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Major NIH Research Awards: Summer/Fall 2020

Probing Predementia and Alzheimer’s

Joe Verghese, M.B.B.S., M.S., received two five-year National Institutes of Health (NIH) grants totaling $13.8 million to study predementia and Alzheimer’s disease. Dr. Verghese is a professor and the chief of the unified divisions of geriatrics and of cognitive & motor aging at Einstein and Montefiore, the Murray D. Gross Memorial Faculty Scholar in Gerontology, and the director of the Resnick Gerontology Center at Einstein.

The first grant, for $7.6 million, funds a study of the predementia condition called motoric cognitive risk (MCR). The study, involving 11,000 older adults in six countries, will look for biomarkers for MCR.

The second grant, for $6.2 million, funds research on at-home use of transcranial direct current stimulation (tDCS), delivered through a head covering. The study will evaluate whether six-month use of tDCS can improve cognition in 100 Alzheimer’s patients.

Predicting the Spread of Breast Cancer

Einstein researchers have received a five-year, $5.1 million grant from the NIH to further develop their novel tests for predicting whether primary breast tumors are likely to spread. The principal investigators are Thomas Rohan, M.B.B.S., Ph.D., D.H.Sc., professor and chair of epidemiology & population health, and John Condeelis, Ph.D., professor and co-chair of anatomy & structural biology.

The test for predicting tumor spread was developed by Dr. Condeelis and his colleagues in the Gruss Lipper Biophotonics Center and its Integrated Imaging Program, both of which he co-directs. They had observed that breast cancer spreads elsewhere in the body when three specific cell types are in direct contact, forming a “doorway” (referred to as a tumor microenvironment of metastasis, or TMEM) that allows tumor cells to enter blood vessels. The greater the number of TMEMs observed in tumors, the more likely the tumor will metastasize.

Understanding ‘Chemo Brain’ in Children

Chemotherapy usually cures children diagnosed with acute lymphoblastic leukemia, but it may affect key cognitive functions, including memory and attention. Elyse Sussman, Ph.D., professor in the Dominick P. Purpura Department of Neuroscience and of otorhinolaryngology-head and neck surgery, along with colleagues at the Rutgers Cancer Institute of New Jersey, has received a five-year, $4.6 million NIH grant to determine how chemotherapy exerts its damaging effects on the brain. They will investigate how chemotherapy disrupts sensory processing, memory, and attention in children; where damage is occurring in the brain; and whether a biomarker can be found to identify those most vulnerable.

Their long-term objective is to develop protective interventions that can prevent permanent harm. The new study will include 240 children between the ages of 5 and 12 at Children’s Hospital at Montefiore and the Rutgers Cancer Institute.

Understanding the Causes of TB Latency

Many people who are infected with Mycobacterium tuberculosis (Mtb), the bacterial pathogen that causes tuberculosis (TB), harbor latent bacteria that later in life reactivate to cause active disease. Determining the mechanisms that regulate Mtb latency is important for understanding how the bacteria inflicts its damage.

Research by John Chan, M.D., suggests that the Mtb gene Rv2623 may play an important role in regulating Mtb latency. The NIH has awarded Dr. Chan a five-year, $4.5 million grant to study how Rv2623—the protein encoded by the Rv2623 gene—regulates the growth of Mtb in an infected host. The findings from this research may reveal how Mtb evades the host’s immune response to persist in a dormant state in infected people, and may suggest novel therapies for treating Mtb infection. Dr. Chan is a professor of medicine and of microbiology & immunology at Einstein and an attending physician in infectious diseases at Montefiore.

Seeking the Roots of Adolescent Depression

Vilma Gabbay, M.D., and colleagues at Einstein and Montefiore have received a five-year, $4 million NIH grant to identify biological and behavioral factors predicting the duration and severity of depression in adolescents. Dr. Gabbay is an associate professor of psychiatry and behavioral sciences and in the Dominick P. Purpura Department of Neuroscience at Einstein and director of the Psychiatry Research Institute at Montefiore Einstein (PRIME).

Her team hypothesizes that inflammation leads to dysregulation of reward circuitry (brain areas involved in feeling pleasure) and, eventually, to depression in adolescents. Previous research has shown that increased inflammation of the brain is associated with the inability to feel pleasure. During three sessions over two years, 120 adolescents with depressive symptoms will receive evaluations for psychiatric illness, functional MRI of reward circuitry, and blood tests for inflammation.

Insights Into TB Drug Resistance

The antituberculosis drug bedaquiline, combined with at least four other drugs, has transformed the treatment of multidrug- and extensively drug-resistant (M/XDR) TB. However, due to serious side effects, up to one-fourth of patients stop treatment early. Bedaquiline has a much longer half-life than the drugs it is combined with, so a halt in treatment means that bedaquiline persists in the bloodstream for many months, allowing TB bacteria to become resistant to it in the absence of other drugs to combat them.

James Brust, M.D., was awarded a five-year, $3.6 million grant from the NIH to investigate the development of resistance to bedaquiline after therapy is interrupted. The study involves patients in South Africa with M/XDR TB and will address fundamental questions about bedaquiline pharmacology and resistance. Dr. Brust is an associate professor of medicine at Einstein and an attending physician at Montefiore.

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