NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 27 ISSUE 1 • JANUARY-FEBRUARY 2019

The Merry Band of Creating a “Spellchecker” for Stadtmans BY LISA YUAN, NIDDK BY LAURA STEPHENSON CARTER

Meet 15 more investigators who have become part of the Earl Stadtman Tenure-Track Investigator Program, which was launched in 2009 and named for the legendary biochemist who worked at NIH for 50 years. The program aims to recruit a diverse group of scientists with interests across the biomedical-research spectrum. Seven of the Stadtmans focus on cancer research and work in the National Cancer Institute. Two work in the National Heart, Lung, and Blood Institute ERNESTO DEL AGUILA III, NHGRI III, AGUILA DEL ERNESTO and both have dual appointments with other institutes. Another hails from the National Institute of Environmental Health Sciences in Research Triangle Park in North Carolina and holds a dual appointment with another institute. The other five Stadtmans each represent a different institute: National Institute CRISPR-Cas9 is a customizable tool that lets scientists cut and insert small pieces of DNA at precise areas along a DNA of Diabetes and Digestive and Kidney strand. Lothar Hennighausen’s team has led the way in describing the extent of unwanted molecular scarring that the Diseases; National Institute of Biomedical CRISPR-Cas9 technique can cause at target sites of mammalian genomes. Imaging and Bioengineering; National Eye Institute; National Institute on Imagine a pair of molecular scissors that could snip and tweak sections of Aging; and the Eunice Kennedy Shriver the genetic alphabet. Or tweezers that could pluck one letter and replace it with National Institute of Child Health and another. These tools have become a reality in recent years, allowing scientists to correct Human Development. “misspellings” in the genetic code. And one NIH lab is taking full advantage of this.

Get to know them a bit. You’ll learn CONTINUED ON PAGE 16 what their research is, what discoveries they’ve made, how they got interested CONTENTS in science, and even a few secrets. And FEATURES • |1, 10| The Merry Band of Stadtmans |1| Creating a “Spellchecker” for Genes if you go online, you’ll learn even more: |3| NIH Distinguished Scholars Program |14| Alejandro Sánchez Alvarado: How Flatworms https://irp.nih.gov/catalyst/v27i1/ Regenerate |18| 2018 Obits |19| America’s Cancer Doctor: Alan Rabson the-merry-band-of-stadtmans. DEPARTMENTS • |2| DDIR: A New Centralized IRB |4, 5| Training Page: Fellows Editorial

CONTINUED ON PAGE 10 Board; Breaking Through the Petri Dish Lid |6, 7| News You Can Use: Office of Patient Recruitment; NIH Library Services |8| Research Briefs |15| The SIG Beat |17| Abbreviations; Take the Survey |20| NIH in History: Celebrating Nobel Laureate Christian B. Anfinsen FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH

A New Centralized Institutional Review Board BY MICHAEL GOTTESMAN, DDIR, AND JONATHAN GREEN, OD

As you almost certainly have Research Subjects Review Board Office are several provisions that will affect heard by now, the NIH Intramural at the University of Rochester (Rochester, all investigators including changes to Research Program is in the process New York). the informed-consent process, new of centralizing and consolidating the We are close to completing one step of exemptions, and the elimination of Institutional Review Board (IRB) the centralization process: the migration of continuing review for some minimal-risk system. The 12 independent IRBs protocol information from three different research. will be transitioning to one IRB information-technology systems to one To ensure compliance with the new office, and the three different protocol central-tracking and data-management rule, all new studies slated for initial and data-management systems are system—iRIS, short for integrated- approval on or after January 21, 2019, will being consolidated into one. The goal research information system. be processed by the IRBO and reviewed is to improve the consistency of IRB The IRBO will handle all protocol by the NIH Intramural IRB. All studies review and the overall efficiency of submissions for the intramural research approved before January 21 will remain the IRB system. program; make exempt and nonhuman under the old rule and do not need to This type of IRB reorganization has subjects determinations; and conduct comply with any of the revised Common been deployed successfully at universities expedited reviews of minimal-risk Rule requirements. Amendments and around the country not only to enhance research. The office will conduct in-depth continuing reviews will continue to be human-research protections but also to pre-reviews before sending protocols to handled by the current NIH IRBs. Over benefit principal investigators on clinical a new, central NIH Intramural IRB the course of the next several months, we protocols by ensuring an efficient review committee. During this process, we will transition each of the committees into process. The IRB reorganization will also hope to identify and address any issues the new structure. ensure that we are compliant with the that could delay approval. The pre-review We are confident that the new IRB revised Common Rule (also known as will be done by trained professional system will be an improvement for the Federal Policy for the Protection of IRB analysts with consultation from everyone. For investigators, there should Human Subjects), which becomes effective IRB chairs, human-research protection be greater consistency in IRB review and on January 21, 2019. program leadership, and other experts more efficient turnaround times. For IRB We have brought on two new team as needed. members, meetings will be shorter with members to lead this effort, Jonathan The new NIH Intramural IRB— fewer agenda items, allowing for greater Green as the director of the Office of consisting of all current NIH IRB preparation and participation. Human Subjects Research Protections members—will use an innovative “flexible We thank you in advance for your (OHSRP) and Tiffany Gommel as the IRB” model and will begin meeting in patience and understanding as we director of IRB Operations (IRBO), a January 2019. Panels will meet multiple undertake this initiative. There will almost new centralized administrative office. times per week, conducting shorter certainly be some bumps in the road as Jonathan joins us from Washington meetings with fewer agenda items than we get going, but with your help we will University School of Medicine in are on current committee schedules. In achieve smooth sailing soon. St. Louis, where he was professor of this way, once ready, protocols can be medicine, pathology, and immunology, scheduled for meetings with less delay. Jonathan Green, M.D., M.B.A., is associate dean for Human Studies, and The revisions to the Common Rule the director of the Office of Human executive chair of the university’s IRB. constitute the first substantive changes Subjects Research Protections. For more Tiffany was executive director of the since its publication in 1991. There information, go to irbo.nih.gov.

2 THE NIH CATALYST JANUARY-FEBRUARY 2019 FEATURE

NIH Distinguished Scholars Program BY CARL HASHIMOTO, OD CHIA CHI CHARLIE CHANG

NIH Distinguished Scholars Program participants gathered for an inaugural meeting in the fall. Front row (from left): DSP scholars Joel Vega-Rodriguez, Joana Vidigal, Eric Calvo, Sadhana Jackson, Hugo Tejeda, and Paule Joseph; and Director of Research Workforce Development Roland Owens. Back row (from left): DSP scholar Freddy Escorcia; Deputy Director for Intramural Research Michael Gottesman; senior investigators and mentors Julie Segre, Veronica Alvarez, and John Tisdale; NIH Director Francis Collins; Chief Officer for Scientific Workforce Diversity Hannah Valantine; Senior Advisor for Faculty Development Carl Hashimoto; and DSP scholars Nida Sen, Faustine Williams, Catherine Cukras, and Sherine El-Toukhy (missing DSP scholars: Jennifer Jones and Joseph Rodriguez).

As part of an effort to enhance research and in promoting diversity and Vidigal (NCI), and Faustine Williams diversity in the scientific workplace, NIH inclusion. The scholars participate as (NIMHD). Candidates for the DSP launched the Distinguished Scholars a cohort in activities designed to foster are nominated by the NIH ICs that Program (DSP), which facilitates the a sense of belonging and to promote have intramural research programs. hiring and career progression of tenure- research and career success. Nominations for the 2019 cohort of track investigators who have demonstrated They receive mentorship from highly scholars will be due in March 2019. a commitment to promoting diversity experienced NIH senior investigators; Financial support for the DSP and inclusion in the biomedical-research professional leadership training and comes from a central fund of workforce. access to workshops on a variety of contributions made by the ICs, which The DSP aims to reduce the barriers management skills and tactics; and so far have committed support for to the recruitment and success of principal informal networking opportunities three cohorts of scholars. Each scholar investigators from underrepresented with NIH leadership such as the NIH receives research funding from the DSP groups in biomedical research (African- director, institute and center (IC) for the first four years of their tenure- Americans, Hispanics, American Indians, directors, and scientific directors. track appointment; the respective ICs and others; people with disabilities; In 2018, the DSP recruited 13 provide any supplemental funding individuals from disadvantaged scholars for the inaugural cohort: during the first four years and full backgrounds; and women). Eric Calvo (NIAID), Catherine funding after that. To build a more diverse and inclusive Cukras (NEI), Sherine El-Toukhy intramural research program, the DSP (NIMHD), Freddy Escorcia (NCI), For further information about the DSP recruits a cohort of up to 15 tenure- Sadhana Jackson (NCI), Jennifer and bios of the 2018 NIH Distinguished track and some clinical investigators Jones (NCI), Paule Joseph (NINR), Scholars, visit https://diversity.nih.gov/ each year. Selection for the program is Joseph Rodriguez (NIEHS), H. Nida programs-partnerships/dsp or contact competitive and recognizes outstanding Sen (NEI), Hugo Tejeda (NIMH), Carl Hashimoto, who leads the DSP, at carl. accomplishments both in scientific Joel Vega-Rodriguez (NIAID), Joana [email protected].

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

NIH Fellows Editorial Board Influencing Science, One Manuscript at a Time BY BRANDI CAROFINO AND ERIKA GINSBURG, NCI

editors. The senior editor finalizes the reports; each author receives a letter that summarizes the board’s overall impressions and a copyedited PDF version of the document. PDF annotation ensures that authors consider the rationale for the edits as they incorporate them into their final document. Generally, the authors receive reports within 10 business days and may also request an in-person meeting with the

BRANDI CAROFINO, NCI BRANDI CAROFINO, editors if desired. Members of the Fellows Editorial Board (from left): Amelia Parker, Brianna Daley, Manju Bhaskar, Alexis Carter (consulting To evaluate and enhance the service member), Iain Sawyer, Brandi Carofino, Lukas Bialkowski, Sarah Deasy, Anowarul Amin, Mariana Mandler, Shailesh Advani, Michelle Saré, and Erika Ginsburg (advisor). provided by the FEB, authors are asked to complete a feedback form for each submission. The FEB frequently receives The NIH Fellows Editorial “See one, do one, teach one.” the highest marks for each query, which Board (FEB) recently celebrated a big The FEB is led by Senior Editor Brandi includes questions on timeliness, clarity, milestone: They edited their 1,000th Carofino(National Cancer Institute, NCI). helpfulness, and likelihood of submitting submission. The FEB, founded in 2002, Each submission is managed by one of future manuscripts to the FEB. FEB- has edited an average of 60 manuscripts a four associate editors, a team that includes edited manuscripts have recently been year for the past 16 years. Anowarul Amin and Manju Bhaskar (both published in high-impact journals such as Companies that offer professional from the National Institute of Neurological Nature Communications, The Proceedings of editing services often charge hundreds of Disorders and Stroke) and Iain Sawyer and the National Academy of Science, Cancer Cell, dollars to review a scientific manuscript. Sarah Deasy (both from NCI). The rest of and The Journal of Biological Chemistry. Luckily, fellows in the NIH intramural the board includes 25 editors—representing Many members use the FEB as a research program and the FDA have a nearly all the NIH institutes and centers springboard to begin careers as professional better option—the free editing services as well as the FDA—who are postdocs, science writers or editors. FEB alumni hold offered by the FEB. The service is for postbacs, and consulting members. positions at the Lancet, the Drug Information fellows and by fellows and provides free, Each submission is managed by an Association, Ripple Effect Communications, fast, and confidential editing for a variety associate editor, who solicits three or four the Susan G. Komen organization, and of scientific documents including journal primary editors from the board to lead the several NIH institutes. A recent alumna, articles, book chapters, and grant proposals. discussion during the weekly FEB meetings, Caeul Lim (National Institute of Allergy Editors highlight confusing sentences, which take place on the Bethesda campus and Infectious Diseases), now an assistant identify where reorganization is needed, and is videocast to several other NIH editor at Cell Press in Boston, said that her and provide suggestions on how to improve locations. The primary editors carefully “experience with the FEB was instrumental writing skills. The editors do not, however, read and edit a submission and serve as the in getting the position.” consider the scientific merit of manuscripts. primary contributors during the meeting. All editing is performed by fellows who After an FEB meeting, primary team The FEB is supported by the NCI Center for volunteer to serve as board members. The members each prepare a report for each Cancer Training’s Office of Training and process of editing helps them hone their submission. The reports are then compiled Education. For more information, visit the FEB editorial, writing, teamwork, and leadership into a single document so that the reviews website at https://ccr.cancer.gov/training/ skills. Prior experience is not required, but are comprehensive but not redundant. The trainee-resources/editorial-board or email new editors are extensively trained by more- process helps newer editors gain experience [email protected]. senior board members on the principle of under the supervision of more practiced

4 THE NIH CATALYST JANUARY-FEBRUARY 2019 THE TRAINING PAGE

Breaking Through the Petri Dish Lid Institutional and Personal Approaches to Enhancing Diversity BY SUSAN CHACKO, CIT

Mentorship and institutional thinking strategically; listening to people and now a nanoscale research scientist and change were the main themes at the and being willing to work as part of a entrepreneur, talked about how her four- symposium “Breaking through the team; learning how to manage conflict; year career break to raise her family made Petri Dish Lid: Ways for Women and and most of all being resilient. Valantine her realize the challenges facing women Underrepresented Groups to Advance recommended that aspiring scientists find who return to the scientific workforce. Their Careers in Science,” held on “sponsors,” a step beyond mentors, too. She founded a nonprofit, the Foundation October 5, 2018. The symposium While individual efforts are part of for American Advancement, to provide featured three panelists—Kathryn the picture, Valantine pointed out that specialized training and fellowships for Zoon, Hannah Valantine, and Nesrine these approaches have had limited success. women returning to science, technology, Taha—who discussed personal and It’s now time to fix the institutions. The engineering, and mathematics (STEM) institutional approaches to changing the culture has not changed over time; women workplaces as well as programs for schools. existing paradigm. and people from underrepresented groups The panel also recognized that NIH’s Debbie Hinton, a PI at the National do not have access to an even playing new anti-harassment policies, which aim Institute of Diabetes and Digestive and field, and there is no reward system for to create a culture of civility and respect— Kidney Disease, presented some sobering enhancing diversity in institutions. She has will foster a safe working environment statistics in her welcome address. In the an evidence-based approach to changing at NIH that is friendly to women and early 1990s, women made up 16.5 percent this culture: For example, scientific underrepresented minorities. The NIH of senior investigators (PIs) at NIH, and in directors are presenting metrics such as leadership is also looking into ways to 2018, the number has barely increased to 24 resource distribution, salary, and speaking- influence change at universities, too. percent, she said. There has been even less engagement demographics to the NIH Audience members eagerly asked change in the upper leadership positions. Equity Committee every two years. questions about every aspect of diversity During this same period the percent of Valantine also suggested that there be in science. “It’s critical to get multiple women getting Ph.D.s in the biosciences more rapid turnover of laboratory and branch perspectives at the table and build diverse increased from 42 percent to 52 percent. chiefs at NIH. Although she acknowledged experiences into policy,” said Valerie The statistics for individuals from that achieving diversity and equity at the top Virta, one of the NIH attendees, who underrepresented groups are even more scientific levels would take time, she was said she had been very inspired by the discouraging. Nationwide, they receive firmly of the belief that within two years, symposium. about 12 percent of Ph.D.s but occupy five new scientific hires at NIH could be half To sum up the conference, Zoon percent of tenured positions, according to women. That’s because with new methods quoted Supreme Court Justice Ruth Bader Valantine, NIH’s chief officer for scientific of hiring that focus on broad, trans-NIH Ginsburg: “Fight for the things you care workplace diversity. searches with a deeper talent pool (such about, but do it in a way that will lead Zoon, a former scientific director as the Stadtman search), the percentage others to join you.” and now scientist emerita at the National of women among new hires has exceeded Institute of Allergy and Infectious the percentage of women applicants. The event was hosted by the NIH Women Diseases, stressed the importance of good Moreover, the proportion of women tenure- Scientists Advisors (WSA) and the Bethesda mentorship—perhaps even having multiple track investigators in the NIH intramural chapter of the Association for Women in mentors—who can help in handling both research program (IRP) is now 40 percent, Science (AWIS). To watch a videocast, visit scientific and life challenges. She identified a significant increase from even a few years https://videocast.nih.gov/launch.asp?26094. several leadership skills for women including ago. In contrast, the percentage of women For more information, go to https://www. networking; having ethics and integrity; in the tenured investigator pool has not niehs.nih.gov/careers/research/fellows/ being creative and innovative in solving increased much over the past 10 years. alumni-outcomes/index.cfm or contact problems; having an awareness of the Taha, a former pre-doctoral researcher Tammy Collins (984-287-3651 or tammy. scientific environment; being flexible; (2013–2014) at the National Eye Institute [email protected]).

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

Office of Patient Recruitment Extending the Reach of NIH Studies BY BRANDON LEVY, OIR

If researchers design a NIH Clinical Center with young African-Americans who have Office of Patient Recruitment (OPR) groundbreaking clinical study, and no At the NIH Clinical Center, individuals who participate in clinical research are type 2 diabetes. Recruiting for the study partners in research and discovery. Our recruitment experts are available to help intramural investigators reach potential patient and healthy volunteers. patients know about it, what’s the use? Contact us for recruitment consultation, planning, and implementation. has been difficult because the condition is The scientists may have a supply closet Some of our recruitment services include the following: (Check those you are interested in) rare in young people. And most patients Study Flyers Social Media Post a recruitment (plus tear­offs!) message about your study on the An online registry ResearchMatch Clinical Center’s Facebook and of people interested in participating in Twitter (ask your IC to share the post on don’t understand how biomedical research bursting with test tubes and Petri dishes, a research. their IC’s social media!)

A Research Study for

women with eekin g evious ter is s tudy. Pr l Cen arch s Women withClinica Endometriosisrese n Health e in a um toxi utes of part icipat f botulin can benefit them. The recruitment team, set of blank consent forms stacked two feet nstit to t i in. l I pain Nationa th pelvic pa The osis and pelvic ch is needed to tesen wi metr i e res ear in wom endo r spasm owever, mo floor research has shown that botulinumpel toxinvic injection may reduce pain and spasm elvic floor. H for of t he p e t reatment iv old. is an effect may be eligible if you:0 years You n, 18­5 with . woma sed pain Are a lly diagno t pelvic • urg ica sisten been s e per Have hav IH • osis and lves: to t he N ometri dy invo visits nth. end : Stu one mo if you re outpatient riod o f eli gible r a p e dy ot be cal • Two or mo ter ove the stu y n ectomy. Cen You ma a hyster Clini cal s following ad incontinence, fe up visit • Have h se. ing follow olap caus • Two placebo a history of urinaryelvic pr may be l toxin or • Have e, or p which ca tion. enc iti ons ychologi injec incontin er cond l, ps ving either botulinum any oth Recei on. ceive Have as gastrointestina fati gue • injec ti may re • chronic r) one gia or (salt wate ing the pelvic pain such myal njection, youon dur s, fibro in. the study i injec ti isord er num tox • After d bot uli tul inu m toxin ome. or in collaboration with specialists from the high, and the latest cutting-edge analytic ne bo are syndr lbumin o period. ons w­u p dicat i aller gy to a d m e ve an year follo tests an • Ha y­re lated • Stud cost. d at no prov ide tal, earch hospi rica’s res H Clinical Center, Ame On the Metro red line The NI aryland. s i n Bethesda, M al Center stop). i (Medic ® alth Into He iscovery rning D on: IH...Tu NIH Publications N For more informati(TTY: 1­866­411­1010) l 1­800­411­1222españo ov habla altrials.g se , clinic 83 onlin e 2­CH­00 or og dy #: 1 Post your recruitment by stu software loaded onto their desktops. But search CC’s Office of Communications and Clinical Research Volunteer message in the NIH Program Request a list of Record and CC volunteers who fit your News LISTSERV Send out a inclusion/exclusion criteria and without any participants, all those test tubes, recruitment message to one payment processing Media Relations, initiated a partnership of our LISTSERVs (over 30,000 subscribers) consent forms, and spreadsheets will remain Telephone Screening with Children’s National Hospital in Callers most closely matching your study’s requirements are empty. We are nothing without our patient referred to your team for follow up. Washington, D.C. Children’s has the largest volunteers. Flyer Distribution We’ll help post your flyer in: endocrinology program in the Northeast. Office of Patient Recruitment • Buildings on NIH campus • Enclosed cases in the Clinical Center NIH Clinical Center Fortunately, the NIH Clinical Center’s • GIANT grocery stores Through the partnership, NIH Call us: 301-402-6380 • University libraries Email us: [email protected] • Community libraries (CC’s) Office of Patient Recruitment is eager • DC/Metro area medical specialists developed digital, video, and social-media • Community Clinics ...and more! to help find participants for intramural NIH...Turning Discovery Into Health® content for Children’s to distribute to studies. In fiscal year 2017, it assisted with their physician and patient audiences. A recruitment for 229 clinical trials performed approaches tailored to studies’ specific target low-cost video about the trial is posted at 19 of NIH’s institutes and centers. populations. The specialists design flyers, on several websites including YouTube. In addition to a staff of knowledgeable postcards, and other printed materials; create Chung routinely shows it to her patients recruitment specialists who work with newspaper and radio ads; and draft messages to encourage them to join her study. In scientists at all stages of the research process, to post on social media and other websites. addition, the NIH recruitment specialists the Office of Patient Recruitment oversees Although these services are provided for free, developed a social-media strategy to target the Clinical Research Volunteer Program, investigators do have to pay if they choose to those patients directly and designed and a database of more than 20,000 healthy purchase advertising space or request larger mailed flyers to clinicians who work with volunteers interested in participating in NIH printed materials such as banners. that population so they can make their research. The registry can be filtered based on What’s more, the recruitment specialists patients aware of the trial. demographic criteria such as age and sex, as can leverage their knowledge of the Representatives from these offices “really well as by more specific characteristics such Institutional Review Board (IRB) approval understood where we were coming from and as whether an individual is taking certain process to ensure that recruitment strategies what we were trying to do,” Chung said. medications. The combination of these two and materials move smoothly through it. “We wanted people to understand why this resources can greatly reduce the difficulty of “Some of our specialists have been [study] is important and how it is going to finding participants for intramural studies. here a long time, so they often can predict affect them and their families. I think part Recently, the Office of Patient how the IRB will react to recruitment of the reason the campaign was so successful Recruitment joined forces with the CC’s materials and whether the IRB would like was that we had a great team.” Office of Communications and Media something phrased or presented a certain Relations. The technical and creative way,” Freimuth said. To learn more about the Office of Patient expertise of the two offices combined One of the researchers who is benefitting Recruitment and how to submit a request means that patient-recruitment services from the efforts of the Office of Patient for services, visit http://intranet.cc.nih.gov/ are significantly enhanced. Recruitment is Stephanie Chung, recruit/index.html. After your request has Using their media savvy and co-director of the Metabolic Research been submitted, a recruitment specialist will understanding of how biomedical research Program in the National Institute of respond within three business days. If you is done, the office’s recruitment specialists Diabetes and Digestive and Kidney have any questions, you can also call the office work with researchers to create recruitment Diseases. She is conducting a clinical trial at 301-402-6380.

6 THE NIH CATALYST JANUARY-FEBRUARY 2019 NEWS YOU CAN USE

NIH Library Services So Much More than Books BY KATHLEEN MCGLAUGHLIN, OD

Need to know how to develop Drupal, an open-source web-content- work with preprints, enhance the journal bibliometrics that will help you management framework, and manages article submission process, and understand evaluate written publications? Want to a federally approved cloud-hosting open-access publishing. The session understand how to use information- solution for the products they develop. concluded with an educational presentation, systems technology? How about getting The team uses their expertise in website “Identifying Scientifically Sound Journals assistance with editing your manuscripts development, information architecture, for Publication.” or managing your data? The NIH Library, and data management to develop innovative located in Building 10, is at your service. In information solutions. Examples include an Data Services addition to managing a vast collection of online portfolio of epilepsy research projects, The Data Services team can help you books and journals and helping you with a database of Alzheimer disease preclinical understand how to manage your data from research questions, the NIH Library offers studies, a portfolio of Alzheimer disease the beginning of your project through the a variety of services to help you acquire and grant-funding data, and a collaborative post-project stage of preserving your data so manage the information you need. Here, website to share ideas and best practices it can be successfully accessed and reused four of them are highlighted. for designing, constructing, operating, and over the long term. Training includes classes maintaining buildings. on data management, data visualization, data Bibliometrics Service Among the events the team organizes analysis, and the programming language R The NIH Library’s Bibliometrics Service are the annual NIH-Library-hosted Drupal (used for statistical computing and graphics). program provides statistical analysis of GovCon event, one of the biggest Drupal NIH staff are also welcome to use the written publications produced by scientists, conferences on the East Coast. Next year’s NIH Library’s high-performance data- grant programs, and institutions at NIH event is scheduled for July 24–26, 2019. sciences workstation, which comes complete and around the world. Such analytics can with a suite of tools for data analysis, help NIH staff measure the productivity of Editing Service processing, and visualization for different researchers, detect collaborations, identify The NIH Library provides free light types of data. NIH Library staff are available research topics, and calculate citation-impact and medium editing services for NIH- to provide help with the tools. scores. Services include consultations on and Department of Health and Human The Data Services team is also designing and using bibliometric analyses, Services–related work. NIH Library investigating how to support working customized analyses that will meet specific editors will review and suggest revisions to with electronic lab notebooks (ELNs) at needs, and training on bibliometrics theory improve your manuscript, slide deck, poster, NIH and recently hosted a series of ELN and techniques. In August 2018, the service and more. Additional services include free meetings for staff already using ELNs as presented a two-day “Bibliometrics and and confidential plagiarism review using well as others who are considering them. Research Assessment Symposium,” which iThenticate; resource suggestions to help The information gathered during these provided a forum to share expertise, ideas, get your draft ready for peer review; and sessions will be used to help the NIH and best practices in bibliometrics services consultation and assistance with copyright Library plan a one-day ELN forum in 2019 via a blend of keynote presentations, poster questions and the PubMed Central to further explore current ELN practices sessions, and training sessions. submission process. and opportunities at NIH. Training includes special events and Custom Information Solutions Service classes for new and experienced authors. For more information, go to https://www.nihli- The Custom Information Solutions In October 2018, the Editing Service brary.nih.gov/services, call 301-496-1080, or (CIS) service brings together information hosted a two-hour workshop, “Choosing email [email protected]. To stay up to date science and technology to develop online a Quality Journal for Publication,” which on NIH Library classes, events, resources, tools and resources that help NIH staff featured a panel discussion with experts and services, subscribe to the NIH Library share their research and collaborate more who offered advice on how to identify LISTSERV at https://list.nih.gov/cgi-bin/ effectively. The CIS team specializes in questionable journals and conferences, wa.exe?SUBED1=NIHLIB-L&A=1.

https://irp.nih.gov/catalyst 7 CATALYTIC RESEARCH Intramural Research Briefs

Ktena, N.S. Trivedi, P.M. Zerfas, V. Hoffmann, advance the treatment of cancer patients. M. Abu-Asab, M.G. Tsokos, D.E. Kleiner, A.G. (NIH authors: S. Yokoyama, Y. Cail, M. Murata, Elkahloun, J. Schnermann, R.J. Chandler, T. Tomita, M. Yoneda, L. Xu, R.E Cachau, and and C.P. Venditti, JCI Insight 3:e124351, 2018; S. Kimura, eLife 7:e37854, 2018; DOI:10.7554/ DOI:10.1172/jci.insight.124351) eLife.37854) [BY SHIOKO KIMURA, NCI] NCI: A BACTERIA TOXIN TRIGGERS RUPTURE OF CANCER CELLS LEADING TO THEIR DEATH Inflammation serves to kill invading bacteria and viruses. Certain molecules on the surface

PATRICIA M. ZERFAS, ORS of the microbes can trigger an inflammatory NHGRI: The figure is an electron micrograph showing cascade, and one example of such a molecule is abnormally shaped and structured mitochondria in the lipopolysaccharide (LPS). Cells can react to LPS liver of a mutant mouse that models methylmalonic acidemia. by triggering a process called pyroptosis that NHGRI, NIDDK, NCI, ORS: ELEVATED causes the cell to burst and die. The released HORMONE FLAGS LIVER PROBLEMS IN MICE cell contents attract blood and lymphatic cells WITH METHYLMALONIC ACIDEMIA that in turn kill the LPS-producing bacteria. NHGRI researchers led a team that discovered LPS was used in the very early days of

that a hormone, fibroblast growth factor 21 medicine to treat cancer, although it has fallen BACK SUSANNE (FGF21), is extremely elevated in mice with out of favor because it causes severe side NIDA: This graphic shows an exodus of from the liver disease that mimics the same condition effects, such as a hyperinflammatory response endoplasmic reticulum (ER) in response to the loss of luminal ER calcium. The cell works to maintain the calcium-deprived in patients with methylmalonic acidemia (sepsis) that can result in death. It was not ER proteome by upregulating KDEL receptors. (MMA). MMA is a genomic disease that impairs known exactly how LPS kills cancer cells. a person’s ability to break down food proteins NCI researchers have now shown that a NIDA: MAINTAINING THE ER PROTEOME and certain fatty acids. The condition affects called secretoglobin family 3A member UNDER CALCIUM DEFICIENCY roughly one in 50,000 children born in the 2 (SCGB3A2), which is produced by the cells A new paper published by NIDA scientists United States and can be detected through that line the lung airways, binds to LPS. Tests describes, for the first time, a novel newborn screening. Children with MMA suffer on mouse immune cells and lung-cancer cells pathological mechanism that may contribute from frequent life-threatening metabolic grown in the laboratory showed that the to a variety of disease states. Within the crises when they encounter a minor viral resulting SCGB3A2-LPS complex can then cells of our body, many of the proteins and illness or other stressors such as trauma, bind to a cell-surface protein called syndecan lipids are produced by a structure within a dietary imbalance, or surgery. They must 1. This binding enables LPS to enter the cell and cell called the endoplasmic reticulum (ER). adhere to a special low-protein diet and take trigger pyroptosis and cell death. The ER also serves as the cell’s primary various supplements their entire lives. Currently available cancer immunotherapy reservoir of calcium. Each of the resident ER Based on the discovery, clinicians treating is targeted primarily to the host immune cells proteins is kept in the ER by a tail sequence patients with MMA will be able to measure whereas the NCI study shows the possibility to called an ER-retention sequence. If a protein FGF21 levels to predict how severely patients’ directly target cancer cells. However, it remains escapes the ER, its tail is recognized by livers are affected and when to refer patients to be examined whether molecules that trigger a receptor called a “KDEL (Lys-Asp-Glu- for liver transplants. The findings also might pyroptosis, like LPS, could also be used to treat Leu) receptor” and returned to the ER. This shed light on more common disorders such cancers other than those from the lung. Further function is critical to the maintenance of a as fatty liver disease, obesity and diabetes by work is also needed to understand in more healthy body. The study shows that when the uncovering similarities in how MMA and these detail how SCGB3A2 and LPS work together calcium concentration drops in the ER, the cell disorders affect energy metabolism. (NIH to cause cancer-cell death. The combination proteins overwhelm this retrieval mechanism authors: I. Manoli, J.R. Sysol, M.W. Epping, L. of cancer immunotherapy and stimulation and redistribute to the outside of the cell. As a Li, C. Wang, J.L. Sloan, A. Pass, J. Gagné, Y.P. of cancer-cell self-destruction could greatly result, protein functions are lost in the ER, and

8 THE NIH CATALYST JANUARY-FEBRUARY 2019 CATALYTIC RESEARCH

unwanted expression occurs outside the cell, NIEHS: MALE MICE GROW OVARIES AFTER NIEHS: SOX17 PROTEIN IS CRITICAL FOR which may contribute to a variety of disease SINGLE TWEAK PREGNANCY pathologies such as diabetes, stroke, Alzheimer By turning on the mammalian gene FOXL2, Using mouse genomic data, genome editing, disease, cardiac diseases, and substance- NIEHS scientists prompted male mice to and bioinformatics, a team led by NIEHS use disorders. This greater understanding grow ovaries. Among vertebrates, there is scientists determined that the protein SOX17 of the most delicate mechanisms in the a wide variation in the signals that trigger may be critical to a woman’s ability to become body suggests that stabilizing ER calcium or sex determination of the gonads. In some pregnant. The researchers found that the increasing KDEL receptors has therapeutic types of turtles and alligators, sex is shaped SOX17 transcription factor works with the potential. (NIH authors: K.A. Trychta, S. Back, by environmental cues such as temperature progesterone receptor in female mice to M.J. Henderson, and B.K. Harvey, Cell Reports or the availability of nutrients. In humans, regulate the ability of the uterus to support 25:1829–1840, 2018) it is written in the composition of the sex embryo implantation. The scientists hope [BY BRANDON K. HARVEY, NIDA] . Although there are differences, they can use the information to eventually many of these organisms use the same turn stem cells into healthy uterine-lining proteins to guide sexual development, such cells, which would help some women with NIDDK, NHLBI, NIAMS: T-REG CELLS as sex-determining region Y (SRY) and infertility or uterine disease. SOX17 regulates SUPPORT INTESTINAL WOUND HEALING SRY-related box 9 (SOX9) in the testis and both development of the uterus and the A subset of regulatory T cells, called CD161+ wingless-related integration site (WNT) genes that support embryo implantation. Treg cells, accelerated wound healing and may family member 4 and forkhead box protein L2 Removing either the SOX17 binding site, also reduce inflammation in the gut, according (FOXL2) in the ovary. which the team determined to be near the to scientists from NIH and the United Male mice were genetically engineered Ihh gene, or the entire SOX17 gene altered Kingdom. The study described the biological to produce FOXL2 protein in their testes. communication between uterine epithelial mechanisms of CD161+ Treg cells in humans, Their gonads morphed into ovaries, cells and the stroma. As a result, the uterus did finding them to be a distinct, stable, and although they retained some molecular and not form properly and was unable to support highly suppressive population of regulatory T structural features related to their original pregnancy. cells. CD161+ Treg cells were also associated sex programming. The study suggests that When SOX17 was present, it worked with with regions of lower inflammation in Crohn sexual development is flexible and may be the progesterone receptor to control the disease. These findings suggest that infusion able to shift in response to different genetic or ability of the uterus to receive an embryo. of CD161+ Treg cells may be a valid therapy environmental factors. The findings could give The team found that mouse SOX17 used the for inflammatory bowel disease. (NIH authors: insight into disorders of sexual development protein Indian hedgehog homolog, which is Y.-C. Chen, D. Chauss, H.-W. Sun, H.-Y. Shih, and defects in fertility. (NIH authors: B. Nicol, coded for by the Ihh gene, to communicate C. Kemper, M. Pirooznia, and B. Afzali, Nat S.A. Grimm, A. Gruzdev, G.J. Scott, M.K. Ray, with and regulate uterine genes. The finding Immunol 19:1403–1414, 2018; DOI:10.1038/ and H.H.C. Yao, Hum Mol Genet 27:4273–4287, has implications for treatment of infertility s41590-018-0230-z) 2018; DOI:10.1093/hmg/ddy312) and diseases in which patients do not [BY BEHDAD AFZALI, NIDDK] [BY MARLA BROADFOOT, NIEHS] respond well to progesterone therapy— such as endometriosis, endometrial cancer, and some infertility cases. (NIH authors: X. Wang, T. Wang, S.-P. Wu, and F.J. DeMayo, Nature Comm 9:Article number 4421, 2018; DOI:10.1038/s41467-018-06652-w) [BY ROBIN ARNETTE, NIEHS]

Read more online: HUMPHREY NIEHS YAO, https://irp.nih.gov/catalyst/v27i1/ NIEHS: The normal mouse testis, left, produces large amounts of a testis-specific marker called SOX9, shown in green. The normal mouse ovary, middle, produces large amounts of an ovary-specific marker called FOXL2, highlighted in research-briefs pink. The genetically tweaked mouse testis, right, produces mostly FOXL2, but retains small amounts of SOX9.

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

Stadtman Investigators

PEDRO J. BATISTA, NCI-CCR ISABEL BEERMAN, NIA JOHN BROGNARD, NCI-CCR CHENGKAI DAI, NCI-CCR BRIAN GLANCY, NHLBI and NIAMS

PEDRO J. BATISTA, PH.D., NCI-CCR (Proc Natl Acad of Sci USA 107:5465–5470, of enzymes as tumor suppressors, over- Research focus: Understanding in 2010). We also demonstrated that DNA turning the established dogma that PKCs what way RNA post-transcriptional damage accumulation was tied to the were oncogenes (Cell 160:489–502, 2015; modifications regulate gene expression quiescent nature of HSCs. (Cell Stem Cell DOI:10.1016/j.cell.2015.01.001). during development and disease. 15:37–50, 2014). These findings suggest a potential for restoring restricted potential What would surprise most people? What discoveries have you made? of aged HSCs by resetting these nonper- I grew up in a rural area and my dad took I found that the RNA modification manent modifications on the DNA. me fishing and hunting. However, after N6-methyladenosine confers flexibility to living in the United Kingdom for six years the transcriptome and modulates the balance What would surprise most people? and observing the effectiveness of making between pluripotency and differentiation Anyone who has heard my off-key hum- gun ownership illegal, I am now an advocate (Cell Stem Cell 15:707–719, 2014). ming would be surprised that I was trained for strict gun laws. to sing classical music and played the organ What is exciting about your work? for my hometown church. I also proudly All the new questions that emerge every time maintain my skill at driving a combine, CHENGKAI DAI, PH.D., NCI-CCR we take a step forward on understanding which I learned growing up on a farm. Research focus: Using multidisciplinary how cells regulate gene expression. approaches to interrogate the role of pro- teomic stability in tumorigenesis and What would surprise most people? JOHN BROGNARD, PH.D., NCI-CCR exploiting proteomic instability as an That I have been practicing martial arts Research focus: Elucidating cancer- intrinsic vulnerability of cancer for therapy. since high school. associated kinases in the unexplored human kinome. We hope to identify novel What discoveries have you made? ISABEL BEERMAN, PH.D., NIA druggable drivers so cancer patients can Our group is among the first to discover benefit from targeted therapies. the unexpected pro-oncogenic role of the Research focus: Understanding the proteotoxic stress response and demonstrate mechanisms that underlie age-associated What discoveries have you made? that cancer cells are addicted to, or functional decline, with a focus on adult I helped define protein kinase B (AKT) as dependent on, this stress response for their tissue-specific stem cells. Reestablishing a critical mediator of survival in lung cancer growth and survival. (Cell 130:1005–1018, the full potential to these aged cells could and determined that combining AKT 2007; and Cell 160:729–744, 2015) mitigate many age-associated phenotypes. inhibitors with chemotherapy could be beneficial for lung-cancer patients Cancer( What do you like to do outside of work? What discoveries have you made? Res 61:3986–3987, 2001). I also helped to Travel to different places and experience My work has contributed to understanding define the protein kinase C (PKC) family different cultures. how aging affects hematopoietic stem cells

10 THE NIH CATALYST JANUARY-FEBRUARY 2019 FEATURE

Stadtman Investigators

RAMIRO IGLESIAS- CHANDRA L. JACKSON, NIEHS KATHERINE MCJUNKIN, NIDDK JAGAN MUPPIDI, NCI-CCR CARLO PIERPAOLI, NIBIB BARTOLOME, NCI-CCR AND NIMHD

BRIAN GLANCY, PH.D., NHLBI AND NIAMS What discoveries have you made? Have you had any significant findings? Research Focus: Determining how My group showed that in mice, the dele- We found, in nationally representative stud- mitochondria are optimized within muscle tion of Gnas and PKA in the skin induces ies, that racial and ethnic disparities in sleep cells to help maintain energy homeostasis basal-cell carcinoma, the most common health are socially patterned: The most dis - during the large change in energy demand form of cancer in humans.(Nat Cell Biol advantaged, low-opportunity groups were caused by muscle contractions. We are 17:793–803, 2015). In trying to determine the most likely to be short sleepers ( Am J also developing and using novel, direct why wounds in the mouth heal faster and Epidemiol 178:1442–1451, 2013). We have measurements of in vivo mitochondrial with less scarring than wounds on the skin, also found that place may matter more than function in skeletal muscle under different we found that certain transcription factors race, suggesting that environmental factors workloads. were consistently upregulated in the oral play a major role in health disparities and wounds but not in skin wounds. The find- should be considered when designing inter- Have you made any discoveries? ings suggest that the molecular signature ventions (Sleep Health 4:420–428, 2018). We demonstrated that skeletal-muscle of the oral mucosa could be used to develop mitochondria form a highly connected therapies for wound healing (Sci Transl Med What is exciting about your work? network resembling that of an electrical 10:eaap8798, 2018). It can provide scientific evidence to inform power grid and are capable of electrical various types of interventions (including conduction of the mitochondrial membrane What is exciting about your work? policies) designed to improve population potential throughout the cell (Nature Its constant dynamic nature. Every day we health while addressing preventable health 523:617–620, 2015). face new problems to solve and questions to disparities. Ultimately, this work has the answer. I enjoy continuously learning about potential to be translated into action. What is exciting about your work? new subjects and new techniques, which we Finding new ways to look at things. It must do daily to be at the top of our field. often involves developing new methods to KATHERINE MCJUNKIN, PH.D., NIDDK evaluate research questions we could not Research focus: Defining the poorly answer previously. CHANDRA L. JACKSON, PH.D., NIEHS AND understood biological functions of NIMHD microRNAs (miRNAs) in the embryo Research focus: Using observational epi- and the mechanisms of miRNA turnover. RAMIRO IGLESIAS-BARTOLOME, PH.D., demiology and mixed-methods approaches We are combining classical Caenorhabditis NCI-CCR to investigate pathways by which factors in elegans–forward genetics with CRISPR- Research Focus: Elucidating the signaling physical and social environments contribute Cas-9-mediated genome editing, next- mechanisms that control and drive tissue- to racial, ethnic, and socioeconomic dispari- generation sequencing, cell biology, and specific stem-cell self-renewal and differ- ties in sleep health and the subsequent risk biochemical techniques. Our work has entiation and their connections to tumor of cardiometabolic conditions. CONTINUED ON PAGE 12 initiation and growth.

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

Stadtmans CONTINUED FROM PAGE 11 the potential to uncover regulatory modules What is exciting about your work? TIFFANY M. POWELL-WILEY M.D., M.P.H., that couple miRNA decay to developmental Being able to understand how normal F.A.H.A., NHLBI AND NIMHD timing. mechanisms of B-cell homeostasis are Research Focus: My group is designing perturbed in lymphoma and what those community-based interventions that address Have you made any discoveries? perturbations can teach us about the biology cardiovascular health disparities in resource- I discovered that embryonically-expressed of B-cell responses and the pathogenesis limited communities in Washington, D.C. microRNAs may act as developmental of lymphoma. We are delineating mechanisms by which timers, keeping certain genes from turning the neighborhood environment influences on too early during development (Genes Dev the development of obesity, diabetes, and 31:422–437, 2017). CARLO PIERPAOLI, M.D., PH.D., NIBIB other markers of cardiometabolic risk; Research focus: My group is identifying methods for incorporating What is exciting about your work? developing noninvasive biomarkers mobile-health technology into interven- Making new scientific discoveries is the that can characterize brain anatomy and tions addressing behaviors associated with best, but since eureka moments happen only physiology across the lifespan. We are cardiometabolic health; and identifying and rarely, I also enjoy mentoring trainees and providing diagnostic and research tools characterizing physiologic pathways influ- seeing their progress in gaining skills and that can use data acquired with imaging enced by the chronic stress that comes from confidence. techniques, such as magnetic resonance living in adverse neighborhood conditions. imaging (MRI), to assess neurological disorders. Have you made any discoveries? JAGAN MUPPIDI, M.D., PH.D., NCI-CCR We were one of the first research Research Focus: Defining how genetic Have you made any discoveries? groups to show that moving to a more changes in B-cell lymphomas contrib- My lab and I pioneered MRI modalities, socioeconomically deprived neighborhood ute to altered B-cell behavior within the such as diffusion tensor imaging was associated with a higher risk of obesity microenvironment and subsequently become (DTI), that are now widely used in the over time (compared with staying in the malignant. I am trying to define the micro- neuroscience research community. We same socioeconomic-level neighborhood environmental factors within lymphoid performed the first DTI study of the or moving to a higher socioeconomic-level tissue that promote the development of human brain. We proposed biomarkers one). The environment really must be malignancy and also the mechanisms by that are informative of white-matter considered along with individual factors which lymphomas exit the site where they structure and organization, reversible that lead to obesity. It was particularly develop and seed distant sites. I hope that brain ischemia, stroke, postnatal surprising how robust the effect of my work may lead to the discovery of new cortical maturation, and a type of neighborhood socioeconomic level as a therapeutic targets for B-cell lymphomas. nerve degeneration called Wallerian neighborhood factor appears to be on degeneration (Neuroimage 13:1174– weight change and obesity (Am J Prev What discoveries have you made? 1185, 2001). Recently, we worked on Med 49:72–79, 2015). I defined a novel tumor-suppressive path- validating diffusion MRI to study brain way involving signals mediated by the small connectivity (PNAS 111:16574–16579, What might surprise most people? G-protein G-alpha-13. My group found 2014). My first career choice was to be an airline that this pathway inhibits the survival of pilot, but poor vision and my tendency to germinal-center B cells and cell migration, What might surprise most people? get motion sickness got in the way. and therefore confines germinal-center B In high school I would bring with me parts cells to a particular location in lymphoid of my motorcycle, such as the carburetor, tissue. We proposed that the loss of this that I would disassemble, under my desk, Read longer profiles online at pathway in certain kinds of lymphoma during the most boring lessons, to discover https://irp.nih.gov/catalyst/v27i1/ might promote the spread of cancer cells how they were made. the-merry-band-of-stadtmans/ to distant sites (Nature 516:254–258, 2014).

12 THE NIH CATALYST JANUARY-FEBRUARY 2019 FEATURE

Stadtman Investigators

TIFFANY M. POWELL-WILEY JOHNNY TAM, NEI FASIL TEKOLA-AYELE, NICHD CHUAN WU, NCI-CCR PING ZHANG, NCI-CCR NHLBI AND NIMHD

JOHNNY TAM, PH.D., NEI of 6 that increases suscepti- sites in inflammatory bowel disease, asthma, Research Focus: My lab is using advanced bility to podoconiosis (a tropical lower-leg and allergies. optical-imaging techniques to understand lymphedema resulting from long-term the onset and progression of retinal diseases barefoot exposure to red-clay soil derived What might surprise most people? at the cellular level. from volcanic rock). The study has shed I was not a good student and almost the first insight into the potential role of dropped out of medical school. None of my Have you made any discoveries? T-cell-mediated immune response in the college classmates and teachers back then My lab has pioneered new ways to image pathogenesis of podoconiosis. (N Engl J Med would have believed that I would become cells and structures in the eye by combining 366:1200–1208, 2012). a scientist one day. technologies such as adaptive optics with other technologies such as autofluores- What is exciting about your work? cence of intrinsic molecules, fluorescence Seeing how some research projects lead to PING ZHANG, PH.D., NCI-CCR microscopy of cells, and angiography of discoveries! Research focus: My laboratory applies a blood vessels. combination of biochemical and structural microscopy and X-ray crystallography What is exciting about your work? CHUAN WU, M.D., PH.D., NCI-CCR approaches to reveal the structural and To this day, I am still mesmerized by seeing Research Focus: My group is trying mechanistic basis of kinases that are closely images of cells in the living human eye. to gain a deeper understanding of how related to human cancers. Observing life’s processes at this level of cell-cell interactions, particularly neuron- detail never gets old. immune interactions on the mucosal surface, How did you get interested in science? orchestrate immune responses that help cells Fundamental questions such as “why are we FASIL TEKOLA-AYELE, M.P.H., PH.D., NICHD cope with environmental insults. here,” “how do we fit into the universe,” and “what is life” have always intrigued me. Sci- Research Focus: Understanding genetic What discoveries have you made? ence can help us turn the last question into influences and their interactions with past I helped identify an inducible kinase called projects leading to discoveries; and tell us and present-day environmental factors in SGK1 as essential for the development of why things are the way they are and how the fetal growth variations/differences and a pathogenic T-helper 17 cell response. In natural world works—from atoms to galaxies. consequent cardiometabolic diseases and addition, our recent work—identifying health disparities. key factors specific for regulatory T cells’ What is exciting about your work? function on the mucosal surface—may Helping to understand how things work What discoveries have you made? lead to the development of therapeutic with the potential for making people’s I helped identify a genetic variant in the modulation of T-cell responses on mucosal lives better. human leukocyte antigen class II region

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

Finding the Elixir of Life Alejandro Sánchez Alvarado Studies How Flatworms Regenerate BY AMRITA MANDAL, NICHD animal” within two weeks, said Sánchez Alvarado. “That’s the equivalent of cut- ting [off] my little finger and watching [it] regenerate me.” In an attempt to find the source of the regenerative potential of these animals, Sánchez Alvarado’s lab combined single-cell RNA sequencing, flow cytometry, genomics, and high-resolution imaging techniques. His lab identified and isolated a subtype of a proliferating cell called a neoblast that is capable of regenerating the whole animal (Cell 173:1593–1608.e20, 2018; DOI:10.1016/j.cell.2018.05.006). These cells express a cell-surface protein-coding CHIA-CHI CHARLIE CHANG CHARLIE CHIA-CHI gene, TSPAN1; single-cell transplantation of Alejandro Sánchez Alvarado, who spoke at a recent Wednesday Afternoon Lecture Series (WALS) lecture, explores a TSPAN1-positive cell can completely rescue the origins of life by focusing on planarian flatworms, simple organisms that are famous for their regenerative ability. a lethally irradiated host that no longer has any stem cells. Sánchez Alvarado concluded Alejandro Sánchez Alvarado may the fossil record suggests that multicellular his talk with a movie that showed for the have found the elixir of life in a simple life may have originated 650–700 million first time ever a neoblast cell dividing in organism that scientists have mostly years ago. But only those organisms a Petri dish. He hopes that because it is ignored: the tiny flatworm planarian possessing an exoskeleton endured the now possible to culture these cells in vitro, Schmidtea mediterranea. The worm has an process of fossilization, he explained; there is a whole new era for the regeneration field amazing ability to regenerate itself from no verifiable and uncontroversial fossil record will open up. the smallest bits of its tissue. for soft-bodied organisms. He pointed out Sánchez Alvarado believes we all have “Alejandro has studied and pioneered that microfossils (tiny remains of bacteria, a bit of “planaria” hidden in our genomes, work in planarians,” said National Institute protists, fungi, animals, and plants) recently according to his website. “You and I are of General Medical Sciences (NIGMS) characterized in western Australia, may turning over a number of cells equivalent Director John Lorsch, who introduced him indicate that life was trying to establish itself to our body weight every year.” at the DeWitt Stetten Lecture on October 3.5–4 billion years ago. “Maybe what we’ve “In addition to his many research accom- 10, 2018. “He sequenced the worm’s genome seen in the record [are] multiple attempts plishments, Sánchez Alvarado [is] also com- and developed a wide variety of approaches for complex life to emerge.” mitted to inspiring the next generation of to search for the specific cells that allow Sánchez Alvarado figured that one way scientists,” said Lorsch. He brings the magic regeneration to occur from even very small to explore the origins of complex life was to of science to middle-school and high-school pieces of the animal.” focus on planarian flatworms, simple organ- students with hands-on classroom activities Sánchez Alvarado—a Howard Hughes isms that are famous for their regenerative to study regeneration and stem-cell biology. Medical Institute investigator at the Stowers ability. (Geneticist Thomas Hunt Morgan Institute for Medical Research (Kansas City, became fascinated with this discovery more The annual DeWitt Stetten lecture, part of Missouri) and recipient of many prestigious than 100 years ago.) The most remarkable WALS, was established by NIGMS in 1982 in awards including being elected to the feature of the asexual form of this planar- honor of Stetten, who was the third director National Academy of Sciences in 2018—is ian is that you can “slice and dice them… of NIGMS. To watch the videocast of Sánchez fascinated by the origins of life. in a number of ways and every one of those Alvarado’s October 10, 2018, talk, go to https:// The Earth is 4.5 billion years old, and fragments will go on to generate a complete videocast.nih.gov/launch.asp?26100.

14 THE NIH CATALYST JANUARY-FEBRUARY 2019 THE SIG BEAT NEWS FROM AND ABOUT THE SCIENTIFIC INTEREST GROUPS

SIG: Adherence Research on adherence measurement and approaches standard practices for CNA studies; share Network Scientific Interest to optimize adherence to treatment and and optimize methods CNA experimental Group prevention regimens. design and analysis; and communicate To join the LISTSERVE for this CNA research across institutes. The CNA The Adherence Research SIG, go to https://list.nih.gov/cgi- SIG meets by WebEx monthly for hour- Network SIG is a transdisciplinary bin/wa.exe?SUBED1=adherence_ long seminars. consortium of NIH institutes and centers network&A=1. For more information, To join the LISTSERV go to https:// (ICs) that provide leadership, vision, and visit https://oir.nih.gov/sigs/adherence- list.nih.gov/cgi-bin/wa.exe?A0=NIH- support to strengthen adherence research research-network-scientific-interest- CNA-SIG. For more information, funded by the NIH. group, or email one of the chairs, Michael contact the chair, Adam Sowalsky (adam. Poor adherence to prescribed Stirratt ([email protected]) or Janet [email protected]), or visit the CNA medications and other recommended de Moor ([email protected]). SIG website at https://oir.nih.gov/sigs/ prevention, screening, treatment, circulating-nucleic-acidsliquid-biopsy- monitoring, and health-behavior regimens interest-group. is common across many chronic illnesses New SIG: Circulating and patient populations. The continued Nucleic Acids/Liquid Biopsy Interest Group

evidence of nonadherence in many chronic L. ALEXANDER/THINKSTOCK.COM conditions, and insufficient evidence for Interest in circulating, cell- how to improve adherence, highlights the free nucleic acids (CNAs) has increased need for transformative research. A critical sharply over the past decade with the public-health need is to build upon the advent of noninvasive liquid-biopsy current evidence base to fully understand techniques that span fields including the conditions that precipitate poor prenatal testing, toxic exposures, and adherence. We also need to develop and tumor characterization. implement next-generation interventions The creation of the CNA SIG was to improve adherence and health outcomes. inspired by a workshop—hosted by the To advance the field of adherence Scientific Interest Groups National Institute of Environmental research, the Adherence Research Health Sciences in September 2018— NIH Scientific Interest Groups Network SIG works to evaluate the state that focused on circulating cell-free DNA. (SIGs) are assemblies of scientists of the science and disseminate scientific Topics discussed included identifying with common research interests. These information and NIH research priorities mechanisms of recurrence in prostate groups engage with their members through conference symposia, meetings, cancer; earlier screening of prenatal via a LISTSERV; sponsor symposia, and white papers. The SIG, in collaboration genomic abnormalities; understanding poster sessions and lectures; offer with the Office of Behavioral and Social tissue damage associated with sickle- mentoring and career guidance for Science Research, also sponsors R01 and cell crises; monitoring stress; measuring junior scientists; help researchers share R21 research grants to improve adherence tissue-specific exposures to environmental the latest techniques and information; to treatment and prevention regimens. toxins in adults and the unborn; guiding act as informal advisors to the Deputy The Adherence Research Network treatment of metastatic tumors; and Director for Intramural Research SIG meets once a month. Regular following patients diagnosed with systemic (DDIR); provide advice for the annual meetings highlight adherence research lupus erythematosus. Other key areas NIH Research Festival; and serve as that is funded by NIH as well as the of discussion included limitations of hosts for the Wednesday Afternoon scientific priorities and related activities detection, the control of error rates in Lecture Series. Most of these groups of participating ICs. Meetings are used analysis, and interpretation of results with welcome interested non-NIH scientists. to advance collaborative projects pursued appropriate biological context. To learn more and see a list of the SIGS, by the SIG. The SIG also hosts a webinar The SIG’s goals are to establish go to https://oir.nih.gov/sigs. series to showcase cutting-edge research

https://irp.nih.gov/catalyst 15 FEATURE

Spellchecker for Genes CONTINUED FROM PAGE 1

“Gene-editing technologies have taken center stage in biomedical research, with boundless impact on translational medicine,” said Lothar Hennighausen, chief of the Laboratory of Genetics and Physiology in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). CRISPR, which stands for “Clustered, Regularly Interspaced, Short Palindromic JENNIFER RYMARUK, NIDDK Repeat,” together with CRISPR-associated 9 (CAS9), has emerged as one of the most promising gene-editing tools to study disease. Known for its efficiency and ease of use, the CRISPR-CAS9 (hereafter CRISPR) gene-editing method works by making cuts at targeted sites on a genome, Lothar Hennighausen’s team has made key discoveries in gene editing. Some of the team members gathered recently altering an organism’s DNA. for a group photo on the steps of Building One. From left: Chengyu Liu, Michaela Willi, Hennighausen, Xianke Zeng, Hennighausen’s lab has embraced this Hye Kyung (HK) Lee, Harold Smith (director of the NIDDK Genomics Core), and Sojung Kim. budding technology and examined the mouse genome (Nucleic Acids Res 44:1052– CRISPR-method-edited mammalian brings fresh air into the genome-engineering 1063, 2016; DOI:10.1093/nar/gkv999). genomes. Using whole-genome sequencing, toolbox and allows us to avoid problems In collaboration with Chengyu Liu—the which reveals an organism’s complete DNA encountered with conventional CRISPR” director of National Heart, Lung, and Blood makeup, the researchers concluded that techniques, said Hennighausen. Institute’s Transgenic Core facility—the CRISPR did not cause unexpected off- With researchers from the NHLBI, the team went on to make key discoveries in target damage throughout the genome (Nat Broad Institute, and Harvard University, gene editing. In 2017, they led the way in Methods 15:756–758, 2018; DOI:10.1038/ Hennighausen’s team explored the fidelity, describing the extent of unwanted molecular s41592-018-0148-2). or accuracy and reliability, of deaminase-base scarring that the CRISPR technique can “This finding was important, as research editing in the mouse genome. The study, cause at target sites of mammalian genomes. must address the safety aspects of CRISPR published in November 2018, found that By mutating 17 genomic sites and analyzing and other new technologies,” said lead author the two classes of base editors—cytosine over 600 mice, the researchers discovered Michaela Willi, a postdoctoral researcher base editors (CBE) and adenine base editors large, unintended DNA deletions and in Hennighausen’s lab. (ABE)—had different fidelities. ABEs were insertions associated with the CRISPR More recently, Hennighausen’s team more accurate and caused no unintended method (Nat Commun 8:Article number used deaminase-base editing, a newer form errors (Nat Commun 9:Article number 4804, 15464, 2017). Other scientists have since of gene editing, to introduce mutations in 2018; DOI:10.1038/s41467-018-07322-7). published similar findings on the random the mouse genome. Most known human Hennighausen’s team also applied insertions and deletions that the technique diseases are caused by mutations in just base editing to linked mutations—two can cause. one of the four letters, or bases, that make or more mutations at different sites in the But what about the CRISPR method’s up DNA. Base editors can correct these same chromosome. Generating linked effects outside the sites targeted for mutations by converting one into mutations through gene editing could correct mutations? In October 2018, with support another. Unlike conventional CRISPR certain genetic diseases. The team’s recently from the Deputy Director for Intramural technology, base editing does not cut published research showed that CBEs can Research Innovation Awards program, through the DNA, reducing the chance accurately introduce linked mutations into Hennighausen’s team published a paper for unwanted errors. mouse embryos without causing unwanted on the frequency of new mutations in “The exceptional precision of base editors deletions at target sites (Sci Rep, 2018;

16 THE NIH CATALYST JANUARY-FEBRUARY 2019 NIH ABBREVIATIONS FEATURE CBER: Center for Biologics Evaluation and Research, FDA CC: NIH Clinical Center CCR: Center for Cancer Research, NCI CIT: Center for Information Technology DCEG: Division of Cancer Epidemiology and Genetics, NCI DOI:10.1038/s41598-018-33533-5). reported that he used CRISPR editing on DIPHR: Division of Intramural Population “Base editing can correct about human embryos to disable a particular gene. Health Research, NICHD FAES: Foundation for Advanced Education 60 percent of known disease-causing Scientists worldwide expressed their outrage in the Sciences mutations,” said Hye Kyung Lee, another over the scientist’s willingness to flout FARE: Fellows Award for Research Excellence postdoctoral researcher in Hennighausen’s international ethics norms. In a November FelCom: Fellows Committee FDA: Food and Drug Administration lab and a lead author on both base-editing 28, 2018, statement, NIH Director Francis FNIH: Foundation for the NIH papers. “A thorough understanding of its S. Collins called for the “development of FNL: Frederick National Laboratory fidelity is thus critical when considering this binding international consensus on setting IRP: Intramural Research Program HHS: U.S. Department of Health technology for human gene therapy.” limits for this kind of research,” without and Human Services Other NIDDK scientists are also which, the world could see a flood of “ill- NCATS: National Center for Advancing applying gene editing to the study of human considered and unethical projects.” Translational Sciences NCBI: National Center for Biotechnology disease. For example, Andy Golden in Applying gene-editing technologies to Information NIDDK’s Laboratory of Biochemistry human health requires a full understanding NCCIH: National Center for Complementary and Genetics uses the CRISPR method of their mechanisms and potential negative and Integrative Health NCI: National Cancer Institute to generate mutations in a worm species consequences as well as thoughtful discussion NEI: National Eye Institute that shares many genes with humans. By and consideration of ethical implications. NHGRI: National studying how these mutations disrupt gene While there is still a long way to go, when Research Institute NHLBI: National Heart, Lung, functioning, the scientists hope to identify used responsibly, the CRISPR method and and Blood Institute potential targets for therapy. base-editing tools could pave a key pathway NIA: National Institute on Aging NIAAA: National Institute on Alcohol In addition, NIDDK’s Genetics of to benefit public health. Abuse and Alcoholism Development and Disease Branch, led by NIAID: National Institute of Allergy Richard Proia, together with NIDDK and Infectious Diseases NIAMS: National Institute of Arthritis staff scientist Maria Laura Allende and and Musculoskeletal and Skin Diseases Cynthia Tifft of the National Human NIBIB: National Institute of Biomedical Imaging and Bioengineering Genome Research Institute’s Medical NICHD: Eunice Kennedy Shriver Genetics Branch, used gene editing in their National Institute of Child Health and recent publication on Sandhoff disease, a Human Development NIDA: National Institute on Drug Abuse deadly childhood genetic disorder. Using the NIDCD: National Institute on Deafness CRISPR method, the researchers created and Other Communication Disorders NIDCR: National Institute of Dental healthy stem cells to form cerebral organoids, Take the NIH Workplace and Craniofacial Research miniature organs that mimic the brain, and Climate and Harassment NIDDK: National Institute of Diabetes compared them with Sandhoff-affected and Digestive and Kidney Diseases Survey NIEHS: National Institute of organoids, gaining new insights into the Environmental Health Sciences disease’s progression (J Lipid Res 59:550– As part of the NIH Anti-Harassment Program, NIGMS: National Institute of a Workplace Climate and Harassment Survey General Medical Sciences 563, 2018; DOI:10.1194/jlr.M081323). NIMH: National Institute of Mental Health will be administered, in early 2019, to NIH The Proia and Tifft labs are using NIMHD: National Institute on Minority the CRISPR method and base editing in staff, trainees, and contractors at all levels Health and Health Disparities of employment. The survey is voluntary, NINDS: National Institute of several current projects, such as correcting Neurological Disorders and Stroke confidential, and anonymous. Results will point mutations in cells from patients NINR: National Institute of Nursing Research with late-onset Tay-Sachs disease, a help to assess the workplace climate at all NLM: National Library of Medicine NIH facilities and identify elements of NIH’s OD: Office of the Director neurodegenerative disorder that affects OITE: Office of Intramural Training people in their 20s and 30s. organizational climate associated with and Education But as much promise as these gene- harassment. Whether your experience has OIR: Office of Intramural Research been positive or negative, we want to hear ORS: Office of Research Services editing tools hold for preventing and ORWH: Office of Research on Women’s Health from you. For more information, visit https:// treating disease, there are ethical issues to be OTT: Office of Technology Transfer considered, too. Recently, a Chinese scientist diversity.nih.gov.

https://irp.nih.gov/catalyst 17 OBITUARIES

IN 2017 (NOT INCLUDED LAST YEAR) animals. His NIH career began in 1961 when and teamwork. A committed mentor, he Novera Herbert Spector (died on November he became a chief in the Veterinary Resources trained a large number of outstanding 15, 2017, at 98) worked in NINDS’s Division Branch, Division of Research Services. immunodermatologists who went on to lead of Fundamental Neurosciences from 1978 to high-quality, independent research programs 1995 and is credited with coining the word Cornelis P.J. (Neil) Glaudemans (died on in the United States, Japan, Korea, and Europe. “neuroimmunomodulation.” February 1, 2018, at 85), whose work led to a single-shot shigella vaccine, retired from NIH Theodor Kolobow (died on March 24, 2018, IN 2018 in 1998 after having spent more than 30 years at 87) was a PI in NHLBI who made important Alfred W. Alberts (died on June 16, 2018, at 87) in NIDDK, where he was chief of its Laboratory contributions to the field of cardiovascular and discovered a chemical compound that led to of Chemistry. pulmonary research including advancements the cholesterol-lowering drug lovastatin in the in the development of artificial organs, and the late 1970s when he was working for Merck. He Alexander Gorbach (died on May 11, 2018, at pathophysiology of acute lung injury. In 1962, worked as a lab technician at NIH (1959–1966) 69) was an NIBIB staff scientist and chief of the he joined NHLBI and later served as Section for biochemist P. Roy Vagelos. infrared imaging and thermometry unit. His Chief of Pulmonary and Cardiac Assist Devices. innovative research included techniques for Valery Bliskovsky (died on November 13, 2018, monitoring tissue perfusion, oxygen content, Charles E. Land (died on January 25, 2018, at at 55) was a staff scientist in the Genomics Core and temperature as well as wireless electronic 87) was an internationally acclaimed statisti- of NCI’s Center for Cancer Research. He began sensors and applications of mobile-phone cal expert on radiation-risk assessment. He his NIH career in 1994 as a visiting fellow in NCI technology. He joined NIH in 1989 as a visiting spent 34 years at NIH and retired in August and, in 2012, he helped initiate next-generation research fellow and guest researcher at NIDDK. 2009 from his position as principal investiga- sequencing operations. tor in NCI’s Radiation Epidemiology Branch. He Margaret Heckler (died on August 6, 2018, and colleagues clarified the pattern of breast- Monique Dubois-Dalcq (died on October 9, at 87) was a former Secretary of Health and cancer risk associated with radiation exposure. 2018, at age 79) was chief of NINDS’s Labora- Human Services (1983–1985). Before her These studies served as the prototype for epi- tory of Viral and Molecular Pathogenesis. She time at HHS, she served eight terms in the demiologic studies of other radiogenic cancers. joined NIH in 1972 as postdoctoral fellow, held U.S. House of Representatives, representing many positions in NINDS, and retired in 1994. the former 10th congressional district in Roger B. Mack (died on April 13, 2018, at 76) southeastern Massachusetts. She served as worked in the Clinical Center for 34 years, first Stanley Falkow (died on May 5, 2018, at 84), U.S. Ambassador to Ireland from 1985 to 1989. in the inhalation-therapy section of the anes- a professor emeritus at Stanford University thesiology department; later as chief of respira- School of Medicine (Stanford, California), is James F. Holland (died on March 22, 2018, tory therapy; and, in the 1980s, he became an considered the father of bacterial pathogenicity. at 92) was a renowned cancer expert and administrator. He retired in 2000. He spent summers at NIAID’s Rocky Mountain considered a founding father of cancer Laboratories in Hamilton, Montana and received chemotherapy. He helped pioneer a lifesaving Bonnie Mathieson (died on January 8, 2018, at many awards including the Lasker in 2008. drug treatment for pediatric leukemia patients. 72) retired in December 2017 after a 43-year In 1972, he shared a Lasker Award for his work. career at NIH. She started in 1975 as an NCI Elizabeth Fee (died on October 17, 2018, at He was the father of Steven Holland, current investigator and made seminal contributions 72) was the chief of NLM’s History of Medicine NIAID scientific director, and the father-in-law to the field of basic T-cell immunology. She Division (1995–2011) and then NLM senior of Maryland Pao, current NIMH clinical director. later became a program officer in the Vaccine historian. She retired in 2018 to become an Branch of NIAID’s Division of AIDS; she most independent researcher, continuing her world- Stephen I. Katz (died on December 20, 2018, recently served as a health-scientist adminis- renowned scholarly research in the history of at 77), the director of NIAMS since 1995, trator in the NIH Office of AIDS Research. medicine and public health. joined NIH in 1974 as a senior investigator in NCI’s Dermatology Branch initiating a Henry Metzger (died on November 20, 2018, at James R. Ganaway (died on October 4, 2018, at highly productive research program in the 86) was inducted into the Public Health Service 91), who retired after 33 years of federal service immunology of skin diseases. His work both in 1959, serving at the NIH. He spent almost his in 1984, was NIH’s principal expert on naturally as director of NIAMS and as an eminent entire career at NIH pursuing basic research in occurring infectious diseases of laboratory scientist in NCI embodied integrity, excellence, molecular aspects of the immune system and

18 THE NIH CATALYST JANUARY-FEBRUARY 2019 OBITUARIES Farewell to America’s Cancer Doctor in administration. He served for 10 years as the Geoffrey Spencer (died on October 27, 2018, Alan Rabson (1926–2018) first scientific director of the newly created at 46) was an accomplished and colorful NIH BY MICHELE LYONS, OD NIAMS. After he retired and became scientist communications professional. He began his NIH emeritus in 2002, he remained as active as an career in 1999 at NHGRI, where he was the pri- When Katie Couric told her boss advisor to the NIH Board of Scientific Directors; mary media-relations contact for the institute that her husband had been diagnosed a liaison to the National Academy of Sciences and its then-director, Francis Collins. Spencer with stage 4 colon cancer, the first thing on “dual use research of concern”; with FAES was later the associate director of communica- he said was, “Call Al Rabson.” Couric, a for more than 40 years; and was a longstanding tions for the Division of Extramural Research; television journalist, related this story at member of the NIH Catalyst editorial board and he joined NCATS communications in 2012. the celebration of Alan Rabson’s life on the Office of NIH History advisory committee. October 30th. Rabson died at the age Judith Vaitukaitis (died on October 19, 2018, of 92 on July 4, 2018. Guests gathered Jun-mo Nam (died on January 4, 2018, at 85), at 78), a reproductive neuroendocrinologist, to share laughter and some tears while an NCI biostatistician, retired after a 43-year came to in NCI in 1970 as a postdoctoral remembering “America’s cancer doctor,” career, but was a special volunteer until mid- researcher, studying human chorionic as he was called by Norman Sharpless, 2017. He published on efficient statistical gonadotropin (hCG). As a senior investigator director of the National Cancer Institute inference, optimal study design, sample-size in NICHD, she and colleagues published a (NCI). Rabson spoke to anyone who calculations, and statistical genetics. landmark paper in 1972 that described an contacted him about a cancer diagnosis assay for measuring elevated hCG levels. The for a loved one or themselves. The day’s Vera Marie Nikodem (died on May 17, 2018, assay became the basis for the first home speakers, including his co-workers, had at 78) was a molecular biologist at NIH from pregnancy tests in 1978. She retired in 2005. all experienced the benefit of Rabson’s 1978 to 2008, and served as a section chief knowledge and compassion. at NIDDK. She worked extensively on the Martha Vaughan (died on September 10, Al Rabson’s research as an NCI mechanism of action of thyroid hormone as 2018, at 92) was a scientist emerita in NHLBI’s pathologist in the NIH Clinical Center well as on various signaling pathways. Laboratory of Metabolic Regulation and former focused mainly on the role of viruses in the chief of its Laboratory of Cellular Metabolism. development of cancer. From 1975 to 1995, Sang-A Park (died on January 22, 2018, at 27), She came to NIH in 1952 and conducted some Rabson was director of the forerunner of a native of South Korea, came to NIH in 2016 of the earliest work on insulin signaling, which the NCI Division of Cancer Biology, which as a visiting postdoctoral fellow in NIDCR’s ultimately helped reveal the insulin receptor. transitioned under him from only conducting mucosal immunology section. She studied Her husband was Jack Orloff, who was the intramural research to also managing the transforming growth factor–beta signaling in scientific director in NHLBI from 1974 to 1988. funding of extramural research and cancer breast-cancer stem cells post-chemotherapy. centers at institutions across the country. In Elliot Vesell (died on July 23, 2018, at 84) this job, Rabson made dozens of contacts Alan S. Rabson (died on July 4, 2018, at served as a clinical associate at NIAMS (1963– with physicians and researchers. He became 92) came to the NIH in 1955 as a resident in 1965) and was head of the section on pharma- deputy director of NCI in 1995 and served in pathologic anatomy in the NIH Clinical Center, cogenetics at the NHLBI (1965–1968). In 1968, that capacity until his retirement in 2015. and joined NCI a year later to pursue research he became the founding chair of pharmacol- in cancer-causing viruses. He held several ogy at the Penn State Health Milton S. Hershey To watch a videocast of the “Recognizing Dr. leadership positions including as acting Medical Center (Hershey, Pennsylvania). Al Rabson” celebration, go to https://video- NCI director. His wife was the late Ruth L. cast.nih.gov/launch.asp?26156. To read a 1997 Kirschstein. (See article on this page.) Alfred Yergey (died on May 27, 2018, at oral history interview with Alan Rabson, go to 76) was a scientist emeritus in NICHD and https://history.nih.gov/archives/downloads/ Wilfred Rall (died on April 1, 2018, at 95), a former head of the the Biomedical Mass rabsontranscript.pdf. pioneer in computational neuroscience, spent Spectrometry Core. He contributed to the most of his career at the NIH until his retirement protein characterization in Niemann-Pick Read more online: in 1994. His work in establishing the integrative disease–type C and identified a key step in Obits: https://irp.nih.gov/catalyst/v27i1/ functions of neuronal dendrites provided a the Legionnaires’ disease infection process. obituaries-2018 foundation for neurobiology in general and After working at NIH (1977–2012), he stayed Rabson story: https://irp.nih.gov/catalyst/ computational neuroscience. active with his research. v27i1/farewell-to-america-s-cancer-doctor

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CATALYTIC REACTIONS? NIH IN HISTORY

If you have a photo or Celebrating Nobel Laureate Christian B. Anfinsen other graphic that reflects BY HUSSAIN ATHER, NICHD, AND ALAN N.SCHECHTER, NIDDK an aspect of life at NIH (including laboratory life) or He won a Nobel Prize in chemistry a quotation or confession that in 1972, and his work still influences scientists might appreciate and research being done today. He was a that would be fit to print in beloved mentor to dozens of scientists the space to the right, why not at the NIH. And he worked tirelessly send it via e-mail: catalyst@ to promote human rights for scientists nih.gov; fax: 301-402-4303; around the world. or mail: The NIH Catalyst, Christian Anfinsen’s research Building 1, Room 333. “continues to underlie new work in biochemistry,” said Alan Schechter Also, we welcome “letters to (chief of NIDDK’s Molecular Medicine

the editor” for publication and NATIONAL LIBRARY OF MEDICINE Branch) at a symposium he organized on your reactions to anything on October 15, 2018, to commemorate his the Catalyst pages. mentor and former colleague, who died in 1995. Anfinsen is also featured in an NIH exhibit that opened earlier this year in the READ MORE ARTICLES, AND central first-floor corridor of Building 10. EXPANDED VERSIONS OF THE ONES IN THIS ISSUE, ONLINE AT Read the whole article at https:// https://irp.nih.gov/catalyst/v27i1. irp.nih.gov/catalyst/v27i1/ nih-in-history-christian-b-anfinsen

PUBLISHER CONTRIBUTING WRITERS EDITORIAL ADVISORY BOARD The NIH Catalyst is published MICHAEL GOTTESMAN BEHDAD AFZALI, ROBIN ARNETTE CHRISTINA ANNUNZIATA, NCI bimonthly for and by the Deputy Director for Intramural Research, OD HUSSAIN ATHER , MARLA BROADFOOT DAN APPELLA, NIDDK intramural scientists at NIH. BRANDI CAROFINO, ERIKA GINSBURG TREVOR ARCHER, NIEHS EDITORS SUSAN CHACKO, JONATHAN GREEN, MICHAEL ESPEY, NCI Address correspondence to: JOHN I. GALLIN BRANDON K. HARVEY AUDRAY HARRIS, NIAID Building 1, Room 333, NIH Associate Director for Clnical Research CARL HASHIMOTO, SHIOKO KIMURA SUSAN LEITMAN, CC Bethesda, MD 20892 Chief Scientific Officer, CC BRANDON LEVY, MICHELE LYONS BERNARD MOSS, NIAID Ph: 301-402-1449 PAUL H. PLOTZ AMRITA MANDAL HYUN PARK, NCI Fax: 301-402-4303 Scientist Emeritus, NIAMS e-mail: [email protected] KATHLEEN MCGLAUGHLIN EMILY PETRUS, NINDS (FELLOW) EDITOR-IN-CHIEF ALAN N. SCHECHTER, LISA YUAN JULIE SEGRE, NHGRI The NIH Catalyst online: LAURA STEPHENSON CARTER ANDY SINGLETON, NIA https://irp.nih.gov/catalyst WRITER-EDITOR PHOTOGRAPHERS/ILLUSTRATORS GISELA STORZ, NICHD CHRISTOPHER WANJEK L. ALEXANDER/THINKSTOCK.COM RONALD SUMMERS, CC Director of Communications, OIR S. BACK, B. CAROFINO, C.-C. CHANG RICHARD WYATT, OIR E. DEL AGUILA III, J. RYMARUK WEI YANG, NIDDK COPY EDITOR H. YAO, P. M. ZERFAS SHAUNA ROBERTS