University of Missouri School of Medicine MU Health School of Medicine

Steven S. Segal, PhD

Steven S. Segal, PhD

Professor
SegalSS@health.missouri.edu

Research Interests

Our research is focused on understanding the control of tissue blood flow in light of how oxygen delivery increases in response to metabolic demand. During exercise, the recruitment of skeletal muscle fibers (motor units) generates electrical and chemical signals in endothelial cells and smooth muscle cells of the microvessels that control the distribution and magnitude of muscle blood flow. Our experiments center on elucidating the cellular and molecular events which initiate these signals, how such signals are transmitted from cell to cell to orchestrate vasodilation and vasoconstriction in microvascular networks, and how these integrative processes are governed by the nervous system. Intravital video microscopy enables direct observations of blood flow control in the mammalian microcirculation. Histochemistry and vascular casting are used to quantify the architecture of neural and microvascular networks. Intracellular recording with dye labeling reveals cell-specific electrical signals which determine the contractile status of smooth muscle and its regulation by the endothelium. Calcium imaging provides unique insight into cellular responses which reflect the activity of ion channels and key regulatory enzymes.

Complementary studies of isolated microvessels and their constitutive cells enable even greater resolution of specific regulatory processes. Pharmacology, immunolabeling and transcript analyses are used to resolve the functional expression of proteins which mediate cell-to-cell coupling through gap junctions and electrical signaling through ion channels. Studies of transgenic mice afford unique insight into how particular signaling pathways affect control processes within the microcirculation. In turn, these basic relationships are being explored in light of how aging affects microvascular structure and function. Opportunities for graduate and postdoctoral training include: Molecular physiology of vascular cells, electrical and optical monitoring of cell signaling, microsurgery and microdissection, intravital video microscopy, conventional and immunohistochemistry, evaluation of gene expression, and modeling the biophysical properties of cells and tissues.

Professional Background

  • BA and MA in Physical Education (Exercise Physiology), UC Berkeley
  • PhD in Education and Physiology, University of Michigan
  • Postdoctoral National Research Service Award (Microcirculation), University of Virginia
  • Fellow, The John B. Pierce Laboratory (1999-2006)
  • Professor of Cellular and Molecular Physiology, Yale School of Medicine (1999-2006)
  • Joined MU Faculty in 2006
  • Professor of Medical Pharmacology and Physiology
  • Margaret Proctor Mulligan Professor in Medical Research
  • Investigator, Dalton Cardiovascular Research Center
  • Adjunct Professor in Biomedical Sciences, Biological Engineering
  • Established Investigator of the American Heart Association
  • Fellow of The American College of Sports Medicine
  • Fellow of the Council on Basic Cardiovascular Sciences, American Heart Association
  • Fellow of the Cardiovascular Section of the American Physiological Society
  • Past President, The Microcirculatory Society, Inc. USA
  • Editorial boards: Am J Physiol: Heart Circ Physiol; Microcirculation; J Vasc Research
  • Research funded by the National Institutes of Health (MERIT Awardee)

Selected Publications

  • Emerson, G.G. and S.S. Segal.  Electrical coupling between endothelial cells and smooth muscle cells in hamster feed arteries: role in vasomotor control.  Circ. Res. 87: 474-479, 2000. PMID: 10988239
  • VanTeeffelen, J.W.G.E. and S.S. Segal. Interaction between sympathetic nerve activation and muscle fibre contraction in resistance vessels of hamster retractor muscle. J. Physiol. 550.2: 563-574, 2003. PMC2343056
  • Looft-Wilson, R.C., G.W. Payne, and S.S. Segal. Connexin expression and conducted vasodilation along arteriolar endothelium in mouse skeletal muscle. J. Appl. Physiol. 97:1152-1158, 2004. PMID: 15169746 
  • Haug, S.J. and S.S. Segal. Sympathetic neural inhibition of conducted vasodilatation along hamster feed arteries: Complementary effects of α1- and α2-adrenoreceptor activation. J. Physiol. 563.2: 541–555, 2005. PMC1665587
  • Domeier, T.L. and S.S. Segal. Electromechanical and pharmacomechanical signaling pathways for conducted vasodilatation along endothelium of hamster feed arteries. J. Physiol. 579.1:175-186, 2007. PMC2075370
  • Uhrenholt, T.R., T.L. Domeier and S.S. Segal. Propagation of calcium waves along endothelium of hamster feed arteries. Am. J. Physiol. Heart Circ. Physiol. 292: H1634-H1640, 2007. PMID: 17098832  
  • Hakim, C.H., W.F. Jackson and S.S. Segal. Connexin Isoform Expression in Smooth Muscle Cells and Endothelial Cells of Hamster Cheek Pouch Arteries and Retractor Feed Arteries. Microcirculation 15:503-514, 2008. PMC2761760
  • Jackson D.N., A.W. Moore and S.S. Segal. Blunting of rapid onset vasodilatation and blood flow restriction in arterioles of exercising skeletal muscle with ageing in mice. J. Physiol. 588.12:2269-2282, 2010. PMC2911225
  • Moore A.W., S.E. Bearden and S.S. Segal. Regional activation of rapid onset vasodilatation in mouse skeletal muscle: Regulation through α-adrenoreceptors. J. Physiol. 588.17:3321-3331, 2010. PMC2976025
  • Bagher P, Davis MJ and Segal SS. Visualizing calcium responses to acetylcholine convection along endothelium of arteriolar networks in Cx40BAC GCaMP2 transgenic mice. Am J Physiol Heart Circ Physiol 301:H794-H802, 2011. PMC3191093 
  • Behringer EJ, Socha MJ, Polo-Parada L and Segal SS. Electrical conduction along endothelial cell tubes from mouse feed arteries: Confounding actions of glycyrrhetinic acid derivatives. Brit J Pharmacol 166:774-787, 2012.  PMC3417504
  • Correa D and Segal SS. Neurovascular proximity in the diaphragm muscle of adult mice. Microcirculation 19: 306–315, 2012. PMC3336045 
  • Behringer EJ and Segal SS. Tuning electrical conduction along endothelium of resistance arteries through Ca2+-activated K+ channels. Circ Res 110:1311-1321, 2012. PMC3467972 
  • Socha MJ, Domeier TL, Behringer EJ and Segal SS. Coordination of Intercellular Ca2+ Signaling in Endothelial Cell Tubes of Mouse Resistance Arteries. Microcirculation 19:715-770, 2012. PMC3502682 
  • Westcott EB and Segal SS. Ageing alters perivascular nerve function of mouse mesenteric arteries in vivo. J Physiol 591.5:1251-1263, 2013. PMID: 23247111 

Methodology/Techniques

  • Microdissection and microsurgery
  • Intravital video microscopy
  • Microvascular physiology and pharmacology
  • Intracellular recording from microvascular endothelium and smooth muscle
  • Calcium photometry of microvascular endothelium and smooth muscle
  • Confocal & multiphoton imaging of microvascular endothelium and smooth muscle
  • Gene expression in microvascular endothelium and smooth muscle
  • Somatic and autonomic neural regulation of tissue blood flow
  • Histology and immunolabeling
  • Vascular casting and network analyses
  • Biophysical properties of microvessels and constitutive cells

Media

Bagher & Segal ACh Convection ThumbMoore & Segal Rapid Onset Vasodilation ThumbSocha & Segal EndoTube CaWaves Thumb

Video 1

Bagher & Segal: Intravital imaging of the cremaster muscle in a transgenic mouse expressing a calcium-sensitive protein selectively in the endothelium. Acetylcholine released as a brief pulse (500 ms) from a micropipette adjacent to an arteriole enters the blood stream and activates an entire network of endothelial cells as it is convected in the flow stream. PMC3191093

Video 2

Moore & Segal: Intravital imaging of the mouse gluteus maximus muscle. Rapid Onset Vasodilation occurs in response to a single tetanic contraction (750 ms, 100 Hz) in response to stimulating the motor nerve. PMC2976025

Video 3

Socha & Segal: Calcium signaling in an endothelial cell tube freshly isolated from a resistance artery of a transgenic mouse. These mice express a calcium-sensitive protein selectively in the endothelium. Application of acetylcholine evokes robust calcium responses throughout the endothelium. 22860994


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