Profile

Leon Epstein  
  Professor, Pediatrics and Neurology

  

Research Interests 
 

My research has largely centered on viral pathogenesis in the nervous system. My initial work with HIV developed while caring for children with HIV infection when the AIDS epidemic began in 1983. This lead to the first description of the clinical and neuropathological features of primary HIV infection of the nervous system. Soon thereafter, we identified HIV (then HTLV-IIIB/LAV) in brain tissue from infected children by transmission to chimpanzees (Gadjusek, Lancet 1985, 1:55) and demonstrated HIV in the brain of AIDS patients by Southern blot and in situ bybridization (Shaw, Science 1985, 227:177). Later we reported evidence of the blood brain barrier penetration by the virus (Epstein, Ann Neurol 1987, 21:397); and developed molecular techniques to identify HIV by PCR amplification directly from brain tissue (Epstein, Virology 1991, 180:583). These studies subsequently identified one important determinant of macrophage tropism in the V-3 loop of the viral envelope (Westervelt, J Virol 1992, 66:2577) and demonstrated that the regulatory gene nef is expressed in brain tissue (Blumberg, J Virol 1992, 65, 5256). For several years our studies focused on HIV induced neuronal injury, blood brain barrier dysfunction, and preclinical drug development (Gelbard, 1995 Neuropathol. Applied Neurobiol; 21:208-217; Fine, 1996 J Biol Chem 271:15303; New 1998 J Biol Chem, 273:17852). We successfully translated observations regarding HIV neuropathogenesis into Phase I/II clinical trials using neuroprotective compounds through the formation of the Dana Consortium on Therapy for HIV Dementia and Related Cognitive Disorders (Rochester/Johns Hopkins/Columbia). (The Dana Consortium 1997 Neurology 49:142). We recently completed a large multi-site program project that assessed the impact of quantitative measures of HIV levels in plasma and CSF on cognitive outcomes in the era of highly active antiretroviral therapy (Marder 2003 Neurology 60:1467-1473). Current activity in my laboratory is focused on the role of Human Herpes Virus 6 and 7 (HHV-6, HHV-7). We found that HHV-6 and HHV-7 are the most common causes of febrile seizures in children (Hall 1994, N Engl J Med 331:432-438) and that HHV-6 can be found localized to the hippocampus of immunosuppressed patients with limbic seizures (Wainwright 2001, Ann Neurol 50:612-619). We are now engaged in a large epidemiological study that will identify 200 children with febrile status epilepticus to determine if primary HHV-6 or HHV-7 infection at the time of presentation, identified by DNA and RT-PCR will correlate with MRI evidence of hippocampal damage (mesial temporal sclerosis) and the development of temporal lobe seizures.

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