Research Notes

Major NIH Research Awards

Major NIH Research Awards

Furthering Intellectual Disability Research

The Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (RFK IDDRC) has received a five-year, $5 million National Institutes of Health (NIH) grant to continue its research and clinical outreach to improve the lives of children with intellectual and developmental disabilities. Key to this effort are the RFK IDDRC’s support of collaborations between bench scientists and clinicians at Einstein and Montefiore and its support of research conducted within the center’s four scientific cores.

The center’s signature research project involves studying mutations in the KDM5C gene, which plays a critical role in neuronal function. KDM5C mutations are an important cause of X-linked intellectual disability in males and are associated with some cases of autism spectrum disorder. Principal investigators on the grant are Steven U. Walkley, D.V.M., Ph.D., professor in the Dominick P. Purpura Department of Neuroscience and co-director of the RFK IDDRC, and Sophie Molholm, Ph.D., professor of pediatrics and co-director of the RFK IDDRC.

Addressing Pandemic-Related Stress in the Bronx

The NIH has awarded researchers at Einstein and Montefiore a five-year, $5 million grant to study interventions for reducing pandemic-related stress among Bronx parents and caregivers and increasing their access to healthcare. The study will enroll 360 Bronx parents drawn from three groups who face unique vulnerabilities during COVID-19: parents of children with autoimmune disorders such as lupus and juvenile arthritis; parents of children with psychiatric conditions; and parents who are healthcare workers.

Participants will be randomized to receive 12 weeks of a mentalization-based group therapy, 12 sessions of parenting education with a healthcare app that also supports communication with healthcare teams, or group therapy plus parenting education with the app. The study’s principal investigator is Vilma Gabbay, M.D., M.S., director of the Psychiatry Research Institute at Montefiore Einstein; the co–principal investigator is Jonathan Alpert, M.D., Ph.D., chair of psychiatry at Montefiore and Einstein.

Helping Infants Born to HIV-Infected Mothers

Although antiretroviral therapy (ART) has revolutionized the care of people living with HIV, infants who are born to women with HIV who are on that therapy still face a greater risk of illness, low birth weight, death, and other negative health outcomes compared with infants born to mothers who are not infected with HIV.

Marcel Yotebieng, M.D., Ph.D., M.P.H., has received a five-year, $3.6 million grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to better understand why infants of HIV-positive mothers often don’t fare well and to develop strategies for improving their health outcomes.

The study will involve a cohort of women in Kinshasa, Democratic Republic of the Congo. Dr. Yotebieng and colleagues will follow 600 women living with HIV on ART treatment, 600 HIV-negative women, and infants born to these women, from delivery through up to 12 months postpartum. Dr. Yotebieng is an associate professor of medicine at Einstein.

New Approach Against a Killer Bacterium

Better treatments are needed for the human gut bacterium Clostridioides difficile (usually referred to as C. diff), which has developed resistance to many antibiotics. C. diff releases toxins that cause severe diarrhea and colitis, leading to about 15,000 deaths each year in the United States, mainly among hospitalized patients.

Vern L. Schramm, Ph.D., is developing drugs that combat C. diff infections by neutralizing the bug’s disease-causing toxins. Dr. Schramm has received a five-year, $3.3 million NIH grant to continue his efforts to develop drugs known as transition-state analogues to combat C. diff infections. By eliminating the toxins but not the bacteria producing them, such drugs should prevent toxin-induced tissue damage without pressuring C. diff to develop resistance, as all too often occurs with standard antibiotics. In addition, the toxin-targeting drugs should not disrupt other microbes in patients’ gut microbiomes. Dr. Schramm is a professor and the Ruth Merns Chair in Biochemistry.

Pursuing a New Osteosarcoma Therapy

Osteosarcoma is the most common primary bone tumor of adolescents and young adults. Only 20% of patients with metastatic osteosarcoma can now be cured. The Wnt signaling pathway drives normal osteoblast (bone-forming cell) differentiation, so researchers have speculated that aberrant Wnt signaling may cause osteosarcoma. The DKK1 protein inhibits Wnt signaling and occurs at high levels in the blood of newly diagnosed osteosarcoma patients.

In research involving a mouse model of human osteosarcoma, David Loeb, M.D., Ph.D., has shown that an antibody that neutralizes DKK1 increases Wnt signaling in the primary tumor and abolishes metastasis. Dr. Loeb has received a five-year, $3.3 million NIH grant to test whether a small-molecule inhibitor of DKK1 affects Wnt signaling, tumor growth, and osteosarcoma metastasis in a mouse model.

Dr. Loeb is a professor of pediatrics and of developmental and molecular biology at Einstein and the chief of pediatric hematology/oncology at Einstein and Montefiore.

Gaining Insights Into Huntington’s Disease

Aldrin Molero, M.D., Ph.D., has received a five-year, $3 million NIH grant to investigate the abnormalities that occur early in neural development in Huntington’s disease. This inherited neurodegenerative disorder is caused by a mutation in the huntingtin gene. In a previous study, Dr. Molero found that disrupting huntingtin’s function impairs the development of interneurons—an important group of cells that modulate the activity of other neurons throughout life.

For his NIH research work, Dr. Molero is studying the underlying mechanisms that alter interneurons during development and how those disrupted interneurons influence the maturation of developing brain circuits that are later affected in Huntington’s disease. Findings from this research may result in the engineering of therapies that can be used at an early stage to modify the progression of Huntington’s disease. Dr. Molero is an assistant professor in the Saul R. Korey Department of Neurology at Einstein.

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