Charles W. Leffler, Ph.D.

Charles W. Leffler, Ph.D.

Professor
Department of Physiology
Department of Pediatrics


The University of Tennessee Health Science Center
309 Nash Research Building
894 Union Avenue
Memphis, TN 38163
Phone: (901) 448-7122;
Fax: (901) 448-7126
Email: Charles W. Leffler



Education

  • Ph.D. Institution: University of Florida, Department of Zoology
  • Postdoctoral: University of Florida, Department of Physiology

Links

Physiology - Charles Leffler

Research Interests

Research in the laboratory concentrates on control of newborn cerebral circulation. A focus of this research is control of the newborn cerebral microvasculature during physiological and pathological situations, and the cellular mechanisms involved in such control. We investigate autocrine and paracrine communication within the neurovascular unit, with specific current focus on two novel, endogenously produced, gaseous transmitter molecules, carbon monoxide (CO) and hydrogen sulfide (H2S). This research is important because the single most prominent cause of mortality and morbidity in newborns is hypoxic-ischemic brain injury, which often leads to lifelong disability in survivors. The neonatal brain is more susceptible to injury from insufficient or inappropriate blood flow for metabolism than that of the adult because of rapid development and proliferation of neurons and vessels, and high susceptibility to inflammation. Successes in developing approaches to avert and treat perinatal hypoxia-ischemic brain damage have been limited by insufficient understanding of the mechanisms that control perinatal cerebral circulation. The gasotransmitters, CO and H2S, are mechanisms of which greater understanding is urgently needed.

Representative Publications

  • Bukiya A, Dopico AM, Leffler CW, Fedinec A. Dietary cholesterol protects against alcohol-induced cerebral artery constriction. Alcohol Clin Exp Res. 2014 May;38(5):1216-26. doi: 10.1111/acer.12373. Epub 2014 Mar 3. PubMed PMID: 24588122; PubMed Central PMCID: PMC4010119.
  • Basuroy S, Leffler CW, Parfenova H. CORM-A1 prevents blood-brain barrier dysfunction caused by ionotropic glutamate receptor-mediated endothelial oxidative stress and apoptosis. Am J Physiol Cell Physiol. 2013 Jun 1;304(11):C1105-15. doi: 10.1152/ajpcell.00023.2013. Epub 2013 Apr 10. PubMed PMID: 23576575; PubMed Central PMCID: PMC3677176.
  • Bukiya AN, McMillan JE, Fedinec AL, Patil SA, Miller DD, Leffler CW, Parrill AL, Dopico AM. Cerebrovascular dilation via selective targeting of the cholane steroid-recognition site in the BK channel β1-subunit by a novel nonsteroidal agent. Mol Pharmacol. 2013 May;83(5):1030-44. doi: 10.1124/mol.112.083519. Epub 2013 Mar 1. PubMed PMID: 23455312; PubMed Central PMCID: PMC3629834.
  • Liang GH, Xi Q, Leffler CW, Jaggar JH. Hydrogen sulfide activates Ca²⁺ sparks to induce cerebral arteriole dilatation. J Physiol. 2012 Jun 1;590(Pt 11):2709-20. doi: 10.1113/jphysiol.2011.225128. Epub 2012 Apr 16. PubMed PMID: 22508960; PubMed Central PMCID: PMC3424726.
  • Parfenova H, Tcheranova D, Basuroy S, Fedinec AL, Liu J, Leffler CW. Functional role of astrocyte glutamate receptors and carbon monoxide in cerebral vasodilation response to glutamate. Am J Physiol Heart Circ Physiol. 2012 Jun 1;302(11):H2257-66. doi: 10.1152/ajpheart.01011.2011. Epub 2012 Mar 30. PubMed PMID: 22467311; PubMed Central PMCID: PMC3378289.
  • Parfenova H, Leffler CW, Basuroy S, Liu J, Fedinec AL. Antioxidant roles of heme oxygenase, carbon monoxide, and bilirubin in cerebral circulation during seizures. J Cereb Blood Flow Metab. 2012 Jun;32(6):1024-34. doi: 10.1038/jcbfm.2012.13. Epub 2012 Feb 22. PubMed PMID: 22354150; PubMed Central PMCID: PMC3367218.

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