Charles W. Leffler, Ph.D.

UTHSC Distinguished Professor

Director, Laboratory for Research in Neonatal Physiology

Departments of Physiology and Pediatrics

University of Tennessee Health Science Center

Voice: 1-901-448-7122

Fax: 1-901-448-7126

email: cleffler@uthsc.edu

Full CV

Education

1969 B.S., University of Miami, Coral Gables, Florida

1971 M.S., University of Florida, Gainesville, Florida

1974 Ph.D., University of Florida, Gainesville, Florida

Research Interest

Research in the laboratory concentrates on control of cerebral circulation. The primary focus of this research involves autocrine/paracrine control of the newborn cerebral microvasculature during physiologically stressful and pathological situations, and the cellular mechanisms involved in such control. We investigate autocrine and paracrine communication within the vessel wall, with specific current focus on the endogenous gasotransmitters, carbon monoxide and hydrogen sulfilde.

These images show the effect of the astrocyte toxin on confluent newborn astrocytes in primary culture. Immunostaining is for F-actin to show the cytoskeletal structure. Note the strong retractions of the astrocyte processes in the two panels treated with the astrocyte toxin as compared to the control panel on the left.
Blood supply of the term newborn cerebral cortex viewed by intravital microscopy. In the brain the arteries and arterioles traverse the surface until the penetrating arterioles lead to the capillaries within the cortex. Capillary effluents are collected in venules that emerge from the gray matter back onto the surface.

Research Support

“Control of neonatal circulation.”  NHLBI/NIH.  4/1/1984-3/31/2013 (Principal Investigator)
 
“Hydrogen sulfide in newborn cerebral circulation.” NHLBI/NIH. 8/1/1990-7/31/2015. (Principal Investigator)
 
"Cerebrovascular stress and brain circulating endothelial cells." NINDS/NIH. 2/1/2010-1/31/2015 (Co-investigator H. Parfenova, PI)
 
"Heme oxygenase and cerebral vascular injury." NHLBI/NIH. 7/1/2005-6/30/2015. (Co-investigator, H. Parfenova, PI)

Current Training Support: “Short term research training.” NIDDK/NIH. Current: 4/1/10-3/31/15. (Associate Director, S.S. Solomon, Director)

Selected Publications

Selected papers relevant to control of newborn cerebral circulation since 2008.

1. Li A., Q. Xi, E.S. Umstot, L. Bellner, M. L. Schwartzman, J. H. Jaggar, and C. W. Leffler. Astrocyte-derived CO is a diffusible messenger that mediates glutamate-induced cerebral arteriolar dilation by activating smooth muscle cell KCa channels. Circ. Res. 102: 234-241, 2008. PMID: 17991880

2. Kanu, A. and C.W. Leffler. Roles of glia limitans astrocytes and CO in ADP-induced pial arteriolar dilation in newborn pigs. Stroke 40: 930-935, 2009. PMID: 19164779

3. Basuroy, S., S. Bhattacharya, C. W. Leffler, and H. Parfenova. Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNFa in cerebral vascular endothelial cells. Am. J. Physiol. 296: C422-432, 2009 PMID: 19118162

4. Xi, Q. E. Umstot, G. Zhao, D. Narayanan, C.W. Leffler, and J. H. Jaggar. Glutamate regulates Ca2+ signals in smooth muscle cells of newborn piglet brain slice arterioles through astrocyte- and heme oxygenase-dependent mechanisms. Am. J. Physiol. 298: H562-H569, 2010 PMID: 19966053

5. Parfenova H., C.W. Leffler, D. Tcheranova, S. Basuroy, and A. Zimmermann. Epileptic seizures increase circulating endothelial cells in peripheral blood as early indicators of cerebral vascular damage. Am. J. Physiol. 298: H1687-H1698, 2010. PMID: 20363895

6. Knecht K.R., S. Milam, D. A. Wilkinson, A. L. Fedinec, and C.W. Leffler. Time Dependent Action of Carbon Monoxide on Newborn Cerebrovascular Circulation. Am. J. Physiol. 299: H70-H75, 2010 PMID: 20435844

7. Leffler C.W., H. Parfenova, S. Basuroy, J. H. Jaggar, E. S. Umstot, and A. L. Fedinec. Hydrogen sulfide and cerebral microvascular tone in newborn pigs. Am. J. Physiol. 300: H440-H447, 2011. PMID 21131483

8. Basuroy S., D. Tcheranova, S. Bhattacharya, C.W. Leffler, and H. Parfenova. Nox4 NADPH oxidase–derived reactive oxygen species, via endogenous carbon monoxide, promote survival of brain endothelial cells during TNF-α-induced apoptosis. Am. J. Physiol. 300: C256-C265, 2011. PMID: 21123734

9. Liang G.H., Adebiyi A., Leo M.D., McNally E.M., Leffler C.W., Jaggar, J.H. Hydrogen sulfide dilates cerebral arterioles by activating smooth muscle cell plasma membrane KATP channels. Am. J. Physiol. 300: H2088-H2095, 2011 PMID: 21421823 [PubMed-in process]

10. Leffler C.W., H. Parfenova, J.H. Jaggar. Invited review: Carbon monoxide as an endogenous vascular modulator. Am. J. Physiol. 301 H1-H11, 2011. PMID: 21498777 PMCID:PMC3129910

11. Xi Q., D. Tcheranova, S. Basuroy, H. Parfenova, J. H. Jaggar, C.W. Leffler. Glutamate-induced calcium signals stimulate CO production in piglet astrocytes. Am. J. Physiol. 301: H428-H433, 2011. PMID: 21572018 PMCID: PMC3154668

12.Kanu A. and C.W. Leffler. Arachidonic acid and prostaglandin E2-induced cerebral vasodilation is mediated by carbon monoxide independent of reactive oxygen species in piglets. .Am. J. Physiol. 301:H2482-7, 2011. PMID: 21984542 PMCID:PMC323381

13.Parfenova H., C.W, Leffler, S. Basuroy, J. Liu, A. L. Fedinec. Antioxidant roles of heme oxygenase, carbon monoxide, and bilirubin in cerebral circulation during seizures. Journal of Cerebral Blood Flow and Metabolism 32:1024-34, 2012 PMID:22354150 [PubMed - as supplied by publisher]

14.Parfenova H., D. Tcheranova, S. Basuroy, A. L. Fedinec, J. Liu, and C.W. Leffler. Functional role of astrocyte glutamate receptors and carbon monoxide in cerebral vasodilation response to glutamate Am. J. Physiol. 302:H2257-H2066, 2012 PMID:22467311[PubMed - as supplied by publisher]

15.Liang G.H., Q Xi, C.W. Leffler CW, and Jonathan H. Jaggar. Hydrogen sulfide activates Ca2+ sparks to induce cerebral arteriole dilatation J Physiol 590: 2709-2720, 2012. PMID: 22508960 [PubMed - as supplied by publisher]

 

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