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Viral and Host Genetics Program

Overview

This program supports basic and clinical research to determine the viral and host genetic factors involved in central nervous system (CNS) impairment caused by HIV-1 worldwide. Viral and host genetic factors contribute to pathophysiology of HIV-1 associated CNS dysfunction. New genetic technologies can enhance our understanding of the pathophysiological mechanisms, and aid in the identification of innovative strategies for the discovery of therapeutic drug targets. The program encourages use of state-of-the-art approaches (e.g., transcriptomics, phenomics, epigenomics, whole genome association studies, next generation sequencing, single cell technologies, and systems biology) to identify and validate viral and host genetic factors that influence the pathophysiology of HIV-1 associated CNS dysfunction.

Areas of Emphasis

Viral Genetics

  • Study the role of HIV-1 sequence diversity in understanding neurovirulence, neurotropism, discordant and compartmentalized viral evolution, CNS cell type-specific infection, regional genetic heterogeneity, and associated functional effects.
  • Examine molecular and genetic mechanisms of potential subtype/clade differences in HIV-1 neuropathogenesis.
  • Identify viral and host genetic signatures associated with HIV-1 associated CNS dysfunction.
  • Study the role of viral epigenetic factors in the pathophysiology of HIV-1 associated CNS dysfunction.
  • Understand the role of viral and host transcriptional regulation (including viral protein modifications, histone modifications, changes in chromatin structure, and non-coding RNA) in HIV-1 neuropathogenesis.

Host Genetics

  • Examine the role of host genetic factors, including epigenetic mechanisms in regulating susceptibility to HIV-1 associated CNS dysfunction.
  • Assess epigenetic host response to viral infection mediated through chromatin modification, non-coding RNAs, and DNA methylation.
  • Study host genetic factors involved in regulating responsiveness to antiretroviral therapy and neuroprotective adjuvant therapies (pharmacogenomics).
  • Delineate the genetic basis of host restriction factors in CNS cell types.

Contact

Jeymohan Joseph, Ph.D.
5601 Fishers Lane, Room 9G20
Rockville, MD 20852
240-627-3869, jjeymoha@mail.nih.gov