Summer 2020

Center for Clinical and Translational Science

e- e-NewsletterNewsletter

Center News The Hospital, IRB, and Center for Clinical and Translational Science All-Hands-On-Deck Response to the COVID-19 Pandemic By Barry Coller, MD In response to the COVID-19 Department, and the IRB, but every to isolate B lymphocyte cells making pandemic, all members of the Rockefeller program and department participated in broadly neutralizing antibodies to SARS- University clinical research enterprise a heroic effort to keep the Hospital open CoV-2 for therapeutic development. Dr. came together to re-engineer processes and functioning, despite the closure of Christian Gaebler, a Clinical Scholar and procedures to support exciting the University, during the height of the in Dr. Nussenzweig’s lab, describes his clinical and translational research to pandemic in City. This made role in the research in an article in this both better understand the of the it possible to arrange for the visits and eNewsletter as well. The success of that infection and develop effective therapies. blood collection from approximately project is a tribute to the dedication and In this issue of the CCTS eNewsletter, 160 volunteers who recovered bravery of the entire staff. articles highlight the efforts by the from COVID-19 as part of Michel Research Facilitation Office, the Nursing Nussenzweig’s lab’s important project Oluwadamilola “Lola” Fayanju, MD Leads Off Seminars in Clinical Research Initiative Focusing on Health Disparities By Barry Coller, MD Disparities among our Patients and the as a woman physician of color and her Doctors Who Treat Them. Dr. Fayanju penetrating insights call attention to serves as Associate Director, Disparities the challenges we face as a nation in and Value in Healthcare, Duke Forge, and addressing systemic racism. Dr. Fayanju Director of the Breast Clinic at the Durham trained in the Duke CTSA KL2 program Veteran’s Administration Medical Center. and now is pursuing her studies under Her presentation focused on the impact an NIH K08 grant. She has received of race on health and her rigorous many honors and is currently a National scholarship on the complex relationship Academy of Medicine (NAM) Emerging between race and socioeconomic status Leaders in Health and Medicine (ELHM) on participation in surgical studies of Scholar. The next speaker in the series Oluwadamilola “Lola” Fayanju breast cancer treatment. Dr. Fayanju’s will be Dr. Chibuzo Enemchukwu, a Dr. Oluwadamilola "Lola" Fayanju, publications span the fields of basic graduate of the Rockefeller University Assistant Professor of Surgery, Division advances in breast cancer therapy, health Center for Clinical and Translational of Surgical Oncology at disparities, and population health. Her Science Clinical Scholars program, delivered the first in a series of seminars 2019 commentary in the Journal of the whose research focuses on the use of pre- on health disparities on August 3rd, American Medical Association, Hiding exposure prophylactic therapy of HIV in entitled Beyond Us and Them: Eliminating in Plain Sight, recounts her experience vulnerable, at-risk populations $2.7M Award to Streamline Collecting Participant Feedback and Drive Improvement to the Clinical Research Enterprise By. Rhonda G. Kost, MD In May, the National Center for TR003206). Principal investigator Dr. on analysis methods and program Accelerating Clinical Translational Rhonda G. Kost, Associate Professor evaluation. Collaborating CTSA hubs Science (NCATS) granted a $2.7 Million in the Center for Clinical Translational for this award are , award to Rockefeller University to develop Science (CCTS), will lead a 6-site Johns Hopkins, Duke, University of new infrastructure facilitating collection collaboration to leverage the Rockefeller- Rochester, and Wake Forest University. of research participant feedback for developed Research Participant Why survey participants? widespread adoption: “Empowering Perception Survey (RPPS) into a new the Participant Voice: Collaborative low-friction informatics and analysis Partnering with patients and research Infrastructure and Validated Tools platform to support rapid collection participants, including those from for Collecting Participant Feedback of actionable participant feedback. Dr. communities disproportionately affected to Improve the Clinical Research Roger Vaughan, head of biostatistics at by health disparities, is essential to Enterprise (PAR-19-099, 1-U01- the Rockefeller CCTS, will collaborate conducting clinical translational research. continued on Page 16 1 The Clinical and Translational Research Facilitation Office Support of Rockefeller COVID-19 Research By Donna Brassil, MA, RN, CCRC The Clinical and Translational screening, which included obtaining a Tolerability, and Pharmacokinetics of Research Facilitation Office (CTRFO) medical history, including COVID-19 Orally Inhaled Hydroxychloroquine supported the development and symptoms. We also obtained telephone Sulfate in Healthy Adult Volunteers. operationalization of COVID studies consent and collectively conducted 63 of The time period from the initiation under conditions of University closure. the 166 participant visits to Rockefeller of Protocol Development Navigation We assisted numerous investigators University Hospital for the study to ACCTS/IRB approval and FDA in developing both clinical and (~38% of the screening visits). Arlene review was less than 2 months, which basic human research protocols and coordinated the study by preparing the is extraordinary for a Phase I study. helped to guide them through rapid medical records for each participant’s Numerous experts within the Center Advisory Committee for Clinical and outpatient visit, coordinating with for Clinical and Translational Science Translational Science (ACCTS) and the Nursing Department on projected (CCTS), Hospital, and University Institutional Review Board (IRB) participant enrollment to ensure an participated in this Navigation process. reviews. We would like to highlight two adequate supply of equipment needed IRB approval was granted on June 20th, of these studies. to collect the research samples, and the first participant was screened on June Arlene Hurley, MA, ANP-BC, CCRC arranging for campus parking for the 24th, and enrollment was completed on conducted Protocol Development study participants through coordination August 10th. Richard Hutt, RN, BA, Navigation of Davide Robbiani’s study, with the Hospital Facilities Specialist CCRC is coordinating this study, which Peripheral Blood of Coronavirus and University Security Department. includes strategizing goals with the Survivors to Identify Virus-Neutralizing Arlene performed internal monitoring sponsor, Pulmoquine Therapeutics, Inc., Antibodies. This COVID-related study of the 166 enrolled participants’ medical and the Contract Research Organization, was the one that saw the most participants records, including monitoring data Cliantha Research Ltd. Richard has on campus during the University regarding the participants’ permission been preparing for weekly external closure. Christian Gaebler, MD, a 3rd to share their research samples. This monitoring, which is being conducted year Clinical Scholar, is the Principal information was provided to Technology virtually. This has necessitated the Investigator of this study. There have Transfer Office and Office of General need for secure electronic platforms been many study amendments since Counsel to aid in their completion of a in which Richard has been uploading initial approval which have included the Material Transfer Agreement between all source documents and essential addition of 15 RU investigators from the Nussenzweig Lab and a start-up regulatory documentation in addition additional Labs on campus to share data company developing a Neutralizing to completing electronic Case Report and samples. To meet the enrollment Antibody assay. Forms and answering data queries. goals of the study team, the four The CTRFO Facilitators also guided Richard has also been performing Facilitators joined the research team Ohad Bentur, MD, a 3rd year Clinical Internal Monitoring. Dr. Bentur has to participate in study implementation Scholar in Dr. Coller’s Lab, through been exemplary as Principal Investigator and conduct of this study by remote the Translational Navigation Process of this complex study, demonstrating screening of the prescreened volunteers, to rapidly develop and implement his outstanding team leadership. and to conduct telephone consenting. study, Phase I Randomized Double Blind We were assigned to contact 193 Placebo Controlled, Single-Dose, Dose potential participants for remote Escalation Study to Evaluate the Safety,

Donna Brassil, MA, RN, CCRC Arlene Hurley, MA, ANP-BC, CCRC Kathleen Dowd, BSN, RN, CCRC Richard Hutt, RN, BA, CCRC

2 Challenges of Staffing the Nursing Department During the COVID-19 Pandemic By Rita K. Devine, RN, MPA The great coach Vince Lombardi the staffing required to maintain safe limited availability of staff, all scheduled once said “Build for your team a feeling participant care and protocol demands, COVID-19- related study visits were of oneness, of dependence upon one while adhering to our essential personnel completed as per the protocols. Several another and of strength to be derived by only policy. non-COVID studies could not be stopped unity.” The nursing staff of Rockefeller And everyone pitched in! Our because they required visits to assess the University Hospital has always worked as largest study required obtaining half- safety of already enrolled participants. a team but the COVID pandemic and the a-pint of blood from each of more As the COVID pandemic in New requirements and restrictions that came than 150 participants, so to scale up we York City evolves, we continue to with it presented new challenges to our needed to obtain samples from more function with the flexibility required to very small team. than one participant at a time. When maintain equilibrium between safe care The urgency to start new COVID we realized that we did not have enough of the research participants and fidelity protocols did not allow the usual luxury scales to measure the amount of blood to the research protocols while adhering of preparedness. Staffing, equipment, being drawn, the Rockefeller University to requirements and restrictions as education and discussion seemed Hospital Bionutrition department loaned mandated from the University and to happen overnight. Adhering to us their scales, along with the Krueger . The dedication of the Rockefeller University Hospital’s essential Lab, which also provided equipment to nursing staff members, who bravely put personnel policy required limited staff on mix the blood with the anticoagulant as their own health at risk in order to fulfill site. Daily communication between the it was being drawn. the University’s mission and perform research teams was required to determine As New York City was hit hard important studies to better understand how many research participants would by COVD-19, the nursing staff was and treat this terrible disease, reflects their be scheduled in addition to the length also affected. Several staff members professionalism, and is an inspiration for and complexity of each visit. Precision required quarantine and self-isolation us all. communication among the nursing staff and some could not return from abroad was required each day to determine because of travel restrictions. Despite the

Kari Bovee CRN & Tia Gareau CRN Jane Rodriguez CRN (OPU Charge Nurse) & Moz Murphy NA

Micahel Dyer, Hospital Facilities Specialist

Regina Butler CRN (IPU Charge Nurse), Tia Gareau CRN & Sonia Legister NA

CRN - Clinical Research Nurse Jill McCabe CRN, Nursing Clinical Operations IPU - Inpatient Unit Manager & Rita Devine MPA, R N, NA - Nursing Assistant Director of Nursing & Patient Care Services OPU - Outpatient Unit 3 Recruitment of Research Participants During the Height of the COVID-19 Pandemic By. Rhonda G. Kost, MD The Recruitment Core of the munities and the study unearthed an blink and were able to quickly determine Clinical Research Support Office (CRSO) enormous surge of altruism from people whether they were eligible, thus supple- provided the strategy, services, and hoping to help find a treatment or cure menting the hundreds of calls and con- operations to support recruitment for for COVID-19. The geographic distribu- versations provided by the recruitment COVID-19 studies at the Rockefeller tion of the more than 900 volunteers who team. This platform opened the door for University Hospital. In March, the responded and were pre-screened by the hosting other on-line activities requiring first study was from the Laboratory Recruitment core before referral to the a HIPAA-compliant and secure platform. of Molecular Immunology, led by Dr. Nussenzweig team for further screening In addition to the logistical Michel Nussenzweig, which required spanned Westchester, the Bronx, Man- challenges, pre-screening under COVID blood donations from individuals who hattan, Queens, Brooklyn, Long Island, identified a number of additional issues: recovered from COVID-19. An initial New Jersey, and Connecticut. Volunteers some individuals called seeking research challenge in planning recruitment was were aged 18-80, with most in their 40- enrollment as a means to obtain scarce the need for flexible eligibility criteria 60s, and roughly balanced between the COVID testing, some volunteers were as the team sought to identify which sexes. The Recruitment team creatively eager to donate convalescent plasma for clinical course (severe? moderate? and rapidly built surge capacity to handle therapeutic purposes as well as participate asymptomatic?) might predict a strong the call volume by training staff from oth- in research and were concerned about immune response. er cores as pre-screeners. This required the timing of contributing to multiple training in Human Subjects Protections medical efforts, many callers were eager to and the scripts of recruitment and the recount their experience with COVID-19 Research Volunteer Repository, provid- infection in case the clinical history would ing secure Zoom phone lines with Rock- help scientists, and some recounted a efeller caller id for remote workers, and dramatic clinical course consistent with creating REDCap intake forms and work- COVID but because of the lack of testing flow to integrate with other applications. could not enroll. Ultimately, there were The surge capacity staff included: Lisa many more eligible responders than Sacerio, Sharon Adams, Maritza Sanchez, could be studied, a tribute to the desire of Robert Hanson, Andrea Ronning, Glenis so many New Yorkers to come to the aid George-Alexander, Dacia Vasquez, Kim- of others . Between March 17th and April berly Vasquez, Anthoneth Jeffrey, and30th, approximately 1000 volunteers Marlyn Appleton. contacted the recruitment team through Driven by the CRSO leadership and the RUCARES voicemail or email; more Recruitment specialist Kadija the Hospital Information Technology than 650 met initial prescreen eligibility, Fofana, MPH, drafted advertisements for (IT) group, with support from Univer- and about 160 were enrolled into the social media, the internet, Rockefeller sity IT, Office of General Counsel, and study. platforms, and hard copy distribution in the IRB, new infrastructure was vetted The recruitment core also helped communities that were affected early by and rapidly put into place to allow volun- Clinical Scholar Dr. Ohad Bentur the virus. Dr. Nussenzweig appeared on teers to self-prescreen through an online successfully accrue the 10 healthy CNN, triggering inquiries from all over weblink hosted on a HIPAA-compliant, volunteers needed for his Phase I study of the country. secure Amazon web Services/REDCap inhaled aerosolized hydroxychloroquine. The research team hosted a Zoom platform. This is one of multiple exam- Recruitment for this study was readily Town Hall meeting to engage the index ples of the COVID-19 crisis accelerating achieved using campus advertising and community of New Rochelle and many the adoption of new processes. Hundreds the Research Volunteer Repository. inquiries followed. Word of mouth was of volunteers calling the 800RUCARES a powerful recruitment tool across com- line and RUCARES elected to use the we-

4 IRB Operations in the Time of COVID-19 By Vanessa Smith, MPS, CIP The Rockefeller University Institutional Review Board (RU IRB) reviews the ethical suitability of all research investigations in the University that involve human participants. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects. This includes all proposals for research as well as ongoing or long-term clinical research protocols. The RU IRB meets in person monthly to review and to approve, modify, or disapprove all research projects involving human participants. When the University began scaling down in-person operations on campus, the IRB Office responded by putting procedures in place to operate The Rockefeller University Institutional Review Board remotely under the skilled leadership Consultations were also had with other key individuals within the HRPP to of Thomas P. Sakmar, MD, Human industry experts to assist the HRPP in maintain open lines of communication. Research Protection Program (HRPP) responding as flexibily as possible while The IRB Office is sincerely grateful for Director and Sarah J. Schlesinger, MD, observing applicable regulations. the teamwork and dedication shown by IRB Chair. Working together, the IRB The IRB Office continues to operate all members of the Rockefeller Research Office, Clinical Research Support Office, Community to support the ethical conduct and Clinical Research Facilitation Office remotely and will do so for the duration of research. We are also very thankful to promptly issued guidance to the research of the pandemic to expeditiously review our IRB members, many of whom have community and IRB members to protocol submissions for current research been members for over a decade, who confirm HRPP operations would remain and assist with any new COVID-19 responded kindly to efforts of IRB Staff fully functional via remote procedures related clinical protocols. As seen in to hold virtual meetings. As always our during the pandemic. To support the the above photograph, monthly IRB first responsibility is the protection of transition to remote procedures, IRB meetings are being held via Zoom and Human Research Participants, but closely Specialists, Vanessa Smith, MPS, CIP will continue until guidance is issued following is our mandate to advance the and Dale Miller, BA, CIP reviewed that it is safe to resume these activities University’s research. The critical nature guidance issued by the Office of Human on campus. IRB Leadership and Staff of this work is especially important now Research Protections and Food and Drug continue to work in close liaison with the and it could not be done without the Administration to become informed Clinical Research Support Office, Clinical excellent teamwork and dedication of the about recommendations for IRB review Research Facilitation Office, Hospital Rockefeller Research Community of research during the pandemic. Informatics, University IT, and many Update on Implementation of the Cerner Electronic Health Record at The Rockefeller University Hospital By Prasanth Manukonda, MS, MA & Maija Neville Williams, MPH The Rockefeller University Hospital Memorial Sloan Kettering Cancer national data sharing initiatives. is continuing implementation of Cerner Center (MSKCC) and LabCorp. Once Once Cerner CommunityWorks is CommunityWorks as our Electronic the system is live, we will be able to fully implemented it will improve quality Health Record (EHR). Unfortunately, order labs from MSKCC and LabCorp and efficiency internally, streamlining when the COVID-19 pandemic hit the through Cerner. We will also be ready operations and promoting national nation in March, our go live date was for data sharing with Healthix, the New patient safety initiatives. Below is the pushed back from April 2020 to February York Health Information Exchange, the revised implementation schedule. 2021. Hospital staff are working diligently national CTSA consortium, and other with Cerner during this difficult time, continuing departmental training and competency review in preparation for our next Integration Testing event. The goal of this event is to validate the solution build and additional integration points like Powerplan, Registration and Scheduling, Analytics, and integration of iRIS and Cerner. One new feature we have been working on during the pandemic is the integration of laboratory tests from 5 Rockefeller Clinical Scholars to Evaluate New Interactive Web-based Individual Development Plan Platform By Editorial Staff An individual development plan Scholars. To address this shortcoming the scholars to map out their career (IDP) is a tool to assist trainees with the Clinical Scholars program leadership plans, generate timelines and Gantt establishing and achieving their career has partnered with the University of charts, and communicate effectively goals, both in the short and long term. By Pittsburgh’s Clinical and Translational with their mentoring teams to ultimately providing an opportunity for reflection Science Institute by participating in achieve their goals. Trainees, mentors, and an analysis of one’s strengths and a cluster-randomized study they are and program administrators have weaknesses, as well as one’s interests and leading comparing the AAAS IDP to the access to the interactive CCDP, thus aspirations, it can help build pathways to KL2 Customized Career Development serving as an efficient communication success and professional satisfaction. Platform (CCDP) they have developed tool. Thus, the online format makes the The Clinical Scholars program to assist Scholars in developing their CDDP a dynamic tool, enabling real- has used the American Association for careers. Unlike the AAAS IDP, which time accessibility for the Clinical Scholar the Advancement of Science (AAAS) is a single questionnaire, the CDDP is to modify the CCDP as plans change. IDP. Since it was designed for use by an online platform that enables trainees Scholars are currently enrolling in the postdoctoral fellows in the sciences, it to document competency-based goals, CDDP and we look forward to their does not address all of the topics and objectives, and milestones related to feedback and their mentors’ feedback on competencies of interest to Clinical research and career progress. This allows using this exciting new educational tool.

Heilbrunn Family Center for Research Nursing Heilbrunn Scholar Symposium By Bernadette ‘Candy’ Capili, PhD, NP-C Each year, the Heilbrunn Family job satisfaction, and intention to leave adherence to medical therapies, LVAD- Center for Research Nursing hosts a their current position. Results from her related complications, and health care symposium at Rockefeller University to cross-sectional survey (n=333) showed utilization. Dr. Rose Mary Xavier, an showcase the research conducted by the that burnout was significantly associated Assistant Professor at the University of Heilbrunn Nurse Scholar awardees. The with job satisfaction, and effective co- North Carolina-Chapel Hill, discussed Scholars meet virtual each month during management of patients with a colleague her work on leveraging novel tools from their award period, but the symposium reduced provider burnout. network science, bioinformatics, and provides an opportunity for the Nurse Dr. Mitchell Knisely, an assistant integrating multiplex high-dimensional Scholars to meet each other in person professor at Duke University, discussed data types (genetics, imaging, cognitive, and share their research and professional his on-going research characterizing the and symptom data). Her goal is to development experiences. genetic pain profiles of participants with identify neuro-biologically informed Due to the COVID-19 pandemic, we sickle cell disease. He is determining psychosis and schizophrenia symptom held two separate virtual 2020 symposia whether functional polymorphisms profiles among adolescents. Ms. Maura on May 7 and May 21. Attendees in candidate (i.e., IL-1B, IL-6, & McCall, a doctoral candidate from the included members of the Rockefeller TNF-α) are associated with pain subgroup , discussed her University Hospital, Rockefeller nurses, membership. Dr. Karen Jennings-Mathis, project to identify temporal patterns nursing faculty from the Tri-State Area, an assistant professor at the University of and relationships of aromatase inhibitor Nurse Scholars’ mentors, and the Nurse Rhode Island, presented her on-going (AI) adherence and symptoms among Scholars’ study team members. research to investigate the relationship postmenopausal women with early-stage The topics for the symposium ranged between early-life adversity, adipokine breast cancer. She will also explore the from primary care provider burnout to status, dietary intake, and physical health role of genotypic variation in temporal aromatase inhibitor adherence. On May among adults. patterns and relationships for AI 7, Drs. Norful, Knisely, and Jennings- On May 21, 2020, Drs. Casida and adherence and symptoms. Mathis presented. Dr. Allison Norful, Xavier and Ms. McCall presented. Dr. In closing, the discussions were an assistant professor from Columbia Jessie Casida, an Associate Professor at robust and engaging. The virtual platform University, discussed the impact of , described was well-received by nurse scholars and primary care providers (physicians, the development of a self-care app for attendees. nurse practitioners, and physician a left-ventricular assist device (LVAD). assistants) co-managing patients with He aims to evaluate the effect of using other clinicians on rates of burnout, the app on patients’ self-efficacy, CTSA Discussion Forum for Nurses in Translational Research By Bernadette ‘Candy’ Capili, PhD, NP-C In March 2020, Dr. Capili, Director to provide a mechanism for nurses at Inaugural members of the group include of the Heilbrunn Family Center for CTSAs to connect, communicate, and Dr. Chris Kovner from New York Research Nursing, led the creation of collaborate. The goals of the DF include University, Dr. Margaret Barton-Burke a Discussion Forum (DF) for nurses discussing emerging topics related to from Memorial Sloan Kettering, and in translational research, under the translational nursing and addressing gaps Dr. Olga Jarrin-Montaner from Rutgers auspices of the CTSA Program Steering in training and education by developing University. Committee. The purpose of the DF is collaborative projects across CTSA hubs.

6 Rockefeller Tops International Ranking of Scientific Research Publication Impact The Rockefeller University website The Centre for Science and Technology for differences between scientific fields in proportion of publications in the top one Studies Leiden rankings of over 1100 citation and collaboration practices. The percent. In fact, 5.5 percent of Rockefeller universities from 65 countries ranked Leiden group found that 33.3 percent publications were considered extremely Rockefeller number one, with the high- of Rockefeller publications were among high impact by this metric. The figure est percentage of frequently cited scien- the top 10 percent most widely cited of for the other institutions in the top-five tific publications as a proportion of the all scientific publications during the time group range from 4.3 to 3.3 percent. total number of its publications. The period studied, 2015 to 2018. Rockefeller Leiden Ranking’s methodology accounts was also ranked first when measuring the All Sciences

Biomedical and Health Sciences

Re-imagining Biostatistical Education – A Combined Course in Critical Thinking, Biostatistics, Scientific Writing, Leadership and Team Science, and Rigor, Reproducibility, and Reporting (R3) By Roger Vaughan, MS, DrPH For over a decade, Rockefeller has point, and an articulated hypothesis as a to interrogate their hypotheses; under- taken a novel approach to biostatistical scaffold, through which we can develop, stand limitations and meaning of results; education in the Clinical Scholars pro- experience, and practice the other skills, describe the results in a way suitable for gram, by presenting information “from including critical thinking, team science the Peer Review process, Study Section, the driver’s seat” perspective rather than and leadership, principles of replicability, or oral communication. We will peri- through a traditional “bottom up” statis- and clear reporting. odically convene as a group to present to tical approach. The biostatistics educa- Rather than creating multiple discrete each other our progress, new methodol- tional program is ready to pivot again, in courses to attend to these related and ogy, results, challenges, and next steps. content and approach, to acknowledge critical skill sets, the re-imagined biosta- These will also serve as mock Peer Review the simultaneous skill sets necessary to tistics course will employ some proven and Study Section sessions (better to get do great science. “flipped classroom” methodology to beaten up by friends…). Each step will be infused with principles of Rigor, Repro- CAPITALIZING ON COMPLEXITY keep all elements alive as the course pro- gresses. We will first ask the incoming ducibility and Team Science. It is becoming increasingly clear that Clinical Scholars to do some basic review There are likely no better real world the hard and soft skills necessary to con- over the summer to refresh them on the vehicles than following a manuscript ceptualize, operationalize, design, man- fundamentals of design and methodol- through the Peer Review process, or age, lead, analyze, communicate, and ogy. We will then do a three-day inten- shadowing a grant through the study replicate – just a sampling of the skills sive concentrated review of the elements section process, to practice, hone, and sets necessary to interrogate a hypoth- of the inferential method and the bases appreciate how important Team Science esis, are not applied serially across the of statistical tests. At the conclusion of and Leadership skills are, how essential life of a project – they are spherical, you the review, each Scholar will articulate clear articulation and presentation skills need them all, and all at once, at all phas- a hypothesis, perhaps one they came to are, and how rock solid methodology and es of an investigation, and in a success- Rockefeller to study, perhaps a practice critical thinking is, to advancing science. ful research career. The new approach placeholder. Using this hypothesis, we We are very excited about the upcoming to biostatistical education attempts to will then use an ongoing series of indi- year. respect that reality. As a sphere, there vidual sessions to: take a deep dive into is no ”starting point”, but we use the el- designs appropriate for their hypotheses; ements of biostatistics as a jumping in develop a suite of analytic tools necessary

7 New Clinical Scholars Join the Center for Clinical and Translational Science By Editorial Staff

On July 1, 2020 five new Clinical Scholars joined the Rockefeller University Clinical Scholars Program. They are Drs. Yelina Alvarez, Charlie Buffie, Katherine Knorr, Mira Patel, and Rashid Rumah.

New Scholar orientation takes place the first Wednesday in July. The orientation is usually in-person for the Scholars and the Clinical Scholars program leadership meet and get to know each other as the curriculum and goals for the Scholars are reviewed and discussed. This year’s orientation was virtual to adhere to the social distancing requirements, but the engagement and interest in the program and for each other was just as interactive as past orientation. Please join us in welcoming the incoming Clinical Scholars.

Yelina Alvarez, MD, PhD Mentors: Daniel Mucida, PhD Laboratory: Laboratory of Mucosal Immunology

Research Interest: Dr. Yelina Alvarez’s research focuses on understanding the mucosal immune system and how it communicates with the rest of the resident cells and microbiota and how dysfunctional interactions can lead to human diseases such as functional disorders and inflammatory bowel disease.

Bio: Dr. Alvarez received her MD and PhD from the School of Medicine. She completed her internal medicine residency at New York University and gastroenterology fellowship at the Hospital of the University of Pennsylvania.

Charlie Buffie, MD, PhD Mentors: Sean Brady, PhD Laboratory: Laboratory of Genetically Encoded Small Molecules

Research Interest: Dr. Charlie Buffie uses a variety of in vitro screening approaches and animal model systems to elucidate the identity and function of genetically-encoded small molecules made by native intestinal bacterial populations, with special attention to the prevalence and abundance of these metabolites in human subjects.

Bio: Dr. Buffie received his PhD from Weill Cornell and his MD from Weill Cornell Medical College. Dr. Buffie completed his internal medicine residency and is completing his Gastroenterology & Hepatology Fellowship at New York-Presbyterian Hospital/.

Katherine Knorr, MD, PhD Mentors: Jeffrey Ravetch, MD, PhD Laboratory: Leonard Wagner Laboratory of Molecular Genetics and Immunology

Research Interest: Dr. Katherine Knorr’s research focuses on research involves defining patterns of aberrant spliceosome protein snRNP500 expression on the surface of malignant myeloid cells. Expression of this protein correlates with durable responses after allogeneic stem cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome. The proposed mechanism of response involves formation of antibodies against the snRNP500 protein.

Bio: Dr. Knorr received her MD and PhD from the . Dr. Knorr completed her internal medicine residency at New York-Presbyterian Hospital/Weill Cornell Medicine and is completing her Oncology Fellowship at Memorial Sloan Ketterin gCancer Center.

continued on Page 9

8 New Clinical Scholars Join the Center for Clinical and Translational Science By Editorial Staff continued from Page 8 Mira Patel, MD Mentor: Dr. Sohail Tavazoie Laboratory: Elizabeth and Vincent Meyer Laboratory of Systems Cancer

Research Interest: Dr. Mira Patel studies the role of immunosurveillance in mechanisms of cancer progression and metastasis, particularly as it relates to germline genetic variants that may predispose to metastatic disease.

Bio: Dr. Patel received her MD from Johns Hopkins University School of Medicine. Dr. Patel completed her Otolaryngology-Head and Neck Surgery at Washington University in St. Louis/ Barnes-Jewish Hospital and is completing her radiation oncology residency at Memorial Sloan Kettering Cancer Center.

Rashid Rumah, MD, PhD Mentors: Vincent Fischetti, PhD Laboratory: Laboratory of Bacterial Pathogenesis and Immunology

Research Interest: Dr. Rashid Rumah’s research focuses on how the gut-brain axis contributes to serious neurological diseases of unknown origin, including multiple sclerosis (MS) and Sudden Infant Death Syndrome (SIDS).

Bio: Dr. Rumah received his MD from Weill Cornell Medical College and his PhD from the Rockefeller University.

CCTS Biostatistics Group Supports a Broad Range of Rockefeller Scholarship By Roger Vaughan, MS, DrPH The mission of the Rockefeller Uni- took the entire CCTS Team to support began as a result of revision requests from versity Center for Clinical and Transla- each publication. the peer review process, where reviewers tional Science (CCTS) is to support high As part of its educational program, rated the quality of the science as high, quality, translational science, and educate but had concerns about the analytic outstanding translational scientists in the the Biostatistics group reinforces approach or methods. As data becomes Clinical Scholars program. the importance of Team Science and more complex, as journals become more emphasizes the value of including a One of the outcome metrics of the re- highly aware of reproducibility and methodologist as early as possible during validity issues, and as reviewers become search support is peer reviewed publica- research protocol development. This more analytically sophisticated, it is tions enabled by the CCTS. To that end, is coupled with a major emphasis on increasingly important that the analytics the CCTS Biostatistics Group, directed by Rigor, Reproducibility, and Reporting be of the highest quality and follow the Dr. Roger Vaughan, and including senior (R3), a new CCTS initiative, to insure the R3 principles. biostatistician Caroline Jiang and statisti- integrity of the research and its reporting. cal programmer Neha Singh, have recent- It is gratifying, therefore, that so many The CCTS Biostatistics group ly co-authored or been acknowledged on of the papers have a current of former remains eager to assist with grant and a series of important publications, as list- Clinical Scholar first authors. manuscript preparations, so please feel free to contact Dr. Vaughan at roger. ed below, in high impact journals. While Many of the collaborations between members of the biostatistics group may [email protected] have been included or acknowledged, it the Biostatistics group and investigators

Select publications: Becher T, Palanisamy S, Kramer D, Eljalby M, Marx S, Wibmer A, Butler S, Jiang C, Vaughan R, Schöder H, Mark A and Cohen P. Brown adipose tissue is associated with improved cardiometabolic health in humans. Nature Medicine, 2020, in press.

Pressl C, Jiang C, Correa Da Rosa J, Friedrich M, Vaughan R, Freiwald W, Tobin J. Interrogating an ICD coded electronic health records database to characterize the epidemiology of prosopagnosia. J Clin Trans Sci., In Press.

Orange D, Yao V, Sawicka K, Fak J, Frank M, Parveen S, Blachere N, Hale C, Zhang F, Raychaudhuri S, Troyanskaya O, Darnell R. RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares. N Engl J Med 2020;383:218-28.

Khodursky S, Svetec N, Durkin S, Zhao L. The evolution of sex-biased expression in the Drosophila brain. Genome Res. gr.259069.119. Published in Advance June 18, 2020 9 Meet the Graduate: Tukisa D. Smith, MD, MS By Editorial Staff strains isolated from patients. It was also thought to contribute to various at that moment that Dr. Smith knew immune mediated diseases. her career path would be in the field of Her latest research project is focused understanding host immune responses on understanding whether patients against microorganisms rather than with HAE are at increased risk of antimicrobial development. It was this COVID-19-related complications, pathway that lead her to medical school some of which may also involve the and subsequently into the field of bradykinin pathway. Some have Allergy and Immunology. Throughout speculated that HAE patients who are her training she was consistently drawn treated with drugs to counteract the to translational research focused on bradykinin pathway may be protected Tukisa Smith understanding disease outcomes in from COVID-19 complications. Dr. Tukisa Smith joined the Clinical patients with immunodeficiencies and immune dysregulation. When asked to share her expectation Scholars program at the Rockefeller and experiences in the Clinical University in 2018. Dr. Tukisa During her final year in fellowship, her Scholars, Dr. Smith replied: Smith received her M.D. from Saint mentor, Dr. Charlotte Cunningham- “I entered the program expecting Louis University and completed Rundles at Mount Sinai, encouraged that I would learn new skillsets as a her internal medicine residency at her to think outside of the box and clinical researcher. I left the program SUNY Downstate. She completed her take time off to conduct translational transformed. I learned the various ways Allergy and Immunology fellowship research. Coincidentally, Dr. Barry by which I could fashion my career at the Icahn School of Medicine at Coller had sent her an email regarding where I can wear multiple hats including Mount Sinai and is a diplomate of the KL2 Clinical Scholars program. Dr. that of a physician, translational the American Board of Allergy and Smith applied to the Clinical Scholars researcher, biotechnologist and Immunology. program, and after interviewing with entrepreneur, patient advocate, and Dr. Smith’s interest in research various heads of lab, she was invited policy influencer. I learned the most peaked during her junior year in to join the Laboratory of Biochemical from my fellow Clinical Scholars, college. As a double major in business Genetics and Metabolism headed who are some of the greatest minds and science, while working as an by Dr. . Dr. Smith was in a wide range of disciplines. Active Organic Chemistry teaching assistant, also co-mentored by Dr. Manish dialogue with my colleagues allowed she realized that the laboratory Ponda, Assistant Professor in the me to become inspired and passionate environment was a welcome contrast Breslow Laboratory and a graduate about my research and I would often from the business school, as it provided of the Clinical Scholars program. It gain inspiration from their work, an exciting opportunity for exercising was a unique opportunity to work commitment, and drive. with scientists outside of her area of precision in experimental design The best part of the program and, execution. There were ritualistic expertise and learn new approaches to understanding immune responses was the opportunity to engage aspects of maintaining a laboratory with world experts in various fields and the demand for perfection and related to the coagulation factor XII contact system, which is a part of the and to hear about their stories and order was appealing. Her interest in career trajectories. Dining with such research was further developed when innate immune system with a role in adaptive immune responses. individuals was truly a privilege that she prepared for experiments that most are not afforded and those are related to the biochemistry of disease Dr. Smith’s research has focused on moments I will always remember. mechanism. a rare autosomal dominant disease I would describe the program, Since Dr. Smith was not a traditional called Hereditary Angioedema (HAE), specifically at Rockefeller University, premed or biology major, she was not clinically characterized by attacks of as one of a kind.” swelling involving the subcutaneous aware of a career path in which one As a recent graduate of the program could become a researcher focused tissue and mucous membranes. HAE attacks are unpredictable, often and now Assistant Professor of on disease mechanism. Given her Medicine at the University, San Diego, deepened interest in research, she extremely painful or disfiguring; when they occur in the neck they can lead to Dr. Smith was asked for her advice to joined the NIH Postbaccalaureate current Clinical Scholars: Intramural Research Training program asphyxiation and death. Most patients have either a quantitative or qualitative “I would say take advantage of at Johns Hopkins in the Division of all opportunities afforded through Infectious Diseases and matriculated abnormality in the major inhibitor of the contact system, C1 esterase the program. Various seminars and into the graduate program in workshops might not directly coincide molecular biology with an emphasis in inhibitor. Dr. Smith is particularly interested in the group of patients with with your research interests; however, biotechnology. She had a natural knack you will be surprised how keeping an at bioassay development and was HAE who have normal C1 inhibitor level and function, also known as HAE‐ open mind will impact your research fascinated with microorganism drug and approach to problem solving. I resistance mechanisms. She recalls her nl‐C1INH, since in most cases, the mechanism is not known. She is also have taken away many learning points growing concern about the dangers of that have equipped me in my present antibiotic resistance when she studied interested in therapeutic development related to the bradykinin pathway, role as a professor, physician, and the minimal inhibitory concentrations clinical and translational researcher.” of antibiotics for various bacterial which is involved in HAE, since it is

10 Meet the Scholar: Christian Gaebler, MD By Editorial Staff Dr. Gaebler’s current research focuses research participants was beyond impres- on the HIV latent reservoir and how the sive!” treatment with anti-HIV broadly neutral- Dr. Gaebler was asked to describe his izing antibodies developed by Dr. Nus- experience in the Clinical Scholars pro- senzweig’s lab impacts the HIV-reservoir. gram, focusing on his expectations when Recently, he shifted some of his efforts joining the program, what he is looking to studying SARS-CoV-2. In fact, since forward to as Co-chief Scholar this year, April 1, his lab has recruited more than and his plans for when he graduates the 150 COVID-19 convalescent individuals program. and studied the SARS- CoV-2 specific “I was hoping for a stimulating and immune responses in these individuals. well-mentored research environment in a He and his colleagues have also identi- group of peers with the same background, Christian Gaebler fied distinct antibodies that neutralize the concerns, and career planning questions. virus very potently and several of these Dr. Christian Gaebler joined the Clin- My expectations were met a thousand are being further developed as therapeu- ical Scholars program at the Rockefeller times, and I am extremely grateful for the tic and preventive drugs. (https://www. University in 2018. He received his MD opportunity that this program has given rockefeller.edu/news/28079-covid19-an- from the Charité-Universitaetsmedizin me. Often I have to remind myself that tibody-response/) in Germany and completed his internal this is real and pinch myself when we are medicine and infectious disease resi- With his shift to SARS-CoV-2 re- for example eating lunch and having sci- dency at the same distinguished institu- search came challenges and opportuni- entific discussions with an expert of his tion. He currently is a third year Clinical ties. When asked to reflect on theses, Dr. field. The whole program is a learning -op Scholar and serves as Co-chief Clinical Gaebler responded: portunity. It is hard to point out specific Scholar. “The pandemic required us to shift occasions. As a medical student, Dr. Gaebler our focus on a completely new research As Co-chief Scholar I am hoping to quickly realized how little is known subject and work with unprecedented ur- give back and contribute to the program about the of disease and gency and speed. At the same time, the in a way that we make the best of the cur- in many cases even less about the mecha- difficulties outside of the lab and especial- rent challenges and create a curriculum nism of successful treatments. He found ly the abrupt shortfall of any support sys- that is valuable for all current Scholars. this disappointing but intriguing which tem, especially with regard to child care, The recent months and the challenges of inspired him to learn the pathophysiol- were overwhelming. The challenge of my COVID-19. have been the most educa- ogy of disease with the intent of discov- wife and I both being essential workers tional. ering new treatments. and working full time (and often more The most valuable aspects of the Clini- Complex systems, such as the nervous intensely and longer than ever) while also cal Scholars program are the protected system and the immune system, espe- taking care of our 2-year-old toddler at time, the endless teaching and learning cially fascinated Dr. Gaebler and so he the same time was physically and psycho- opportunities, and the strong mentor- logically extremely tough.” was attracted to immunology research ship. The highlights were the experience of in Dr. Michel Nussenzweig’s Laboratory After I graduate, I hope to stay a bit of Molecular Immunology at Rockefeller everyone coming together and working longer in New York and at Rockefeller University. He interviewed with Dr. Nus- towards one goal. The motivation and to keep working on our clinical trials on senzweig and was invited to join his lab. dedication of everyone, including our COVID-19 and HIV. “ R3 Enhancing Scientific Rigor, Reproducibility, and Reporting Series The R3 Enhancing Scientific Rigor, Reproducibility, and Reporting Methodology Series will start September 24, 2020 and Roger Vaughan, MS, DrPH, Director of Biostatistics will be the first speaker of the series. In a joint effort between the CCTS, University IT, and the Markus Library, The Rockefeller University has created the “R3 -Enhancing Scientific Rigor, Reproduc- ibility, and Reporting” seminar series designed to help improve reproducibility in science, by presenting advances across a range issues including, Data Storage and Repositories, Statistical Analysis, Pipeline Documentation, and Drug Formulation. The series will be via Zoom from 2:00 PM - 3:00 PM

Methodology Series dates September 24, 2020 February 18, 2021 October 22, 2020 March 18, 2021 November 19, 2020 April 15, 2021 December 17, 2020 May 20, 2021 January 21, 2021

11 How The Kidney Reacts to Nutritional Changes By Dana Bielopolski, MD, PhD Hypertension is a disease of which DASH achieves its effect is not 1 hypertensive volunteers to a high the westernized world, as it stems understood. The overall goal of my project potassium and low sodium DASH diet from lifestyle habits: salt and alcohol is to learn more about its mechanism. will change the composition of renal ion consumption, lack of physical activity, One hypothesis is that the additive channel in an aldosterone-dependent smoking, and obesity. Since publication affect is attributed to the increasing the manner, leading to excretion of both of the original Dietary Approach to Stop consumption of potassium. sodium and potassium and a reduction Hypertension (DASH) diet study in 1997 Observational studies highlight in blood pressure. many additional controlled studies have the role of potassium in preventing The aims of the study are to 1) demonstrated the clinical efficacy of the stroke, reducing blood pressure and characterize urinary exosomes before and DASH diet to meaningfully lower blood cardiovascular morbidity, and protecting during the DASH diet, and 2) validate pressure. the kidneys from damage caused by the urinary sodium/potassium ratio as The DASH diet emphasizes fruits, hypertension. But how does potassium a measure of DASH adherence. We are vegetables, and low-fat dairy products exert its beneficial effect? Potassium is recruiting ten healthy volunteers with and is reduced in fat and cholesterol. the trigger for release of aldosterone, a relatively mild (stage 1) hypertension It is exceedingly unlikely that a “magic hormone, from the adrenal glands that and they will consume the DASH diet as nutrient” can explain its additive effect results in excretion of the additional inpatients at the Rockefeller University over simply a low salt diet. Rather the potassium. Potassium excretion obligates Hospital for two weeks. Participants impressive BP reductions reported are sodium excretion, so, potassium acts like will undergo daily blood pressure best interpreted as a combined effect a diuretic drug, but without drug side measurements, daily blood and urine from multiple dietary factors rather than effects. To assess whether the DASH sample collection, 24-h urine collection, the effects of a single factor. Lower salt diet results in aldosterone-induced and 24-h ambulatory blood pressure consumption reduces blood pressure, but changes in ion channel composition in monitoring (ABPM). the DASH diet is much more effective, the kidneys’ epithelium, we will monitor The diagram below summarizes lowering blood pressure as efficiently as urine exosomes, which contain epithelial the causal pathway we propose to one anti-hypertensive drug. cell membranes. characterize the mechanism of the DASH Certain dietary patterns have been Traditionally, adherence to the diet, underscored by a list of performance associated with low BP. Observational DASH diet has been evaluated using indicators we will measure to test the studies and clinical trials have associated questionnaires, but we have learned hypothesis. vegetarian diets with lower BP, yet the that patients commonly underreport the The menu was planned based upon nutrients responsible for the BP-lowering amount of sodium they consume. One the guidelines of the National Heart effects of these diets have remained of the great strengths of the Rockefeller Blood and Lung Institute (NHBLI) of the uncertain. Attention has focused on University Hospital staff’s extensiveNational Institute of Health (NIH). macronutrients (particularly the type experience in conducting long-term, in- In designing the study, our and amount of fat), micronutrients hospital nutritional studies with research challenges were to meet the diet (potassium, magnesium, and calcium), volunteers, is that we can monitor requirements while making the menu and fiber. However, data fromcarefully food intake and collect biologic palatable and appealing. The main observational studies and small-scale samples to independently assess dietary differences from the American style diet trials have been extremely inconsistent. adherence, outcomes, and mechanisms. are the low salt (2.3 grams of sodium The precise mechanism through We hypothesize that exposing stage recommended compared to more than

continued on Page 13

12 How The Kidney Reacts to Nutritional Changes continued from Page 12 4.5 grams in a typical American diet) and and staff and patient safety. These nutrition influences blood pressure the high potassium. To achieve these include asking participants to complete and potentially lead the way to new goals, the DASH diet has an abundance a symptom survey prior to arrival on therapeutics that target ion channels. of fruits and vegetables. To avoiding the campus and testing for the virus before We also hope that by introducing potential confounding effect of weight admission. our participants to better nutritional reduction on blood pressure, we also had The first participant was enrolled on choices we will be able to not only to calculate caloric intake to maintain June 14th, 2020. Below is an example reduce their blood pressure during the weight stability throughout the study. of the impact the diet had on the intervention, but help them to carry The clinical protocol was developed participant’s 24-hour ambulatory blood the lessons home, modify their lifestyle, with assistance from many Rockefeller pressure. The most dramatic change continuing eating a healthier diet after Center for Clinical and Translational is during sleep where the participant’s the study, and sustaining the lower blood Science (CCTS) and Hospital staff under blood pressure decreased from 120/74 to pressure without requiring medication. the Translational Research Navigation 109/67 mmHg. This enhanced “nocturnal This article affords me a great process. Under the ongoing threat of dipping” is associated with improved opportunity to thank the great staff of COVID-19, the protocol was interrupted cardiovascular health and reduced all- the Rockefeller University Hospital, just as it began, and to resume, had to be cause mortality. the Navigation team, and the Clinical re-Navigated to incorporate the new rules Understanding the mechanism Research Support Office headed by Dr and challenges related to risk assessment, underlying the DASH diet may shed Rhonda Kost, who made this trial come to social distancing, SARS-CoV-2 testing, light on the physiologic process by which life with the reopening of the University.

24-hour Ambulatory Blood Pressure Monitoring. A: Baseline, B: Day 11.

A

B

13 The Time-Restricted-feeding effects on Inflammation and Obesity (TRIO) Study By José O. Alemán MD PhD The impact of early time restricted feeding on metabolism and inflammation in obesity

Time Restricted Feeding (TRF) is a form of intermittent fasting that confines food intake to active daytime hours and involves fasting for 12 to 14 hours. Circadian misalignment caused by changes in sleeping and eating behaviors has emerged as having a detrimental impact on weight, glucose metabolism, and other cardiovascular disease- related outcomes. Feeding during active periods appears to be advantageous for weight, glucose metabolism and related outcomes whereas feeding during the inactive period confers deleterious effects on these outcomes. Therefore, TRF shows great promise as a novel intervention for addressing obesity and related Figure 1: Schematic of Proposed measurements in the TRIO study. Under cardiovascular outcomes. To address this Usual Feeding Pattern (UFP), glucose levels alternate with meal consumption, potential, we are conducting a randomized preventing ketogenesis and contributing to stable soluble RAGE levels. Under 7-day isocaloric crossover feeding study Time Restricted Feeding (TRF), overnight fasting enables glucose depletion titled “The Time-Restricted-feeding and ketogenesis, decreasing inflammation, soluble RAGE (sRAGE) over the effects on Inflammation and Obesity” length of the clinical study. (TRIO), in humans with prediabetes and obesity. We will study the effect of the most notable of which is the long-term weight loss and maintenance, restricting the timing of caloric intake Receptor for Advanced Glycation End- but the dynamics of sRAGE within each to earlier in the day (TRF) versus later in Products (RAGE) signaling pathway, circadian rhythm are not well understood. the day (usual feeding pattern, UFP) on and treating obesity will decrease this We hypothesize that decreased glucose glucose levels and inflammation.. form of inflammation. However, we and AGEs would decrease signaling In the TRIO study Dr. Jose Aleman, lack interventions to decrease this form through the RAGE pathway, and over 7 a graduate fo the Clinical Scholars of systemic inflammation when weight days lead to a reduction in sRAGE with program who is now Assistant Professor is stable, such as when maintaining TRF, which has not been tested previously of Medicine at NYU, will explore the weight after bariatric surgery. Activation in the context of a detailed feeding study. impact of TRF on systemic inflammation of the RAGE pathway can be assessed Through the proposed metabolomic and shifts in glucose metabolism over 1 by measurements of soluble RAGE analysis, we will be able to measure AGEs week, as well as its effects on surrogate (sRAGE), an inhibitor of the pathway. in the context of this detailed dietary markers of diabetes and cardiovascular We hypothesize that the downstream intervention, linking timing of feeding disease while weight remains stable. Dr. consequences of RAGE activation are directly to RAGE signaling. Jan Breslow, Head of the Laboratory of reductions in energy expenditure and The study will enroll 10 persons with Biochemical Genetics and Metabolism, glucose tolerance, increased white blood obesity (BMI>30 kg/m2) and prediabe- will serve as Co-PI. cell (WBC) counts and inflammatory tes (HbA1c 5.7-6.4%) and randomize Animal studies suggest that timing gene expression, and greater levels of them TRF or UFP. In the TRF arm, par- of feeding, including intermittent circulating cytokines. Low levels of ticipants consume all food between 8 am fasting or TRF, decreases inflammation sRAGE are associated with long-term and 2 pm, producing a 16-hour fast each and causes ketosis. We are unaware of risk of diabetes, cardiovascular disease, day, and eat 80% of their calories prior to any data in humans on these potential and premature mortality. 1 pm. In the UFP arm, participants con- mechanisms. Dr. Aleman’s independent This collaborative research project sume their calories between 8 am and work at NYU aims to understand the role integrates the Rockefeller University midnight and eat 50% of their calories of inflammation in fat towards causing Hospital’s expertise in conducting after 4 pm. In both arms, participants the complications of excess weight. His sophisticated nutritional studies with consume diets with the same macro- team is pursuing this goal by obtaining Dr. Aleman’s group’s expertise in obesity, and micronutrients based on their home detailed phenotyping of subjects with dietary interventions,.. exercise, and diet, analyzed by Bionutritonists in the obesity undergoing bariatric surgery metabolic studies (Popp et al. 2016, Rockefeller Bionutrition Department, and observing how metabolic and Vanegas et al. 2017). Figure 1 details using the validated Vioscreen Food Fre- inflammatory phenotypes change with the timing of the TRF intervention quency Questionnaire (that captures the one form of bariatric surgery called sleeve within a 2-day period and the predicted participants usual intake within the last gastrectomy. The overall hypothesis is changes in metabolic and inflammatory 3 months). The study has crossover de- that obesity is associated with activation parameters.. Systemic and adipose tissue sign, with subjects switching to the other of inflammatory signaling pathways, inflammation are known to decrease with intervention arm after completing the continued on Page 15 14 The Time-Restricted-feeding effects on Inflammation and Obesity (TRIO) Study continued from Page 14 first 7 day intervention (Figure 2). Sub- high sensitivity C-reactive protein (CRP), tion decreases with TRF interventions, jects will act as their own control, and we plasma metabolomic profiles by liquid but will test sRAGE, clinical markers of will be able to monitor compliance with chromatography/mass spectrometry, in inflammation such as high sensitivity C- the TRF intervention by monitoring con- addition to collecting urine and stool for reactive protein (CRP), plasma metabo- tinuous glucose monitoring (CGM) trac- future analyses. lomic profiles by liquid chromatography/ ings. CGM technology is widely used in As part of Drs. Aleman and Breslow’s mass spectrometry, in addition to collect- the care of patients with diabetes, and the commitment to training the next gen- ing urine and stool for future analyses. TRIO study will be the first application of eration of obesity and cardiovascular CGM at Rockefeller Hospital. We know researchers, nutritionist clinical fellows that glycemic variation decreases with from the NYU American Heart Associa- TRF interventions, but will test sRAGE, tion Obesity Center, Dr. Collin Popp and clinical markers of inflammation such Dr. Sally Vanegass, will participate in the as high sensitivity C-reactive protein deployment and execution of the TRIO (CRP), plasma metabolomic profiles by study in collaboration with Rockefeller liquid chromatography/mass spectrom- Bionutrition Department. We hope the etry, in addition to collecting urine and TRIO study will yield new connections stool for future analyses. with the TRF between metabolism and inflammation, intervention by monitoring continuous while testing for additional benefits of glucose monitoring (CGM) tracings. this creative dietary intervention in the CGM technology is widely used in the clinical setting. with the TRF intervention care of patients with diabetes, and the by monitoring continuous glucose moni- TRIO study will be the first application of toring (CGM) tracings. CGM technology CGM at Rockefeller Hospital. We know is widely used in the care of patients with that glycemic variation decreases with diabetes, and the TRIO study will be the TRF interventions, but will test sRAGE, first application of CGM at Rockefeller clinical markers of inflammation such as Hospital. We know that glycemic varia-

Figure 2: TRIO Study Design

15 $2.7M Award to Streamline Collecting Participant Feedback and Drive Improvement to the Clinical Research Enterprise continued from Page 1 Recruitment, retention, and representative across sites, have stalled uptake and sampling remain major challenges to collaboration related to participant research. Assessing participants’ research outcomes. When collected, participant experiences provides essential outcome experience data can provide the evidence data for improving the clinical research base to support the impact of innovative enterprise, yet those experiences go practices. Figure 1 shows the change in largely unmeasured. The paucity of one measure of participant experience direct participant experience data to support evaluation of research practices before and after a team implemented is a critical translational gap. This grant a video designed to enhance informed is directed at addressing this crucial consent. Figure 1 shows the responses need to improve clinical investigation. to the RPPS question “How well did the To execute the project aims, the Figure 1 discussions and information provided teams will collaborate in Year 1 to and NCATS – will be refined in the path before the study prepare you for your develop integrated RPPS/REDCap to widespread use. A key element of research experience?” The frequency tools and dashboard and analytics deliverable in dissemination is to gain of the response “completely” from modules, as wells as formalize the the critical mass of users to support valid participants in this study (blue), was 50- implementation framework to afford inter-institutional benchmarking. 53% in the preceding years (2015-2017), institutions flexibility in their specific but rose to 75% in the year after the new deployments of demonstration cases, Valid tools, good intentions, and per- video (green) came into use inlate 2017. while preserving common elements and sisting barriers standards for future data integration By comparison, the response scores and benchmarking. In Years 2 and 3, Through aseries of multi-site for the same question for all studies at sites will implement use cases – study- projects from 2010-2018, Dr. Kost led Rockefeller (orange) were unchanged in level surveys, departmental aggregation the development of a suite of validated the same time frame. While limited by of project surveys, and institutional Research Participant Experience Survey retrospective design and sample size, this level surveys – among different targeted (RPPS) tools in collaboration with example illustrates the kind of impact populations and using various outreach investigators at 15 NIH funded academic data that could be collected to via a platforms to demonstrate the usability health centers. The RPPS collectsstreamlined RPPS/REDCap platform. and value of the infrastructure and Despite the availability of the valid make refinements. Key deliverables actionable data about study conduct, RPPS, institutions report persisting are the examples of actionable findings informed consent, trust, respect, gleaned from participant feedback that education and communication. The RPPS barriers to broad implementation, institutions then use to drive measurable tools - available in English and Spanish pointing to the need for a ready-to- improvements to research experiences. and in long, short and ultrashort versions use platform, standardized approach, In Years 3 and 4, the team will actively - have been in use to drive improvements low-cost institutional infrastructure, disseminate the infrastructure across the in research at Rockefeller since 2013, at and plug-and-play visualization and REDCap user community and CTSA Johns Hopkins University since 2017, , analysis tools to streamline collection of Consortium hubs. The value proposition and in some form at up to 16 CTSA hubs participant feedback. for different for different stakeholders – in total. Requirements for infrastructure investigators, clinical research managers, Leveraging a platform in wide adop- department and institutional leadership, to support implementation, redundant tion continued on Page 17

16 $2.7M Award to Streamline Collecting Participant Feedback and Drive Improvement to the Clinical Research Enterprise continued from Page 16 REDCap(https://projectredcap. such as web services that allow integrated participant populations, and produce org) is a secure, web-based application data collection through other platforms. actionable findings to generate impactful with workflow and software designed When complete, the integrated RPPS/ improvements; and 3) embrace of the exclusively to support rapid development REDCap tools will be made available value proposition of RPPS/REDCap and deployment of data capture tools for for direct download through the SDIL. infrastructure evidenced by an expanded research studies, with minimal training A preliminary map of the data flow for a set of users, including REDCap users and of the user. REDCap has security and project level or institutional level survey, institutional leadership, and participation usability features specifically designed to without inter-institutional integration is in consortium benchmarking. The goal is support participant-facing surveys and shown at the left. to provide value to a range of stakeholders to sustain broad uptake and use of flexible deployment strategies. REDCap Defining Success was developed at Vanderbilt by project participant feedback to improve research. collaborator Dr. Paul Harris, and has With many deliverables along the The RPPS/REDCap project is been used by over 970,000 users at way, both process-oriented and tangible, also supported in part by an award to more than 3,500 institutions to support the ultimate measures of the success of Rockefeller University from the National more than 725,000 research projects. the project will be: 1) the production Center for Accelerating Tranlsational Virtually all of the CTSAs use REDCap. of an Implementation Guide, RPPS/ Science, 1U TR0001866. The REDCap Shared Data Instrument REDCap project tools, and infrastructure Library (SDIL) makes validated data ; 2) outcome data from completed collection instruments available to demonstration projects at the sites that researchers , and supports technologies illustrate the utility of the RPPS/REDCap to collect representative feedback from

17 CCTS Biostatistics Group Supports a Broad Range of Rockefeller Scholarship continued from Page 9 Select publications (con’t):

Rahman N, Bubnys A, Kandel H, Moene O, Vaughan R, Kow LM, Tabansky I, Pfaff D. “Equation representing the dark-entrained transition from inaction to action in male and female mice”. Behavioural Brain Research, 392 (2020), 112673.

Frew J, Jiang C, Singh N, Grand D, Navrazhina, K, Vaughan R, Krueger J. Malignancy and infection risk during adalimumab therapy in hidradenitis suppurativa. Clinical and Experimental Dermatology. 2020, doi:10.1111/ced.14264

Ostendorf B, Bilanovic J , Adaku N, Tafreshian K , Tavora B , Vaughan R. Tavazoie, S. Common germline variants of the human APOE gene modulate melanoma progression and survival. Nature Medicine, https://doi.org/10.1038/s41591-020-0879-3.

Jung M, Ramanagoudr-Bhojappa R, van Twest S, Ozgur Rosti R, Murphy V, Tan W, Donovan F, Lach F, Kimble D, Jiang CS, Vaughan R, Mehta P, Pierri F, Dufour C, Auerbach A, Deans AJ, Smogorzewska A, and Chandrasekharappa S. Association of clini- cal severity with FANCB variant type in Fanconi anemia. Blood. 2020;135(18):1588-1602.

Frew J, Jiang C, Singh N, Grand D, Navrazhina K, Vaughan R, Kruger J. Clinical Response rates, placebo response rates and sig- nificantly associated covariates are dependent on choice of outcome measure in hidradenitis suppurative: A post hoc analysis of PIONEER 1 and 2 individual patient data. J Am Acad Dermatol 2020 May; 82(5): 1150-1157.

Orange DE, Blachere NE, DiCarlo EF, Mirza S, Pannellini T, Jiang CS, Frank MO, Parveen S, Figgie MP, Gravallese EM, Bykerk VP, Orbai AM, Mackie SL, Goodman SM. Rheumatoid arthritis morning stiffness is associated with synovial fibrin and neutrophils. Arthritis Rheumatol. 2020 Apr; 72(4): 557-564.

Orange DE, Agius P, DiCarlo EF, Mirza S, Pannellini T, Szymonifka J, Jiang CS, Figgie MP, Frank MO, Robinson WH, Donlin LT, Rozo C, Gravallese EM, Bykerk VP, Goodman SM. Histologic and transcriptional evidence of subclinical synovial inflammation in rheumatoid arthritis patients in clinical remission. Arthritis Rheumatol. 2019 Jul; 71(7): 1034-1041.

Lorenz E, Dodig-Crnković T, Kotliar I, Pin E, Ceraudo E, Vaughan R, Uhlèn M, Huber T, Schwenk J, Sakmar T. Multiplexed analy- sis of the secretin-like GPCR-RAMP Interactome. Science Advances, 2019;5:eaaw2778.

Li J, Fukase Y, Shang Y, Zou W, Munoz-Felix J, Buitrago L, van Agthoven J, Zhang Y, Hara R, Tanaka Y, Okamoto R, Yasui T, Na- kahata T, Imaeda T, Aso K, Zhou Y, Locuson C, Nesic D, Duggan M, Takagi J, Vaughan R, Walz T, Hodivala-Dilke K, Teitelbaum S, Arnaout MA, Filizola M, Foley M, and Coller B. Novel pure αVβ3 integrin antagonists that do not induce receptor extension, prime the receptor, or enhance angiogenesis at low concentrations. ACS Pharmacology & Translational Science, 2019;2(6): 387- 401.

Azevedo EP, Pomeranz L, Cheng J, Schneeberger M, Vaughan R, Stern S, Tan B, Doerig K, Greengard P, Friedman J. A role of Drd2 hippocampal neurons in context-dependent food intake. Neuron (2019),102:1-14.

Dallner O, Marinis J, Y-Hsueh L, Birsoy K, Werner E, Fayzikhodjaeva G, Dill B, Molina J, Moscati A, Kutalik Z, Marques-Vidal P, Kilpelainen T, Grarup N, Linneberg A, Zhang Y, Vaughan R, Loos F, Lazar M, Friedman J. Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity. Nature Medicine (2019): 25(3):507-516.

Schlesinger SJ, Romanick M, Tobin JN, Brassil D, Kost RG, Devine R, O’Sullivan B, Vaughan RD, Liang Y, da Rosa JC, Williams M, Krueger JG, Coller BS. 2018. The Rockefeller University Clinical Scholars (KL2) Program 2006-2016. J Clin Trans Sci. 2018;1:285- 91.

Recent Published Abstracts: Bagiella E, Christos P, Kim M, Lee S, Zhong J, Vaughan R. Principles of Statistical Education for Translational Scientists in the Age of Rigor, Reproducibility, and Reporting. June, 2020 Journal of Clinical and Translational Science 4(s1):50-51.

Kost R, Boone L, Cook S, Nelson S, Wilkins C, Stroud M, Dunkel L, Byrne L, Jones M, Harris P, Vaughan R. Infusing a CTSA Program with Causal Pathway Thinking to Transform Evaluation from Operations to Impacts. June, 2020 Journal of Clinical and Translational Science 4(s1):73-74.

Vaughan R, Romanick M, Brassil D, Kost R, Schlesinger S, Coller B. Assessing Leadership Skills in Translational Science Training: The Rockefeller University Leadership Survey. June, 2020 Journal of Clinical and Translational Science 4(s1):116-117.

Brassil D, Vaughan R, Hurley A, Dowd K, Hutt R, Coller B. The Use of Checklists Throughout the Lifecourse of a Clinical Research Study: The Rockefeller University Checklist Suite. June 2020, Journal of Clinical and Translational Science 4(s1):69-69.

MacArthur RB, Rockwell K, Johnson A, Vaughan R, Coller B. Phase 1 Sterile Product Formulation and Manufacturing at Academ- ic Medical Centers: An Introduction for Translational Researchers June 2020, Journal of Clinical and Translational Science 4(s1):42-43. 18 Clinical Scholars Program Celebrates New Graduates By. Michelle Romanick On June 4, 2020, the Center for first descriptions of epithelialized tunnels Center. Dr Knorr will also continue Clinical and Translational Science as mediators of inflammation, as well as as Visiting Assistant Professor in the celebrated the graduation of 6 Clinical identifying novel mechanisms of therapy, Ravetch Lab. Scholars with a virtual celebration via sonographic and molecular Biomarkers Zoom. Despite the lack of physical of disease activity in Dr. James Kreuger’s Dr. Franck Rapaport’s research proximity, the celebration was a laboratory. Dr. Frew accepted the position investigates the inborn errors of wonderfully warm and inspiring event, of Staff Specialist and Associate Lecturer immunity involved in the etiology of with the Mentors speaking about their in the Department of Dermatology at the acute appendicitis, which will help Scholars and Scholars sharing their University of New South Wales, Sydney, improve our understanding of the disease experiences in the program. Dr. Sarah Australia. and eventually contribute to the design Schlesinger, Director of the Clinical of new clinical tests in Dr. Jean-Laurent Scholars program, welcomed the Dr. Krithi Irmady’s research Casanova’s laboratory. Dr Rapaport participants with inspiring words about investigates the changes in gene expression will continue as Instructor in Clinical the Scholars’ achievements and the pride and their regulation in Parkinson's Investigation at Rockefeller University in that the entire CCTS leadership has disease patients to understand disease the Casanova Laboratory. in the Scholars. Dr. Barry Coller, Co- pathogenesis and identify potential new Director of the program concluded the biomarkers and therapeutic strategies Dr. Tukisa Smith’s research focused festivities by congratulating the Scholars in Dr. Robert Darnell’s laboratory. Dr. on the contact system consists of a plasma and their families and emphasizing how Irmady will continue as Instructor in protease cascade that has been suggested the COVID-19 pandemic highlights the Clinical Investigation in the Darnell Lab, in the pathophysiology of various disease importance of translational scientists in while considering academic positions in states in Dr. Jan Breslow’s laboratory. addressing vital health needs. Neurology. Although increasing investigations have shown the contact system’s role in host Dr. Tobias Becher studied Brown Dr. David Knorr’s research tested immune defenses against microbes, fewer fat dissipates energy as heat and is a testing whether Fc-enhanced anti-CD40 studies have explored its role in regulating promising therapeutic target against antibody is safe to deliver intratumorally immune homeostasis and inflammatory obesity and associated diseases in Dr. in patients with cancer. The studies are response, which is the aim of Dr. Smith’s Paul Cohen’s laboratory. His research also looking for preliminary evidence research by characterizing this pathway's explored the effects of brown fat on of efficacy and include several corollary biomarkers in various inflammatory and cardiometabolic health in humans. Dr. laboratory-based studies to define the immune-mediated diseases. Dr. Smith is Becher accepted the position of Clinical effects of CD40 agonism in humans. Assistant Professor in the Department of Science Leader Cardiovascular at Roche Dr. Knorr was awarded a NIH National Clinical Immunology at the University of Diagnostics, in Rotkreuz, Switzerland. Cancer Institute Mentored Clinical California San Diego. Scientist Research Career Development Dr. John Frew’s research discovered K08 grant. Dr. Knorr is Assistant novel inflammatory mediators inAttending in the Department of Medicine Hidradenitis Supppurativa providing the at Memorial Sloan Kettering Cancer

‘Virtual’ photo of the graduates and Clinical Scholar program leaders. Drs. Barry Coller, Sarah Schlesinger, Krithi Irmady, Tukisa Smith, Franck Rapaport, John Frew, David Knorr, Tobias Becher, and James Krueger 19 Rockefeller Historical Vignette: The Birth of Modern By Elizabeth (Betsy) Hanson Hospital, made a bold statement about was published in a landmark book, the essential nature of viruses that set Filterable Viruses, in 1928. Rivers’ the course of virology for decades to hypothesis led to many advances in come. He said: “Viruses appear to be the culturing and characterization of obligate parasites in the sense that viruses that cause human disease. their reproduction is dependent on living cells.” Thomas M. Rivers received the BA from Emory College in 1909 and In stating that viruses needed the MD from The Johns Hopkins living cells in order to replicate, University Medical School in 1915. Rivers was contradicting many After an internship and residency workers in the field, includingin pediatrics, he joined the Army in , the director of the 1918, serving on commissions with Rockefeller Institute, who claimed the U.S. Army Medical Corps that to have isolated and cultivated the investigated outbreaks of pneumonia polio virus in a cell-free medium. and empyema. He returned to Johns But Rivers had both laboratory and Hopkins for a research appointment clinical experience on which to base in 1919, and joined the Rockefeller Rivers, Thomas his view. When, in 1926, the Society of Institute Hospital in 1922. In 1937 Courtesy of the Rockefeller Archive Center American Bacteriologists invited him Rivers became director of the hospital, to organize a symposium on viruses, a position he held until 1953, when he In the 1920s virology was not an and deliver a lecture, he reviewed the became Vice President and Director established discipline. Although body of knowledge on viruses. Several of the Institute. He retired in 1955. researchers could study the effects of observations on the problem of Rivers was elected to the U.S. National viral diseases in humans, animals, and growing viruses in the laboratory led Academy of Sciences. He served as plants, they had no criteria to describe him to his conclusion: the difficulty of president of the American Society for viruses chemically--in fact, the very cultivating viruses on artificial media Clinical Investigation, the American definition of a virus was a subject for could not be explained; although Association of Immunologists, the debate! The best scientists could do viruses were small, size should not Society of American Bacteriologists, was to say that, if an infectious agent prevent their cultivation; viruses were and the Third International passed through a fine porcelain filter not particularly delicate or susceptible Congress for Microbiology, and that held back bacteria, then it was to destruction during laboratory received honorary degrees from probably a virus (“a filterable agent”). procedures; nor had any viruses been , the University of In 1926, Thomas M. Rivers (1888- found multiplying free in nature. Rochester, the , 1962), director of the Rockefeller His synthesis of the state of virology and the Rockefeller Institute.

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