GURUDUTT N. PENDYALA, PhD
Instructor, Howard Fox Laboratory
985800 Nebraska Medical Center
Omaha, NE 68198-5800
Keywords: SIV/HIV, Methamphetamine (METH), Proteomics, Mass Spectrometry
Methamphetamine (METH) is a stimulant drug that has been around for decades. Its popularity has waxed and waned over the years, but its use seems to be increasing in many parts of the United States and in several population subgroups.
Being addictive, it can be injected thereby increasing sexual arousal while reducing inhibitions. Because of these attributes, a majority of METH users are at a high risk of contracting HIV/AIDS. This emerging double epidemic of substance abuse and HIV infection is a multifaceted problem requiring understanding the causal mechanism of how such drug of abuse could affect the host-virus dynamics and accelerate its progression.
While profiling of biofluids such as CSF and plasma have identified potential markers, the real clues that can divulge associated changes during disease progression is by analyzing the brain itself. However, given the complexity of the brain, not much progress has been accomplished at this front. Using rhesus monkeys infected with the simian immunodeficiency virus (SIV) as a model, our lab employs classical biochemical sub cellular fractionation techniques coupled to quantitative mass spectrometry based proteomics to unravel the changes at the level of the synapse. Such analysis holds great promise for improving our understanding of synaptic molecular composition during neuroplasticity during a comorbid condition.
Techniques used in the Laboratory
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- Isolation of brain organelles by biochemical fractionation
- OFFGEL fractionation of proteins and peptides
- Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) coupled to mass spectrometry for profiling organelles and biofluids (plasma and CSF)
- Pendyala G, Trauger SA, Siuzdak G, Fox HS. Quantitative Proteomic Plasma Profiling Reveals Activation of Host Defense to Oxidative Stress in Chronic SIV and Methamphetamine Comorbidity. AIDS Res Hum Retroviruses. 2010 Oct 7.
- Pendyala G, Fox HS. Proteomic and metabolomic strategies to investigate HIV-associated neurocognitive disorders. Genome Med. 2010 Mar 30;2(3):22.
- Pendyala G, Trauger SA, Siuzdak G, Fox HS (2009). "Quantitative plasma proteomic profiling identifies the vitamin E binding protein Afamin as a potential pathogenic factor for SIV induced CNS disease" J Proteome Res 2010 Jan;9(1):352-8.
- Pendyala G, Trauger SA, Kalisiak E, Ellis, RJ, Siuzdak G, Fox HS (2009). "Cerebrospinal fluid proteomics reveals potential pathologenic changes in the brains of SIV-infected monkeys" J Proteome Res 8 (5), 2253-2260.
- Darna M, Schmutz I, Richter K, Yelamanchili SV, Pendyala G, Holtje M, Albrecht U, Ahnert-Hilger G (2009). "Time-of-day dependent sorting of vesicular glutamate transporter to the plasma membrane" J Biol Chem 284 (7), 4300-4307
- Wikhoff WR, Pendyala G, Siuzdak G, Fox HS (2008). "Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques" J Clin Invest 118 (7), 2661-2669
- Pendyala G, Want EJ, Webb W, Siuzdak G, Fox HS. (2007). "Biomarkers for neuroAIDS: The widening scope of Metabolomics" J Neuro Imm Pharma 2 (1), 72-80
additional articles in pubmed.gov