Associate Professor of Medicine (Nephrology) and Public Health (Chronic Disease Epidemiology); Director, Clinical and Translational Research Accelerator (CTRA); Course Director, Interpretation of the Medical Literature; Co Director, Human Genetics and Clinical Research Core
Targeting Histone Deacetylase in Focal Segmental Glomerulosclerosis: From Mice to Patients
Our prior research in a mouse model of proteinuric kidney disease revealed upregulation of a protein called histone deacetylase (HDAC). Inhibition of this protein with valproic acid (VPA) resulted in improved kidney function and survival in mice. The purpose of this research is to understand the mechanism linking histone deacetylase activity to worsening kidney function in mice and to confirm that such effects might be present in humans, using several large national databases.
The first aim of this study is to confirm the VPA effects using another HDAC inhibitor called suberanilohydroxamic acid (SAHA). The next aim will confirm that HDAC is the important factor mediating the effect of VPA by knocking this gene out of key cells in the kidney. The third aim will determine which genes are up- or down regulated by HDAC in order to better understand how the protective effect occurs. The fourth aim will examine the effect of VPA exposure in three large cohorts totaling over 4.5 million individuals, some receiving care at VA hospitals and some at a large community-based health system. Finally, the fifth aim will identify which patients most strongly benefit from VPA exposure.
Project Funding
Funding for this project comes, in part, from the following grant:
W81XWH-17-1-0663 (Department of Defense)
"Targeting Histone Deacetylase in Focal Segmental Glomerulosclerosis - From Mice to Patients"
Leadership
Professor of Medicine (Nephrology); Director, Undergraduate Summer Research Program for Nephrology; Director, Research Fellowship; Director for Educational Enrichment, George M. O'Brien Center, Nephrology
Collaborators
Targeting Histone Deacetylase
Alex Chang, MD
Clinical Investigator in Nephrology, Geisinger Health Systems
Maria Ciareglio, PhD
Associate Professor of Biostatistics, School of Public Health, Yale University
Morgan Grams, MD, MHS, PhD
Associate Professor of Medicine, Nephrology, Johns Hopkins University
Amy Justice, MD, PhD
Professor of Medicine, (General Medicine) and of Public Health, Yale University and VA Connecticut Healthcare System
Janet Tate, MPH, ScD
Assistant Professor, (General Medicine) Yale University