Research Notes

Major NIH Research Awards: Winter/Spring 2023

Major NIH Research Awards: Winter/Spring 2023

Einstein and Montefiore investigators received more than $200 million in research funding from the National Institutes of Health during federal fiscal year 2022.

Evaluating an Alzheimer’s Screening Tool

Investigators at Einstein, Montefiore, the Regenstrief Institute, and the Indiana University School of Medicine have received an $11 million grant from the National Institutes of Health (NIH) to evaluate an Einstein-developed test for assessing cognitive impairment and dementia. The five-minute screening tool was designed for people from a range of racial and ethnic backgrounds, education levels, and socioeconomic circumstances, with the goals of reducing disparities in predementia and dementia diagnosis and treatment and of improving dementia care overall. The study will enroll 6,600 participants presenting with cognitive concerns in 22 primary-care clinics in the Bronx and Indiana. Joe Verghese, M.B.B.S., M.S., is the principal investigator on the grant, chief of the unified divisions of geriatrics in the department of medicine and of cognitive & motor aging in the Saul R. Korey Department of Neurology at Einstein and Montefiore, and director of the Montefiore Einstein Center for the Aging Brain.

Leading a New York Research and Training Consortium

The NIH has awarded Einstein a five-year, $6.6 million grant to lead a New York–based consortium of medical schools to train up to 10 young scientists annually in kidney, urology, and hematology research. The grant establishes the New York Consortium for Interdisciplinary Training in Kidney, Urological, and Hematological Research, bringing together more than 100 research and education experts from Einstein, Columbia University Irving Medical Center, the Icahn School of Medicine at Mount Sinai, and the Renaissance School of Medicine at Stony Brook University. The consortium will recruit up to 10 trainees each year, who will focus on diseases such as sickle-cell and kidney disease that disproportionately affect Black and Hispanic people and other marginalized groups. The grant’s principal investigator is Michal Melamed, M.D., M.S., professor of medicine, of pediatrics, and of epidemiology & population health at Einstein and a nephrologist at Montefiore.

Studying Heart Failure in Hispanics

Researchers at Einstein and Montefiore have received a five-year, $5.2 million NIH grant to explore the underlying causes of heart failure among Hispanics/Latinos, who are at heightened risk for heart disease. Investigators will simultaneously evaluate heart function and the relationship between the heart and the aorta, the artery conveying oxygen-rich blood from the heart’s left ventricle to the rest of the body. Researchers will recruit 1,600 Hispanic/Latino men and women over age 45 for the study. Participants will receive echocardiograms and other tests to determine the stiffness and functioning of the aorta, possible aorta–left ventricle coupling abnormalities, and the possible presence of heart failure and pre–heart failure. Carlos J. Rodriguez, M.D., M.P.H., the principal investigator on the grant, is a professor of medicine and of epidemiology & population heath at Einstein and the director of clinical cardiology research and of cardiovascular epidemiology at Einstein and Montefiore.

The Link Between HIV Infection and Depression

Depression is the most common neuropsychiatric illness among people living with HIV (PLWH). Three Einstein researchers have received a five-year, $3.85 million NIH grant to investigate the neurobiological mechanisms that may connect the two comorbidities. The researchers will test their hypothesis that systemic inflammation disrupts the blood-brain barrier (BBB) and allows peripheral blood mononuclear cells to cross the BBB, altering the brain’s reward circuity and contributing to depression in PLWH. The project may lead to strategies for improving both mental health and overall health in PLWH. Project leader Vilma Gabbay, M.D., is the director of the Psychiatry Research Institute at Montefiore Einstein for Biomarkers and Dimensional Psychiatry. Anjali Sharma, M.D., M.S., is a professor of medicine at Einstein and an internist at Montefiore. Joan W. Berman, Ph.D., is a professor of pathology and of microbiology & immunology and the Irving D. Karpas Chair in Medicine at Einstein.

Risk-Benefit Analysis of Playing Soccer

More than 25 million Americans play soccer, which is the world’s most popular sport. Soccer benefits brain health by boosting blood flow to that organ, but recent studies show that highly repetitive heading of the ball is associated with structural brain changes and worse cognitive performance, similar to changes caused by concussion. The NIH has awarded Einstein researchers a five-year, $3.4 million grant to assess the trade-offs between soccer’s aerobic brain benefits and the adverse effects from heading. The study will involve neuroimaging, exercise testing, and cognitive testing of 280 young men and women, half of them soccer players. The principal investigator is Michael Lipton, M.D., Ph.D., professor of radiology and of psychiatry and behavioral sciences, associate professor in the Dominick P. Purpura Department of Neuroscience, and associate director of the Gruss Magnetic Resonance Research Center at Einstein and director of MRI services at Montefiore.

Targeting Huntington’s Disease Mechanisms Early

Deficits in cortical interneurons (which transfer signals between sensory and motor neurons) have been detected in people with Huntington’s disease (HD), but their role in HD development has not been investigated. Mark F. Mehler, M.D., has received a five-year, $3.4 million NIH grant to test whether preventing interneuron deficits from causing adverse effects can prevent HD or ameliorate its severity. Studying a mouse model of HD, Dr. Mehler and colleagues will use cell-transplantation techniques to investigate whether it’s possible to restore impaired brain function during early stages of the disease. Dr. Mehler is a professor in and the chair of the Saul R. Korey Department of Neurology at Einstein and Montefiore, and a professor in the Dominick P. Purpura Department of Neuroscience and of psychiatry and behavioral sciences, the director of the Institute for Brain Disorders and Neural Regeneration, and the Alpern Family Foundation Chair in Cerebral Palsy Research at Einstein.

Getting to the Heart of 22q11.2 Deletion Syndrome

One in 4,000 live births is affected by 22q11.2 deletion syndrome. Approximately 60% of patients with the syndrome have congenital heart disease, most commonly cardiac outflow tract (OFT) defects, varying in severity from mild to severe. Approximately half of infants born with OFT defects require surgery to survive. Bernice Morrow, Ph.D., has received a four-year, $3.1 million grant from the NIH to better understand the developmental and genetic explanations for the wide variability in OFT defect severity. She and colleagues will analyze whole-genome sequences from people with 22q11.2 deletion syndrome, some with OFT defects and others without them. DNA variants identified in this way will then be validated in zebrafish using gene editing. Dr. Morrow is a professor of genetics, of obstetrics & gynecology and women’s health, and of pediatrics, the Sidney L. and Miriam K. Olson Chair in Cardiology, and the director of translational genetics at Einstein.

Developing New Drug Targets for HIV

To improve treatment for HIV, there is a need for longer-acting antiretroviral drugs to which HIV will not become resistant. One approach is to target host-virus interactions. Ganjam V. Kalpana, Ph.D., has received a five-year, $3.1 million NIH grant to develop drugs that disrupt the interface between an HIV-1 enzyme and a host-cell protein. That host-cell protein mimics a segment of HIV-1 RNA that also interacts with the same HIV-1 enzyme to enable viral replication, so drugs that disrupt HIV-1 enzyme/host-cell protein interactions are also likely to inhibit viral replication. Dr. Kalpana and colleagues plan to develop dual-acting drugs that interfere with both virus/host-cell protein interactions and viral protein/viral RNA interactions. Ideally, such drugs would inhibit HIV-1 replication without inducing drug resistance. Dr. Kalpana is a professor of genetics and of microbiology & immunology and is the Mark Trauner Faculty Scholar in Neuro-oncology at Einstein.

Unraveling the Role of a Mitochondrial Protein

ATP molecules provide the energy required for most cellular processes. Almost all ATP is synthesized in mitochondria by a protein complex known as the mitochondrial ATP synthase. This protein complex has also been thought to function in a different form as the mitochondrial permeability transition pore, which is involved in necrotic cell death. Richard Kitsis, M.D., has received a four-year, $2.8 million NIH grant to conduct studies to better understand the functions of the mitochondrial ATP synthase. Using mouse models with cardiomyocytes deficient in this protein complex, Dr. Kitsis’ lab will study the complex’s role in cellular energetics and test whether it also functions as the mitochondrial permeability transition pore. Dr. Kitsis is a professor of medicine and of cell biology, the Dr. Gerald and Myra Dorros Chair in Cardiovascular Disease, and the director of the Wilf Family Cardiovascular Research Institute at Einstein, and a cardiologist at Montefiore.

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