NATIONAL INSTITUTES OF HEALTH • OFFICE OF THE DIRECTOR | VOLUME 27 ISSUE 3 • MAY-JUNE 2019

Gene Therapy Turns The Dermatology Branch at NIH 30 Years Old Research, Colleagues, and a Shift from NCI to NIAMS An NIH First That Almost Didn’t BY MOHOR SENGUPTA, NEI, AND LAURA STEPHENSON CARTER, OD Happen BY CHRISTOPHER WANJEK, OD

When Steven Rosenberg reviewed a draft email-blast message advertising his upcoming keynote address at a May 9, 2019, meeting at the University of Pennsylvania, he was struck by the final paragraph: “This symposium comes at a historic time. Thirty years ago this May, ISAAC BROWNELL AND LINGLING MIAO, NIAMS MIAO, LINGLING AND BROWNELL ISAAC Dr. Rosenberg and colleagues shepherded in the era of gene therapy when they removed, genetically altered, and returned cells to a patient with malignant melanoma.” “This is not the kind of thing I keep track of, these historic events,” said Rosenberg, who as long-serving chief of the National Cancer Institute (NCI) Surgery Branch was the first to insert foreign genes into a human. “I’m too busy keeping track Merkel cells (green) are clustered in touch-sensitive areas called touch domes. Shown: Neonatal mouse touch dome. of today’s events.” Nevertheless, he pulled out a set of In Spring 1975, desperate parents brought their six-year-old daughter to handwritten notes in faded pencil and the NIH Dermatology Branch to be treated for a rare, chronic skin disease—coupled with ink, circa 1990, listing the dates of the arthritis—that had plagued her for more than four years and was making her miserable. unprecedented 16 reviews needed to perform Her doctors “were at the end of the line in terms of what to do,” said Stephen Katz in the world’s first gene-therapy experiment a 2018 oral-history interview. He was a senior investigator in 1975 and had joined the on a human. Next came a copy of the Dermatology Branch, which was then part of the National Cancer Institute (NCI), only 1990 paper in the New England Journal of the year before. “She had been treated with everything.” He biopsied some of the affected Medicine (N Engl J Med 323:570–578, 1990) CONTINUED ON PAGE 12 describing the 1989 experiments, along with Rosenberg’s own printed list of historic NIH CONTENTS “firsts” around this period. FEATURES • |1| Gene Therapy Turns 30 Years Old |1| Dermatology Branch at NIH |6,7| NINDS Then he rattled off names of colleagues Scientific Directors: New and Former|9| DeMystifying Medicine: From Deep Sea Vents to Our and descriptions of patient volunteers as if Own Stomachs |11| My Room, Your Room the historic events transpired yesterday. DEPARTMENTS • |2| DDIR: Equity and Diversity |3| The SIG Beat |4| Training Page: Do-It-

CONTINUED ON PAGE 10 Yourself Training |5| News You Can Use: Technology Transfer |7| Abbreviations |8| Research Briefs |16| Colleagues: Recently Tenured |20| Photographic Moment: Giant MRI FROM THE DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH

Equity and Diversity in the NIH Intramural Research Program BY MICHAEL GOTTESMAN, DDIR, AND GISELA STORZ, CHAIR, NIH EQUITY COMMITTEE

How can equity and diversity in investigator-selection process that would October 2018 the NEC submitted a the NIH intramural research program ensure diversity; equity and inclusion document to the DDIR with four main (IRP) continue to be improved? The goals; and recommendations for how the recommendations: NIH Equity Committee (NEC) was NEC and the Chief Officer for Scientific 1. Each IC must clearly define the established in November 2017 to help Workforce Diversity can help the IC duties and expectations of lab and branch address this question. Modeled on the achieve those goals. chiefs (or their equivalents). Central Tenure Committee, the NEC At the meeting with the NEC, the SD 2. The effectiveness of all lab and comprises 20 members—18 senior gives a presentation about the informa- branch chiefs (or their equivalents) must scientists and two scientific directors tion provided. Two committee members be evaluated every four years by the BSCs. (SDs)—representing almost all insti- serve as primary reviewers and prepare a (Although the BSCs now evaluate the tutes and centers (ICs). As quality of intramural research its first task, the committee at least every four years, they has been meeting with the One striking trend is the under- don’t always evaluate the lead- SDs from each IC to learn representation of certain groups in ership effectiveness of the lab about the demographics and and branch chiefs.) resource distribution in their biomedical research . . . in leadership 3. Lab and branch chiefs intramural programs. positions. should remain in their posi- In advance of each meeting, tions for no more than three the SD—often with the help four-year BSC review cycles of the clinical director (CD) (plus time prior to the initial report that the NEC chair presents at a for that IC—provides de-identified review and up to two years after the joint meeting of the SDs and CDs. The information about the IC’s tenure-track third cycle of positive reviews), except in reports are constructed to share each IC’s scientists, tenured scientists, senior extraordinary circumstances. This recom- best practices as well as identify areas that scientists, and senior clinicians. The SD mendation assumes that the BSC reviews need attention. To date, the NEC has also provides an organizational chart are positive; if any of the reviews are nega- evaluated the intramural programs of 12 showing the demographics of the IRP tive, it’s anticipated that the turnover of ICs. The SDs have indicated that review- leadership and a written summary that lab and branch chiefs would happen more ing these data and getting feedback from comments on the data and addresses the quickly. the NEC has been a valuable experience. hiring procedures, review practices, and 4. Leadership appointments must The presentations have been high- selection process for ad hoc Board of occur through open and transparent lighting trends across the IRP. One strik- Scientific Counselors (BSC) members. processes. ing trend is the under-representation of [The Deputy Director for Intramural certain groups in biomedical research— Research (DDIR) and NIH Committee The NEC’s recommendations— women, Asian Americans, and others—in Management approve the members of the with input from the SDs, CDs, and leadership positions. The presentations main BSC and ensure diversity; the ad NIH senior leadership—have now been also highlight extremely long tenures hoc members are chosen by the ICs]. The converted into policy. Discussions are for some lab and branch chiefs (or their summary also specifies how discretionary still ongoing about how this policy will equivalents). funding is awarded to investigators and be implemented. For example, one new Given that a dynamic organization includes proposed corrections to the policy will be that current lab and branch thrives on diversity and new ideas, in

2 THE NIH CATALYST MAY-JUNE 2019 THE SIG BEAT NEWS FROM AND ABOUT THE SCIENTIFIC INTEREST GROUPS

is to generate innovative approaches in the field of digital pathology through artificial- intelligence tools. For more information HOUSSEIN A. SATER, NCI SATER, A. HOUSSEIN about the MxIF SIG and instructions for how to join the LISTSERV mailing list, contact the group chair and advisor: Houssein A. Sater (houssein.abdulsater@ chiefs whose service exceeds the three nih.gov). cycles of BSC review will be expected to step down within two years after the A multiplex spectrally unmixed immunofluorescence image of a lung-cancer tissue stained with seven biomarkers. New SIG: Epilepsy next BSC review of their lab or branch. Each IC is expected to have a completed The Epilepsy Scientific Interest plan by January 2020. Each SD will pres- New SIG: Multiplex Immuno- Group (SIG) brings together investigators, ent their implementation plans to both fluorescence clinicians, and researchers who are inter- the DDIR and NEC in the coming year. ested in epilepsy and in understanding its Intramural and extramural scien- Other trends are also being noted pathophysiology and the effects of treat- tists who are using multiplex immuno- by the NEC. As a result of the frequent ment on neural function and connectivity. histochemistry and immunofluorescence comment that many potential tenure-track Epilepsy studies at NIH take place in sev- technologies to study complex tissue struc- candidates are not even aware of the tre- eral institutes including NINDS, NIMH, tures (such as tumor microenvironments) mendous benefits of working in the IRP, and NICHD. NIH intramural researchers can share their knowledge via the Multi- the NEC recommended that a “Rising are using structural and functional imag- plex Immunofluorescence (MxIF) SIG. Stars” seminar program be developed: ing before and after surgical resection; These technologies are used to identify the Extramural junior scientists who are doing investigating how surgical resection on presence of multiple biological markers in exciting research will be invited to give regions of the human cortex affect neural a single tissue sample or different samples. seminars at NIH. This recognition will plasticity and cognitive function; explor- The methodology can be an invaluable tool allow IC investigators to become familiar ing intraoperative and long-term record- for tumor-tissue immune-profiling and as a with the work of the Rising Stars, who will ings of neural activity that are routinely way to identify multiple treatment targets in turn learn about the IRP. The NEC was acquired in the course of treatment; and in the same tissue section. This approach encouraged by the very large response to evaluating human brain tissue samples to requires critical thinking and bioinformatic the first call for nominations. Look for understand the physiology and molecular tools for effective segmentation, algorithm “Rising Star” talks in the coming months. and genetic pathways in both normal and building, and advanced spatial analysis. This Much still remains to be done, however, diseased brains. The Epilepsy SIG pro- SIG aims to disseminate information about to improve equity and diversity across the vides a forum for facilitating interactions these technologies and foster new research IRP. The NEC is very interested in any among clinicians and researchers, and for collaborations across the NIH campus and ideas you might have. Please send us your sharing progress in ongoing studies and around the world. The MxIF SIG welcomes ideas: [email protected] or gottesmm@ investigations across institutes and centers. pathologists, clinicians, postdocs, computer mail.nih.gov. The SIG holds meetings approximately scientists, bioinformaticians, and others every two months; each meeting provides who have an interest in or are helping to Gisela Storz is an NIH Distinguished Inves- an opportunity for investigators and cli- move this field forward. The group meets tigator in the Eunice Kennedy Shriver nicians inside or outside NIH to present monthly to discuss topics that include, but National Institute of Child Health and their work. For more information about are not limited to, technical difficulties Human Development. For more infor- the Epilepsy SIG and how to join the with staining, optimization, and validation. mation on the way that BSCs work, go LISTERV mailing list, contact one of the The MxIF SIG will host a seminar series to https://oir.nih.gov/sourcebook/pro- chairs: Kareem Zaghloul (kareem.zag- featuring NIH and outside experts in the cesses-reviewing-nih-intramural-science/ [email protected]) or Sara Inati (sara.inati@ field (times will be determined later). The boards-scientific-counselors. nih.gov). long-term premise of this new community

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

From the Fellows Committee Do-It-Yourself Training BY AUTUMN HULLINGS, NCI

received an “excellent” or “very good” rating and appear to have increased the fellows’ scientific knowledge and skills. On average, only 10 percent of the attendees rated themselves as having a “very good” or “excellent” knowledge or skill in the subject matter before each seminar. Afterward, about 70 percent reported their knowledge had improved. Chia and Mamais are pleased that many fellows, once they’ve been to an LNG seminar, volunteer to teach. Thinking ahead, Chia and Mamais plan to work as a team and recruit other organizers on a rolling basis. They have even thought about JILLIAN H. KLUSS, NIA

Ruth Chia (left) and Adamantios Mamais, who worked together to start a training program in which fellows teach forming a committee of fellows to run the fellows, welcomed attendees at a recent seminar. Chia and Mamais are pleased that many fellows, once they’ve been series. Their success comes in part from the to a seminar, volunteer to teach. support they’ve received from their PIs, including the chief of the LNG, Andrew Fellows can now get peer-to- series that emphasized peer-to-peer Singleton. The seminars “are a great peer training on the latest scientific training. example of junior folks taking control,” he topics and techniques. Since 2017, Ruth Chia and Mamais then organized a said. “They’ve taken care of everything— Chia (then a research fellow and now a program that allowed postdocs to not only the agenda, [determining] what’s of interest, staff scientist) andAdamantios Mamais teach new knowledge but also demonstrate and [figuring out] ways to self-assess. It’s a (visiting fellow) at the National Institute skills for conducting science in a real-life great training opportunity on several levels.” on Aging (NIA) have been organizing setting. Each seminar is about two hours NIH fellows have many exciting new seminars in which fellows teach fellows long and includes a lecture and hands-on workshops to look forward to in 2019 topics ranging from managing big training, Mamais explained. including “Tracing Tools for Neuronal data to conducting machine learning Without this demonstration portion, Circuit Mapping” and “Python for Data in genetics. The pair hopes to create “the details between A [and] Z [of the Analysis.” Don’t worry if these topics more opportunities for fellows to feel science] are left out,” said Chia. These are completely new to you. Fellows are comfortable teaching and learning from seminars “highlight the nitty-gritty tips encouraged to “just come,” said Chia. “You each other. of how to do a scientific [technique] that don’t need any background.” Mamais and Chia, who are both in you can’t learn from a textbook.” Chia and Mamais hope these seminars NIA’s Laboratory of Neurogenetics (LNG), Although seminars are organized by will break barriers to learning, provide came up with the idea of running a seminar NIA fellows, trainees from other institutes teaching opportunities, and ultimately on big data and cell-morphology analysis and centers (ICs) are welcome to attend. create a support network among fellows. as a way to integrate and share their skills Typically, 20 to 30 people attend each with other trainees. Their seminar was seminar, and fellows from more than a The 2019 seminars are held in Building 35, well-attended and received with great dozen ICs have participated. Room GG 607, from 10:00 a.m. to noon. For enthusiasm. During an LNG retreat, the Chia and Mamais have also more information and a schedule, contact lab’s fellows expressed an interest in having developed assessment tools to evaluate Adamantios Mamais (adamantios.mamais@ more training and teaching opportunities, the seminars. Feedback has been positive nih.gov) or Ruth Chia ([email protected]). and their enthusiasm grew for a seminar and encouraging so far. Past seminars

4 THE NIH CATALYST MAY-JUNE 2019 NEWS YOU CAN USE

Technology Transfer: Matching Researchers with Industry to Help Get NIH Inventions to Patients BY ALLISON CROSS, NCI Steven Rosenberg developed a technology that led to the drug, which is a CD19- targeted CAR T-cell immunotherapy. After promising early-phase clinical trials conducted at NCI, the drug was licensed to Kite Pharmaceuticals for further development and commercialization and received FDA approval in October 2017. And, in September 2018, the FDA approved moxetumomab pasudotox, a bacterial toxin–based drug, for the treatment of some patients with hairy cell leukemia (HCL). The antibody moxetumomab was originally generated by Ira Pastan and colleagues at NCI and later licensed to MedImmune/AstraZeneca for clinical development. The FDA approval makes TECH TRANSFER CENTER, NCI TRANSFER CENTER, TECH moxetumomab, marketed as Lumoxiti, the NCI Tech Transfer Center (TTC) metrics for FY2007–2018. The NCI TTC handles technology transfer for NCI research first treatment approved for patients with labs as well as for labs from nine other NIH institutes and centers. Key: CDA (confidential disclosure agreement); CRADA (cooperative research and development agreement); CTA, (clinical trial agreement); MTA (material transfer agreement). HCL who have already undergone at least two lines of standard treatments. In September 2016, M was diagnosed studies and first-in-human clinical trials Commercial Partners with metastatic Merkel-cell carcinoma (conducted at the NIH Clinical Center). The “If you look through the success stories (MCC), a rare and aggressive form of preclinical research showed that avelumab [of] the products that have come out of skin cancer. At the time of his diagnosis, allows T cells to efficiently kill a variety the intramural program, most if not all patients with MCC were usually offered of tumor cells including MCC. The team’s of them involve a commercial partner,” standard treatments that included surgery, multicenter clinical phase 2 trial—funded said Tom Misteli, the scientific director radiation therapy, and/or chemotherapy. by NCI, Merck KGaA of Darmstadt, of NCI-CCR. But M’s doctors recommended that Germany, and Pfizer—established safety NIH does not perform product he participate in a clinical trial for the and pharmacokinetic data on the drug development or commercialization. And immunotherapy drug avelumab. M is and successfully demonstrated the use of unlike their counterparts at universities, now in remission and in March 2017, due avelumab in people with MCC. It is one of NIH investigators cannot spin out a in part to the success of that clinical trial, three drugs that received FDA approval in company around an invention. So it’s avelumab became the first FDA-approved the past two years as a result of successful essential that there be a way for intramural treatment for MCC. collaborations between investigators in the ideas and technology to be transferred to That drug was brought to market thanks NCI Center for Cancer Research (NCI- industry partners. to collaborations between NIH investigators CCR) and commercial partners. Working with Tech Transfer and industry partners. Avelumab, an Axicabtagene ciloleucel, another Tech-transfer coordinators and offices antibody that targets programmed death– FDA-approved immunotherapy drug that throughout NIH facilitate these ligand 1, was developed for clinical use by resulted from a successful NIH-industry collaborations by helping researchers EMD Serono Inc. The company collaborated collaboration, is used to treat adults with choose from an assortment of with National Cancer Institute (NCI) relapsed or treatment-resistant large B-cell scientists, who performed the preclinical lymphomas. A team led by NCI-CCR’s CONTINUED ON PAGE 19

https://irp.nih.gov/catalyst 5 FEATURE

NINDS Welcomes Lorna Role as New Scientific Director Plans to Expand Mentorship and Training Opportunities BY EMILY PETRUS, NINDS

The first email from Lorna Role perspective” than she does. to the scientists and staff of the National As a department chair, Role doubled Institute of Neurological Disorders and the size of the department at SUNY Stony Stroke (NINDS) read “TALK TO Brook and increased the number of female ME.” And, as the new NINDS scientific faculty from one to six. Her commitment director (SD), that’s exactly what she to increasing the representation of women wants people to do. Role hopes to “serve in science will continue at NINDS. the faculty and do everything I can to Role obtained an A.B. in applied make the environment as positive and mathematics from Harvard University productive as possible,” she said. (Cambridge, Massachusetts) and a Ph.D. in The first order of business was to physiology from Harvard Medical School assemble an executive advisory council, (Boston). She did her postdoctoral training composed of NINDS principal investigators in pharmacology at Harvard Medical (PIs) and scientific staff, to provide her with School and at Washington University valuable input and feedback on program School of Medicine (St. Louis) with Gerald planning. The committee members were Lorna Role, new SD for NINDS. Fischbach, who later served as the director selected based on differences in their of NINDS (1998–2001). experiences and expertise as well as with Role raised two daughters—Lindsay an eye toward gender and seniority balance. neural systems in genetically modified mice, and Masha (short for Marussia)—as a Role has already found the diverse opinions but has recently expanded to include human single mother in the city of New York. expressed helpful in considering potential studies with a novel cholinergic positron- Today, Lindsay is a psychiatrist at Johns organizational changes. emission-tomography tracer. She has been Hopkins University (Baltimore) and Among many important areas of focus, the principal investigator on numerous NIH- Masha is a clinical psychologist at Tufts one of great interest to Role is mentoring funded grants, supported continuously since University (Boston). Role is excited to be and training. Role hopes to create more 1982, and has received many awards. geographically closer to Lindsay, who has a training opportunities, especially for Before coming to the NIH, Role was 14-month-old son, Role’s first grandchild. NINDS junior scientists. She will also a full professor at Columbia University Although it can be harrowing to have two expand mentorship opportunities for junior College of Physicians and Surgeons and daughters in the field of mental health, who scientists; formalize mentoring committees then a State University of New York now roll their eyes at their mother’s antics so that each includes three or more mentors; (SUNY) Distinguished Professor and “with authority,” Role is exceptionally proud and require documented annual meetings. Chair of the Department of Neurobiology of their accomplishments. In addition to her role as the NINDS and Behavior at SUNY Stony Brook. Beyond spending time with family and SD, Role will also have her own lab— She was also co-director of SUNY Stony her husband David Talmage (a molecular the Circuits, Synapses and Molecular Brook’s Neurosciences Institute. geneticist at the National Institute of Signaling Section—where her research Role has brought with her Simon Mental Health), Role enjoys doing and will focus on the brain’s cholinergic system Halegoua, who served as her vice-chair looking at “ahht” (that’s “art” with a Boston over the lifespan. Cholinergic signaling, and continues as a professor at SUNY Stony accent) and listening to jazz. She and her which is essential for attention, cognitive Brook in the Department of Neurobiology husband are keeping their New York processing, and memory, is compromised in and Behavior. Halegoua is an NINDS apartment, which was previously occupied neurological disorders including Alzheimer senior advisor to the NINDS Office of the by jazz legend Thelonious Monk. disease and Parkinson disease. Role’s work Scientific Director. Role enjoys working in these domains has focused primarily on with Halegoua, she said, because he “always Read more about Lorna Role in the “Recently physiological approaches to circuits and sees issues from a completely different Tenured” section, which begins on page 16.

6 THE NIH CATALYST MAY-JUNE 2019 NIH ABBREVIATIONS FEATURE CBER: Center for Biologics Evaluation and Research, FDA CC: NIH Clinical Center CCR: Center for Cancer Research, NCI Former NINDS SD, Alan Koretsky CIT: Center for Information Technology DCEG: Division of Cancer Epidemiology and Stepping Forward (Not Back!) to the Lab Genetics, NCI DIPHR: Division of Intramural Population BY EMILY PETRUS, NINDS Health Research, NICHD FAES: Foundation for Advanced Education in the Sciences FARE: Fellows Award for Research Excellence FelCom: Fellows Committee FDA: Food and Drug Administration FNIH: Foundation for the NIH FNL: Frederick National Laboratory IRP: Intramural Research Program HHS: U.S. Department of Health and Human Services NCATS: National Center for Advancing Translational Sciences NCBI: National Center for Biotechnology Information NCCIH: National Center for Complementary RITA DEVINE, NINDS NINDS DEVINE, RITA and Integrative Health Former NINDS SD Alan Koretsky (front row, center) was given a wonderful thank you from the 2019 NINDS summer interns. NCI: National Cancer Institute NEI: National Eye Institute NHGRI: National Human Genome Research Institute During Alan Koretsky’s 12 years as pioneering magnetic-resonance-imaging NHLBI: National Heart, Lung, the scientific director (SD) of NINDS, (MRI) technology such as arterial spin and Blood Institute widespread changes occurred to make labeling, which is used in functional MRI NIA: National Institute on Aging NIAAA: National Institute on Alcohol the institute larger and more cohesive to measure blood flow. His group also pushes Abuse and Alcoholism while maintaining it at the frontiers of MRI-resolution capabilities to detect single NIAID: National Institute of Allergy neuroscience research. Milestones met cells as they migrate throughout the brain; and Infectious Diseases NIAMS: National Institute of Arthritis during Koretsky’s tenure include the uses novel contrast agents to identify synaptic and Musculoskeletal and Skin Diseases completion of the John Edward Porter connections; and is developing sensors NIBIB: National Institute of Biomedical Imaging and Bioengineering Neuroscience Research Center (Building that are capable of detecting changes in NICHD: Eunice Kennedy Shriver 35), modernization of the clinical physiology. Koretsky said he is excited to National Institute of Child Health and Human Development program, enhancement of core facilities for return to this research full time even though NIDA: National Institute on Drug Abuse neuroscientists, and the recruitment of an he is proud of the accomplishments of NIDCD: National Institute on Deafness outstanding—and increasingly diverse— NINDS under his leadership. and Other Communication Disorders NIDCR: National Institute of Dental group of PIs. Outside of the lab, Koretsky enjoys and Craniofacial Research Some of the most satisfying experiences spending time with his family, including NIDDK: National Institute of Diabetes Koretsky encountered during his time as SD his wife Tracy Koretsky (who’s in the office and Digestive and Kidney Diseases NIEHS: National Institute of came from mentoring staff at all career levels. of scientific review in the National Institute Environmental Health Sciences “Alan has had immeasurable influence of General Medical Sciences) and their three NIGMS: National Institute of General Medical Sciences on my career,” said NINDS senior children. Evan is a senior studying chemistry NIMH: National Institute of Mental Health investigator Daniel Reich. “He’s been a at the University of California at Berkeley NIMHD: National Institute on Minority tremendously supportive scientific director, (Berkeley, California); after graduation he Health and Health Disparities NINDS: National Institute of striking what I think is a delicate and plans to do a brief stint in the pharmaceutical Neurological Disorders and Stroke often difficult balance between providing industry and then go on to medical school. NINR: National Institute of Nursing Research opportunities to individual PIs while Mathew is at the University of Vermont NLM: National Library of Medicine OD: Office of the Director remaining fair to everyone. His vision for (Burlington, Vermont) studying data science, OITE: Office of Intramural Training the NINDS [IRP] has made it a unique statistics, and skiing. Anna is a senior at and Education place in the world of neuroscience, spanning Walt Whitman High School (Bethesda, OIR: Office of Intramural Research ORS: Office of Research Services a far greater range of expertise and research Maryland) and plans to attend college in ORWH: Office of Research on Women’s Health interests than any other place I know.” the fall to study physics and math. OTT: Office of Technology Transfer Koretsky is probably best known for

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

and Jawad syndrome, which are rare genetic humans and may pave the way for new treat- diseases characterized by facial, skin, and ments for addiction, pain, depression, and finger abnormalities; developmental delays; other conditions. Ongoing experiments at and microcephaly. (NIH Authors: S.N. Andres, NIDA are already applying this technology to and R.S. Williams, J Biol Chem 294:3312–3320, study malfunctioning brain circuits and their 2019; DOI: 10.1074/jbc.RA118.006759.) relevance to development of drug addiction. [BY JANELLE WEAVER, NIEHS] (NIDA authors: J. Bonaventura, J.L. Gomez, and M. Michaelides, Science 364:eaav5282, 2019; DOI: 10.1126/science.aav5282) NCI-DCEG: CONTROLLING CERVICAL CANCER Scientists in NCI-DCEG are among the leaders NINDS: WANT TO LEARN A NEW SKILL? TAKE of a growing global effort to greatly reduce SOME SHORT BREAKS the number of deaths each year from cervi-

SARA ANDRES AND SCOTT WILLIAMS, NIEHS In a study of healthy volunteers, NINDS cal cancer. They are building upon a legacy NIEHS: A model for the Ctp1-DNA bridging filament is researchers found that our brains may solidify of research advances for this malignancy, that depicted as orange Ctp1 protein tetramers bound to silver the memories of new skills we just practiced DNA strands, shown on a blue background of atomic- resulted from decades of investment in natu- force imaging. a few seconds earlier by taking a short rest. ral-history studies. By leveraging support from The results highlight the critically important the Cancer Moonshot, partnerships with non- NIEHS: PROTEIN USES FILAMENTS TO BRIDGE role rest may play in learning. (NINDS authors: profit organizations, integrated health-care BROKEN DNA M. Bonstrup, R. Thompson, G. Cruciani, systems, pharmaceutical and medical-research A protein called Ctp1 mediates the repair of and L.G. Cohen, Current Biology 29:1346– companies, and others, NCI-DCEG investiga- DNA double-strand breaks by forming fila- 1351, 2019; DOI:https://doi.org/10.1016/j. tors have launched a multi-faceted, highly- ments that bridge two DNA strands, according cub.2019.02.049) integrated research program to improve both to a study in yeast by NIEHS researchers and primary and secondary prevention for a malig- their colleagues. The findings could provide NIAID: EPSTEIN-BARR VIRUS VACCINE nancy that affects more than half a million insight into a defect in DNA repair that causes A research team led by NIAID scientists has women each year and causes over 300,000 Seckel and Jawad syndromes in humans. determined how several antibodies induced deaths worldwide. Read more at http://bit. In what is the first molecular snapshot of by Epstein-Barr virus (EBV), a herpesvirus that ly/2GUQoDs. the Ctp1 protein bound to DNA, the research- causes infectious mononucleosis and is asso- ers used atomic-force-microscopy imaging to ciated with certain cancers, block infection of NIDA: THE GENIUS OF CHEMOGENETICS observe how Ctp1 interacted with DNA. They cells grown in the laboratory. They used this NIDA scientists and others funded by the discovered that while it was bound to double- information to develop novel vaccine candi- institute have published findings showing the stranded DNA, Ctp1 clustered into tetramers, dates that, in animals, elicited potent anti-EBV development of a new, groundbreaking che- each with an average length of approximately antibody responses that blocked infection of mogenetics technology for modulating brain 15 base pairs. These Ctp1 tetramers formed cell types involved in EBV-associated cancers. function in a remote, precise, and ultra-sensi- filaments that each spanned approximately [NIAID authors: W. Bu, M.G. Joyce, H. Nguyen, tive manner in living subjects. These findings 180 base pairs and bridged two double- D.V. Banh, F. Aguilar, Z. Tariq, R.A. Gillespie, describe new chemogenetic ion channels for stranded DNA molecules. To mediate zipping S.F. Andrews, S.R. Narpala, A.B. McDermott, neuron activation and silencing that are con- the DNA, multiple Ctp1 tetramers lined up next G.J. Nabel, M. Kanekiyo, and J.I. Cohen, Immu- trolled by very low doses of the anti-smoking to one another. Mutations that prevented Ctp1 nity pii:S1074-7613(19)30127-X, 2019; DOI: medication varenicline. This drug is an espe- from forming multiunit complexes severely 10.1016/j.immuni.2019.03.010] cially attractive molecule for chemogenetic impaired DNA bridging. Moreover, mutations applications in part because it is well-tolerated that changed the DNA bridging made cells Read more briefs and longer versions of by patients, effectively penetrates the brain, especially sensitive to radiation and chemi- these online: and has long-lasting effects. This technique cals that produce double-strand breaks. The https://irp.nih.gov/catalyst/v27i3/ for modulating neuronal function, reported findings could provide insight into the DNA- research-briefs in laboratory animals, has potential for use in repair defect that causes Seckel syndrome

8 THE NIH CATALYST MAY-JUNE 2019 FEATURE

From Deep Sea Vents to Our Own Stomachs Demystifying How Bacteria Thrive in Extreme Environments BY MEGAN ROEGNER, NIDDK

What could microorganisms that to imagine the connection to human health. STEFAN SIEVERT, WOODS HOLE WOODS SIEVERT, STEFAN exist in extreme environments such as Yet many of these bacteria are closely related hot springs in the crushing depths of our to those that live, and cause disease, in our oceans have to do with bacteria that reside own bodies. Relatives of Campylobacter in our own bodies? This is the question (which causes food poisoning), Helicobacter that the “Demystifying Medicine” lecture (which causes ulcers), and Arcobacter (a series attempted to answer on February Campylobacter-like organism that can 5, 2019. Bridging a huge gap, from tolerate oxygen) are all found along the

2,500 meters under the sea to inside our deep-sea vents. Microorganisms that exist in deep-sea hydrothermal vents own intestines, Stefan Sievert and John While not genetically identical to their like this one have a lot in common with the microorganisms that live inside our bodies. Relatives of Campylobacter (which Dekker (National Institute of Allergy land-locked relatives, these bacteria do have causes food poisoning), Helicobacter (which causes ulcers), and Infectious Diseases) explained how some similar traits including a glycosylation and Arcobacter (a Campylobacter-like organism that can intricately connected these two worlds are pathway that aids in interactions with any tolerate oxygen) are all found along the deep-sea vents. and how new genomic technologies can host species. The bacteria also tend to be These techniques have been used to help us understand the evolution of these highly adaptive, for example by having diagnose rare diseases and to track the microorganisms. highly plastic genomes due to a lack of evolution of Ebola outbreaks in West Sievert is a microbial ecologist at the DNA-repair mechanisms, perhaps giving Africa. An even newer technology, nanopore Woods Hole Oceanographic Institution them the unique ability to exist in extreme sequencing with a pocket-sized sequencing in Falmouth, Massachusetts. His primary environments such as the deep oceans and device, allows this analysis to be completed interest is the microbes that live in deep- the human intestinal system. faster and with greater accuracy. During sea hot springs or hydrothermal vents. Did the sea and terrestrial bacteria evolve the 2015 Ebola outbreak, on-site use of Temperatures around the vents vary from together or did the evolution take place later? nanopore sequencing allowed researchers 41 to 662 degrees Fahrenheit. The warm New genomic techniques introduced by the to track the evolution of the virus in real temperature gradients coupled with chemical next speaker, John Dekker, may hold the time. Dekker also presented work from his compounds from the vent fluids create a secret to unlocking this mystery. own lab in which it used rapid nanopore chance for life to thrive even in the dark Although Dekker did not talk about sequencing to identify antibiotic resistance and food-starved deep sea. the same bacteria as Sievert, he reviewed mechanisms in bacteria. Instead of getting energy from light, recent advances from labs around the The application of genomic techniques as plants do in photosynthesis, these world involving the application of genomic helps researchers understand how bacteria microbes use chemical energy in a process techniques to identify other human evolved to develop resistance to antibiotics called chemosynthesis. The microbes pathogens—such as Leptospira (which is and adapt to new environments. Perhaps form the base of the food chain at these passed from animals to humans), astrovirus these same techniques applied to disease highly productive ecosystems that were (a major cause of acute diarrhea in children), outbreaks can answer the question of how only discovered about 40 years ago. The and Ebola virus. deep-sea bacteria came to play a part in our microbes use chemical compounds such as Dekker takes specimens from infected day-to-day lives. hydrogen sulfide and hydrogen rising out patients and applies high-throughput of the vents, along with oxygen and nitrate sequencing to generate a huge number Read more online at from the deep-ocean water, to create the of short “reads” of the DNA base-pair https://irp.nih.gov/catalyst/v27i3/from- biological compounds needed for life from sequences which are then analyzed deep-sea-vents-to-our-own-stomachs/ carbon dioxide. computationally. All the human reads To see a videocast of the whole lecture: As Sievert showed images of deep-sea are filtered out, and the remaining reads https://videocast.nih.gov/launch. vents and otherworldly creatures drifting by are cross-referenced against databases of asp?27302 a deep-ocean submersible vehicle, it was hard bacterial, viral, and fungal pathogens.

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

Gene Therapy Turns 30 Years Old CONTINUED FROM PAGE 1

In 1988, NIH researchers switched from experiment could only move forward with bone marrow to white blood cells as the a unanimous vote from the RAC. Perhaps cell of choice to “infect” with the retrovirus, miraculously, Rosenberg got just that—a which dramatically increased the number 13 to 0 RAC vote—on December 9, 1988. of correct genes taken up by the cells in And that unanimous approval again should animal experiments. This result set the stage have been the green light. for Rosenberg’s group, who in 1988 were However, upon Wyngaarden’s approval, the first to use non–genetically modified American economic and social theorist tumor-infiltrating lymphocytes (TIL) cells Jeremy Rifkin, representing the Foundation to successfully mediate tumor regression. on Economic Trends, filed suit against the On May 22, 1989, Rosenberg and his NIH. Rifkin, well known as an activist team attempted a retroviral-mediated gene against certain biotechnology trends, argued transduction to introduce the gene coding that the RAC approval was not at a public for resistance to neomycin into human TIL meeting and violated NIH guidelines. This

NCI cells before their infusion into patients; the matter took several more months to resolve.

Thirty years ago this May, Steven Rosenberg and colleagues goal was to help determine the traffic of With the success of the initial gene- shepherded in the era of gene therapy when they removed, the infused cells in the body. The results therapy experiments, Anderson, working genetically altered, and returned cells to a patient with malignant melanoma. of this proof-of-concept experiment with with Blaese and Rosenberg at the NIH, marked TIL cells, first performed on a stepped up the game in 1990 with the Rosenberg’s surprise over the 30th 52-year-old truck driver from Indiana, therapeutic use of a virus to deliver the anniversary perhaps was more of a tempus demonstrated that the engineered virus correct gene to two girls, ages 4 and 9 years fugit feeling. Time flies when you’re can be used safely in humans and also old, with ADA deficiency. The results also pioneering the development of effective elucidated the prolonged survival of the were successful, albeit limited. immunotherapies and gene therapies for transferred cells in the patient. Progress in gene therapy has since patients with advanced cancers. The initial experiments on the truck exploded, with more than 2,000 clinical As far as classic clinical studies go, the driver and four other patients were a success, trials worldwide, according to the Gene set of gene-therapy experiments in 1989 with no signs of toxicity or ill effects of Therapy Clinical Trials Worldwide was akin to the NIH face that launched the procedure, although all the patients Database. These trials include dozens a thousand research ships. Gene therapy ultimately died of their cancer. of clinical trials at the NIH testing is now performed worldwide, with several The preceding year, however, had been immunotherapy for cancers and other cell- gene-therapy drugs approved by the FDA, filled with trouble and angst. In mid-1988, based therapies for diseases such as sickle including one that Rosenberg helped Rosenberg sought permission from the NCI cell. To facilitate even more experimentation, develop (axicabtagene ciloleucel, trade name and NHLBI institutional review boards to the NCI has invested in a 6,000-square-foot Yescarta, for the treatment of adult patients conduct his experiment. It was so novel that facility with sterile cell-processing units to with relapsed or treatment-resistant large more and more reviews were needed. On create naturally occurring and genetically B-cell lymphoma). October 3, 1988, the Recombinant DNA modified lymphocytes for patient therapy. Thirty years ago, Rosenberg and his Advisory Committee (RAC) approved the This facility is under construction between team were building on the pathbreaking Rosenberg-led experiment by a margin of Buildings 10 and 30 on the NIH Bethesda, experimentation by French Anderson 16 to 5. That approval should have been Maryland, campus. (National Heart, Lung, and Blood Institute, the green light. The impact will be huge, and it all NHLBI), Michael Blaese (National However, given the controversy of started right here 30 years ago. Human Genome Research Institute), and gene therapy—with some members of others at the NIH who in 1985 used a the public opposed to scientists “playing To read a profile of Steven Rosenberg that retrovirus to carry a correct human gene God” and tinkering with the human appeared in the January-February 2018 issue for adenosine deaminase (ADA) into patient genome—the NIH Director at the time, of the NIH Catalyst, go to https://irp.nih.gov/ cells in a tissue culture. James Wyngaarden, mandated that the catalyst/v26i1/steven-a-rosenberg-md-phd.

10 THE NIH CATALYST MAY-JUNE 2019 FEATURE

My Room, Your Room Blue Devils. Sharpless was a medical such as infections and heart disease, at a Room 212, The Cloister student at Duke’s arch rival school—the rate that is different from the general U.S. BY LAURA STEPHENSON CARTER, OD University of North Carolina (UNC) School population,” she said. Such information is of Medicine (Chapel Hill, North Carolina), important for oncologists to understand so home of the Tarheels. The two engaged in they know how to appropriately monitor NIH Medical Research Scholar some good-natured teasing. and treat their patients’ unique disease risks. Nicole Dalal knew she was living in a When Sharpless was an NIH-HHMI Population-based research “allows historic building once occupied by nuns. program participant, he did research on HIV scientists to study so many more patients— But what she didn’t know was that her with the late Monique Dubois-Dalcq, who in different socioeconomic groups and residence—Room 212 in the Cloister was the chief the Laboratory of Viral and geographic locations—than can be (Building 60), built in 1923 and taken Molecular Pathogenesis in the National conventionally studied in clinical trials,” over by NIH in 1984—had its own Institute of Neurological Disorders and she said. special history: Former National Cancer Stroke. After graduating from medical But past and present MRSP scholars do Institute (NCI) Director—now Acting school and completing his residency in more than spend time in the lab. Sharpless Commissioner of the FDA—Ned internal medicine and a hematology– and Dalal enjoyed being so close to Wash- Sharpless had lived there in the early oncology fellowship, he spent two years ington, D.C., cooking pizza, and playing 1990s. He was a medical research scholar on the Harvard Medical School (Boston) sports. Sharpless played tennis and basket - when the program was run as a partnership faculty. In 2002, he accepted an appointment ball and loved running in Rock Creek Park. between NIH and the Howard Hughes at the UNC School of Medicine later Dalal enjoys running, too, and recently ran Medical Institute (HHMI). becoming the Wellcome Professor of Cancer in the “Rock ‘n’ Roll Marathon” in Wash- The Medical Research Scholars Program Research and director of UNC–Chapel ington, D.C., along with two other Cloister (MRSP) provides a year of intensive Hill’s Lineberger Comprehensive Cancer residents. training for medical, dental, and veterinary Center. In 2017, he was sworn in as the 15th students—typically between their third and director of NCI, and on April 5, 2019, he For more information about the MRSP, go to fourth years of professional school—at the went on leave from that position to become https://cc.nih.gov/training/mrsp/index.html. NIH campus in Bethesda, Maryland. The the Acting Commissioner of the FDA. program is a successor program to the NIH- Sharpless still conducts research, too. HHMI Research Scholars Program that His current work is on understanding the ran from 1985 to 2012. biology of the aging process that promotes “I thought it was pretty cool [that Ned the conversion of normal self-renewing cells Sharpless] lived in the same room as me,” into dysfunctional cancer cells. He has made said Dalal. seminal contributions to the understanding Sharpless, who visited his old room and of the relationship between aging and cancer met Dalal in January, was pleased that the and in the preclinical development of novel room—which is really a small one-bed- therapeutics for melanoma, lung cancer, and room apartment—looked pretty much as breast cancer. he remembered it. One difference was that ERNIE BRANSON Dalal, who hopes to become an in the 1990s, the shelves were filled with oncologist one day, is doing cancer textbooks and reprints of journal articles; epidemiology research with Lindsay Dalal’s shelves are nearly bare. Nowadays, Morton, a senior investigator in the NCI’s medical students often use online materials, Radiation Epidemiology Branch. Using so there’s little need to have physical books the Surveillance, Epidemiology, and End Medical Research Scholar Nicole Dalal (right) was delighted and printouts around. to meet Acting FDA Commissioner Ned Sharpless who Results database, which provides detailed Suddenly, Sharpless noticed the Duke had lived in her room in the Cloister (Building 60) when population-based statistics on cancer, Dalal he was part of the NIH-HHMI Research Scholars Program University banner hanging on the wall and in the 1990s. Dalal, who attends Duke University School of is trying to determine the causes of death of gasped in mock disbelief. Dalal is a student Medicine (notice the banner in the background), teased people who survived their cancers. “With Sharpless about having attended medical school at Duke’s at Duke University School of Medicine better treatments, patients are surviving their arch rival—the University of North Carolina at Chapel Hill. (Durham, North Carolina), home to the cancers but may be dying of other causes,

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

Dermatology Branch CONTINUED FROM PAGE 1 until 2001 even after being made Director Early Dermatology Research of the National Institute of Arthritis Dermatology research was being conducted and Musculoskeletal and Skin Diseases at NIH as far back as the 1930s, before NIH (NIAMS) in 1995. During his tenure as was divided into institutes and centers (ICs). chief, the branch grew into a formidable The Division of Industrial Hygiene, for force and trained dozens of scientists who example, investigated the health of workers went on to assume leadership positions in different industries. In 1939, the division’s in dermatology departments throughout scientists described industrial dermatitis the world—including Germany, Austria, (redness, itchiness, cracking, and blistering of England, Hungary, Belgium, Switzerland, the skin caused by tar and other substances) Japan, Korea, Taiwan, and the United States. and melanosis (a form of hyperpigmentation He’s also largely responsible for building caused by increased melanin). The research NIAMS an awareness that the skin is an important led to procedures for protecting workers’

NIAMS Director Stephen Katz, who died on December 20, part of the body’s immune system and that skin. The Occupational Safety and Health 2018, was a leader in the study of skin-based immunology abnormalities in the immune system are Administration, and then the National and trained more than 45 people who have gone on to play significant roles in dermatology. associated with many skin diseases. Institute for Occupational Safety and Health Under Katz’s guidance, Dermatology (part of CDC) and the Environmental areas of her skin and scheduled her to Branch scientists have made many Protection Agency, have taken over much return in July for a follow-up visit. discoveries including the: of what the division used to do. After analyzing the biopsied tissue and • Pathogenesis of xeroderma pigmen- NIH’s Division of Infectious Diseases, conferring with his brother, who was also tosum (XP), a genetic disease that makes led by Rolla E. Dyer, focused on a wide a dermatologist, Katz determined that the cancer more likely and is associated with range of diseases caused by bacteria, viruses, child had a rare disease called erythema developmental abnormalities and cellular and fungi. In 1934, Chester Emmons, elevatum diutinum. It’s characterized by hypersensitivity to ultraviolet radiation an expert on fungi as a cause of disease, painful, necrotizing vasculitis that causes • Use of synthetic retinoids to treat established the current classification system thick red, purple, brown, and yellow patches severe disfiguring acne and as chemopre- of dermatophytes (fungi that infect the hair, on knees, elbows, hands, and other areas vention agents skin, and nails, causing ringworm). of the body. He had even come up with a • Composition and function of the skin The Division also studied leprosy (today, plan for how to treat it. “I knew that this immune system with special emphasis on Hansen disease), a contagious disease caused rare disease responded to a drug that wasn’t Langerhans cells by a Mycobacterium species that affects usually included when one says, ‘She was • Cytokines and chemokines that medi- the skin, nerves, and eyes. In Hawaii, the treated with everything,’” said Katz. “This is ate cutaneous inflammation a drug called dapsone, which was otherwise • Structure of adhesive junctions that used [for] treatment of leprosy.” Colleagues mediate the attachment of keratinocytes laughed in disbelief when Katz told them to each other and to underlying basement what he had in mind. membranes But when the girl returned for her • Characterization of patient autoanti- follow-up visit on the July 4 weekend, Katz bodies that react with adhesive structures did treat her with dapsone and within a and that cause skin-blistering diseases couple of days, she was 98 percent better, • Characterization of dendritic-cell HIV he said. “She’s been on that drug for 40-some interactions; identification of mechanisms years because if she stops, the disease comes that regulate leukocyte and cancer-cell back.” To this day, dapsone is the first line localization of treatment for this rare disease. • Characterization of normal tissue and COMMONS CREATIVE ARENTS, PIERRE Katz, who died in December 2018, cancer stem cells Early dermatology research at NIH included studies of leprosy. Shown: Twenty-four year old man from Norway, became the chief of NCI’s Dermatology suffering from leprosy (circa 1886). Branch in 1980 and served in that capacity

12 THE NIH CATALYST MAY-JUNE 2019 FEATURE

division’s Leprosy Investigation Station lesions and may eventually spread to other invented orthopedic devices to correct parts of the body. During his tenure, he deformities caused by nerve damage and collaborated on XP research with other NCI found that malnourishment (particularly scientists, including Kenneth Kraemer, deficiencies in vitamin B1 and calcium) who was a postdoc in the Dermatology increased susceptibility to leprosy. It was Branch in the early 1970s and is now a not until the late 1940s that the causative senior investigator in NCI’s Laboratory of CHRIS NAGAO, NIAMS organism was found and an antibiotic Cancer Biology and Genetics. treatment for leprosy was developed. In 1969, Lutzner recruited Gary Peck, Beginning in 1937, NCI (which had who studied how retinoids could change been established by Congress as a separate epidermal differentiation from keratin- entity within the Public Health Service and producing to mucus-producing. He became a division of NIH in 1944) funded a collaborated with Peter Elias (currently Former Dermatology Branch Chiefs Steve Katz and Mark Udey, as well as others in the branch, made important Public Health Methods study on the number a world-renowned skin biologist at the discoveries concerning Langerhans cells, which are dendritic and characteristics of cancer deaths in the University of California at San Francisco) cells of the skin and present in all layers of the epidermis. Shown: Langerhans cells (green) visualized in whole-mount United States using records dating back and John DiGiovanna on research that skin. The purple circles are hair follicles. to 1900. Among the findings were that led to the widespread use of retinoids in although more people in the northeast died patients who were at high risk for multiple Branch Chief in 1977 and permanent of cancer, more people in the South had skin cancers. Peck, who left NIH in the chief in 1980. Under Katz’s leadership, cancer. The scientists thought the difference 1990s to become the founding director of the branch started having a greater focus was because of the greater prevalence of skin the Melanoma Center in the Washington on the skin as an immunological organ. cancer in the South. Cancer Institute (Washington, D.C.), later There was an increasing interest in skin won several awards in recognition of his immunology worldwide at the time, and discovery of isotretinoin (Accutane) for the Branch Founded in the 1960s Katz was considered a pioneer in the field. treatment of severe, recalcitrant nodulocystic There wasn’t a formal Dermatology Branch Katz’s “research showed that skin is an acne and other applications, including the at NCI until 1961, when Eugene Van Scott important component of the immune system prevention of basal-cell carcinomas. became its first chief. He left NIH in the both in its normal function and as a target in Peter Steinert, an international expert late 1960s to head Temple University’s immunologically mediated disease,” wrote in the structural biology of the skin, came to (Philadelphia) dermatology department Benjamin Barkin in a 2016 article in The NCI’s Dermatology Branch in 1973. In 1990 and later founded a company that became Dermatologist. In addition, “Dr. Katz and he started the Laboratory of Skin Biology a major skin-care corporation. His work his colleagues have added considerable new in NIAMS. He died in 2003. on psoriasis led to the development of knowledge about inherited and acquired DiGiovanna went on to become the methotrexate, which is to this day a first- blistering skin diseases.” Katz discovered an head of the Dermatology Clinical Research line systemic drug for its treatment. He antigen that is associated with pemphigus Unit in NIAMS in 1994. His group also won a Lasker Award in 1972 “for his vulgaris, an antibody-mediated autoimmune discovered the genes underlying several outstanding contribution to the concept skin disease that results in blisters (J Clin severe skin disorders. Currently a senior of topical chemotherapy in the treatment Invest 70:281–288, 1982). research physician in NCI, he continues to of mycosis fungoides” (the most common In addition, Katz did landmark studies work with Kraemer on the clinical, basic, form of the skin-cancer cutaneous T-cell on Langerhans cells, which are dendritic and translational studies of DNA-repair lymphoma). cells of the skin and present in all layers disorders. Marvin Lutzner became branch chief of the epidermis. His first stint with the next. He and two French dermatologists cells was when he and Georg Stingl, then discovered Lutzner cells, a mutated form Steve Katz as Chief (1980–2001) a postdoctoral fellow from Vienna (he later of T lymphocytes. Lutzner cells can cause Katz, who had come to NIH in 1974 and became professor and chair of dermatology at cutaneous T-cell lymphoma, a type of non- had started his own laboratory with Ken Hodgkin lymphoma that starts as skin Hertz and a technician, became Acting CONTINUED ON PAGE 14

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

Dermatology Branch CONTINUED FROM PAGE 13

Mark Udey as Chief (2001–2017) Today’s Dermatology Branch Udey, who had been an assistant professor In 2017, soon after Udey’s departure, the of medicine (dermatology) at Washington Dermatology Branch moved from NCI to University School of Medicine (Saint Louis), NIAMS. The move made sense, according was drawn to NIH in 1989 because it was to NIAMS Scientific DirectorJohn O’Shea, doing research in areas that interested him: because the institute studies skin diseases skin immunology and Langerhans cells. as well as arthritis and musculoskeletal He became internationally recognized for diseases. Despite the administrative shift, his work on cutaneous immunophysiology branch scientists didn’t even have to move and for his seminal research on the biology their labs because they were already adjacent of Langerhans cells including the role of to NIAMS labs in the NIH Clinical Center epithelial cadherin (which plays a role in cell (Building 10). migration and adhesion) and transforming- Today, the Dermatology Branch is growth-factor–beta (which controls cell headed by Acting Chief Edward Cowen growth, proliferation, and differentiation) and continues to conduct clinical and basic

BENJAMIN VOISIN, NAGAO LAB, NIAMS in the cells’ development and localization. investigations of skin biology and researches

Hair follicles are the epicenter of immune cells in the skin. Udey rose from the position of the etiology, diagnosis, and treatment of skin Shown: Innate lymphoid cells (ILC) that have been guided to investigator to senior investigator in 1996 disease. Research areas of interest include the upper hair follicles where they control sebaceous gland (SG) function to tune the microbial balance on skin surface. and to branch chief in 2001. Under his the skin as an immunological organ and leadership, the branch expanded its clinical- the role of tissue-leukocyte-microbiota research program and broadened its range cross-talk in mediating immunological and the Medical University of Vienna in Vienna), of research to include studies of graft- structural homeostasis; inflammatory skin investigated the immunological functions versus-host disease (GVHD) and Merkel diseases in patients and in mouse models; the of surface markers of Langerhans cells. cells. The branch also continued to be a human microbiome in healthy individuals These studies, done in collaboration with training ground for dermatologists. Udey as well as in patients with atopic dermatitis David Sachs (now a professor emeritus considers one of his major accomplishments and primary immunodeficiencies; long- at Harvard Medical School in Boston), to be the recruitment and mentoring of Ed term clinical and laboratory studies and led to the new discovery that Langerhans Cowen, Heidi Kong, Isaac Brownell, and investigator-initiated therapeutic trials in cells could originate from a mobile pool of Chris Nagao, who are all leaders in NIH’s chronic GVHD, neurofibromatosis, and cells in the bone marrow and likely play an Dermatology Branch now. autoinflammatory skin disease; skin stem important role in allogeneic graft rejection. Udey left NIH in 2017 to become a cells; and cutaneous malignancies including (Nature 282:324–326, 1979). professor in the Department of Medicine Merkel-cell carcinoma. In his long association with the (Dermatology) at the Washington University On the facing page are highlights of Dermatology Branch, Katz supervised School of Medicine. He has also been the Dermatology Branch current activities. dozens of trainees, many of whom went on the editor of the Journal of Investigative to become notable leaders in dermatology Dermatology since 2017. around the world. In 1995, he became the director of NIAMS, but he remained the Dermatology Read more online including comments Branch Chief until 2001, when Mark Udey about Stephen Katz from his former took over. Katz also continued his own trainees and a description of other dermatology research until his death in 2018. dermatology research happening at NIH: “I don’t know anyone who’s had as broad https://irp.nih.gov/catalyst/v27i3/ an impact as Steve Katz,” said Udey. “He the-dermatology-branch-at-nih/ trained over 45 people” who have gone on to play significant roles in dermatology. Mark Udey

14 THE NIH CATALYST MAY-JUNE 2019 FEATURE

Dermatology Branch at NIAMS

Dermatology Consultation Cutaneous Development and recurrent viral infections of the skin and Service Carcinogenesis Section respiratory system and typically have Head: Senior Clinician Edward Cowen, Head: Investigator Isaac Brownell, M.D., allergies, asthma, and an increased risk M.D., M.H.Sc. Ph.D. for some types of cancer. The Dermatology Consultation Service This section studies the regulation of Since 2007, Kong has partnered with evaluates patients with a variety of rare cutaneous stem cells and the molecular Julie Segre (National Human Genome diseases that have cutaneous manifestation pathogenesis of skin cancer, especially Institute) to perform many large-scale as well as patients who experience adverse Merkel cells and Merkel-cell carcinoma. DNA-sequencing skin-microbiome studies. reactions to experimental therapeutic agents Brownell oversaw a clinical trial that Their analyses have shown that human or develop unrelated skin conditions while led to the 2017 FDA approval of avelumab microbiota varies by specific regions of the at the NIH. Dermatology Branch clinical to treat Merkel-cell carcinoma. His team skin surface and among individuals. fellows, fellows from other NIH ICs, and collaborates with the National Center for Cutaneous Leucocyte Biology visiting dermatology residents from around Advancing Translational Science to do Head: Stadtman Investigator Keisuke the country receive training on the service. drug-discovery studies for this disease and (Chris) Nagao, M.D., Ph.D. Cowen is one of a very few plans to test one of the drugs in a clinical The section is exploring the mutual cross- dermatologists in the United States studying trial in collaboration with the NCI Rare talk that occurs among the skin epithelium, cutaneous GVHD. He discovered that total- Tumors Initiative and AstraZeneca, which the microbiota, and the immune cells that body radiation during conditioning before manufactures a nanoparticle version of this are involved in maintaining immunological hematopoietic-cell transplantation poses a drug. and microbial homeostasis in skin. In risk for the development of a debilitating particular, Nagao’s group has identified form of skin thickening caused by GVHD. Cutaneous Microbiome and hair follicles as the control towers of skin He also found that adverse reactions to the Inflammation Section immunity; the follicles guide the localization antifungal agent voriconazole can cause Head: Investigator Heidi H. Kong, M.D., of skin-resident immune cells and enhance immunosuppressed patients, including M.H.Sc. their survival by producing chemokines and patients with GVHD, to develop squamous- The section studies the skin microbiome— cytokines. In turn, the immune cells help cell carcinoma. in both healthy individuals and patients with shape the function of the skin barrier. The Assistant Research Physician skin diseases—with the goal of expanding group has established that such cross-talk Dominique Pichard studies patients the understanding of host-microbe is crucial in regulating the balance of the with rare diseases such as chronic GVHD interactions. The Kong group has examined skin microbiota during homeostasis and that and neurofibromatosis 1 (NF1). She the role of microbes in atopic dermatitis imbalance, or dysbiosis, of the microbiota is conducting clinical trials to test the and other eczematous skin diseases. Current drives inflammation in atopic dermatitis. efficacy of the topical Janus kinase inhibitor work has expanded to include investigations Nagao collaborates with Kong and ruxolitinib as a treatment for epidermal into human-skin fungi and viruses. investigators in NIAID to understand the chronic GVHD and to test the efficacy Kong is collaborating with NCI human-disease pathology that underlies of a systemic mitogen-activated-protein- investigators to look at the skin microbiome inflammation and susceptibilities to kinase-kinase (MEK) inhibitor in NF1 of cancer patients who are undergoing certain microbial agents. In particular, cutaneous neurofibromas. treatment with immunotherapies. She also Nagao focuses on patients with severe drug works closely with intramural researchers hypersensitivities and monogenic diseases from other ICs to study and care for patients that manifest as atopic skin inflammation. Read more about the NIH Dermatology with dedicator of cytokinesis 8 (DOCK8) He receives cross-support for his work from Branch and its training programs at immunodeficiency who are undergoing other ICs in the form of collaborations with https://irp.nih.gov/catalyst/v27i3/ stem-cell transplants. The syndrome is a investigators in the NCI, NIAID, the the-dermatology-branch-at-nih/ rare immune disorder that causes immune National Heart, Lung, and Blood Institute, cells to malfunction; patients suffer from and the National Institute on Aging.

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

Recently Tenured

LORENZO LEGGIO, NIAAA and FRANK MALDARELLI, NCI-CCR ALEKSANDRA URSZULA NITA- LORNA ROLE, NINDS EDWINA H. YEUNG, NICHD NIDA LAZAR, NIAID

LORENZO LEGGIO, M.D., PH.D., M.SC., NIAAA Outside interests: Listening to music; watch- between alcohol-related seeking behaviors AND NIDA ing movies; going to the opera and the microbiome-gut-brain axis. Future Senior Investigator and Chief, Section on Website: https://irp.nih.gov/pi/ research includes work on the effects of Clinical Psychoneuroendocrinology and lorenzo-leggio bariatric surgery on alcohol-related seeking Neuropsychopharmacology (CPN), a joint behaviors. National Institute on Alcohol Abuse and Alco- Research interests: My laboratory con- Our preclinical work—in collaboration holism (NIAAA) and National Institute on ducts clinical and translational inpatient with other laboratories—and human Drug Abuse (NIDA) laboratory; Associate and outpatient studies to identify pos- studies in our lab aim to shed light on the Director for Clinical Research, Medication sible novel medications for addiction. possible role of these pathways in alcohol- Development Program, NIDA My group uses a combination of state- and substance-use disorders. Education: Catholic University of Rome, of-the-art, innovative biobehavioral and Rome (M.D.; Ph.D. in physiopathology of pharmacological procedures performed nutrition and metabolism); Department of under well-controlled laboratory condi- FRANK MALDARELLI, M.D., PH.D., NCI-CCR Clinical Physiopathology, University of Flor- tions. Brain-imaging techniques, such as Senior Investigator and Head, Clinical Ret- ence, Florence, Italy (M.Sc.) functional magnetic-resonance imaging, rovirology Section, HIV Drug Resistance Training: Residency in internal medicine, are also used. We are particularly inter- Program Host-Virus Interaction Branch, Agostino Gemelli University Polyclinic, ested in the role of the gut-liver-brain axis Center for Cancer Research, National Cancer Catholic University of Rome, Rome; postdoc- in alcohol- and drug-seeking behaviors. Institute toral fellowship in psychiatry and human Specifically, we are currently Education: Johns Hopkins University, behavior, Brown University (Providence, investigating the potential role of feeding- Baltimore (B.A. in biology); City University Rhode Island) related pathways—such as those for the of New York, New York (Ph.D. in biomedical Before coming to NIH: Assistant professor, hormones ghrelin, leptin, oxytocin, and sciences); Mount Sinai School of Medicine, Warren Alpert Medical School and Public glucagon-like peptide 1—as possible New York (M.D.) Health Program, Brown University new neuropharmacological targets for Training: Residency in internal medicine, The Came to NIH: In 2012 as a tenure-track clini- the treatment of alcohol- and substance- Presbyterian Hospital (New York); medical cal investigator use disorders. We are also investigating staff fellow and senior staff fellow, Labora- Selected professional activities: Professor other neuroendocrine pathways such as tory of Molecular Microbiology, National (adjunct), Department of Behavioral and the aldosterone-mineralocorticoid receptor Institute of Allergy and Infectious Diseases Social Sciences, Brown University; member, pathway. (NIAID) American College of Neuropsychopharma- We have recently expanded our Came to NIH: In 1988 for training; became a cology; member of several editorial boards research to look at the role of the gut clinical associate in NIAID in 1996; became of scientific journals; member of several microbiome in heavy drinkers of alcohol. clinical associate in NCI in 1998; became advisory boards Our special emphasis is on the relationships staff physician in 1999; in 2012, became

16 THE NIH CATALYST MAY-JUNE 2019 COLLEAGUES

doctoral associate, Massachusetts Institute head of Clinical Retrovirology Section, HIV studies, we will be determining the roles of Technology (Cambridge, Massachusetts) Dynamics and Replication Program of these clonal populations in reactivation Came to NIH: In 2009 Selected professional activities: Attending of HIV after antiretroviral therapy is Selected professional activities: Executive physician in NIAID and in the HIV Service in interrupted. editor, Journal of Proteomics; member of the NIH Clinical Center’s Critical Care Medi- In a second research project, we are Human Proteome Organization Council cine Department investigating the genetic structure of HIV Outside interests: Taking every opportunity Website: https://irp.nih.gov/pi/ populations in infected individuals. The to actively spend time outside with her son frank-maldarelli goal of this study is to understand the and her husband; reading; knitting; running nature of the forces (mutation, selection, and coaching running at the county running Research interests: HIV infection can be drift, and recombination) that mold the club; doing and teaching yoga. controlled, but not cured, by current com- genetic diversity of virus populations Website: https://irp.nih.gov/pi/ bination antiretroviral therapy (cART); before and after cART is introduced. aleksandra-nita-lazar a large reservoir of HIV-infected cells We are determining the roles of HIV that persists during cART prevents HIV population size, genetic drift, selection, and Research interests: My research focuses eradication and contributes to long-term recombination in shaping HIV populations on understanding the changes that occur in morbidity and mortality. My laboratory and in the emergence of drug resistance the cell proteome in response to exogenous is conducting clinical studies at the NIH during cART. factors such as pathogen-derived molecules, Clinical Center to investigate mechanisms We have also adapted these genetic cytokines, and chemokines. These factors underlying HIV persistence during cART. approaches to investigate the spread of alter the differentiation state of cells in the We are also studying the long-term effects HIV, including drug-resistant variants, in immune system or characterize specific of HIV persistence including the emer- populations. In studies with investigators disease states. My group is especially inter- gence of resistance to HIV drugs in indi- in NIAID and NCI, as well as with ested in large-scale absolute-quantitative viduals undergoing cART and the spread collaborators at Georgetown University and measurements of immune-cell signaling of HIV within individuals in populations. George Washington University (both in cascade components and in the character- One of the most critical challenges Washington, D.C.), we are characterizing ization of post-translational modification limiting the development of curative the origin and spread of the HIV epidemic (PTM) dynamics on a global scale. We strategies for HIV is the lack of in Washington, D.C., which has the use the resulting large datasets to create understanding of the precise mechanisms highest prevalence of HIV in the United predictive models of molecular interactions underlying HIV persistence during cART. States. Our studies will be an important by use of the Simmune software generated We and others have demonstrated that part of the effort to control and eliminate by NIAID’s Computational Biology Sec- HIV-infected cells may persist for many this epidemic. tion. The predictions of these models will years during cART and undergo clonal in turn be employed to elucidate biological expansion. In new studies at the NIH responses to stimuli at multiple scales of Clinical Center, we are investigating the ALEKSANDRA URSZULA NITA-LAZAR, PH.D., biological organization including the cell, origin and persistence of long-lived clonal NIAID tissue, and, eventually, the whole organism. populations of infected cells. In most cases, Senior Investigator and Chief, Cellular With state-of-the art equipment and we have found that clonal expansion is not Networks Proteomics Section, Laboratory of technologies available in our laboratory and driven by the integrated provirus but is Immune System Biology, National Institute at NIH, we use mass-spectrometry-based the result of normal T-cell behavior. We of Allergy and Infectious Diseases technology together with other proteomic are determining the distribution of these Education: University of Warsaw, Warsaw, and biochemical methods. infected cell clones within T-cell subsets Poland (M.S. in molecular biology); Univer- In one of our projects, we are and in anatomic compartments within sity of Basel, Basel, Switzerland (Ph.D. in investigating the protein modifications infected individuals. In clinical studies, biochemistry) involved in cell signaling. Because we are investigating whether clinical Training: Postdoctoral fellow, Stony Brook dynamic PTMs such as phosphorylation, events, such as co-infections, drive clonal University (Stony Brook, New York); post- expansion and HIV persistence. In new CONTINUED ON PAGE 18

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

Recently Tenured CONTINUED FROM PAGE 17 Stony Brook’s Thomas Hartmann Center for for mapping cholinergic projections, and Parkinson Research; 1985–2008: professor we have been collaborating on studies of ubiquitination, or glycosylation are essential of cell biology, Department of Neurobiology new imaging probes for the assessment of for the regulation of cell signaling, it is and Behavior, Columbia University College cholinergic-terminal integrity in dementia. crucial to quantitatively map the PTMs of Physicians and Surgeons (New York) For more about Lorna Role, who was of proteins involved in signaling cascades. Came to NIH: In February 2019 recently appointed scientific director of Examples of our interests include toll-like Selected professional activities: Elected NINDS, see “NINDS Welcomes Lorna receptor signaling in macrophages. Fellow of the American Association for the Role as New Scientific Director” on page 6. In another project, we are interested Advancement of Science; elected Fellow in the absolute quantification of protein in the American College of Neuropsycho- expression and protein-protein interactions. pharmacology; reviewing editor for several EDWINA H. YEUNG, PH.D., NICHD We have established a methodology for scientific journals Senior Investigator, Epidemiology Branch, analyzing the lipid-induced signaling Outside interests: Spending time with Eunice Kennedy Shriver National Institute pathways in which sphingosine-1- family; looking at and doing art (paint- of Child Health and Human Development phosphate (S1P) receptor 1 and S1P2 ing and sculpture); studying the history of Education: Johns Hopkins University, receptor play a role in monocyte and architecture and traveling to experience it; Baltimore (B.A. in natural sciences area macrophage cell lineage–derived osteoclast enjoying jazz and classical music and public health studies); Johns Hopkins precursors that control cell mobilization at Website: TBA Bloomberg School of Public Health, Balti- bone surfaces. We are currently working more (Sc.M. in clinical epidemiology; Ph.D. on the absolute quantification of molecules Research interests: My research focuses in cardiovascular disease epidemiology) in the macrophages exposed to different on the brain’s cholinergic system over the Training: Postdoctoral fellow in epidemiol- toll-like receptor ligands, which play a key lifespan. Cholinergic signaling—which is ogy, NICHD role in the innate immune system. essential for attention, cognitive processing, Came to NIH: In 2008 for training; became and memory—is compromised in tenure-track investigator in 2011 neurological disorders including Alzheimer Selected professional activities: Editorial LORNA ROLE, PH.D., NINDS disease and Parkinson disease. The lab board member, Fertility & Sterility Senior Investigator, Circuits, Synapses and has focused primarily on physiological Outside interests: Cooking; fishkeeping (an Molecular Signaling Section; Scientific approaches to cholinergic circuits and aquarium hobby) Director, National Institute of Neurological neural-systems analysis in genetically Website: https://irp.nih.gov/pi/ Disorders and Stroke modified mice. Recently, we have expanded edwina-yeung Education: Harvard University, Cambridge, our research to include human studies of Massachusetts (A.B. in applied mild cognitive impairment. In this work, Research interests: My research aims to mathematics); Harvard Medical School, we are using a novel positron-emission understand the developmental origins of Boston (Ph.D. in physiology) tomography tracer of cholinergic neurons health and disease (DOHaD), a theory Training: Postdoctoral training with Gerald in the brain. that hypothesizes that a fetus’s adaptive D. Fischbach (who later became the director We are using new molecular genetic responses to a broad range of environ- of NINDS and served from 1998 to 2001) at approaches to dissect the role of cholinergic mental cues influence its long-term health. Harvard Medical School and at Washington modulation in the encoding of high- Specifically, I am examining the effects of University School of Medicine (St. Louis) salience memories. Detecting saliency infertility treatment, obesity during preg- Before coming to NIH: 2008–2018: State (the quality of something standing out or nancy, and their related comorbidities on University of New York (SUNY) Distin- being noticeable) facilitates learning and the “programming” of different health out- guished Professor and Chair, Department of survival by enabling organisms to focus comes including early childhood develop- Neurobiology and Behavior, College of Arts their perceptual and cognitive resources on ment and cardiometabolic risk. and Sciences and the Renaissance School the most pertinent subset of the available Most recently, a few studies have of Medicine, SUNY Stony Brook (Stony sensory data. examined the cardiometabolic health Brook, New York); co-director, Neurosci- We are also developing high-volume of children conceived by infertility ences Institute and co-director of SUNY imaging and computational approaches treatment. There is some indication that

18 THE NIH CATALYST MAY-JUNE 2019 COLLEAGUES NEWS YOU CAN USE

CONTINUED FROM PAGE 5 now collaborates with several commercial vascular alterations may have occurred partners through three CRADAs and three in the children who were conceived by agreements—including material-transfer licenses (other agreements are in the works). such treatments. The rationale remains agreements, collaborative agreements, Thanks to these partnerships, antibodies to unclear, but scientists hypothesize that the licensing agreements, clinical-trial target two cell-surface proteins, glypican-3 supraphysiological exposure to hormonal agreements, and cooperative research and (GPC3) on liver cancer cells and GPC2 treatment may be a potential mechanism. development agreements (CRADAs)—and on neuroblastoma cells, will likely begin As such, it is important to investigate by managing licenses and patents. in clinical trials this year. not only children conceived by assisted The offices can also help investigators Alternatively, an investigator may reproductive technologies but also children develop translational strategies and find need to reach out to their tech-transfer conceived by ovulation-induction methods. commercial partners. For example, NCI’s office before talking to a company about To this end, I have overseen the completion Technology Transfer Center (TTC) their ideas. This is certainly the case if they of the first phase of the Upstate KIDS acts as an “NIH version of Match.com” develop something that may be patentable. Study and continue to lead its prospective by advertising NIH technologies to the Once something is introduced to the follow-up. The Upstate KIDS Study is a extramural community and working to find public, whether by talk or publication, it large exposure-matched cohort from New the relevant industry partners to develop “starts a [patent] clock ticking,” said Mark York state that was formed to determine those ideas, explained Michael Salgaller, Rohrbaugh, NIH Special Advisor for whether children conceived by infertility supervisor of the Invention Development Technology Transfer. A patent must be treatments differ from their peers in and Marketing Unit in NCI’s TTC. filed in the United States within a year, growth and development. Yet many investigators aren’t aware of all but foreign rights are lost upon publication. There is increasing recognition that that tech-transfer offices can do for them. parental obesity may influence not only Challenges and Resources Every institute and center (IC) has a the metabolic health but also the cognitive Many of the ideas and inventions that come technology-transfer coordinator and access development of the child. We hypothesize out of NIH labs are very early in product to a technology-transfer office. Some ICs that exposure to increased inflammation development and sometimes too risky for have their own tech-transfer offices, whereas in utero may be the mechanism, but causal a commercial partner to be interested. But others are served by bigger ICs. For example, evidence is lacking. My research has also tech-transfer offices can help investigators the National Human Genome Research examined whether epigenetic differences overcome this hurdle. Some ICs, such as Institute has its own and so does the (specifically DNA methylation) exist and NCI, the National Institute of Neurological National Institute of Allergy and Infectious act as mediators of later health conditions. Disorders and Stroke, and the National Diseases. NCI’s TTC, which is the largest However, because DOHaD research has Center for Advancing Technology Sciences, tech-transfer center at NIH, serves nine traditionally focused on mothers, I am have special programs to move early-stage other ICs; the National Heart, Lung, and also leading a new initiative to look at technologies forward. Blood Institute serves six others. the father’s contribution. In an upcoming In 2018, NIH entered into 82 pregnancy cohort, we will examine the How Partnerships Begin CRADAs, executed 298 licenses to NIH effect of cardiometabolic health status of Partnerships between labs at NIH and inventions, and obtained 94 newly issued both parents on the neonatal health of commercial entities usually begin in one U.S. patents. But NIH “would like there to their offspring. of two ways. In one common scenario, a be more relationships” between NIH labs company may reach out to an investigator and industry, said Rohrbaugh. after reading their paper(s) or hearing a talk Investigators are encouraged to sit down at a scientific meeting. For example, several with their tech-transfer coordinators and companies approached NCI investigator describe their ideas, said Salgaller. “That’s Mitchell Ho after seeing posters presented the first step.” by his postdocs during the 2018 American Association for Cancer Research meeting To find your institute’s technology- in Chicago. Ho’s lab develops antibody- development coordinator, visit the Office of engineering technologies that target and Technology Transfer website at https://www. validate tumor antigens in solid tumors. He ott.nih.gov/tdcs.

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If you have a photo or World’s Largest Brain Scanner Delivered to NIH other graphic that reflects an aspect of life at NIH The world’s most powerful (including laboratory life) or magnetic-resonance-imaging (MRI) a quotation or confession that scanner was delivered to NIH in March scientists might appreciate and and installed in the NIH Clinical Center that would be fit to print in (Building 10). The 11.7-Tesla magnet, the space to the right, why not weighing 51 tons, was built in Italy, send it via e-mail: catalyst@ journeyed across the ocean by cargo nih.gov; fax: 301-402-4303; ship to Baltimore, and then transported or mail: The NIH Catalyst, by tractor-trailer truck to NIH. A huge Building 1, Room 333. crane gently lifted the scanner and slid it via a special trolley through an opening Also, we welcome “letters to in side of the building. Scientists hope the editor” for publication and the scanner’s high resolution will help your reactions to anything on bridge the gap between scanners and the Catalyst pages. microscopes and invasive electrode recording of neural activity. Clinical scanners are 1.5-Tesla and research READ MORE ARTICLES, AND scanners are typically 3-Tesla. NIH also EXPANDED VERSIONS OF THE has two 7-Tesla MRI scanners. But the ONES IN THIS ISSUE, ONLINE AT 11.7-Tesla scanner is the strongest. OD NGUYEN, DINH https://irp.nih.gov/catalyst/v27i3. For a video of the delivery, go to https://youtu.be/BeFoeBfKKL0.

PUBLISHER CONTRIBUTING WRITERS EDITORIAL ADVISORY BOARD The NIH Catalyst is published MICHAEL GOTTESMAN A. CROSS, A. HULLINGS CHRISTINA ANNUNZIATA, NCI bimonthly for and by the Deputy Director for Intramural Research, OD E.PETRUS DAN APPELLA, NIDDK intramural scientists at NIH. M. ROEGNER TREVOR ARCHER, NIEHS EDITORS M. SENGUPTA MICHAEL ESPEY, NCI Address correspondence to: JOHN I. GALLIN G. STORZ AUDRAY HARRIS, NIAID Building 60, Room 232, NIH Associate Director for Clnical Research J. WEAVER SUSAN LEITMAN, CC 1 Cloister Court Chief Scientific Officer, CC ONLINE: M. BROADFOOT, K. HOFF BERNARD MOSS, NIAID Bethesda, MD 20892 PAUL H. PLOTZ HYUN PARK, NCI Ph: 301-402-1449 Scientist Emeritus, NIAMS Fax: 301-402-1434 PHOTOGRAPHERS/ILLUSTRATORS EMILY PETRUS, NINDS (FELLOW) EDITOR-IN-CHIEF e-mail: [email protected] S. ANDRES AND S. WILLIAMS JULIE SEGRE, NHGRI LAURA STEPHENSON CARTER E.BRANSON ANDY SINGLETON, NIA The NIH Catalyst online: WRITER-EDITOR I. BROWNELL, L. MIAO, C. NAGAO GISELA STORZ, NICHD https://irp.nih.gov/catalyst CHRISTOPHER WANJEK R. DEVINE, J.H. KLUSS RONALD SUMMERS, CC Director of Communications, OIR D. NGUYEN, H.A. SATER RICHARD WYATT, OIR S. SIEVERT, B. VOISIN WEI YANG, NIDDK COPY EDITOR TECH TRANSFER CENTER, NCI SHAUNA ROBERTS