Charles W. Leffler, Ph.D.
UTHSC Distinguished Professor
Director, Laboratory for Research in Neonatal Physiology
Departments of Physiology and Pediatrics
956 Court Ave
Memphis, TN 38163
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
Postdoctoral Fellow, University of Florida, Gainesville. (Department of Physiology).
Research in the laboratory concentrates on control of newborn cerebral circulation. The focus of this research is control of the newborn cerebral microvasculature during physiological and pathological situations, and the cellular mechanisms involved in such control. Our studies are novel in bringing to bear multiple complementary approaches to attack the problem from intact in vivo measurements to isolated cells. We have a virtually unique capability to measure H2S and CO with great sensitivity and specificity by gas chromatography-mass spectrometry, and a H2S electrode. These multilayer approaches provide a unique overall perspective that focuses on novel, rational, and testable hypotheses. This research is particularly important because our focus is on the newborn, where much less is known about the mechanisms of cerebrovascular regulation and dysregulation and where complications result in life-long severe morbidity in surviving babies. 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 brain damage have been limited by insufficient understanding of the mechanisms that control perinatal cerebral circulation and how these mechanisms may be compromised before, during or after birth.
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.
- Pourcyrous M., S. Basuroy, D. Tcheranova, K. Arheart, M. Elabiad, C.W. Leffler, and H. Parfenova. Brain-derived circulating endothelial cells in peripheral blood of newborn infants with seizures: A potential biomarker for cerebrovascular injury. Physiol Rep. Mar;3(3). pii: e12345. doi: 10.14814/phy2.12345, 2015.
- Nnorom C. C., C. Davis, A. L. Fedinec, K. Howell, J.H. Jaggar, H. Parfenova, M. Pourcyrous and C.W. Leffler. Contributions of KATP and KCa channels to cerebral arteriolar dilation to hypercapnia in neonatal brain. Physiol Rep. 2 (8): 2014, e12127, doi: 10.14814/phy2.12127, 2014.
- Liang G. H., Q. Xi, C.W. Leffler, and J. H. Jaggar. Hydrogen sulfide activates Ca2+ sparks to induce cerebral arteriole dilation. J Physiol. 590:2709-2720, 2012.
- Parfenova H., D. Tcheranova, S. Basuroy, A. L. Fedinec, Jianxiong 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.
- Leffler C.W., H. Parfenova, and J.H. Jaggar. Invited review: Carbon monoxide as an endogenous vascular modulator. Am J Physiol. 301 H1-H11, 2011.
- 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.