Description of Research Expertise
Mechansims and determinants of HIV induced neuronal injury. Neuronal cell responses to virus induced injury.
Key words: neuron, hippocampus, apoptosis, gene expression, single-cell mRNA, HIV, chemokine receptor, NMDA receptor.
Description of Research
The Kolson lab focuses the roles for inflammation, immune activation, and oxidative stress in virus-induced neurodegeneration. Major areas of focus involve immunodeficiency viruses (HIV and simian immunodeficiency virus/SIV). Research in the lab involves analysis of human brain specimens from HIV infected individuals, studies of neurodegeneration and neuroinflammation in SIV-infected Rhesus macaques, in vitro modeling of HIV-induced neurodegeneration, and oxidative stress responses in vitro and in vivo. We also study responses to HIV infection in cohorts of individuals participating in national/international clinical cohort trials.
We have developed a unique in vitro model of HIV-induced neurodegeneration, and we combine this model with analyses of autopsied human brains from HIV infected individuals and SIV-infected Rhesus macaques to identify pathways of neurodegeneration and modulating effects of host antioxidant response genes. We have identified a defect in the human host anti-oxidant response to HIV infection of the brain that determines an individual's risk for neurodegeneration and neurocognitive impairment in HIV infection. This has led to a pilot proof-of-principle neuroprotection drug study in Rhesus macaques. In neurogenetic studies, we have linked a common genetic polymorphism ((GT)n dinucleotide repeat length variation) in the antioxidant gene heme oxygenase-1, to risk for neuroinflammation and neurocognitive impairment in HIV-infected persons.
Dr. Kolson has had active NIH funding for his laboratory since 1992, and he has trained PhD and MD-PhD students in his lab. Several of his students have been awarded a Ruth L. Kirschtein (F30, F31) National Research Service Award (NRSA) to support their own research training. He is active in training graduate and medical students as a laboratory research mentor, and he also gives interested trainees an opportunity for exposure to translational aspects of neurovirology/neuroimmunology research by offering students an opportunity to attend his weekly multiple sclerosis outpatient clinic.
Kolson DL, Sabnekar P, Baybis M and Crino PB: Gene expression in TUNEL-positive Neurons in HIV-infected brain J. Neurovirol. 10 ((suppl. 1)): 102-7,2004.
Patel SH, Kolson DL, Glosser G, Matozzo I, Ge Y, Babb JS, Mannon LJ and Grossman RI.: Correlation between percentage of brain parenchymal volume and neurocognitive performance in HIV infected patients. Am. J. Neuroradiol. 23 : 543-549,2002.
Chen W, Sulcove J, Frank I, Jaffer S, Ozdener H and Kolson DL.: Development of a human neuronal cell model for HIV/macrophage-induced neurotoxicity: apoptosis induced by HIV-1 primary isolates and evidence for involvement of the Bcl-2/Bcl-xL-sensitive intrinsic apoptosis pathway. J. Virology 76 : 9407-9419,2002.
Ge Y, Grossman RI, Babb JS, Rabin ML, Mannon LJ and Kolson DL.: Age-related total gray matter and white matter changes in normal adult brain. Part I. Volumetric MR imaging analysis. Am. J. Neuroradiol. 23 : 1327-1333,2002.
Ge Y, Grossman RI, Babb JS, Rabin ML, Mannon LJ and Kolson DL.: Age-related total gray matter and white matter changes in normal adult brain. Part II: quantitative magnetization transfer ratio histogram analysis. Am. J. Neuroradiol. 23 : 1334-1341,2002.
O’Donnell, LA, Chen W, Agrawal A, Sulcove J and Kolson DL.: Potential neuroprotective role of APJ/apelin interactions: protection against HIV-induced apoptosis. NIMH workshop: Viral and Host Genetic Factyors Regulating HIV/CNS Disease, Rockville, MD. : 2002.
Martin-Garcia J, Kolson DL, Gonzalez-Scarano F.: Chemokine receptors in the brain: their role in HIV infection and pathogenesis. AIDS (in press). : 2002.
Ge Y, Grossman RL, Udupa JK, Babb JS, Kolson DL and McGowan JC.: Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis. Am. J. Neuroradiol. 22 : 470-475,2001.
Ge Y, Grossman RL, Udupa JK, Babb JS, Nyul LG and Kolson DL.: Brain atrophy in relapsing-remitting multiple sclerosis: fractional volumetric analysis of gray matter and white matter. Radiology 220 : 606-610,2001.
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University of Pennsylvania
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