NIH GRANTS

Preventing Diabetes in Minority Men—For people with pre-diabetes, a lifestyle intervention called the Diabetes Prevention Program (DPP) has been shown to reduce their risk of developing type 2 diabetes by 60 to 70%. Einstein was instrumental in developing the DPP and evaluating its long-term effectiveness. Men of color, however, have not reaped the benefits: they are far less likely to enroll in the 12-month DPP and to remain engaged if they do enroll.To address this challenge, researchers at Einstein helped develop a version of DPP tailored specifically to Black and Latino men. Now, Earle Chambers, Ph.D. and Jeffrey Gonzalez, Ph.D. have been awarded a 5-year, $3.1 million National Institutes of Health grant to evaluate the effectiveness of that intervention, called Power-Up. Black and Latino men with prediabetes will be randomly assigned to enroll in a traditional, co-ed DPP program, or the new men-only Power-Up intervention. Over 12 months, the Einstein researchers will evaluate the participants’ engagement (enrollment and continued participation), as well as weight loss and improved levels of hemoglobin A1c (a blood test indicative of diabetes).

Studying Diseases Affecting People Living with HIV—The National Institutes of Health (NIH) have awarded a seven-year, $23 million grant to Kathryn Anastos, M.D., principal investigator, and Anjali Sharma, M.D., M.S., co-principal investigator, to study HIV and the chronic illnesses that often accompany HIV infection, including cardiovascular and lung disease, diabetes, and cancer. The new grant builds on previous scientific and clinical research from the 26-year-old Women’s Interagency HIV Study (WIHS), a multi-center study of women who are either living with HIV or at risk for HIV infection. The NIH has merged the WIHS study with a comparable parallel study in men known as the Multicenter AIDS Cohort Study, which began in 1984. Together, those studies enrolled thousands of participants and spurred more than 2,300 publications on HIV-related topics.

Research Project Grants (R01)

Regulation of Gut Metabolism—Metabolic syndrome is a significant health problem affecting more than 44 percent of the U.S. population over than 50 years of age, and is a major factor predicting reduced survival. Studies will determine a new mechanism regulating dietary fat uptake and will examine how the dysregulation of this mechanism promotes obesity. The National Institute of Diabetes and Digestive and Kidney Diseases has awarded Rajat Singh, M.D., M.B.B.S., a five-year grant to study the molecular regulation of gut lipid metabolism by mTOR and autophagy proteins. These studies will be critical for the development of new strategies against metabolic syndrome stemming from increased dietary fat uptake. Dr. Singh is an associate professor of medicine (endocrinology) and of molecular pharmacology at Einstein. R01 DK123327-01

Restricting Calories to Extend Health Span—Caloric restriction (CR) extends the life span and health span in multiple species, although one drawback of CR is poor compliance. This has led to alternative dietary approaches aimed at extending health span. Age-related diabetes/metabolic syndrome is a significant health problem in the United States that increases sharply in some 44 percent of individuals older than 50. Type 2 diabetes, a major predictor of reduced survival from cardiovascular events, is also thought to predispose people to neurodegenerative diseases, including Alzheimer’s dementia. Studies in this application will dissect the interplay between autophagy and the core circadian protein cryptochrome-1 (CRY1) in prevention of age-related diabetes by isocaloric twice-a-day feeding. These studies aim to identify and develop novel small-molecule compounds that will reverse diabetes by preventing the age-related decline in levels of CRY1 protein in the liver. The National Institute on Aging has awarded Rajat Singh,M.D., M.B.B.S., a five-year, $2 million grant to study circadian mechanisms of diabetes prevention in aged mice. Dr. Singh is an associate professor of medicine (endocrinology) and of molecular pharmacology at Einstein. R01 AG065985-01.

Targeting Calcium Channels in Heart Failure—Cardiovascular disease along with subsequent heart failure is the leading cause of morbidity and mortality in the United States. The adult heart is composed of diverse cell types, including cardiomyocytes, fibroblasts, and endothelial and perivascular cells, which participate in repair processes. After a heart attack, the complex interactions among these cells are dramatically disturbed, often resulting in excessive or detrimental cardiac fibrosis - a hallmark of heart failure. Cardiomyocyte function is known to be regulated by calcium channels, but much less is known about the role of calcium in fibroblast functioning and in modulating fibrosis. The National Heart, Lung, and Blood Institute has awarded Gaetano Santulli, M.D., Ph.D., a five-year, $2 million grant to study the roles played by calcium channels in regulating cardiac fibrosis. Dr. Santulli is an assistant professor of medicine (cardiology) and of molecular pharmacology at Einstein. R01HL146691-01A1

Targeting Signals in Alzheimer's—Diminished somatotropic signaling (i.e., signaling that stimulates body growth) leads to delayed aging and longer life spans both in model organisms and in people. Centenarians, in fact, have several mutations that weaken somatotropic signaling. Sofiya Milman, M.D., M.Sc., has received a five-year, $4 million grant from the National Institute on Aging (NIA) to identify genes and gene functions that inhibit growth-related signaling. She and her colleagues will study participants in Einstein's LonGenity study —a cohort of 1,400 older adults, half of them the offspring of centenarians. The researchers will investigate the role that somatotropic signaling plays in the brains of aging humans. They hope to identify mechanisms that confer cognitive resilience by delaying aging; such findings that could lead to therapies to help protect against Alzheimer's and other aging-associated diseases. Dr. Milman is an associate professor of medicine (endocrinology) and of genetics at Einstein and an attending physician in medicine at Montefiore. R01AG061155-01

Protecting against Fungal-Caused Meningitis—The fungus Cryptococcus neoformans causes a devastating form of meningitis, cryptococcal meningitis (CM), which primarily affects patients with HIV, which suppresses patients’ immune systems. Use of antiretroviral (ARV) therapy in the United States has reduced the risk that HIV-infected patients will develop CM. But CM continues to devastate patients where ARV therapy is not available, and survival of patients with CM is only six months. Currently, there is no way to predict which HIV-infected patients will develop CM. The National Institute of Allergy and Infectious Diseases has awarded a five-year, $3.1 million grant to Liise-anne Pirofski, M.D., to look for links among natural antibodies, B-cell responses to C. neoformans, and resistance to CM and develop a risk profile to identify patients most likely to develop CM. The findings could lead to better ways to diagnose and treat CM. Dr. Pirofski is a professor of medicine (infectious diseases) and of microbiology & immunology and the chief of infectious diseases at Einstein and Montefiore, and holds the Selma and Dr. Jacques Mitrani Chair in Biomedical Research. R01AI143453-01

Unraveling the B-Cell Response Against TB—The bacterial species Mycobacterium tuberculosis (Mtb) caused 1.3 million tuberculosis (TB)-related deaths in 2017. Infection triggers a well-studied T-cell response against Mtb, but the B-cell immune response leading to antibody production is not clearly understood. John Chan, M.D., received a five-year, $3.5 million grant from the National Institute of Allergy and Infectious Diseases to investigate the role of IgM antibodies in the host immune response to Mtb. Dr. Chan and colleagues will use mouse and ex vivo macaque TB models to better understand the role, importance, and regulation of IgM in immune regulation during the early and chronic stages of TB. Findings from this study may lead to novel therapies against TB infection. Dr. Chan is a professor of medicine (infectious diseases) and of microbiology & immunology at Einstein and an attending physician in infectious diseases at Montefiore. (1R01AI139297-01A1)

KL2: Institute for Clinical and Translational Research (ICTR)

The KL2 awards provide funding for junior faculty members (instructors or assistant professors) with doctoral degrees to devote the majority of their effort to clinical or translational research and training for two to three years.

HIV chronic Pain and Medical Marijuana—Until recently, opioids were the primary treatment for chronic pain in this population. But there is growing interest in using medical cannabis for treating chronic pain in people living with HIV. The ICTR has awarded Deepika Slawek, M.D, M.P.H., M.S., a KL2 Mentored Clinical/Translational Research Career Development Award to study how medical cannabis affects pain and inflammation in people living with HIV. Dr. Slawek, an assistant professor of medicine (general internal medicine), works to improve outcomes for people living with HIV, many of whom are affected by chronic pain. Read more about Dr. Slawek here.

Analyzing biomarkers to develop targeted therapies in Lupus Nephritis—Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE) and is associated with high morbidity and mortality. Only 24-50% of LN patients respond to current treatments at 6 months and more than 10-30% progress to ESRD within 10 years. The complement system is known to play a central role in the pathogenesis of LN. With the emergence of therapeutic complement inhibitors, there is a potential to approach LN in novel ways, and a need to identify patients in whom complement-driven inflammation plays a major cause of kidney injury. Shudan Wang, M.D., an assistant professor of medicine (rheumatology), was awarded a KL2 to study complement C9 as marker of renal injury and poor therapeutic response in patients with lupus. Dr. Wang will analyze biomarkers that would identify predictors of response, and to develop targeted therapies in LN. This will lead to better understanding of the ways in which complement participates in lupus injury, and reliable markers of complement activation to identify which patients may benefit from novel targeted complement therapies. Dr. Wang will collaborate with investigators at New York University School of Medicine and Dr. James Pullman, an expert renal pathologist to validate C9 immunohistochemistry staining in the laboratory.

Mentored Patient-Oriented Research Career Development Award (K23)

Hemolysis and Platelet Activation during Continuous Flow Mechanical Circulatory Support—Heart failure (HF) has reached epidemic proportions effecting over 5.4 million people worldwide and its burden is expected to grow exponentially in the next decade. The advent of continuous flow mechanical circulatory support (CF MCS) devices for patients with severe heart failure has led to marked improvements in survival; however, pump operation remains fraught with adverse thrombotic events such as stroke. Despite alterations in device design, the rate of disabling stroke remains elevated and the hematologic mechanisms behind these devastating adverse events remain unknown. The National Heart, Lung, and Blood Institute has awarded Omar Saeed, M.D., an assistant professor of medicine (cardiology) a grant to investigate if CF MCS hemolysis creates a pro-thrombotic state through increasing platelet activation and if pharmacologic potentiation of nitric oxide signaling by an oral phosphodiesterase-5 inhibitor sildenafil lowers platelet activity. Elucidating mechanisms of hemolysis induced thrombosis may inform targeted anti-thrombotic strategies for prevention of end organ damage.

Does implicit bias influence medical decision-making?—Implicit, or unconscious, bias may influence physician behaviors when they communicate with patients or make medical decisions about their care. Current efforts to train physicians to overcome the potential influence of implicit bias on their behaviors are limited because there are no outcomes to show if the interventions are effective or not. The National Institute on Minority Health and Health Disparities (NIMHD) has awarded Cristina Gonzalez, M.D., an associate professor of medicine (hospital medicine), a grant to develop and scientifically validate outcome metrics related to physician behavior and measure the influence of implicit bias on physician medical decision-making. The evidence for a correlation between physician racial implicit bias and disparities in communication by physicians with Black and White patients is strong. In contrast, research investigating the relationship between physician racial implicit bias and medical decision-making, has led to conflicting results. Moreover, investigators seeking to design skills-based interventions to enable physicians to recognize their biases and mitigate their influence on their clinical practice behaviors are limited by the lack of validated outcome metrics, such as checklists and global rating scales. The grant seeks to build on her expertise as a medical educator and qualitative researcher with new skills in standardized patient case development, psychometric measurement, validity evidence, statistical analysis, and clinical study design. The outcome of this final aim will address an important gap in knowledge relevant to the design future intervention studies. Dr. Gonzalez will emerge from this K award transformed from a medical educator into a clinician investigator able to conduct multi-institution intervention studies addressing physician racial implicit bias and patient outcomes. Read more about Dr. Gonzalez receiving the AAMC New Investigator Award.

2019 Geriatrics Academic Career Award—Rachel Chalmer, M.D., has been awarded a 2019 Geriatrics Academic Career Award by the US Health Resource & Services Administration (HRSA). This five-year award supports the career development of junior faculty clinician educators who will become leaders in academic geriatrics. Dr. Chalmer is an assistant professor of medicine (geriatrics) and a consultant geriatrician in the Montefiore-Einstein Center for the Aging Brain (CAB). The Geriatrics Academic Career Award will help Dr. Chalmer to obtain the skills to effectively teach the interprofessional team (IPT) in diverse settings to deliver more comprehensive, patient-centered, value-based care to people with CID in an urban, medically underserved population and to pursue her goals to become an expert clinician-educator in geriatric medicine with a focus on people with cognitive impairment including dementia (CID).

Justina Groeger, M.D., is an awardee of a K12 Learning Health System Career Development Award (PI Michael Rinke, M.D., Ph.D.), to study health systems approaches to improving opioid management. Her research is focused on improving the quality of opioid prescribing within the Montefiore Health System. Dr. Groeger, an assistant professor of medicine (general internal medicine), is developing IT tools, such as an opioid dashboard to monitor opioid prescribing variability and change over time within our health system and is learning the critical methods and tools in the field of improvement science as a participant in Montefiore’s Performance Improvement Fellowship. She is concurrently applying these tools to develop and study performance improvement interventions (such as reports to providers and clinical decision support tools) to guide a standardized approach to patient-specific opioid prescribing. A major aim of this work is to decrease the opioid discharge dose differential, the difference between the opioid dose administered in the 24 hours prior to hospital admission and the opioid dose prescribed at hospital discharge, because abrupt changes in opioid dose (e.g. a large opioid discharge dose differential) can harm patients.

NIH Exploratory/Developmental Research Grant Program (R21)

The National Institute of Mental Health (NIMH) has awarded Viraj Patel, M.D., an award to study the impact of multiple stigmas on HIV care continuum outcomes for key populations. The goal of Dr. Patel’s research, based in India, is to understand how different types of stigma precisely impact engagement and retention in HIV treatment among transgender women living with HIV and among sexual minority men (e.g., gay/bisexual, etc.) living with HIV, and then what can organizations do to mitigate this impact and improve health outcomes. Dr. Patel, assistant professor of medicine (general internal medicine), recently traveled to India to launch this study with a national partner.

NIH CFAR Supplemental Fund Awards

In September 2019, NIH announced supplemental awards to institutions participating in the NIH-funded Centers for AIDS Research (CFAR) program and NIMH-funded AIDS Research Centers (ARC) program. These awards, which will help enhance the implementation science knowledge base needed for the proposed Ending the HIV Epidemic: A Plan for America, are one-year awards to support pilot and formative studies to prepare for more extensive implementation science research proposals expected in 2020. Three of the five NIH CFAR supplemental funded projects are led by PI’s in the Department of Medicine.

PI: Matthew Akiyama, M.D., M.Sc., assistant professor of medicine (general internal medicine)
HIV Healthcare Systems and Differentiated Care Approaches to Improve Viral Suppression: Enhancing a universal testing and treatment strategy in jail to promote viral load suppression among justice-involved people living with HIV. Co-Investigators: Victoria Philips (Emory) and Anne Spaulding (Emory)

PI: Uriel Felsen, M.D., assistant professor of medicine (infectious diseases)
Innovative Technologies for Basic Research on HIV and Co-morbidities: Machine learning to identify patterns of care among HIV at-risk patients and inform PrEP implementation

PI: Viraj Patel, M.D., assistant professor of medicine (general internal medicine)
Minority HIV/AIDS Funds: Understanding preferences for engaging in PrEP
A strategy for reducing racial/ethnic disparities in PrEP uptake. Dr. Patel and investigators will conduct a discrete choice experiment among Black and Latinx gay, bisexual and other sexual minority men at high risk of getting HIV and living in the 50+ counties/areas with the highest HIV burden in the U.S. (as defined by the national End the Epidemic plan). The goal of the research is to rigorously identify novel preferences for PrEP implementation/care delivery among groups most likely to benefit, that local health departments and care providers could implement to improve PrEP use and prevent new infections. Co-Investigators: Christian Grov (CUNY); Denis Nash (CUNY); Anthony Freeman (NYC DOHMH)

OTHER RESEARCH GRANT AWARDS

Minimizing Heart-Failure Damage—The death of heart-muscle tissue caused by heart attacks all too often leads to heart failure. The heart’s fibroblasts synthesize extracellular matrix (ECM) that provides structural support for the heart and its cells. But heart failure triggers fibroblasts to deposit large amounts of ECM proteins, which can precipitate deadly heart rhythm abnormalities and also increase the stiffness of the heart. A stiff heart fails to relax properly, leading to pressure overload (increased pressure in the heart’s chambers) that contributes to shortness of breath. Nikolaos Frangogiannis, M.D., and colleagues have found that expression of the protein transglutaminase-2 (TG2) greatly increases in failing hearts and that TG2 is a major mediator of effects that occur during heart failure. The United States Army has awarded Dr. Frangogiannis a three-year, $2 million grant to examine how TG2 influences the two most common situations associated with heart failure: heart attacks that lead to heart failure by killing cardiac muscle, and the pressure overload that causes heart failure in patients with high blood pressure. The research may provide insights into the pathogenesis of heart failure and may identify TG2 inhibition as a new heart-failure therapy. Dr. Frangogiannis is professor of medicine and microbiology & immunology and the Edmond J. Safra/Republic National Bank of New York Chair in cardiovascular medicine at Einstein.

Award for Patient-Oriented Opioid Research—The New York State Department of Health’s Empire Clinical Research Investigator Program (ECRIP) has awarded a two-year, $574,166 grant to the Montefiore/Einstein Center for Comparative Effectiveness Research (CCER). The CCER will look for ways to help patients with or at risk for opioid use disorder (OUD) achieve better outcomes. Led by Julia Arnsten, M.D., M.P.H., chief of the division of general internal medicine at Montefiore and Einstein, the CCER was established in 2013 to improve patient-centered health outcomes in urban, diverse, and underserved populations. The five projects funded by the new grant will include studies to see how medical cannabis compares with opioids for controlling chronic pain in people living with HIV; examine using medical cannabis for reducing opioid use in patients with head and neck cancer; assess strategies for safer opioid prescribing for patients with sickle cell disease; and improve treatment access for people with opioid use disorder.

Edmund H. Sonnenblick MD Research Award in Heart Failure—The Montefiore Einstein Center for Heart and Vascular Care has awarded Omar Saeed, M.D., assistant professor of Medicine (cardiology), the inaugural Edmund H. Sonnenblick M.D. Research Award in Heart Failure. The award honors Dr. Sonnenblick, a noted researcher and cardiologist, and celebrates his legacy, which is an important part of Montefiore’s history. The first award was presented to Dr. Saeed for his NIH-funded work on platelet physiology in heart failure at the recent MonteHeart meeting, held at Montefiore in February 2019. This $3000 award, which will be given once a year to a promising young heart failure researcher, is endowed by proceeds of the MonteHeart meeting, held every year during American Heart Month. Dr. Sonnenblick made seminal contributions to the understanding of cardiovascular physiology and authored over 600 manuscripts. His studies of the function of cardiac muscle cells during the 1960s shaped the basis of both cardiovascular physiology and the modern treatment of cardiovascular disease, making possible the development of ACE inhibitors.

Unintended Risks of Opioid Tapering—The use of opioid tapering - reducing opioid doses for patients on chronic opioid therapy to decrease their risk of overdose - has increased in recent years but may lead to unintended consequences. In a new study published online on August 19 in the Journal of General Internal Medicine, Hector R. Perez, M.D., and colleagues at Montefiore found that opioid tapering may be associated with termination of care, or patients leaving a healthcare system. Using electronic medical records of more than 1,600 patients who were being treated with opioids, the investigators found that patients who were tapered off opioids were significantly more likely to terminate their care than chronic opioid users whose doses were continued. The researchers note that termination of care could lead to poor outcomes including increased risk for chronic diseases such as asthma, diabetes and HIV infection. Dr. Perez is an assistant professor of medicine at Einstein and attending physician of internal medicine at

Dr. Cristina Gonzalez Receives AAMC New Investigator Award
In November 2019, Cristina Gonzalez, M.D. traveled to the Association of American Medical Colleges’ “Learn Serve Lead” meeting in Phoenix, AZ to accept its 2018 New Investigator Award. The honor, which is offered by the AAMC’s Research in Medical Education Committee, touts her paper, “How to Make or Break Implicit Bias Instruction: Implications for Curriculum Development.” The award included publication in a November 2018 online supplement to the journal Academic Medicine. Read more.

Pinnacle Research Award—The American Association for the Study of Liver Diseases (AALD) has awarded Eve Billerbeck, Ph.D., the 2019 Pinnacle Research Award. The three-year basic science award provides young scientists with support for their research to bridge the gap between completion of research training and attainment of status as an independent research scientist. The award is intended to develop the potential of outstanding, young scientists and encourage research in liver physiology and disease. Dr. Billerbeck, is assistant professor in the departments of medicine (hepatology) and microbiology & immunology. Her research is focused on intrahepatic immunity during viral hepatitis and fatty liver disease. Immune responses in the liver play a key role in the clearance of hepatotropic viruses such as hepatitis C virus (HCV) but they can also cause liver injury and may contribute to disease progression in viral hepatitis or NASH. New mechanistic insights into factors that contribute to the development of an effective antiviral immune response and regulate liver damage during inflammation are essential for the development of HCV vaccine strategies and immunotherapeutic options for the treatment of progressive liver diseases. Limited access to human liver tissue and the lack of immune-competent small animal models has impeded studies of hepatic antiviral immune mechanisms. However, Dr. Billerbeck and colleagues recently succeeded in establishing the first immune-competent mouse model of an HCV-related virus, Norway rat hepacivirus (NrHV). The initial characterization of this model revealed significant virological and immunological similarities with HCV infection in humans. Using this novel model, they aim to gain new insights into the role of hepatic immune cell subsets, such as NrHV-specific CD8+ T cell subsets, in viral clearance, memory response formation and tissue pathology during a hepacivirus infection in vivo. In a second approach they aim to utilize the NrHV model in combination with mouse models of diet-induced NASH in an effort to develop a robust model of advanced liver pathology, such as fibrosis or HCC and to characterize the role of hepatic T cells in liver disease progression in these models.

Eric Lontchi Yamigou Ph.D., M.P.H., received the Next Einstein Forum (NEF) fellowship, a prestigious global award for young African scientists. Dr. Lontchi is postdoctoral researcher at Albert Einstein College of Medicine’s Diabetes Research Center and Global Diabetes Institute. As part of the award, Dr. Lontchi Yimagou will be among the hundreds of established and up-and-coming researchers attending the NEF global gathering next year in Nairobi, Kenya. He’ll also have opportunities to showcase his work, mentor young people interested in pursuing scientific careers, and establish collaborations with other researchers who share his passion for the study of diabetes. Read more about Dr. Lontchi-Yamagou’s NEF Award.