process, they worked hard dead. I loved reading Greek mythol- sacrifice my love of the bench, at least as a team and spoke it into existence. ogy as a teenager and still watch mov- not yet. This has truly enriched my I am grateful that they all lived to see ies pertaining to Greek mythology. It students’ lives and my life. me obtain a Ph.D. My research pro- is an honor to introduce undergradu- gram is based on the love, structure, ates and master’s students to the joys honesty and directness that my heroes of research and co-author manuscripts provided for me; this model has with them within in a field that is in About the served me well as a mentor. its infancy. On my worst day, know- Research Spotlight ing that I can walk into my lab full of What is it that keeps you vibrant, intelligent, creative and eager The American Society for Bio- chemistry and Molecular Biol- working hard every day? students who may be playing music (while being productive) or introduc- ogy’s Research Spotlight high- My curiosity, always learning and ing me to new slang such as “rekt” lights distinguished biomolecular choosing the correct discipline; I like (wrecked or destroyed) while keeping and biomedical scientists from pursuing edgy projects. I am fortu- score of their rekt assailants on the diverse backgrounds as a way to inspire up-and-coming scientists nate to investigate a field of enzymes white board, will make me smile. The to pursue careers in the molecu- (protein tyrosine phosphatases) that joy that keeps me going is that they lar life sciences. Eligible candi- will celebrate its 30th anniversary develop into these amazing young dates include Ph.D. students, this year. More importantly, I am scientists, the majority of whom enter postdoctoral fellows, and new or absolutely thrilled to investigate a doctoral programs. They are the ones established faculty and research- unique catalytically inactive member who are cited as first authors on the ers. To nominate a colleague for (MK-STYX) of this field whose pro- papers in the field; that is an amazing this feature, contact education@ totype’s name alludes to the river Styx legacy for us. Lastly, I am still work- asbmb.org. in Greek mythology, the river of the ing alongside them. I haven’t had to

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