Durham Research Center 1, Room 8011
985880 University of nebraska Medical Center
Omaha, NE 68198-5880
Keywords: drugs of abuse, HIV, autophagy, endoplasmic reticulum stress, epigenetics, microRNAs
InterCOM | July/August 2017
My long-term goal is to investigate the epigenetic changes that occurred during HIV-1 infection and drug abuse leading to glial cells (microglia and astrocytes) activation and to identify potential therapeutic strategies for HAND treatment.
Epigenetics is defined as heritable changes in gene activity and expression that occur without alterations in the DNA sequence per se. It is well-known that three major epigenetic modifications tightly regulate these non-genetic alterations: DNA methylation, histone tail modifications, and microRNAs. These critical epigenetic changes have been established to share a close association with cocaine abuse and HIV-1 infection. The detailed epigenetic and molecular mechanism(s) underlying the cumulative effects of HIV-1 and drug abuse on microglial activation however, remain poorly understood. To address this, my research mainly focusses on the epigenetic promoter DNA methylation and neuroinflammation in the context of HIV-1 and cocaine. Information gleaned from these studies will form the basis for the future development of epigenetic targets as adjunctive therapeutic modalities for alleviating the symptoms of HAND in the era of cART.
- Periyasamy P, Guo ML, Buch S. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy. Autophagy. 2016;12(8):1310-29. PMID: 27337297.
- Cai Y, Arikkath J, Yang L, Guo ML, Periyasamy P, Buch S. Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders. Autophagy. 2016;12(2):225-44. PMID: 26902584.
- Guo ML*, Liao K*, Periyasamy P, Yang L, Cai Y, Callen SE, Buch S. Cocaine-mediated microglial activation involves the ER stress-autophagy axis. Autophagy. 2015;11(7):995-1009. PMID: 26043790. * equal first author.
- Pendyala G, Periyasamy P, Callen S, Fox HS, Lisco SJ, Buch SJ. Chronic SIV and morphine treatment increases heat shock protein 5 expression at the synapse. J Neurovirol. 2015;21(5):592-8. PMID: 26037114.
- Palsamy P, Bidasee KR, Shinohara T. Selenite cataracts: activation of endoplasmic reticulum stress and loss of Nrf2/Keap1-dependent stress protection. Biochim Biophys Acta. 2014;1842(9):1794-805. PMID: 24997453.
- Palsamy P, Bidasee KR, Ayaki M, Augusteyn RC, Chan JY, Shinohara T. Methylglyoxal induces endoplasmic reticulum stress and DNA demethylation in the Keap1 promoter of human lens epithelial cells and age-related cataracts. Free Radic Biol Med. 2014;72:134-48. PMID: 24746615.
- Palsamy P, Bidasee KR, Shinohara T. Valproic acid suppresses Nrf2/Keap1 dependent antioxidant protection through induction of endoplasmic reticulum stress and Keap1 promoter DNA demethylation in human lens epithelial cells. Exp Eye Res. 2014;121:26-34. PMID: 24525405.
- Elanchezhian R, Palsamy P, Madson CJ, Lynch DW, Shinohara T. Age-related cataracts: homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection. Chem Biol Interact. 2012;200(1):1-10. PMID: 22964297.
- Palsamy P, Ayaki M, Elanchezhian R, Shinohara T. Promoter demethylation of Keap1 gene in human diabetic cataractous lenses. Biochem Biophys Res Commun. 2012;423(3):542-8. PMID: 22683333.
- Elanchezhian R, Palsamy P, Madson CJ, Mulhern ML, Lynch DW, Troia AM, Usukura J, Shinohara T. Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells. Cell Death Dis. 2012;3:e301. PMID: 22513875.