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Manisha Patel, Ph.D.

Associate Professor, Department of Pharmaceutical Sciences

Mailing address:
4200 E. 9th Ave, C238
Denver, CO 80262

Telephone:
Voice:     303-315-2973  
Lab:        303-315-2974    
Fax:        303-315-0274
E-Mail:   Manisha.Patel@uchsc.edu

Affiliations:
University of Colorado, Program in Neuroscience
National Jewish Medical & Research Center, Department of Medicine

Training and Education:
B.S., Pharmacy, M.S. University
Ph.D., Pharmacology and Toxicology, Purdue University
Post-doc, Neuroscience, Duke University. 

Research Interests:
The overarching theme of the laboratory is to understand the role of reactive species and mitochondrial mechanisms in neuronal disorders. Research in the laboratory is focused on three major areas.

Oxidative stress and mitochondrial dysfunction in temporal lobe epilepsy
Epilepsy is a recent addition to the diverse array of acute and chronic neurological disorders in which the role of oxidative stress and mitochondrial dysfunction is rapidly emerging. Work from our laboratory has identified distinct subcellular sources and mechanisms of seizure-induced free radical production and impaired mitochondrial redox status. Ongoing efforts are aimed at determining the role of mitochondrial dysfunction and oxidative mechanisms in epileptogenesis.

  • Liang LP, Y.S. Ho and Patel M. Mitochondrial superoxide production in kainate-induced hippocampal damage. Neuroscience 101(3):563-570, 2000.
  • Liang LP, Patel M. Mitochondrial oxidative stress and increased seizure susceptibility in Sod2-/+ mice Free Rad. Biol. Med. 36(5):542-554, 2004.
  • Patel M, Li QY, Chang L-Y, Crapo JD, Liang L-P. NADPH oxidase activation and extracellular superoxide radicals in seizure-induced neuronal death. J. Neurochem. 92(1)123-131, 2005.
  • Liang LP, Patel, M. Seizure-induced changes in mitochondrial redox status Free Rad. Biol. Med. 40(4): 2006.
  • Patel M, Liang L-P, Hou H, Williams BB, Kmiec M, Swartz, HM, Fessel J, Roberts LJ. Seizure-induced formation of isofurans: novel products of lipid peroxidation whose formation is positively modulated by oxygen tension J. Neurochem.104:264-270, 2008.
  • Jarrett SJ, Liang LP, Hellier J, Staley, KJ, Patel M. Mitochondrial DNA damage and impaired base excision repair during epileptogenesis, Neurobiol. Dis. 2008 In press

    • Mitochondrial mechanisms of oxidative damage in Parkinson’s Disease
    One important mechanism of superoxide toxicity is based on its direct oxidation and resultant inactivation of iron-sulfur (Fe-S) proteins such as aconitases and ability to act as a precursor of more potent oxidants e.g. hydroxyl radical. Current efforts in the laboratory are focused on addressing the hypothesis that superoxide toxicity via oxidative inactivation of mitochondrial aconitase contributes to neuronal death in animal models of Parkinson’s disease. We have identified a novel pool of mitochondrial iron that correlates with mitochondrial aconitase inactivation in experimental Parkinson’s disease. Efforts are also underway to determine mitochondrial mechanisms by which environmental redox cycling agents generate reactive oxygen species.

  • Liang LP and Patel M. Iron-sulfur enzyme mediated mitochondrial superoxide toxicity in experimental Parkinson’s disease. J. Neurochem.90:1076-1084, 2004.
  • Castello PR, Drechsel D, Patel M. Mitochondria are a major source of paraquat-induced reactive oxygen species production. J. Biol. Chem. Vol 282 (19): 14186-14193, 2007.
  • Fariss MW, Chan CB, Patel M, Van Houten B, Orrenius S. Role of mitochondria in toxic oxidative stress. Molecular Interventions 5(2):94-111, 2005.

    • Manganese Porphyrin Catalytic Antioxidants as Neuroprotective Agents
    A major goal of our research is to develop neuroprotective therapeutic entities designed to scavenge and detoxifying reactive oxygen species. One approach has been to utilize mice that overexpress endogenous superoxide dismutases (SOD1/2/3). A second approach is the use of manganese porphyrin compounds that can catalytically eliminate a variety of reactive oxygen species. We utilize a two-tier approach composed of vitro and in vivo models to assess neuroprotective actions of manganese porphyrins and correlate them with their pharmacokinetic parameters and ability to protect cellular targets against oxidation. We have recently identified an orally active metalloporphyrin that is efficacious in a mouse model of parkinsonism.

  • Patel M and Day BJ. Metalloporphyrin class of therapeutic catalytic antioxidants. Trends Pharmacol Sci 20:359-364, 1999.
  • Patel M. Metalloporphyrins improve the survival of Sod2 deficient neuronal cultures. Aging Cell 2(4):219-222, 2003.
  • Castello P.R., Drechsel, DA, Day BJ, Patel M. Inhibition of mitochondrial hydrogen peroxide production by glyoxylate metalloporphyrins J. Pharm. Exp. Ther.  2008 In press.
  • Liang L-P, Huang J, Fulton R, Day BJ, Patel M. An orally active metalloporphyrin protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in vivo. J. Neurosci. 27(16):4326-4333, 2007.

    • Teaching:
    Professional Program: Instructional Methods II, Integrated Organ Systems IV (neuropharmacology)
    Graduate Program: TXCL 7322 (Principles of Toxicology), University of Colorado, Department of Medicine

    Curriculum Vitae

    Last updated: 2/14/08