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 novel gasotransmitter, carbon monoxide.

Research Support

Principal Investigator: Charles W. Leffler, Ph.D. Agency: National Heart, Lung, and Blood Institute
2 R37 HL 42851 MERIT Award 8/16/91 - 7/31/10. "Carbon monoxide in newborn cerebral circulation"
The research proposed is designed to address the hypothesis that CO is an integral component of microvascular control in the neonatal cerebral circulation.

Principal Investigator: Charles W. Leffler, Ph.D. Agency: National Heart, Lung, and Blood Institute
2 RO1 HL 34059 4/1/85-3/31/12. "Control of neonatal circulation."
The research proposed is designed to address the hypothesis that perivascular astrocyte HO-2 makes CO that is involved in control of newborn cerebrovascular circulation during glutamatergic stimulation

Current Training Support: Short term research training. NIH. Current period : 4/1/05-3/31/10. (Associate Director, S.S. Solomon, Director)

Selected Publications

Publications: 2003-Present

1. Heinonen, K., A. Fedinec, and C.W. Leffler. Dexamethasone pretreatment attenuates cerebral vasodilative responses to hypercapnia and augments vasoconstrictive responses to hyperventilation in newborn pigs. Pediatr. Res. 53: 260-265, 2003.
2. Winestone, J.S., C. Bonner, and C.W. Leffler. Carbon monoxide as an attenuator of vasoconstriction in piglet cerebral circulation. Experimental Biology and Medicine 228: 46-50, 2003.
3. Parfenova, H., A. Fedinec, and C. W. Leffler. Ionotropic glutamate receptors in cerebral microvascular endothelium are functionally linked to heme oxygenase. J. Cerebral Blood Flow Metab. 23:190-197, 2003.
4. Fiumana, E., H. Parfenova, J.H. Jaggar, and C.W. Leffler. Carbon monoxide mediates vasodilator effects of glutamate in isolated pressurized cerebral arterioles of newborn pigs. Am. J. Physiol. 284: H1073-H1079, 2003.
5. Daley, M.L., M. Pourcyrous, S. Timmons, and C.W. Leffler. Intracranial pressure dynamics: changes in bandwidth as an indicator of cerebrovascular tension. Medical Engineering and Physics 25:679-689, 2003.
6. Leffler, C.W. L. Balabanova, C. D. Sullivan, X. Wang, A. L. Fedinec, and H. Parfenova. Regulation of CO production in cerebral microvessels of newborn pigs. Am. J. Physiol. 285: H292-H297, 2003
7. Leffler, C.W. L. Balabanova, A. L. Fedinec, C. M. Waters and H. Parfenova. Mechanism of glutamate stimulation of CO production in cerebral microvessels. Am. J. Physiol. 285: H74-H80, 2003
8. Carratu, P., M. Pourcyrous, A. Fedinec, C.W. Leffler, and H. Parfenova. Endogenous heme oxygenase prevents impairment of cerebral vascular functions caused by seizures. Am. J. Physiol. 285: H1148-H1157, 2003
9. Pasley, R.L., C.W. Leffler, and M.L. Daley. Modeling modulation of intracranial pressure by variation of cerebral venous pressure induced by ventilation. Ann. Biomed. Engineering 31: 1238-1245, 2003
10. Koneru, P. and C.W. Leffler. Role of cyclic GMP in carbon monoxide induced vasodilation in piglets. Am. J. Physiol. 286: H304-H309, 2004
11. Xi, Q., D. Tcheranova, H. Parfenova, B. Horowitz, C.W. Leffler, and J.H. Jaggar. Carbon monoxide activates KCa channels in newborn arteriole smooth muscle cells by increasing the apparent Ca2+ sensitivity of the ?-subunit. Am. J. Physiol. 286: H610-H618, 2004.
12. Parfenova, H., M.L. Daley, P. Carratu, and C.W. Leffler. Heme oxygenase inhibition reduces neuronal activation evoked by bicuculline in newborn pigs. Brain Res. 1014: 87-96, 2004.
13. Daley, M.L., M. Pourcyrous, S.D. Timmons, and C.W. Leffler. Assessment of cerebrovascular autoregulation: changes of highest modal frequency of cerebrovascular pressure transmission with cerebral perfusion pressure. Stroke 35:1952-19566, 2004.
14. Pourcyrous, M.P., H.S. Bada, K.E. Blaho, M.M. Randolph, H. Parfenova, T.D. Mandrell, K. Arheart, S.B. Korones, and C.W. Leffler. Chronic prenatal exposure to cocaine alters cerebrovascular responses in newborn pigs. Exp. Biol. Med. 229:819-825, 2004.
15. Barkoudah, E., J. H. Jaggar, and C. W. Leffler. The permissive role of endothelial NO in CO-induced cerebrovascular dilation. Am. J. Physiol. 287: H1459-H1465, 2004.
16. Parfenova, H., V. N. Parfenov, and C. W. Leffler. Nuclear functions of cyclooxygenase in cerebral vascular endothelial cells. Pages 63-82 in Biochemistry of Lipids in Vascular Function, M. Alberghina (Ed.), Research Signpost, Kerala, India, 2004.
17. Ahmed, A., C. M. Waters, C.W. Leffler, and J. H. Jaggar. Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries. Am. J. Physiol. 287: H2061-H2069, 2004.
18. Parfenova, H., P. Carratu, D. Tcheranova, A. Fedinec, M. Pourcyrous, and C.W. Leffler. Epileptic seizures cause extended cerebral vascular dysfunction that is prevented by HO-1 overexpression. Am. J. Physiol. 288:H2843-H2850, 2005.
19. Leffler, C. W., A. L. Fedinec, H. Parfenova, and J. H. Jaggar. Permissive contributions of NO and prostacyclin in CO-induced cerebrovascular dilation in piglets. Am. J. Physiol. 289: H432-H438, 2005.
20. Leffler, C.W., L. Balabanova, A.L. Fedinec, and H. Parfenova. Nitric oxide increases carbon monoxide production by piglet cerebral microvessels. Am. J. Physiol. 289: H1442-H1447, 2005
21. Yakubu, M.A., and C.W. Leffler. Regulation of cerebral vascular endothelial cell cyclooxygenase-2 message and activity by blood derived vasoactive agents. Brain Res. Bulletin 68:150-156, 2005.
22. Jaggar, JH, A. Li, H. Parfenova, J. Liu, E. S. Umstot, A. M. Dopico, and C. W. Leffler. Heme is a carbon monoxide receptor for large-conductance Ca2+-activated K+ channels. Circ Res. 97: 805-812,2005.
23. Daley, M.L., C.W. Leffler, M. Czosnyka, and J.D. Pickard. Plateau waves: changes of cerebrovascular pressure transmission. Acta Neurochir [Suppl] 95: 327-332, 2005
24. Leffler, C.W., H. Parfenova, J. H. Jaggar, R. Wang. Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation. Invited review. J. Appl. Physiol. 100:1065-1076, 2006.
25. Kanu, A., D. Gilpin, A.L. Fedinec, and C.W. Leffler. Cyclooxygenase products stimulate carbon monoxide production by piglet cerebral microvessels. Exp. Biol. Med. 231:181-185, 2006
26. Parfenova, H., S. Basuroy, S. Bhattacharya, D. Tcheranova, Y. Qu, R.F. Regan, and C.W. Leffler Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection. Am. J. Physiol. 290: C1399-C1410, 2006
27. 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. Am. J. Physiol. 291:1118-1125, 2006
28. Daley, M.L,, C.W. Leffler, M. Czosnyka, and J.D. Pickard. Intracranial pressure monitoring: modeling cerebrovascular pressure transmission. Acta Neurochir Suppl. 96:103-107, 2006
29. Kanu, A., J. Whitfield, and C.W. Leffler. Carbon monoxide contributes to hypotension-induced cerebrovascular dilation in piglets. Am. J. Physiol. 291: H2409-H2414, 2006
30. Basuroy, S., S. Bhattacharya, D. Tcheranova, Y. Qu, R.F. Regan, C.W. Leffler, and H. Parfenova. Heme oxygenase-2 provides endogenous protection against oxidative stress and apoptosis caused by TNFa in cerebral vascular endothelial cells. Am. J. Physiol. 291:C897-C908, 2006
31. 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
32. Daley, M.L., M. Pourcyrous, S. D. Timmons, and C. W. Leffler. Mode Changes of Cerebrovascular Pressure Transmission Induced by Cerebral Vasodilation. J. Neurotrauma 24: 559-566, 2007
33. 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
34. Holt, D.C., A.L. Fedinec, A.N. Vaughn, and C.W. Leffler. Age and species dependence of pial arteriolar responses to topical carbon monoxide in vivo. Exptl. Biol. Med. 232:1465-1469, 2007
35. 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
36. Parfenova, H. and C.W. Leffler. Cerebroprotective functions of HO-2. Current Pharmaceutical Design. (in press)
37. 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. (in press)

Last modified 1/18/08 11:02 AM