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.
This image shows 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.  4/1/1984-3/31/2012 (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 from 2006-Present

1. Li, A., A. Adebiyi, C.W. Leffler, and J.H. Jaggar. KCa channel insensitivity to Ca2+ sparks underlies fractional coupling in newborn cerebral artery smooth muscle cells. Am. J. Physiol. 291:1118-1125, 2006. PMID: 16603686
2. Leffler, C.W., H. Parfenova, A. L. Fedinec, S. Basuroy, and D. Tcheranova. Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs. Am. J. Physiol. 291: H2897-H2904, 2006. PMID: 16891404

3. Zimmermann A., C.W. Leffler, D. Tcheranova, A. L. Fedinec, and H. Parfenova. Cerebroprotective effects of the CO-releasing molecule, CORM-A1, against seizure-induced neonatal vascular injury. Am. J. Physiol. 293: H2501-H2507, 2007. PMID: 17630349

4. Kanu, A. and C.W. Leffler. Carbon monoxide and Ca2+-activated K+ channels in cerebral arteriolar responses to glutamate and hypoxia in newborn pigs. Am. J. Physiol. 293: H3193-H3200, 2007 PMID: 17766483

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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]

14. 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 [PubMed-in process]

15. 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 [PubMed-in process]

 

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