NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 24 ISSUE 4 • JULY-AUGUST 2016

Digitizing and Demystifying Medicine Preserving Medical Bridging the Gap Between Basic Research and Clinical Medicine History BY LAURA STEPHENSON CARTER JOHNS HOPKINS UNIVERSITY APPLIED PHYSICS LABORATORY/SOUTHWEST RESEARCH INSTITUTE BY JEFFREY S. REZNICK, NLM

Libraries around the world are digitizing their historical treasures and making them more accessible via the Internet than ever before. Leading the way is the National Library of Medicine (NLM), the world’s largest biomedical library, located on the NIH campus in Bethesda, Maryland. The NLM traces its origins to 1836, when it consisted of a few dozen books in what was then the Library of the Office of the Surgeon General of the United States Army. Since then, its vast collections have been built over multiple generations, literally passed down from one generation to the next, and they contain material from antiqui- ty to the present and nearly every part of the world: from books, journals, photographs, and films and videos to artwork, postcards, pamphlets, and much, much more. One of the Demystifying Medicine sessions featured a space scientist who talked about the importance of biomedical The library opened its doors on the research that addresses the medical needs of future space travelers. Shown: Artist’s concept of the New Horizons NIH Bethesda campus in 1962, and it has spacecraft encountering Pluto and its largest moon, Charon, in July 2015. served the world ever since in translating What do you get when you combine a clinician, a Ph.D. scientist, and biomedical research into practice, in leading a patient? A course called “Demystifying Medicine” that bridges the gap between in information innovation, and, every day via basic research and clinical medicine and covers a range of topics from genetics to the Internet, in serving millions of scientists, infectious disease to the effect of spaceflight on humans. The course is the brain- health professionals, and members of the child of Irwin “Win” Arias, who started it at NIH in 2002 after having run a similar public. CONTINUED ON PAGE 10 The NLM holds one of the world’s largest and most treasured collections that CONTENTS includes both historical and contemporary FEATURES • |1| Digitizing and Preserving Medical History |1| Demystifying Medicine items in a variety of media. One of the |11| Demystifying Health Effects of Global Warming |12| Demystifying Space Medicine oldest items dates from the year 1094. DEPARTMENTS • |2| DDIR: Red Team Report Update |4| Training Page |5| News Briefs It is an Arabic manuscript entitled The |6| News You Can Use: Crowdsourcing for Data Analysis |7| New Methods: Tool to Study Brain CONTINUED ON PAGE 14 Cells |8| Research Briefs |13| The SIG Beat |15| NIH History: AIDS at 35 |15| Abbreviations |16| Colleagues: Recently Tenured |19| Kudos |20| NIH History: Computers a Go-Go FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH

Making a Great Institution Even Greater Red Team Report Update BY MICHAEL GOTTESMAN, DDIR

The NIH Clinical Center is one of was established to obtain expert outside Collins, who described the current the most distinctive and influential advice about possible remedies. In the structure of the Clinical Center and research hospitals in the world. Many of course of its four-month-long review, the some of its many contributions to modern its patients have rare and difficult-to-treat Red Team raised questions about whether medicine. Dr. Collins related that the press conditions, and the Clinical Center— the distributed organizational structure of coverage of the Red Team report had with its numerous first-in-human studies, the Clinical Center, and the absence of delivered a significant blow to staff morale a dedicated staff of unique talent, and a certain fail-safe systems and appropriate because it seemed to imply that the quality backbone of hundreds of NIH principal oversight, could lead to risks to patient of patient care is routinely compromised investigators conducting research in safety and quality of care. at the Clinical Center, which is simply surrounding NIH institutes and incorrect. He stated unequivocally centers (ICs)—is often the last that the vast majority of physicians, hope for these patients. Despite nurses, and other staff who work at the often insurmountable odds, this The Clinical Center lies at the Clinical Center are highly capable and extraordinary staff seeks to cure physical and emotional heart compassionate health-care providers, patients, extend lives, and reduce deeply dedicated to patient care. suffering. Indeed, in 2011, the of the NIH Bethesda campus. In addition, Dr. Forese indicated Clinical Center won the prestigious We intend to keep it there, for that every member of the Red Lasker-Bloomberg Public Service Team made it clear that they would Award. Bricks and steel and pretty no living and dynamic entity not hesitate to be a patient in the sunlit atriums don’t win such can survive without its heart. Clinical Center themselves. And in a awards. People do. And the Lasker- remarkable series of testimonials, each Bloomberg award went to the entire of the members of the new Hospital Clinical Center staff. Board (including two representatives of the New Research Hospital Board Patient Care Advisory Group) reiterated One of the Red Team’s major Making Something Great Even Greater their confidence in the dedication of the recommendations was to establish a new The challenge before us now is how to Clinical Center staff. Clinical Center Research Hospital Board. make something great even greater. One of the new board members is Paul That group met for the first time on Friday, Recently, the “Red Team” (a working O’Neill, former Alcoa CEO and United July 15, 2016, in an open meeting. All group of the Advisory Committee to States Secretary of the Treasury, who has NIHers were invited to attend in person the Director, ACD) was asked to review dedicated much of his career to improving or listen in on the presentations and multiple aspects of the Clinical Center. employee safety and more recently to discussions that dealt with how to improve The sentinel event that led to the need for patient-safety issues. He was eloquent systems that improve patient safety and this review occurred in May 2015 when in his description of the importance of governance of the Clinical Center (https:// the FDA identified significant deficiencies engaging the entire community in efforts videocast.nih.gov/launch.asp?19791). in the Clinical Center pharmacy, leading to improve safety for both patients and The board, chaired by Laura Forese, a to the closure of the Pharmaceutical employees, noting that health-care workers pediatric orthopedist and chief operating Development Section. An internal review have the highest incidence of on-the-job officer of the New York–Presbyterian then revealed several other areas of concern injuries of any U.S. industry. Laura Lee, hospital system, was introduced to the in the Clinical Center. The Red Team director of Patient Safety in the Clinical Clinical Center by NIH Director Francis

2 THE NIH CATALYST JULY-AUGUST 2016 FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH

Center, noted that for standard metrics, the the formal leader of ORSC while a national decisions must await the arrival of a new Clinical Center has a strong track record of search is underway. To assist Dr. Griffith, CEO), some features have been endorsed patient safety—but the goal, as articulated Valerie Bonham, previously legal counsel by the IC directors, including the direct by Mr. O’Neill, is “the pursuit of perfect.” with NIH’s Office of General Counsel, has reporting of all clinical directors to their stepped in as Deputy Director of ORSC IC directors. This reporting relationship Changes and will provide regulatory knowledge will establish that each IC director is In reaching for this goal, the Red Team and management skill. Furthermore, providing oversight for quality of patient identified some aspects of the Clinical Bruce Burnett, an experienced manager care and clinical research. The Red Team Center that needed work. John Gallin, of Current Good Manufacturing also strongly advocated for the formation of director of the NIH Clinical Center, Practice facilities and clinical activities a Clinical Practice Committee consisting Avindra Nath, chair of the Medical at Duke University School of Medicine of clinical experts at different levels Executive Committee, and Henry (Durham, North Carolina), will be a major and in different areas of patient care, to Masur, representing the chairs of the contributor to the leadership of this office. establish the highest possible standards of Clinical Center departments, presented (He arrived at NIH on July 18). He will practice in the Clinical Center. The precise constructive ideas for how to make needed begin by meeting our clinical directors makeup, scope of responsibility, reporting improvements. Many of the changes that and scientific directors and acquainting arrangements, and interactions with the have to be made will need to originate himself with current practices while we Medical Executive Committee will be from the professional and support staff at devise better support mechanisms for important areas for future discussions with the Clinical Center, especially those who clinical research in all of our ICs. If you staff and among leadership. have direct and intensive patient-care hear from any of these people, trust that responsibilities. they are here to help our clinical programs Steven Holland has already moderated function with the highest possible safety Helping the Clinical Center address the a series of six open meetings with staff at and efficiency. Red Team’s recommendations will be one all levels in the Clinical Center, and these of the most important tasks of my tenure as meetings have given NIH leadership an • Search for chief executive officer Deputy Director for Intramural Research, opportunity to hear directly about the A search committee has been established and we are only beginning this process. concerns and ideas of our colleagues. and an advertisement has been placed for The Clinical Center lies at the physical Additional meetings and focus groups are a new chief executive officer to manage and emotional heart of the NIH Bethesda being planned to get into more detail about the operations of the Clinical Center. campus. We intend to keep it there, for changes that can be made. Discussion of the characteristics of a new no living and dynamic entity can survive Dr. Collins and NIH Principal Deputy Clinical Center CEO emphasized hospital- without its heart. Director Lawrence Tabak summarized management skills, because it is expected some of the changes that have already taken that there will also be a chief scientific For further reading (and viewing), see Michael place to date including: officer responsible for the clinical research Gottesman’s editorial in the May–June 2016 conducted by the Clinical Center staff and issue of the NIH Catalyst (http://irp.nih.gov/ • New Office of Research Support and the principal investigators in the ICs. catalyst/v24i3/from-the-deputy-director-for- Compliance (ORSC) intramural-research) and the presentation Establishment of a new ORSC in the • Governance structure that he and Clinical Center Director John Office of Intramural Research, under the One model for a possible new governance Gallin made at the April 22 town hall meeting supervision of the Deputy Director for structure for the Clinical Center was (NIH only, at http://videocast.nih.gov/launch. Intramural Research. Kathryn Zoon, proposed by Dr. Tabak. He stressed that asp?19639). The NIH response to the Red former scientific director of NIAID, ably this model was only a starting point for Team’s report was approved by the ACD served as inaugural acting director of ORSC discussion, and he hopes and expects there on June 9. You can download the response for the first couple of months but retired on to be modifications with input from all of (http://acd.od.nih.gov/Red_Team_final_ June 23. Andrew Griffith has generously the stakeholders across and outside NIH. report_4262016.pdf) and slides from the agreed to become acting Deputy Director Although the details of this structure ACD presentation (http://acd.od.nih.gov/ for Intramural Clinical Research and will be are therefore not yet established (many presentations/062016_RedTeam.pdf).

http://irp.nih.gov/catalyst 3 THE TRAINING PAGE

SPECIAL FROM THE NIAID FELLOWS WORKSHOP Collaborating for Success BY OMOZUSI ANDREWS, NIAID

“If you want to walk fast, walk culture when accepting a job. Other medical science liaison at AstraZeneca, alone. If you want to walk far, walk panelists spoke about the importance an assistant professor of medicine at the together,” observes an old African proverb of time management, conducting Indiana University School of Medicine that symbolizes the value of collaboration, informational interviews, prioritizing (Indianapolis), and an investigator at the said National Institute of Allergy and work, and enrolling in networking and National Cancer Institute (NCI)—shared Infectious Diseases (NIAID) Training other classes for self-improvement. their strategies for landing bench-specific Director Wendy J. Fibison at the 10th The panelists also described successful jobs including formulating e-mails, annual NIAID Fellows Workshop. experiences during their job search as assessing career websites, maintaining a Postdocs and graduate students, some of well as useful lessons they had learned visible LinkedIn profile, and relying on whom had come from as far as NIAID’s throughout their careers. In response to word of mouth. labs in Hamilton, Montana, had gathered the question, “What things would you NCI investigator Joe Ziegelbauer on April 11 for a day of activities that have done differently as a postdoc?” some advised trainees to “learn how to promised to help them learn how to begin shared that they wished they had explored quickly immerse” themselves in their “navigating collaborative avenues for new environments. The “Research career success.” Advice for pursuing career Management” panelists also To get things started, encouraged trainees to master and NIAID Deputy Director Hugh options after postdoctoral merge more than one field such as Auchincloss presented a review of training: Be committed to your bioinformatics with their research, the institute’s research achievements, improve their time-management and including studies on antiretroviral goals; know the difference grant-writing skills, and actively build therapies for patients with human between needs and wants; their own niche. immunodeficiency virus (HIV); the In his keynote address, Keith development of vaccines; and the understand the requirements Micoli (Director of the Postdoctoral importance of continuing basic-science for success; do your best; and Program at New York School of research. Medicine in New York) urged trainees Trainees were then provided a never give up. to take purposeful steps towards their variety of career options beyond the future goals. He likened the journey bench during the “Career Options” panel opportunities away from the bench, tried after postdoctoral training to a challenging discussion. Panel members—whose new things so they could break out of solo 125-mile hike that he completed in jobs ranged from senior lead reviewer at their comfort zone, and networked more. roughly 10 days. His hike taught him the FDA to the China Media Project It was refreshing to hear the similarities valuable lessons including the importance manager for the American Institute of and differences among the panelists’ of being committed to your goals, knowing Physics—advised the trainees to build experiences. Given the challenges of the the difference between needs and wants, their communication, teamwork, and job market, trainees were inspired by the understanding the requirements of success, networking skills. words from FDA’s Cynthia Chang, who doing your best, and never giving up. Gaia Vasiliver-Shamis (Director of commented, “Your career and your job do Career Development at Emory University not define you.” The workshop was sponsored by the NIAID School of Medicine in Atlanta), who said The trainees enjoyed a networking Office of Training and Diversity. The theme, she got her job through networking, urged lunch with invited guests and former speaker selection, and program were almost trainees to “play well with others in the NIH postdocs and afterwards attended entirely executed by the NIAID Fellows Work- sandbox” and learn how to interact with a “Research Management” panel shop Planning Committee, which was led by their managers. She also encouraged discussion that also echoed the theme NIAID postdoctoral fellow Caleb McKinney trainees to think about the workplace of collaboration. The three panelists—a and NIAID graduate student Jessica Hostetler.

4 THE NIH CATALYST JULY-AUGUST 2016 NEWS BRIEFS

A recipient of many awards, Brennan is New Associate Director for a past-president of the American Medical AIDS Research Informatics Association and a member M a u r e e n M . G o o d e n o w wa s of the National Academy of Medicine recently appointed as NIH associate (formerly the Institute of Medicine). “[Dr. director for AIDS research and director Brennan is] ideally suited to lead the NLM of the NIH Office of AIDS Research in the era of precision medicine, as the (OAR). She brings nearly 30 years library becomes the epicenter for biomedical of experience in AIDS and human data science, not just at NIH, but across the immunodeficiency virus (HIV) research biomedical research enterprise,” said NIH and advocacy to the position. She is Director Francis Collins when announcing Patricia Flatley Brennan expected to join NIH in July 2016 to lead Brennan’s appointment in May. Patricia Flatley Brennan to OAR’s efforts. She will work closely with Lead NLM the NIH institutes and centers to pursue Holland Named NIAID new tools for preventing HIV infection Patricia Flatley Brennan has been Scientific Director including a vaccine, improved treatments, named the director of the National and ultimately, a cure. S t e v e n M. Hol l a n d h a s been Library of Medicine (NLM), succeeding Before coming to NIH, Goodenow was appointed scientific director of the Donald Lindberg, who retired in 2015. a professor of pathology, immunology, and National Institute of Allergy and Brennan is expected to begin her new role laboratory medicine and the Stephany W. Infectious Diseases (NIAID), succeeding in August 2016. Holloway University Endowed Chair for Kathryn Zoon, who retired recently. Brennan is the Lillian L. Moehlman AIDS Research at the University of Florida NIAID Principal Deputy Director Hugh Bascom Professor at the University of at Gainesville. She was also the director Auchincloss was acting scientific director Wisconsin at Madison’s School of Nursing of the Center for Research in Pediatric after Zoon stepped down last year. and College of Engineering. She also leads Immune Deficiency. She led a research Holland, who is an NIH Distinguished the Living Environments Laboratory at program in molecular epidemiology, patho- Investigator, has served as NIAID’s chief the Wisconsin Institutes for Discovery genesis, and vaccines for HIV-1 and related of the Laboratory of Clinical Infectious (Madison, Wisconsin), which develops viruses, including viruses that cause cancer. Diseases (LCID) since 2004 and as NIH new ways for effective visualization of high- deputy director for intramural clinical dimensional data. research since 2011. His research areas Appointment of a New She has been a pioneer in the have included Job’s syndrome, a rare Chief of BTRIS development of information systems for immunodeficiency disorder, and the patients. She developed ComputerLink, On July 10, Jose Galvez became the genetic conditions predisposing people to an electronic network designed to new chief of the Biomedical Translational mycobacterial infections. reduce isolation and improve self-care Research Information System (BTRIS) More recently, Holland has been among home-care patients. She directed in the NIH Clinical Center. He was the interested in genetic conditions associated HeartCare, a web-based information program director of Clinical and Transla- with severe coccidioidomycosis—an and communication service that helps tional Informatics with the NIH’s Center infection caused by inhaled spores of a soil home-dwelling cardiac patients recover for Biomedical Informatics and Infor- fungus found in the southwestern United faster and with fewer symptoms. She also mation Technology. NIH-wide resource States, parts of Mexico, and Central and directed Project HealthDesign, an initiative supporting clinical-research studies across South America—and acquired forms of designed to stimulate the next generation the Intramural Research Program (IRP), anticytokine autoimmunity that predispose of personal health records. Brennan also and as the interface between the IRP and one to opportunistic infections. conducts external evaluations of health- extramural investigators. information technology architectures and Excerpted from the July 1, 2016 edition of the Read longer versions online at http://irp. works to repurpose engineering methods NIH Record (https://nihrecord.nih.gov/news- nih.gov/catalyst/v24i4/news-briefs. for health care. letters/2016/07_01_2016/milestones.htm).

http://irp.nih.gov/catalyst 5 NEWS YOU CAN USE

Crowdsourcing for Data Analysis Web Platform Makes Public Gene-Expression Data More Accessible BY HILLARY HOFFMAN, NIAID

The 29 immunologists who data and perform simple analyses and “helps and form comparison-group pairs (CGPs). gathered in the Rathskeller Room, to democratize the mining of public data Each CGP comprises two collections of nestled in the basement of NIH’s sets,” said Tsang. gene-expression profiles from a single Cloisters (Building 60), were brandishing Tsang and his team designed OMiCC study. For example, researchers could only laptops—not beer steins—as they as a community-based platform to capitalize create a CGP to compare blood samples took part in the Omics Compendia on the biological expertise of its users. Public from people with lupus with those from Commons (OMiCC) Jamboree in database entries typically contain raw study healthy control subjects. Throughout the April. They were eager to gain hands-on data that need to be structured for analysis. day, members of Tsang’s team circulated experience exploring publicly available In OMiCC, researchers can create groups through the room to answer questions and gene-expression data sets and delving into of data, use a standardized vocabulary to offer advice. the crowdsourcing web platform that was annotate them, and assign parameters such Within OMiCC, users can perform developed by scientists at the National as sample-type and disease. OMiCC saves statistical analyses on CGPs from Institute of Allergy and Infectious these user-created groups and associated different studies to search for biological Diseases (NIAID). metadata, making them available to other relationships. Taking such a meta- John Tsang, chief of the Systems users for reuse. analysis approach to pool information Genomics and Bioinformatics Unit in “It’s kind of like Wikipedia, but instead from multiple studies has the potential for NIAID’s Laboratory of Systems Biology, of user-generated articles, you end up with uncovering more robust biological signals, began developing OMiCC three years ago annotations and groups of data that can be Tsang explained. OMiCC users also can after he noticed one of his postdoctoral reused to conduct new analyses, generate generate basic visualizations and export fellows struggling with her project because new hypotheses, and address novel scientific the underlying data for further analysis she didn’t have the computational expertise questions,” said Tsang. “We hope to kick with other programs. Currently, Tsang and to make good use of public data. Data off a positive feedback loop: As more people his team are compiling preliminary results retrieval, processing, and analysis typically group and annotate data, the OMiCC stemming from the work done during the require computer programming skills that platform will become even more useful, April jamboree. many experimental biologists lack, Tsang and more people will join the OMiCC Tsang hopes that using OMiCC to noted. As a result, the wealth of public data community.” analyze data from multiple studies will remains largely untapped, accessible only To introduce OMiCC to the NIH help biologists obtain fresh insights and to researchers who have the appropriate community and help test its capabilities, inform the design of new experiments. But, computational skills and experience. The Tsang and his team, including NIAID he cautioned, OMiCC is not intended to OMiCC web interface, however, enables clinical fellow Rachel Sparks, organized replace collaborations with statistical and biologists without that experience to explore the OMiCC Jamboree, the first such bioinformatics experts to perform advanced event they’ve led. Their goal was for the data analysis. His team hopes to host more jamboree participants—25 from NIH, jamborees in the future to further assess two from FDA, and two from nearby whether convening teams of volunteers to universities—to meta-analyze and use public datasets is an effective way to compare autoimmune diseases in humans generate and test research ideas. and mouse models. At the beginning of the day, Tsang’s The OMiCC platform (and perhaps future team divided the participants into groups jamborees) is applicable to other biomedical researchers, too. Researchers can access

NIAID of three based on their individual expertise OMiCC at http://omicc.niaid.nih.gov. The Jamboree participants were eager to gain hands-on and assigned each a particular area to experience exploring publicly available gene-expression explore such as mouse studies of multiple website also provides videos and a step- data sets and delving into the capabilities of OMiCC, a by-step tutorial to help users navigate the crowdsourcing web platform developed by NIAID. sclerosis or human studies of lupus. The participants had to identify relevant data platform.

6 THE NIH CATALYST JULY-AUGUST 2016 NEW METHODS

New Tool Enables Studies of Brain Structure and Function NIEHS Researchers Developed Genetically Modified Mouse Lines to Help Identify Brain-Cell Types BY ROBIN ARNETTE, NIEHS

said NIEHS staff scientist Nicholas Plummer, who shared first authorship on the Cell Reports paper with postdoctoral fellow Natale Sciolino. “Using viruses limits you to examining fairly compact populations of cells,” Plummer said. “With our mouse lines, we can label and control the activity of widely dispersed cells, and we can activate them any time during development.”

Current research The mouse lines will help researchers

PATRICIA JENSEN, NIEHS PATRICIA answer key questions about

Tool identifies individual brain cells. This micrograph displays brain cells, from one of Patricia Jensen’s new mouse developmental and functional lines, that express hM3Dq when activated by the agent clozapine N-oxide. In the color version of this image, the cells diversity within the noradrenergic appear red as a result of the fluorescent protein mCherry, which is co-expressed with hM3Dq. Electrodes (white lines) are used to measure the cellular activity of a cell expressing hM3Dq-mCherry (blue dye indicates the cell being measured). system—the neurons that use the neurotransmitter norepinephrine, also called noradrenaline. The noradrenergic Researchers at the National Identifying distinct cell populations system is disrupted in several conditions Institute of Environmental Health The mouse lines allow researchers to such as anxiety disorders, depression, Sciences (NIEHS) recently designed identify distinct populations of brain cells Alzheimer disease, Parkinson disease, genetically modified mice that will defined by the expression of different and drug addiction. help neurobiologists address one of the genes during development, determine “For the first time, we’ll be able to most fundamental questions in brain where these populations are located, and manipulate small subsets of these neurons research: What are the different cell investigate their function. and ask which ones are important for types in the brain, and what are their The 2015 paper described mouse lines anxiety-type or impulsive behaviors,” functions? in which fluorescent proteins were used Sciolino explained. The new mouse lines will let scientists to label and visualize cells. The mouse Although Jensen’s group is studying identify specific populations of brain cells lines described in the 2016 article allow the nervous system, the mouse lines may and determine how they control behavior. researchers to noninvasively increase also be used to investigate almost any The findings will advance our understanding the activity of cells and observe the type of cell, including pancreatic beta of neurological disorders such as Alzheimer behavioral and physiological effects in cells and hepatocytes. disease, drug addiction, and depression. freely moving animals. This control of “The system can be used in virtually It took about six years to develop and cell activity is achieved by the expression any cell that has the Gq-coupled characterize the seven mouse lines, said of a laboratory-created mutated cell- signaling pathway,” Jensen said. NIEHS scientist Patricia Jensen, who is surface receptor hM3Dq. the corresponding author of the article Developed by Bryan Roth at that appeared recently in the journal Cell the University of North Carolina at For more NIEHS research news, check out Reports (Cell Rep 15:2563–2573, 2016) Chapel Hill, hM3Dq is most often the online NIEHS Environmental Factor and of a companion paper published introduced into brain cells by injection newsletter at http://www.niehs.nih.gov/ in 2015 in the journal Development with engineered viruses. But the viral- news/newsletter/2016/7/. (Development 142:4385–4393, 2015). injection procedure has drawbacks,

http://irp.nih.gov/catalyst 7 CATALYTIC RESEARCH

different types of cancer. Past research Intramural Research Briefs showed that physical activity reduces the risk of heart disease and death from any cause in addition to lowering the odds of developing colon, breast, and endometrial cancers. However, much less is known about its influence on other cancers. To examine this issue, the investigators evaluated data on self-reported physical activity levels and the prevalence of 26 different types of cancer from 12 datasets that were part of the Physical Activity Collaboration of NCI’s Cohort Consortium. Altogether, the data included information on 1.44 million American and European adults, ages 19 to 98. The analysis confirmed that leisure-time physical activity is associated with a lower risk of colon, breast, and endometrial cancers. It also determined that leisure-time physical activity was associated FOR NCI © 2013 TERESE WINSLOW LLC, U.S.TERESELLC,RIGHTS 2013 WINSLOW GOVERNMENT © CERTAIN HASNCI FOR with a lower risk of 10 additional cancers, with Paraganglioma, a rare tumor that often forms near the carotid artery, is one of two types of tumors that may cause the same symptoms as attention-deficit hyperactivity disorder (ADHD) in children. It may also form along nerve pathways the greatest risk reductions for esophageal in the head and neck and in other parts of the body. adenocarcinoma, liver cancer, cancer of the gastric cardia, kidney cancer, and myeloid NICHD, CC: RARE CANCERS MAY nine children no longer experienced ADHD leukemia. Myeloma and cancers of the head MASQUERADE AS ADHD IN CHILDREN symptoms. The study authors suggest and neck, rectum, and bladder also showed Rare tumors called pheochromocytomas that high blood pressure accompanying risk reductions that were significant, but not and paragangliomas may cause the same a diagnosis of ADHD could be a warning as strong. Risk was reduced for lung cancer, symptoms as attention-deficit hyperactivity sign that the child may have something but only for current and former smokers; the disorder (ADHD) in children, leading more than a hyperactivity disorder and that reasons for this are still being studied. to inappropriate treatment that could pheochromocytomas and paragangliomas The authors propose that physical worsen their symptoms and potentially should be on the list of potential causes. activity may reduce cancer risk by altering endanger their health. The tumors secrete (NIH authors: M. Batsis, A. Stratakis, T. concentrations of certain hormones such catecholamines—substances that stimulate Prodanov, G.Z. Papadakis, K. Adams, M. as estrogen and insulin; by reducing the central nervous system. NICHD and Lodish, and K. Pacak, Horm Metab Res inflammation and oxidative stress; and by CC researchers evaluated 43 children with DOI:10.1055/s-0042-106725, http://dx.doi. boosting immune function. Future studies these tumors from January 2006 to May org/10.1055/s-0042-106725). by the group will examine how specific types 2014. Nine of the children (21 percent) had and amounts of physical activity affect cancer been diagnosed with ADHD before their NCI: INCREASED PHYSICAL ACTIVITY risk. (NIH authors: S.C. Moore, J.N. Sampson, tumors were discovered. Four of the nine ASSOCIATED WITH LOWER RISK OF 13 C.M. Kitahara, S.K. Keadle, H. Arem, A. had been treated with stimulant drugs TYPES OF CANCER Berrington de Gonzalez, P. Hartge, D.P. Check, typically prescribed for ADHD (amphetamine, A new study by NCI researchers reports that N.D. Freedman, M.S. Linet, C. Schairer, and dextroamphetamine, or methylphenidate), more leisure-time physical activity (such C.E. Matthews, JAMA Intern Med 176:816– which caused some to develop headaches, as walking, running, swimming, and other 825, 2016, http://archinte.jamanetwork.com/ excessive sweating, and hypertension. After moderate-intensity to vigorous activities) article.aspx?articleid=2521826) their tumors were removed, three of the is associated with a lower incidence of 13

NCI BRIEF PREPARED BY BRANDON LEVY (NINDS)

8 THE NIH CATALYST JULY-AUGUST 2016 CATALYTIC RESEARCH

NIAID, CC: INVESTIGATIONAL MALARIA travelers and military personnel. Durable pro- the show’s participants “overall were quite VACCINE PROTECTS HEALTHY ADULTS tection is also important for mass vaccination successful at long-term weight loss com- An experimental malaria vaccine protected campaigns aimed at interrupting transmis- pared with other lifestyle interventions,” the a small number of healthy, malaria-naïve sion in malaria-endemic regions, according researchers reported. “Therefore, long-term adults in the United States from infection to the authors. (NIAID authors: A.S. Ishizuka, weight loss requires vigilant combat against for more than one year after immunization, A. DeZure, F.H. Mendoza, M.E. Enama, I.J. persistent metabolic adaptation that acts according to results from a phase 1 trial. The Gordon, L.-J. Chang, U.N. Sarwar, K.L. Zephir, to proportionally counter ongoing efforts vaccine, known as the PfSPZ vaccine, was L.A. Holman, S.H. Plummer, C.S. Hendel, M.C. to reduce body weight.” (NIH authors: E. developed and produced by Sanaria Inc. of Nason, L. Novik, P.J.M. Costner, J.G. Saun- Fothergill, J. Guo, L. Howard, R. Brychta1, Rockville, Maryland, with support from several ders, B. Flynn, W.R. Whalen, J.P. Todd, J. K.Y. Chen, M.C. Skarulis, M. Walter, P.J. Small Business Innovation Research (SBIR) Noor, S. Rao, K. Sierra-Davidson, G.M. Lynn, Walter, and K.D. Hall, Obesity DOI:10.1002/ awards from NIAID. NIAID researchers and B.S. Graham, M. Roederer, J.E. Ledgerwood, oby.21538, http://onlinelibrary.wiley.com/ collaborators at the University of Maryland R.A. Seder; CC authors: H. DeCederfelt, M.A. doi/10.1002/oby.21538/abstract) School of Medicine in Baltimore conducted Kemp, and G.A. Fahle, Nature Med 22:614– the clinical evaluation of the vaccine, which 623, 2016, http://www.nature.com/nm/ NIAMS, NIAID: RAPID-RESPONSE IMMUNE involved immunizing and exposing willing, journal/vaop/ncurrent/full/nm.4110.html). CELLS ARE FULLY PREPARED BEFORE healthy adults to the malaria-causing parasite INVASION STRIKES Plasmodium falciparum in a controlled setting. FOGARTY: ANALYSIS OF 1976 EBOLA OUT- Through the use of powerful genomic The phase 1 trial took place at the NIH BREAK HOLDS LESSONS RELEVANT TODAY techniques, NIAMS and NIAID researchers Clinical Center and at the University of Mary- With the recent Ebola epidemic in West Africa have found that during the development land Medical Center (Baltimore) and enrolled reviving interest in the first outbreak of the of immune cells called innate lymphoid 101 healthy adults aged 18 to 45 years who deadly hemorrhagic fever 40 years ago, cells (ILCs), these cells gradually become had never had malaria. Of these volunteers, scientists led by Joel Breman of NIH’s Fogarty better prepared for rapid response to infec- 59 received the PfSPZ vaccine; 32 partici- International Center have released a report tion. ILCs appear to play a critical role in pants served as control subjects and were not highlighting lessons learned from the smaller, defending the body’s barrier regions, such vaccinated. Vaccine recipients were divided more quickly contained 1976 outbreak. (NIH as the skin, lungs, and gut, through which into several groups to assess the roles of the author: J.G. Breman, J Infect Dis DOI:10.1093/ microbes must pass to make their way into route of administration, dose, and number of infdis/jiw207, http://jid.oxfordjournals.org/ the body. Working in mice, the researchers immunizations in conferring short- and long- content/early/2016/06/28/infdis.jiw207. analyzed regions of the genome that control term protection against malaria. abstract) the cytokine genes produced by both ILCs Collectively, the data showed that the and T cells. The study reflected earlier find- PfSPZ vaccine provided malaria protection for NIDDK: SOME “BIGGEST LOSERS” GAIN ings that ILC and T-cell subclasses produce more than one year in 55 percent of people BACK THE WEIGHT similar sets of cytokines, but those earlier without prior malaria infection. In those indi- It’s hard enough to lose weight, but when the studies also revealed differences in how the viduals, the vaccine appeared to confer sterile body counters your efforts by slowing your two cell types control the activities of these protection, meaning the individuals would resting metabolic rate (RMR) and burning key immune response genes. While the be protected against disease and could not fewer calories, it’s hard to keep the weight regulatory landscapes of ILCs are primed transmit malaria to others. The vaccinations off. An NIH follow-up study of 14 contestants for a quick defense upon infection, those were also well-tolerated by participants, and in the TV show The Biggest Loser found that of T cells are minimally prepared when the there were no serious adverse events attrib- six years later they’d regained an average of pathogen invades. Only after infection are uted to vaccination. 90 pounds after having lost an average of modifications in the landscape made that Additional results showed that antibod- 130 pounds. In addition, their RMR was, on enable T cells to launch their attack. (NIH ies may play a role in malaria protection early average, as low as it had been at the end of authors: H.-Y. Shih, G. Sciumè, Y. Mikami, after the final immunization, but inducing T the competition. Despite the weight regain, L. Guo, H.-W. Sun, S.R. Brooks, J.F. Urban cells in the liver is likely necessary for durable Jr., F.P. Davis, Y. Kanno, and J.J. O’Shea, protection. Long-term, reliable protection is Read more briefs online at http://irp.nih. Cell 165:1120–1133, 2016, http://dx.doi. important for people who are vaccinated but gov/catalyst/v24i4/research-briefs. org/10.1016/j.cell.2016.04.029) not exposed to malaria for months, such as

http://irp.nih.gov/catalyst 9 FEATURE

Demystifying Medicine CONTINUED FROM PAGE 1

the curriculum, and consequently M.D. screening; inflammatory diseases; addiction; students had little exposure to research. undiagnosed diseases; precision medicine; the To make matters worse, Ph.D. programs microbiome, and much, much more. in the biomedical sciences did not provide Most of the presenters are NIHers— training in pathobiology, so graduates of some are even institute directors such as those programs had little understanding of Anthony Fauci (National Institute of clinical disease, advances in diagnosis and Allergy and Infectious Diseases), who has therapy, and the major unsolved clinical given talks on Ebola, the Zika virus, and problems that challenge basic research. other infectious diseases. Arias created the course as one way to The 2016 session was kicked off by

Win Arias bridge the ever-increasing gap between Nobel laureate Eric Kandel (Columbia advances in basic biology and their University, New York) who spoke about course at Tufts University School of application to human disease. “The Age of Insight: The Quest to Medicine (Boston) for eight years. Arias “The whole idea of training Ph.D.’s Understand the Unconscious in Art, Mind, was a professor and chair of cellular and about disease is so they can communicate and Brain from Vienna 1900 to the Present.” molecular physiology at Tufts before with clinicians,” said Arias. It’s about Kandel, who trained in neurobiology at coming to NIH in 2001 for what was “building bridges” between the basic NIH in the 1950s and in psychiatry at to have been a nine-month position as scientists and the clinicians. And bringing in Harvard Medical School (Boston), shared a Fogarty Scholar. He has been at NIH patients “puts a human face on the disease.” the 2000 Nobel Prize in Physiology or ever since and is now a senior scientist The 20-week course, made up of weekly Medicine with Arvid Carlsson and Paul emeritus in the National Institute of two-hour classes and held from January Greengard for discoveries about signal Child Health and Human Development, through May each year, reaches national transduction in the nervous system. an assistant to the Deputy Director for and international audiences. About 900 Fauci talked about “Ebola, MERS and Intramural Research, and director of the Ph.D. and M.D. students, fellows, and staff Likelihood of More Epidemics”; and Eric NIH’s “Demystifying Medicine” course. register annually; each week, an average Green, the director of the National Human Arias, who has an M.D. degree and of 85 people attend classes in person and Genome Research Institute, talked about considers himself a physician-scientist, has about 250 attend via live videocast; and “The Future of Medicine: Personalized, done pioneering research in the pathobiology thousands more in the United States and Precision, and Other.” The rest of the 2016 of acquired and inherited liver disease that has around the world view the archived video- season was equally exciting with such topics led to a better understanding of how the liver casts later either through the NIH videocast as the microbiome, aging, trauma, cancer, functions. He discovered the mechanisms archive or on YouTube. The course has also and the effect of space flight on humans. of inheritable jaundice; that ATP-binding been replicated at 21 institutions in North You can read this month in the NIH cassette transporters (ABC transporters) America and in 18 foreign countries. Catalyst about two of the sessions: “Global mediate bile transport; and that AMP kinase The topics are wide ranging and Warming: Effect on Vector Distribution, and liver kinase-B1 regulate hepatocyte have included sessions on all types of Disease, and Natural Product Research” polarization, mitochondrial fusion, ATP cancer; emerging and re-emerging and “Robotic Planetary Exploration and production, and bile transporters. infectious diseases; AIDS and human Thoughts about Human Spaceflight.” Physician-scientists combine immunodeficiency virus; heart disease; investigator, clinician, and teacher skills diabetes; obesity; sleep; prions; autoimmune For more about the course—which is and were a flourishing breed from World diseases; stem cells; transplantation; all administered by the NIH Clinical Center— War II through the 1970s. But as basic- types of dementia and other neurological including speakers’ CVs, references, and science research became more complex disorders; aging; hearing loss; agents of PowerPoint presentations, go to https:// and research and training budgets began potential bioterrorism including smallpox and demystifyingmedicine.od.nih.gov. You can shrinking, medical schools could no longer anthrax; three-dimensional (3-D) and 4-D view past videocasts at https://videocast.nih. incorporate basic-science training into imaging to study organs and cells; genetic gov/PastEvents.asp?c=45.

10 THE NIH CATALYST JULY-AUGUST 2016 FEATURE

Demystifying the Health Effects of Global Warming Nature’s Bounty at Risk! BY MANJU BHASKAR, NINDS

Scientists are shedding light on how global warming may be adversely affecting biodiversity, triggering the spread of diseases, and threatening the supply of medically useful natural products. Jonathan Sleeman, director of the National Wildlife Health Center at the United States Geological Survey (USGS), and David Newman, former chief of the National Cancer Institute’s Natural Products Branch, talked about the threats at the April 12, 2016,

“Demystifying Medicine” lecture. SURVEY GEOLOGICAL U.S. Sleeman explained that climate change—with rising global temperatures, rising sea levels, and changes in precipitation patterns—is already having significant impacts on animal and human diseases and on the incidence and geographic distribution of pathogens. For example, the bluetongue virus—an insect-borne viral disease of To monitor and control public-health which added to the already warmer waters cattle, sheep, goats, and yaks as well as of threats, Sleeman explained, a “One caused by climate change. Warmer wild deer, elk, and other ruminants—is Health” approach is being promoted. The temperatures can kill the tiny marine algae spreading northward in Europe and the concept is ancient, but the name is recent. required to maintain the health of coral United States. Warmer temperatures One Health recognizes how the health and give it color. allow the insect—a midge—to survive at of humans is connected to the health of Newman also talked about how higher latitudes and altitudes and increase animals and the environment. genome mining—targeted discovery its ability to carry and transmit the virus. David Newman, an international of new natural products from microbes The economic costs of such a hard-to-treat expert in the development of therapeutics obtained from extreme environments—has disease include reproductive losses, damaged based on natural products, discussed how led to the identification of a gene cluster wool, and decreased milk production. changes in the environment worldwide are directing the biosynthesis of a lasso peptide Sleeman also talked about efforts to affecting plants and other sources of medi- that could be used as a therapeutic. understand how avian influenza virus cally useful natural products, the increas- strains evolve and how scientists are trying ingly devastating effects and challenges for To view the videocast of the April 12 to develop methods to prevent outbreaks. saving, creating repositories, and detecting Demystifying Medicine lecture “Global Wild waterfowl serve as natural reservoirs unexpected mutations affecting natural Warming: Effect on Vector Distribution, for the low-pathogenic flu virus, which product synthesis in biologic specimens. Disease, and Natural Product Research” by can jump to domestic poultry and then He described how human activities and Jonathan Sleeman (U.S. Geological Survey) to people. In addition, he discussed the global environmental change have affected and David Newman (NCI), go to http:// human-health and agricultural implications the rich biodiversity of the Antarctic and videocast.nih.gov/launch.asp?19618. of white-nose syndrome, which has killed southern oceans. Coral bleaching, for millions of insect-eating bats in North example, was triggered by a temperature America since the winter of 2007–2008. spike due to the El Niño weather pattern, CONTINUED ON PAGE 12

http://irp.nih.gov/catalyst 11 FEATURE

Demystifying Medicine CONTINUED FROM PAGE 11 Demystifying Space Medicine The Health Risks of Spending Time in Outer Space BY EMILY MULLIN, NIAID

was launched in 2006, and in July 2015, it made headlines around the world when it completed the first flyby of Pluto. NASA has also been developing the capabilities needed to send humans to Mars by the 2030s. To do so, researchers will need to learn more about human physiology in space and the necessary adaptation for long-term manned spaceflights. During his talk at NIH, Krimigis said astronauts traveling in space for long periods of time likely have a higher risk for a wide range of medical problems, including balance disorders, visual alterations, cardiovascular deconditioning, bone loss, NASA/JOHNS HOPKINS UNIVERSITY APPLIED PHYSICS LABORATORY PHYSICS APPLIED UNIVERSITY HOPKINS NASA/JOHNS and cancer. Isolation and confinement in The “Demystifying Medicine” class that focused on the effects of spaceflight on health, featured space scientist Stamatios space may also lead to behavioral issues and “Tom” Krimigis, who helped design NASA’s New Horizons spacecraft that orbited Pluto. This enhanced view from New Horizons zooms in on the southeastern portion of Pluto’s great ice plains, where at lower right the plains border rugged, sleep disorders. The distance from Earth dark highlands informally named Krun Macula. also means astronauts can’t come home for medical treatments, driving the need for As NASA and private companies such at the Johns Hopkins University Applied autonomous medical care. as SpaceX and Blue Origin plot manned Physics Laboratory in Laurel, Maryland, Krimigis cited NASA data showing missions to Mars, human space flight where he is the emeritus head of the Space that, during space travel, astronauts’ beyond the moon may be inevitable in the Department. The Space Department has percentage of muscle decreased during next few decades. But space scientist and designed, built, and operated more than 161-day and 194-day missions on the physicist Stamatios “Tom” Krimigis, a 64 spacecraft and 200 instruments, and International Space Station (ISS). “Some longtime champion of robotic technology it conducts space science and engineering of the astronauts have a hard time walking to explore space, doesn’t think humans are research for both civilian and national when they get back,” he said. ready to go to Mars—yet. security applications. Krimigis was the Studies have also shown that bone- One of the major hurdles of long-term principal investigator on several NASA mineral density, a measurement of how manned space flights is that scientists don’t spacecraft, including Voyagers 1 and 2, much calcium and other types of minerals yet know enough about how extended time and a co-investigator on many others. He is are in bone, dropped for astronauts who in space affects the human body, Krimigis still active on missions to Mercury, Saturn, spent time in space. The most troubling recently told an NIH audience at a “Demys- Pluto, and the heliosphere. aspect of long missions that last more tifying Medicine” lecture on May 10. He is widely credited with resurrecting than 90 days is the potential for radiation Krimigis is the only scientist in the the idea of a space-probe exploration exposure, which may increase the risk for world to have built instruments that have to Pluto. NASA had planned but then cancer, Krimigis said. He explained that flown to every planet in the solar system. canceled a mission to the dwarf planet in astronauts aboard the Russian Space Station He has pioneered the exploration of our 2000. Krimigis formed the New Horizons Mir, which operated from 1986 to 2001, solar system and beyond for more than 45 team, which engineered the interplanetary were exposed to about 70 millisieverts (mSv) years while serving in various positions space probe. The New Horizons probe of radiation over 90 days while in orbit. The

12 THE NIH CATALYST JULY-AUGUST 2016 THE SIG BEAT NEWS FROM AND ABOUT THE SCIENTIFIC INTEREST GROUPS

NEW: FIBROSIS add your name to the NIH-DATASCIENCE-L The Fibrosis SIG provides a forum for individu- LISTSERV at https://list.nih.gov/cgi-bin/ als from NIH and the extramural community wa.exe?SUBED1=nih-datascience-l&A=1. to discuss basic, translational, and clinical Announcements will be posted at http:// research related to fibrosis. The SIG will meet datascience.nih.gov/community/datascience- monthly to organize seminars and engage in at-nih/sigs. For questions, contact Ben Busby average person living in the United States interactive discussions. The inaugural meeting at [email protected]. is exposed to 3.1 mSv per year, according will be held on Wednesday, September 7, 4:00– NOTE: The recently established Research to the United States Nuclear Regulatory 5:00 p.m., in CRC conference room 5-2550, Repositories and Patient Registries SIG will Commission. A 100-day mission to Mars Building 10. For more information and/or to be incorporated under the Data Science in could expose humans to 1,000 mSv of join the SIG’s LISTSERV, contact Resat Cinar Biomedicine SIG. Please register for the NIH- radiation, dramatically increasing cancer (NIAAA; [email protected]) or Bernadette DATASCIENCE-L LISTSERV described above. risk, Krimigis said. Gochuico (NHGRI; [email protected]). NASA scientists are working on NEW: STATISTICS mathematical models to gauge radiation NEW: MYALGIC ENCEPHALOMYELITIS/ This SIG, which will meet quarterly, will support and other risks, but Krimigis said there is CHRONIC FATIGUE SYNDROME the growing community of statisticians at NIH. a huge need for more research. The SIG is open to all interested intramural The focus is on statistical methods used in “Animal models will be needed to and extramural investigators and hopes to the design and analysis of clinical trials and in assess clinical significance,” he said. That foster new research collaborations across the explorations in epidemiology and population represents an area that NIH scientists could NIH campus. It is led by NINDS Clinical Direc- science, as well as on biomedical science. To investigate. tor Avi Nath, who is the primary investigator join, add your name to the STATISTICS-NIH-L Krimigis also said that biomarkers will of the Intramural ME/CFS initiative, and mod- LISTSERV at https://list.nih.gov/cgi-bin/ be needed to assess individuals’ sensitivity erated by lead associate investigator Brian wa.exe?SUBED1=STATISTICS-NIH-L&A=1. and risk to radiation before astronauts are Walitt (NINR). The ME/CFS SIG will present a Announcements will be posted at http:// selected for manned missions. During these bimonthly seminar series and more. For infor- datascience.nih.gov/community/datascience- missions, pharmaceutical and nutritional mation and notices of meetings and events, at-nih/sigs. For questions, contact Tammy countermeasures against radiation could be join the LISTSERV (https://list.nih.gov/cgi-bin/ Massie ([email protected]). used to mitigate risk to radiation exposure. wa.exe?SUBED1=ME-CFS&A=1) or contact After returning to Earth, astronauts may Brian Walitt at [email protected]. NEW: TEXT MINING need special occupational health care, This SIG will provide a community for NIH personalized cancer screening, and even NEW: DATA SCIENCE IN BIOMEDICINE researchers who use text mining in their work individualized cancer treatment. The goal of the Data Science in Biomedicine and would like to learn more about what is Although a manned mission to Mars— SIG is to foster the growing community of being done in this area at NIH. The SIG will hold or to any planet for that matter—is likely biomedical data scientists at NIH through meetings, provide networking opportunities, still many years away, Krimigis said it will improving communications, providing and host a clearinghouse of descriptions of be important for biomedical scientists to a forum for scientific discussions, and text-mining tools that can be used on campus determine the effects that space travel catalyzing collaborations. The SIG will work or can be promoted more widely. The SIG also will have on humans, address the medical with established SIGs and community groups intends to work closely with the Data Science in concerns, and ensure the health and safety that focus on components of data science to Biomedicine Interest Group to provide exper- of astronauts and others who may venture coordinate activities and increase awareness tise about text mining as a specific discipline into outer space. of opportunities in data science. This SIG will within data science. To join the SIG distribution meet quarterly on campus, sometimes with list, e-mail Lena Pons at [email protected]. To see a videocast of the May 10, 2016, other SIGs, and host a seminar series featuring Demystifying Medicine lecture “Robotic Plan- NIH and outside speakers, organize an annual etary Exploration and Thoughts about Human Read more online at http://irp.nih.gov/ poster session, and collect user input on Spaceflight” by Stamatios Krimigis, go to catalyst/v24i4/the-sig-beat. workshops and courses needed at NIH. To join, http://videocast.nih.gov/launch.asp?19675.

http://irp.nih.gov/catalyst 13 FEATURE

Digitizing Medical History CONTINUED FROM PAGE 1

journal literature, now including 3.9 million articles spanning the early 19th-century to the present day. But digitization is only part of the story. Our responsibility extends to being a good steward, which means preserving the collection for future generations by taking Some of the many contributors to NLM’s blog. good care of it both during and long after Three Times Around and we make digital copies of it. It also means Still Circulating The Arabic manuscript entitled The Comprehensive Book ensuring that a wide audience knows about on Medicine, dated 1094, is one of the NLM’s oldest items. and appreciates the collection for the vast POSTED ON JULY 1, 2016 knowledge and experience it can offer. Three years ago, we launched the website Comprehensive Book on Medicine (Kitab The NLM’s award-winning exhibition Circulating Now to explore, share, and al-Hawi fi al-tibb), by one of the era’s great program has been achieving this last goal celebrate the value of NLM’s world-renowned physicians, Abū Bakr Muhammad ibn for many years, revealing important stories historical collections and programs for Zakarīyā al-Rāzī (circa 850–circa 925), about the human condition to hundreds of research, education, enrichment, and learning known in the Western world as Rhazes. thousands of individuals via its traveling about the human condition. The NLM’s newest collections, com- banner exhibitions that travel the world By several measures, we’ve achieved our prising websites and social media about the and to millions more via its companion goal. In three years Circulating Now has given recent Ebola and Zika outbreaks, will be the exhibitions on the web. The library’s blog, voice to over 100 individuals—from guest historical records of the future. And perhaps Circulating Now, which recently marked writers to event speakers to our own talented one of the most remarkable 20th-century its third anniversary, shines a light every staff—who have shared their own perspectives. items and available for anyone to explore week onto the rich collections. (See sidebar.) With over 500 posts, Circulating Now online and experience through a traditional The NLM is also working with has offered readers worldwide insights on a visit to the NLM, is the first summary of the other organizations such as the National wide and wonderful range of subjects in the genetic code—on several sheets of standard, Endowment for the Humanities (NEH) to history of medicine—military history, women’s taped-together paper—by 1968 Nobel lau- support new ways of studying its growing history, African-American history; public reate Marshall Nirenberg, whose research digitized collections and related data sets as health, advocacy, legislation; botany, genetics, career at NIH spanned 50 years. well as the related digitized collections and biotechnology; to name just a few. Scholars from around the world use the associated data of historical medical libraries Circulating Now has showcased the varied NLM’s historical collections to advance and archives around the world. Along these formats of the NLM’s historical collections, their research. Educators use them to teach lines, during the past three years, NLM and enabling readers to experience and learn and inspire. Students use them to learn NEH have collaborated on several initiatives from our monographs, manuscripts, photo- about the human condition. By carefully in cooperation with several organizations graphs and prints, films, audio files, and born- digitizing these collections and making and institutions. On April 11–13, the NLM digital collections. And it has highlighted the them more accessible than ever before, hosted the NEH-funded interdisciplinary range of NLM resources that support histori- we’re liberating a global and centuries-long workshop “Images and Texts in Medical cal research and make the collections avail- record of medicine to help inform research, History: An Introduction to Methods, Tools, able—from the NLM’s Digital Collections, education, and learning in the 21st century. and Data from the Digital Humanities.” to the IndexCat database of millions of bib- The NLM’s Digital Collections repository liographic citations spanning centuries; from Jeffrey Reznick is the chief of the History of currently offers more than 80,000 items, the NLM’s award-winning Exhibition Program Medicine Division at NLM. To read about the including books, films, and images, and is to historical content in PubMed Central; and workshop, go to http://irp.nih.gov/catalyst/ rapidly growing. This resource complements from “Profiles in Science” to “Medical Movies v24i4/nlm-workshop-images-and-texts-in- PubMed Central, NLM’s free, full-text on the Web.” Read more online at https:// medical-history. archive of biomedical and life-sciences circulatingnow.nlm.nih.gov/2016/07/01/ three-times-around-and-still-circulating/. 14 THE NIH CATALYST JULY-AUGUST 2016 NIH ABBREVIATIONS FROM THE ANNALS OF NIH HISTORY CBER: Center for Biologics Evaluation and Research, FDA CC: NIH Clinical Center AIDS at 35 CCR: Center for Cancer Research, NCI The NIH Played a Major Role in Discovering the AIDS Virus CDC: Centers for Disease Control and Prevention BY MICHAEL GOTTESMAN, DDIR CIT: Center for Information Technology DCEG: Division of Cancer Epidemiology and Genetics, NCI Sometime in the early 1970s, or first “AIDS” patient came to the NIH FAES: Foundation for Advanced Education perhaps even earlier, a virus capable Clinical Center in 1981, before anyone in the Sciences FARE: Fellows Award for Research of severely compromising the human knew what the disease was. In 1986, Bob Excellence immune system made its way from central Gallo (National Institute of Allergy and FelCom: Fellows Committee Africa to the United States via Haiti. Infectious Diseases, NIAID) would earn FDA: Food and Drug Administration FNL: Frederick National Laboratory With a long incubation period before his second Lasker award for determining IRP: Intramural Research Program symptoms appeared, and with limited that human immunodeficiency virus type HHS: U.S. Department of Health incidence of infections, the virus was on 1 (HIV-1) causes most cases of AIDS. and Human Services NCATS: National Center for Advancing no one’s radar screen. But that situation The NIH developed the first blood Translational Sciences changed dramatically on June 5, 1981, tests to detect HIV, too. A wonderful NCBI: National Center for Biotechnology Information when the Centers for Disease Control telling of these early events is captured NCCIH: National Center for and Prevention (CDC) published a report in a virtual exhibit and collection of oral Complementary and Integrative Health in its Morbidity and Mortality Report histories titled “In Their Own Words: NCI: National Cancer Institute NEI: National Eye Institute newsletter about a mysterious cluster NIH Researchers Recall the Early Years NHGRI: National Human Genome of Pneumocystis pneumonia (PCP) in of AIDS,” created by the Office of NIH Research Institute five homosexual men in Los Angeles History in the 1990s (https://history.nih. NHLBI: National Heart, Lung, and Blood Institute (http://www.cdc.gov/mmwr/preview/ gov/NIHInOwnWords/). NIA: National Institute on Aging mmwrhtml/june_5.htm). What’s hinted at in these oral NIAAA: National Institute on Alcohol Abuse and Alcoholism Although the public wouldn’t be aware histories, collected between 1988 and NIAID: National Institute of Allergy of the burgeoning epidemic for a few more 1993, is the cocktail of treatments and Infectious Diseases years, public-health experts—including developed in the 1990s that would NIAMS: National Institute of Arthritis and Musculoskeletal and Skin Diseases those at the NIH—were both intrigued transform AIDS from a death sentence NIBIB: National Institute of Biomedical and concerned by the report. “The patients into a manageable chronic disease, at Imaging and Bioengineering NICHD: Eunice Kennedy Shriver did not know each other and had no known least in wealthier countries. The NIH National Institute of Child Health and common contacts or knowledge of sexual intramural program has been instrumental Human Development partners who had had similar illnesses,” the in developing these therapies. NIDA: National Institute on Drug Abuse NIDCD: National Institute on Deafness report stated. “Three patients had profound- On June 15, 2016, as part of the and Other Communication Disorders ly depressed in vitro proliferative responses Clinical Center Grand Rounds series, NIDCR: National Institute of Dental and Craniofacial Research to mitogens and antigens.” NIAID Director Anthony Fauci delivered NIDDK: National Institute of Diabetes And so the mystery began. Over the next a talk titled “AIDS at 35: Is the End in and Digestive and Kidney Diseases 18 months, health experts discovered more Sight?” (http://videocast.nih.gov/launch. NIEHS: National Institute of Environmental Health Sciences PCP clustering and cases of Kaposi’s sarcoma asp?19752). Fauci is perhaps the most NIGMS: National Institute of among gay men in California cities, giving knowledgeable person on Earth when it General Medical Sciences rise to the term gay-related immune defi- comes to AIDS, both its history and its NIMH: National Institute of Mental Health NIMHD: National Institute on Minority ciency, or GRID. Yet this GRID syndrome pathology. His talk was an enlightening Health and Health Disparities was also seen in heroin users, people with overview of an epidemic for which much NINDS: National Institute of Neurological Disorders and Stroke hemophilia, and people from Haiti, leading work still needs to be done. NINR: National Institute of Nursing Research some researchers to use the term “4H dis- The NIH is making history today with NLM: National Library of Medicine ease.” It wasn’t until July 1982 that the CDC its work on Ebola and Zika, and its past OD: Office of the Director OITE: Office of Intramural Training coined the name that would stick, acquired successes and experiences, both good and and Education immune deficiency syndrome (AIDS). bad, can guide us here. This is one of the OIR: Office of Intramural Research The NIH played a major role in iden- reasons why capturing and remembering ORS: Office of Research Services tifying the virus in the early 1980s. The our history is so important. ORWH: Office of Research on Women’s Health OTT: Office of Technology Transfer

http://irp.nih.gov/catalyst 15 COLLEAGUES

Recently Tenured

ROBERT L. HANSON, NIDDK JAMES W. HODGE, NCI CHARLES MATTHEWS, NCI STEFAN A. MULJO, NIAID MIHAELA SERPE, NICHD

ROBERT L. HANSON, M.D., M.P.H., NIDDK JAMES W. HODGE, PH.D., MBA, NCI-CCR Senior Investigator, Head, Genetic and other populations. We use classical Senior Investigator; Head of the Epidemiology and Statistics Unit, Phoenix techniques of epidemiology (descriptive, Recombinant Vaccine Group, Laboratory of Epidemiology and Clinical Research Branch, analytic, and experimental) as well as Tumor Immunology and Biology, Center for National Institute of Diabetes and Digestive genetic epidemiology to study the genetic Cancer Research, National Cancer Institute and Kidney Diseases and nongenetic risk factors for diabetes, Education: University of Tennessee, Martin, Education: University of Kansas, Lawrence, obesity, and complications of diabetes. Tenn. (B.S. in biology and chemistry); Uni- Kan. (B.A. in chemistry); University of Kansas We also study gene transcription, protein versity of Tennessee, Knoxville, Tenn. (M.S. School of Medicine, Kansas City, Kan. (M.D.); expression, and cellular metabolism. The in microbiology; Ph.D. in comparative and Columbia University School of Public Health, branch is also investigating the effect of experimental medicine); George Washing- New York (M.P.H.) lifestyle interventions, such as promoting ton University, Washington, D.C. (M.B.A. in Training: Residency in internal medicine, weight loss, in helping to prevent diabetes medicine and health care) University Hospital, State University of New and its complications. Training: Intramural Research Training Award York (SUNY) at Stony Brook (Stony Brook, We have conducted several clinical postdoctoral fellow, NCI N.Y.); residency in Preventive Medicine and trials to intervene in the natural history Came to NIH: In 1993 for training; held posi- Public Health, SUNY–Stony Brook; U.S. Public of diabetes and to prevent the develop- tions of senior staff fellow, staff scientist, Health Service Epidemiology Fellow, NIDDK ment of the disease and its resulting severe and senior scientist (1996–2011); became (Phoenix, Ariz.) complications. Although our genomic and investigator in 2011 Came to NIH: In 1991 for training; became molecular research does not have imme- Selected professional activities: Chair- staff scientist in 1998 and staff clinician in diate clinical applications, it is helping us man, Immunomodulation Committee, NRG 2011 gain an understanding of the processes Oncology; senior visiting professor (adjunct), Selected professional activities: Member, that lead to diabetes and related conditions. Department of Radiation Oncology and American Diabetes Association Grant Review Ultimately, we hope that this knowledge Surgery, Albert Einstein College of Medicine Committee will lead to better treatments and preven- (New York) Website: http://irp.nih.gov/pi/robert-hanson tive strategies for these diseases. Outside interests: Running marathons and The technology for studying the genetic triathlons Research interests: The Phoenix and molecular aspects of diabetes is con- Website: http://irp.nih.gov/pi/james-hodge Epidemiology and Clinical Research tinuing to improve. The greatest challenge Branch conducts research on the causes is to develop analytical methods that will Research interests: My group is devel- and correlates of type 2 diabetes, obesity, allow scientists to interpret the results from oping novel recombinant vaccines and and diabetic complications. My research these technical advances and to ensure vaccine-combinatorial therapies. We study has focused on the epidemiology of these that diverse populations are included in both mechanistically and operationally how disorders, particularly on the genetic and genomic and molecular research. certain radiation modalities, chemotherapy molecular aspects, in American Indian agents, small-molecule targeted therapies,

16 THE NIH CATALYST JULY-AUGUST 2016 COLLEAGUES

and immune modulators alter tumors or their CHARLES MATTHEWS, PH.D., NCI-DCEG Research has shown that moderate- microenvironments to make them more sen- Senior Investigator, Metabolic Epidemiology to vigorous-intensity exercise is associated sitive to immunostimulatory vaccines. Branch, Division of Cancer Epidemiology with reduced risk of many cancers with Immune consequences of cancer therapy and Genetics, National Cancer Institute the most evidence available for colon include both direct effects on tumor cells Education: University of Massachusetts cancer, postmenopausal breast cancer, and and modulation of the immune system. Amherst, Amherst, Mass. (B.S. in exercise endometrial cancers. But we don’t know My laboratory has focused on immuno- science; Ph.D. in epidemiology); University precisely how much exercise is required genic modulation and immune subset of South Carolina, Columbia, S.C. (M.S. in to reduce the risk for these malignancies conditioning. exercise science) or what the metabolic mediators are. I Immunogenic modulation describes Training: Postdoctoral fellow, Division am currently conducting studies to better how anticancer therapies alter the biology of Preventive and Behavioral Medicine, understand the minimal amount of exercise of the surviving tumor cells to render them University of Massachusetts Medical School needed to provide benefit, the effect of more sensitive to immune-mediated killing. (Worcester, Mass.) aerobic exercise on circulating hormones, The modulation encompasses a spectrum Before coming to NIH: Assistant professor and other metabolic factors that could of molecular alterations in the cancer cell of medicine, Vanderbilt University School of explain the observed associations. I am biology that independently or collectively Medicine (Nashville, Tenn.) also exploring whether excessive sedentary make the tumor more amenable to cytotoxic Came to NIH: In 2009 behavior (“too much sitting”) may be linked T-lymphocyte–mediated destruction. Selected professional activities: Associ- to an increased risk for certain cancers Immune subset conditioning describes ate editor, Medicine and Science in Sports independent of the effect of exercise. My how anticancer therapies mediate the and Exercise, American College of Sports long-term goal is to understand the optimal peripheral and/or intratumoral reduction Medicine’s flagship journal; epidemiology ratio of sedentary time (which is a necessity of negative regulatory elements into a and biostatistics representative on Program for many in modern life) to physically active more immune-permissive environment Committee for the 2016 American College of time for lower cancer risk and better health. for vaccine immunotherapy. Understanding Sports Medicine Annual Meeting To help achieve this goal I engage the underlying mechanisms of these Outside interests: Enjoying family meals; in methodological research to develop areas provides a rationale for the use of riding bikes; playing with dogs; watching base- better tools to measure the full spectrum immunotherapy in combination with ball; listening to music; digging for vinyl LPs of physical-activity behaviors in large radiation, chemotherapy, small-molecule Website: http://irp.nih.gov/pi/ population-based studies. We have learned inhibitors, and immune modulators. charles-matthews a great deal about the important role that Our team has worked independently exercise can play in cancer prevention using and collaboratively with the Laboratory Research interests: I study the relation- simplistic questionnaires, but it may be of Tumor Immunology and Biology on ship between physical-activity behaviors that our traditional questionnaire-based the design, engineering, and development and the development of cancer. These approach limits our ability to rigorously of recombinant poxvirus and yeast-based behaviors range from the purely sedentary test new hypotheses about sedentary cancer vaccine platforms. The poxviral to high-intensity physical activity such as behavior and the potential benefits from vector–based vaccines contain transgenes for running; they reflect the continuum of routine activities of everyday living. We are tumor antigens and for multiple synergistic human movement that we engage in each now testing and refining next-generation costimulatory molecules. These vaccines day. An individual’s overall profile of physi- measurement methods that rely on mobile based on three costimulatory molecules cal behavior has an important influence on technologies and accelerometers to capture (TRICOM) have led to several clinical the amount of energy he or she expends a more complete, accurate, and precise trials showing improved patient survival each day and the underlying metabolism. measure of human behavior. I hope that for a range of human carcinomas. The In my etiologic studies, I seek to understand by implementing these tools in future prostate-specific antigen (PSA)–TRICOM how the full spectrum of physical behavior studies, we will accelerate discoveries that vaccine, designed to generate a robust influences cancer risks, the dose-response could lead to fundamentally new strategies immune response against PSA-expressing relationships between active and sedentary for cancer prevention through increased tumor cells, is in a phase 3 clinical trial for behaviors and cancer, and the biological physical activity. metastatic prostate cancer. mechanisms underlying these relationships. CONTINUED ON PAGE 18

http://irp.nih.gov/catalyst 17 COLLEAGUES

Recently Tenured CONTINUED FROM PAGE 17

STEFAN A. MULJO, PH.D., NIAID To address these fundamental MIHAELA SERPE, PH.D., NICHD Senior Investigator, Chief, Integrative issues, we use an integrative systems- Senior Investigator; Head of the Section on Immunobiology Section, Laboratory of biology approach to reverse engineer the Cellular Communication, Eunice Kennedy Immunology, National Institute of Allergy molecular logic of cellular differentiation. Shriver National Institute of Child Health and Infectious Diseases We combine genome- and transcriptome- and Human Development Education: Johns Hopkins University, wide measurements with experimental Education: University of Bucharest, Bucha- Baltimore (B.A. in biology honors program; perturbations in order to test and refine rest, Romania (M.S. in biochemistry); State M.H.S. in molecular microbiology and our models. As one example of our success, University of New York at Buffalo, Buffalo, immunology; Ph.D. in molecular biology and we identified the RNA-binding protein N.Y. (Ph.D. in biochemistry) genetics) LIN-28 homolog B (LIN-28B), which Training: Postdoctoral training in develop- Training: Visiting postdoctoral researcher, causes hematopoietic stem cells (HSCs) mental biology and neurobiology, University Department of Molecular and Cell Biology, from bone marrow of adults to acquire of Minnesota and Howard Hughes Medical University of California, Berkeley (Berkeley, some of the attributes of fetal HSCs. Institute (Minneapolis) Calif.); postdoctoral research fellow, Depart- We helped show that human Lin- Came to NIH: In 2008 ment of Pathology, Harvard Medical School 28B can activate a program that includes Selected professional activities: Organizer of (Boston) fetal hemoglobin expression during the Genetics Society of America Drosophila Came to NIH: In 2008 erythroid differentiation, providing meeting (2014) Selected professional activities: Advisory a novel avenue toward the treatment Outside interests: Listening to all kinds of board member (Immunology section) of of beta-thalassemia and sickle-cell music (from jazz to classical); hiking; baking Oncotarget; faculty member of NIH-Penn disease, inherited conditions that affect Website: http://irp.nih.gov/pi/mihaela-serpe Immunology Graduate Partnership Program hemoglobin and arise from mutations in Outside interests: Cooking; eating; traveling; adult beta-globin. Furthermore, using Research interests: The purpose of talking about science with his wife (also a LIN-28B–reprogrammed adult HSCs my lab’s research is to understand the scientist); keeping their kids entertained and in a transplant, particularly in pediatric mechanisms of synapse development out of trouble patients or someday in utero, offers the and homeostasis. We focus on three Website: http://irp.nih.gov/pi/stefan-muljo potential for the blood and immune key processes in synaptogenesis: 1) systems to develop anew, similar to how trafficking of components to the proper Research interests: The Integrative the immune system develops in a fetus site, 2) organizing those components Immunobiology Section is interested or a newborn. Converting adult human to build synaptic structures, and 3) in understanding how gene-expression HSCs into more fetal-like cells with LIN- the maturation and homeostasis of the programs are orchestrated as cells 28B also offers an easy and ethical way to synapse to optimize its activity. My differentiate from stem cells into further study fetal HSCs in the laboratory. laboratory addresses the underlying various lineages in the immune system. mechanisms using a powerful genetic In particular, my lab studies how these Recently Tenured? system, Drosophila melanogaster, and a systems are controlled by microRNAs, comprehensive set of approaches including long noncoding RNAs, and RNA- If you have been tenured within the past genetics, biochemistry, molecular binding proteins. Our major goal is to year, the NIH Catalyst will be contacting biology, super-resolution imaging, and discover novel molecular circuits that you for your help in preparing an article electrophysiology recordings in live control cell fates in the hematopoietic and about you. We will ask for your CV and animals and reconstituted systems. immune systems because perturbations a photo, consult your website, and then We use the neuromuscular junction in their genetic programming underlie draft an article for your review. You’ll be (NMJ) as a model for glutamatergic many diseases and disorders including able to revise and make additions. We synapse development and function. cancer, immunodeficiency, autoimmunity, look forward to working with you. Individual NMJs are uniquely suited inflammation, allergy, and infectious The Editors, NIH Catalyst for in vivo studies on synapse assembly, diseases. growth, and plasticity, because they can be reproducibly identified from animal 18 THE NIH CATALYST JULY-AUGUST 2016 ANNOUNCEMENTS: KUDOS

New Members of NAS and relies on the continual interplay between Ronald Germain and Eugene Koonin have basic research, which teases apart the signaling been elected to the National Academy of mechanisms that underlie normal immune-cell to animal and are easily accessible for Sciences (NAS) for 2016. They join the more development, and the study of primary human electrophysiological and optical analysis. than 40 active NIH scientists in this prestigious cells and mouse models. His laboratory has dis- Although many neurological disorders academy. On June 8, they presented their covered multiple specific forms of immunode- are linked to defects in synaptogenesis, research at a minisymposium honoring their ficiency including those caused by mutations the initial clustering functions are poorly election. (To view the videocast, go to http:// in the genes encoding the intracellular signal- understood. We discovered an obliga- videocast.nih.gov/launch.asp?19738.) ing molecule Janus kinase 3. For more about tory auxiliary protein, neuropilin and Germain is an NIH Distinguished Investiga- Leonard’s work, go to http://irp.nih.gov/pi/ tolloid-like (Neto), which is absolutely tor in the NIAID Lymphocyte Biology Section, warren-leonard. required for the ionotropic glutamate where he studies basic aspects of innate and Lichten is a senior investigator in the NCI receptors (iGluRs) clustering and NMJ adaptive immune function, with an empha- Laboratory of Biochemistry and Molecular functionality. sis on the biochemical mechanisms involved Biology. He uses budding yeast as a model Neto belongs to a family of highly in discrimination between self and foreign system to study homologous recombination conserved auxiliary proteins that regulate peptide-associated major histocompatibility and chromosome structural changes that glutamatergic synapses, the major complex (MHC) molecules by T cells as well occur during meiosis. Recombination and its excitatory synapses in the human brain. as on T-cell antigen-presenting cell interac- crossover products are essential for proper Our investigations uncovered essential tions and the subsequent delivery-of-effector chromosome segregation during meiosis. roles for Neto during synapse development function. Germain was elected to the National Chromosome mis-segregation, caused by and support the notion that Neto tightly Academy of Medicine, formerly the Institute of defects in meiotic recombination, leads to regulates the trafficking of iGluRs on Medicine, in 2013. For more on Germain’s work, chromosome imbalance in gametes. These the muscle membrane, their synaptic go to http://irp.nih.gov/pi/ronald-germain. chromosome imbalances are a leading cause recruitment and stabilization, and their Koonin is a senior investigator in the NLM of infertility and birth defects in humans. For function. Furthermore, Neto appears to be NCBI Evolutionary Genomics Research Group. more about his work, go to http://irp.nih.gov/ at the center of trans-synaptic complexes His research is in many areas of evolutionary pi/michael-lichten. that monitor synapse activity and relays genomics and takes advantage of the advances this information to the presynaptic bone of comparative genomics and systems Service to America Medal Finalist morphogenetic protein (BMP) signaling biology to address fundamental problems BY ROBIN ARNETTE, NIEHS pathway. in evolutionary biology. He hypothesized We have recently discovered a in 2005 that “spacer DNA” in the clustered NIEHS epidemiologist Allen Wilcox is one of completely novel BMP-signaling modality regularly interspaced short palindromic repeats 32 federal employees named as finalists for that is genetically distinguishable from (CRISPR) loci of bacteria and archaea, which the 2016 Samuel J. Heyman Service to America any other known BMP pathways. At matched sequences of bacteriophages, could Medals (also known as Sammies), in recognition the NMJ, this novel BMP pathway be a key part of a sort of adaptive immune of his “pioneering the epidemiologic study of is triggered by selective postsynaptic system. For more on Koonin’s research, go to human reproduction, fundamentally chang- iGluRs and acts locally to promote http://irp.nih.gov/pi/eugene-koonin. ing both scientific and public understanding the stabilization of these receptors at of fertility and pregnancy.” The winners will be synaptic sites. Thus, BMPs may monitor announced at a black-tie gala in September. Leonard and Lichten Elected to synapse activity and coordinate it with Wilcox is a senior investigator and head of “Older” AAAS synapse growth and maturation. We are the NIEHS Reproductive Epidemiology Group. Warren Leonard and Michael Lichten have currently trying to elucidate the molecular For more about his work, go to http://irp.nih. been elected to the American Academy of Arts components, regulation, and function gov/pi/allen-wilcox. of this novel BMP-signaling modality, and Sciences, which was founded in 1780. Leonard, an NIH Distinguished Investigator which appears to have a broad, ancestral Read longer versions online at in the NHLBI Laboratory of Molecular Immu- role in regulating cellular junctions. http://irp.nih.gov/catalyst/v24i4/ nology, applies a broad range of methodolo- announcements-kudos. gies to both human cells and mouse models

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