Research Notes

Major NIH Research Awards: Summer/Fall 2023

Major NIH Research Awards: Summer/Fall 2023

Gaining Insights Into TB

Michael Berney, Ph.D., has received two five-year National Institutes of Health (NIH) grants totaling $5.7 million to study Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB). One grant funds research on phthiocerol dimycocerosate (PDIM)—a lipid in Mtb’s cell envelope that strongly influences Mtb’s virulence and drug resistance. Spontaneous PDIM loss has plagued TB research for decades. Dr. Berney and colleagues are developing new tools to prevent PDIM loss, allowing reproducible research into TB pathogenesis and discovery of vaccines and drugs. Under the second grant, Dr. Berney and a Swiss collaborator will use a new methodology combining metabolomics and CRISPR interference to characterize large libraries of anti-TB compounds with unknown modes of action. Their resulting atlas of Mtb gene/drug/metabolic interactions should aid in developing new drugs to help eradicate TB. Dr. Berney is an associate professor of microbiology & immunology at Einstein.

Investigating the Rise of Type 2 Diabetes in Children

The number of youths under age 20 living with type 2 diabetes nearly doubled between 2001 and 2017. Aside from a rise in childhood obesity, the reasons for this increase aren’t clear. The NIH has awarded the Children’s Hospital at Montefiore (CHAM) and Einstein a six-year, $4.1 million grant to participate in a national study to identify possible biological and social factors (such as food insecurity and housing insecurity) that may be causing children and adolescents to develop the condition. The site was chosen in part because Bronx children have elevated rates of obesity-related metabolic disorders. The national study will enroll 3,000 children at 15 clinical sites. At CHAM and Einstein, 250 overweight or obese children between ages 9 and 14 will be enrolled. The project leader is Carmen R. Isasi, M.D., Ph.D., professor of epidemiology & population health and of pediatrics and associate director of the New York Regional Center for Diabetes Translation Research at Einstein.

Assessing Brain Activity to Predict Dementia Risk

The ability to detect dementia early—before a person’s daily functioning is noticeably impaired—might allow for interventions that delay cognitive decline. The NIH has awarded Pierfilippo De Sanctis, Ph.D., a five-year, $3.8 million grant to test whether dementia can be predicted by measuring patterns of brain activity in older adults engaged in complex gait (walking) tasks. Using novel portable electroencephalographic devices that they’ve developed, Dr. De Sanctis and colleagues will determine the neural signature of functional decline by comparing cognitively unimpaired older adults with and without subclinical Alzheimer’s disease as they perform complex gait tasks. By accurately predicting dementia risk at an early stage, this noninvasive and relatively inexpensive approach may help elderly people maintain their quality of life. Dr. De Sanctis is an assistant professor of pediatrics and in the Saul R. Korey Department of Neurology at Einstein.

Curbing Smoking Among People with HIV

About half of the people with HIV (PWH) in the United States smoke cigarettes, and smoking is now the leading killer of PWH. The National Cancer Institute (NCI) has awarded Jonathan Shuter, M.D., and colleagues a five-year, $3.5 million grant to test whether a novel harm-reduction approach designed specifically for PWH who smoke can reduce morbidity and mortality. The intervention includes cutting down on cigarettes, screening for lung cancer, and controlling blood pressure. Four hundred PWH who smoke will receive either the harm-reduction intervention or routine care. After nine months, participants in the two groups will be assessed for primary outcomes, including changes in the number of cigarettes smoked daily, the proportion of participants screened for lung cancer, and changes in blood pressure. Dr. Shuter is a professor of medicine and of epidemiology & population health at Einstein and an infectious-disease specialist at Montefiore.

Hope for a Herpes Vaccine

No vaccines can prevent herpes simplex virus (HSV) infections, which cause serious health problems. Previous failed vaccine efforts targeted HSV glycoprotein D (gD), which elicits only neutralizing antibodies. Betsy Herold, M.D., and colleagues have developed a “non-gD” candidate vaccine that elicits antibodies that generate antibody-dependent cell-mediated cytotoxicity (ADCC). The NIH has awarded them a five-year, $3 million grant to characterize these ADCC-mediating monoclonal antibodies in mouse models of HSV infection; determine how deletion of gD allows for the generation of ADCC; and study interactions between gD and the immunomodulatory molecule herpes entry mediator, which most immune cells express. The findings may lead to vaccines for HSV and other pathogens. Dr. Herold is a professor of pediatrics, of microbiology & immunology, and of obstetrics & gynecology and women’s health at Einstein, and is the chief of the division of pediatric infectious diseases and vice chair for pediatric research at CHAM and Einstein.

Studying Redevelopment’s Impact on Heart Health

Researchers led by Earle Chambers, Ph.D., M.P.H., have received a four-year, $2.9 million grant from the NIH to study how neighborhood redevelopment affects cardiovascular disease (CVD) among older Black and Hispanic residents in the Bronx, home to the poorest urban congressional district in the United States and to numerous redevelopment projects. CVD is the country’s leading cause of death. The researchers will compare the prevalence of CVD events (such as heart attacks and strokes) and CVD risk factors (such as hypertension, diabetes, and obesity) among cohorts of midlife and older residents of two Bronx neighborhoods: the Jerome Avenue area, which is undergoing redevelopment, and the Southern Boulevard area, which is not. Dr. Chambers is a professor and the director of research in the department of family and social medicine and a professor of epidemiology & population health and of psychiatry and behavioral sciences at Einstein.

Training Cancer Specialists to Focus on Health Equity

The NCI-designated Montefiore Einstein Comprehensive Cancer Center (MECCC) has received a five-year, $2.9 million NCI grant to train physicians and scientists to conduct clinical and translational oncology research, with a special emphasis on investigating and addressing health inequities in the Bronx. The funding, part of the Paul Calabresi Career Development Award for Clinical Oncology (PCACO), will support up to four scholars for two to three years. The MECCC has enrolled 24 scholars since receiving its first PCACO grant in 2010. Principal investigators are Amit Verma, M.B.B.S., MECCC’s associate director of translational science and director of the division of hemato-oncology at Einstein and Montefiore; and Yvonne Saenger, M.D., co-director of the cancer therapeutics program and director of the cancer immunotherapy program at MECCC and associate professor of oncology, of microbiology & immunology, and of pathology at Einstein.

Developing Novel Compounds Against Bladder Cancer

The survival rate for bladder cancer—one of the most common cancers in the United States—has not improved over the past three decades. Xingxing Zang, Ph.D., has received a five-year, $2.7 million grant from the NCI to identify and develop novel immune checkpoint inhibitor (ICI) drugs for treating bladder cancer. ICIs are monoclonal antibodies that prevent tumor cells from suppressing attacks by immune cells. Dr. Zang has already identified a novel therapeutic target: the previously unrecognized immunosuppressive pathway in which the protein HHLA2 on bladder-cancer cells binds to the receptor KIR3DL3 on T cells and natural killer cells. He will study the function of the KIR3DL3/HHLA2 pathway in bladder cancer and develop ICIs to interrupt the pathway. Dr. Zang is a professor of microbiology & immunology, of oncology, of medicine, and of urology, the Louis Goldstein Swan Chair in Women’s Cancer Research at Einstein, and a member of MECCC.

Understanding Brain Activity During Sleep and Wakefulness

Sleep and wakefulness influence both cognitive and overall health, yet the neural mechanisms that regulate them are not well understood. The NIH has awarded Renata Batista-Brito, Ph.D., a five-year, $2.6 million grant to investigate the role played by long-range inhibitory neurons of the cerebral cortex during sleep and wakefulness. Dr. Batista-Brito and her colleagues hypothesize that the activity of cortical long-range inhibitory neurons that express SST and nNOS—the so-called SST/nNOS neurons—generate slow cortical rhythms that regulate the transition from the brain’s highly active “up” state to its less-active “down” state. Since those rhythms are believed to affect memory and other brain functions, the activity of SST/nNOS neurons may therefore profoundly influence our sleeping and waking lives. Dr. Batista-Brito is an assistant professor in the Dominick P. Purpura Department of Neuroscience, of genetics, and of psychiatry and behavioral sciences at Einstein.

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