New Research Grants - October 2018

Ravi Ranjan, MD, PhD

Division of Cardiovascular Medicine

NIH/National Heart, Lung, and Blood Institute

Myocardial Substrate Driven Mechanistic Insights into Atrial Fibrillation – R01

9/01/2018 – 8/31/2022

Ablation is the most effective treatment for atrial fibrillation but its success is not very good for persistent atrial fibrillation. The goal of this project is to develop a mechanistic understanding of atrial fibrillation involving the structural changes in the atrial wall. The structural changes will be characterized using high density electrical mapping and imaging including MRI. Based on these measurements potential sites that drive the atrial fibrillation will be identified and targeted during ablation. A mathematical model will also be developed incorporating the structural information to further understand the mechanistic implications as well as test potential ablation targets.

Jerry Cochran, MSW, PhD

Division of Epidemiology

Centers for Disease Control and Prevention

Optimizing Pregnancy and Treatment Interventions for Moms 2.0 – R01

9/30/2018 – 9/29/2021

Medication assisted treatment combined with psychosocial services is the standard of care for opioid dependent pregnant women; however, it is not clear in the field which psychosocial service is optimal. One promising intervention is patient navigation (PN). This study will further develop and refine a PN intervention to prevent postnatal drug use relapse, establish protocols for a multisite randomized clinical trial, and pilot test the finalized intervention and multisite protocols within two health systems with high rates of opioid use disorder among pregnant women.

Sankar Swaminathan, MD

Division of Infectious Diseases

National Cancer Institute

Cancer Center Support Grant Administrative Supplement to Stimulate Research in HIV/AIDS Cancer Research Projects at NCI-designated Cancer Centers

5/1/2018 - 4/30/2020

This proposed project will study the role of epigenetic modifications of the Epstein-Barr Virus (EBV) genome in the oncogenesis of diffuse large B-cell lymphomas (DLBCL) in AIDS patients. 

Non-Hodgkins lymphomas (NHL), are the most common malignancies in HIV-positive patients in the United States (1). Prior to the introduction of combination antiretroviral therapy (cART), the incidence of NHL in AIDS patients was 165-fold that of people without AIDS (2). Despite the introduction of cART, the incidence of DLBCL has only been reduced by approximately 55% and the prognosis of AIDS-associated DLBCL remains poor. The association of Epstein-Barr virus (EBV) with DLBCL is also much higher than in the general population. More than 50% of newly diagnosed DLBCL in HIV infected individuals are EBV+ (3). The factors besides immunosuppression that lead to this increased risk for EBV-positive DLBCL in HIV patients remain to be elucidated.

This project will examine epigenetic and genetic factors that may influence the development of EBV+ DLBCL in HIV patients.  We will examine the role of cellular chromatin modifying proteins CTCF and cohesin that regulate cellular transcription and alter the three-dimensional conformation of chromatin.  These proteins may play a role in EBV gene expression in HIV + DLBCL. By performing ChIP and RNA seq studies, we will assess the function of these proteins in DLBCL tissue samples from AIDS patients.  

Recent studies have identified mutations in key cellular genes that are associated with development of DLBCL.  By performing next generation DNA sequencing of lymphoma samples from AIDS patients, we hope to determine whether EBV substitutes for or synergies with these mutations in AIDS-associated lymphomas.