Research Notes

Major NIH Research Awards: Summer/Fall 2019

Major NIH Research Awards: Summer/Fall 2019

Focusing on Post-HIV Problems

The National Institutes of Health (NIH) has awarded Kathryn Anastos, M.D., and Anjali Sharma, M.D., a seven-year, $23 million grant to study HIV and the chronic illnesses that often accompany HIV infection, including cardiovascular and lung disease, diabetes, and cancer.

The multicenter trial merges two existing studies that for decades have followed women and men who are HIV positive or at risk for HIV infection. The team will enroll 2,500 new participants as well. Researchers will also study disease-related outcomes such as heart attacks and strokes, conduct neuropsychiatric testing to assess cognition, and administer detailed psychiatric evaluations.

Dr. Anastos is a professor of medicine, of epidemiology & population health, and of obstetrics & gynecology and women’s health at Einstein and a general internist at Montefiore. Dr. Sharma is an associate professor of medicine at Einstein and an internist and infectious-disease physician at Montefiore.

Targeting Deadly Viruses

The National Institute of Allergy and Infectious Diseases (NIAID) has awarded an international consortium led by Kartik Chandran, Ph.D., a five-year, $22 million grant to develop antibody-based therapies against four lethal viruses for which approved vaccines or treatments are lacking.

The viruses are the tick-borne Crimean-Congo hemorrhagic fever virus and three hantaviruses, which are spread by rodents: Andes virus, Sin Nombre virus, and Puumala virus. The NIAID has designated all except the Puumala virus as category A agents—emerging infectious diseases or pathogens that pose the highest risk to national security and public health.

Other participating institutions are the U.S. Army Medical Research Institute of Infectious Diseases, Mapp Biopharmaceutical, the University of Texas at Austin, and Adimab, a biotech company. Dr. Chandran is a professor of microbiology & immunology and the Harold and Muriel Block Faculty Scholar in Virology at Einstein.

Obesity and Hypertension

Dongsheng Cai, M.D., Ph.D., received two NIH grants totaling $4.5 million to study the role of the hypothalamus in obesity and hypertension. Dr. Cai has found that sustained activation of astrocytes (cells that surround and support neurons) may contribute to the metabolic dysregulation and subsequent weight gain caused by pro-inflammatory signaling in the hypothalamus.

He was awarded a four-year, $2 million grant to study how hypothalamic astrocytes are altered in inflammation and how those altered astrocytes influence hypothalamic neurons to dysregulate metabolism.

Evidence also indicates that inflammation-induced activation of hypothalamic astrocytes plays a role in obesity-related hypertension (OHT), which accounts for 75% of hypertension cases and is difficult to control. The second grant, for $2.5 million over four years, sponsors Dr. Cai’s research into how the astrocyte-neuron relationship in obesity contributes to OHT. Dr. Cai is a professor of molecular pharmacology at Einstein.

Opioids, HIV, and Brain Damage

HIV can invade the brain and cause chronic neural inflammation and, ultimately, cognitive impairment in most HIV-infected people. Antiretroviral therapies don’t completely relieve the inflammation or reduce brain damage—and opioid abuse makes things worse.

The National Institute on Drug Abuse has awarded Joan W. Berman, Ph.D., and Harris Goldstein, M.D., a five-year, $4.2 million grant to investigate molecular mechanisms that worsen HIV-related inflammation in people who abuse opioids. By analyzing HIV and opioid-induced gene-expression changes, they hope to identify new drugs to quell HIV-caused brain inflammation.

Dr. Berman is a professor of pathology and of microbiology & immunology at Einstein, the Irving D. Karpas Chair in Medicine, and the senior academic adviser to the Sue Golding Graduate Division of Biomedical Sciences. Dr. Goldstein is a professor of pediatrics and of microbiology & immunology and the Charles Michael Chair in Autoimmune Diseases.

A Potential Path to an HIV Cure

Curing HIV-infected individuals has not been possible because neither the human immune system nor antiretroviral therapy can eliminate cells that are latently infected with HIV. These cells become reactivated and reintroduce systemic infection when treatment is halted.

The NIAID awarded Harris Goldstein, M.D., and Steven Almo, Ph.D., a five-year, $4.2 million grant to develop novel immunomodulatory biologics to precisely and markedly expand HIV-specific CD8+ (“killer”) T cells to target and eliminate latent HIV-infected CD4+ T cells intentionally reactivated to make them “visible” to the CD8+ cells. The novel treatment strategy could lead to long-lasting HIV remission or even a functional cure for HIV infection.

Dr. Goldstein is the director of the Einstein-Rockefeller-CUNY Center for AIDS Research. Dr. Almo is a professor and the chair of biochemistry, a professor of physiology & biophysics, and the Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology at Einstein.

Targeting Signals in Alzheimer’s

Diminished somatotropic signaling (i.e., signaling that stimulates body growth) leads to delayed aging and longer life spans in both model organisms and people. Centenarians, in fact, have several mutations that weaken somatotropic signaling.

Sofiya Milman, M.D., has received a five-year, $4 million grant from the National Institute on Aging 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—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 and of genetics at Einstein and an attending physician in medicine at Montefiore.

Unraveling the B-Cell Response Against TB

The bacterial species Mycobacterium tuberculosis (Mtb) caused 1.6 million tuberculosis-related deaths in 2017, according to the World Health Organization. Infection triggers a well-studied T-cell response against Mtb, but the B-cell immune response that leads to antibody production is not clearly understood.

John Chan, M.D., received a five-year, $3.5 million grant from the NIAID to investigate IgM antibodies—the first antibodies that respond to infection—and their role in the host immune response to Mtb. Dr. Chan and colleagues will use mouse and ex vivo macaque tuberculosis (TB) models to better understand the role and importance 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 and of microbiology & immunology at Einstein and an attending physician in infectious diseases at Montefiore.

MS Patients, Mobility, and Falls

Impaired mobility is the most obvious symptom of multiple sclerosis (MS), and falls are common. The life expectancy of MS patients has increased, but studies on mobility and falls among older MS patients are scarce.

Research by Roee Holtzer, Ph.D., suggests that the integrity and proper functioning of the brain, especially the prefrontal cortex, are critical for cognitive control of mobility. He has received a five-year, $3.5 million grant from the National Institute of Neurological Disorders and Stroke to identify brain systems governing mobility in older adults (120 MS patients and 120 controls) to determine whether brain function during active walking can predict falls.

Neuroimaging techniques will measure prefrontal cortex activity and assess the brain’s structural integrity. The findings may identify biomarkers that can be modified to prevent falls. Dr. Holtzer is a professor in the Saul R. Korey Department of Neurology at Einstein.

Sleep and Cognitive Decline

Disturbed sleep is common among older adults and may lead to cognitive decline and Alzheimer’s disease. Carol A. Derby, Ph.D., has received a four-year, $4 million grant from the National Institute on Aging to partner with the ongoing Einstein Aging Study (EAS) to examine the association between sleep patterns and cognition in 500 older Bronx adults.

The research will be a collaboration with Pennsylvania State University professor Orfeu Buxton, Ph.D. In Dr. Derby’s project, EAS participants will wear special watches to collect daily information on sleep and will wear devices to measure their oxygen levels overnight. The data may reveal sleep’s impact on cognition and suggest strategies for preventing cognitive decline.

Dr. Derby is a research professor in the Saul R. Korey Department of Neurology and in the department of epidemiology & population health and is the Louis and Gertrude Feil Faculty Scholar in Neurology at Einstein.

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