Dalton Cardiovascular Research Center

University of Missouri

Steven S. Segal, PhD

Curators' Distinguished Professor, Professor of Medical Pharmacology and Physiology
Office Location: Ma438 Medical Science Bldg
Office Phone: 573-882-2553
SegalSS@health.missouri.edu

Research Interests

• Mechanisms of blood flow regulation
• Cell-to-cell signaling in the vascular wall
• Skeletal muscle injury and regeneration
• Microcirculation during aging
• Cardiovascular regulation

Research Description

Research in the Segal laboratory centers on understanding blood flow regulation as exemplified by skeletal muscle in response to exercise. Contraction of muscle fibers generates electrical and chemical signals in microvascular endothelial cells and smooth muscle cells. Gap junctions enable these signals to spread from cell to cell both axially (via the endothelium) and radially (between endothelial cells and smooth muscle cells) along vessel branches. Intercellular communication thereby coordinates vasodilation and vasoconstriction along vascular resistance networks according to local (muscle fiber) needs for oxygen and nutrients carried in the bloodstream. Thus, as metabolic demand increases, signals initiated within the smallest microvessels (capillaries and terminal arterioles) spread upstream ("ascend") to encompass intermediate arterioles that control the regional distribution of blood flow together with feed arteries governing total flow into the microcirculation. In such manner, ascending vasodilation is also manifest in vascular beds of other tissues subject to metabolic demand, as shown for the heart and brain. Our studies center on elucidating the nature of signaling between skeletal muscle fibers and microvessels as well as between microvascular endothelium and smooth muscle cells in light of how these interactions are modulated by autonomic, sensory and somatic innervation. Experiments involve imaging and manipulating the intact microcirculation, isolated microvessels and their constitutive cell layers in light of functional gene expression. Electrophysiology and calcium imaging provide mechanistic insight into the dynamic nature of cell-type specific as well as heterocellular (myoendothelial, neuromuscular, neurovascular) signals that govern vasomotor control. Experimental data are complemented by computational modeling of the biophysical properties that enable such signaling to occur. Fluorescence imaging enables 4-dimensional mapping and analyses of microvascular architecture to underscore our studies of vasomotor control, network remodeling and regeneration following skeletal muscle injury. Physiological, pharmacological and genetic manipulations provide critical insights into determinants of microvascular structure and function in light of crosstalk with muscle fibers and peripheral nerves. Our goal is to gain definitive new insight into mechanisms of blood flow regulation and apply this knowledge towards combating the deleterious effects of aging, injury and disease on the ability to engage in physical activity and enjoy life.

Professional Background

Position

• Curators' Distinguished Professor
• Professor of Medical Pharmacology and Physiology
• Investigator, Dalton Cardiovascular Research Center

Undergraduate

1976,          BA (Physical Education), University of California Berkeley        

Graduate

1978,          MA (Exercise Physiology), University of California Berkeley

Graduate

1984,          PhD (Education/Kinesiology and Physiology), University of Michigan    

Postdoctoral Training

 1987,     Microcirculation, University of Virginia

Awards & Honors

• Fellow, American College of Sports Medicine (ACSM; 1989)
• Fellow, Cardiovascular Section, American Physiological Society (1996)
• Established Investigator Award, American Heart Association (1993-1998)
• Fellow, Council on Basic Cardiovascular Sciences, AHA (2001)
• President of the Microcirculatory Society, Inc. USA (2008-2009)
• Margaret Proctor Mulligan Professorship in Medical Research, MU (2008-present)
• Method to Extend Research in Time (MERIT) Award, NHLBI, NIH (2008-2019)
• Malpighi Award, European Society for Microcirculation (2013; Birmingham, UK)
• Chancellor’s Professor of Research Excellence, University of Missouri (2013)
• Excellence in Trainee Research Mentoring Award, MU School of Medicine (2015)
• Eugene M. Landis Award, the Microcirculatory Society, Inc. (2016)
• Curators' Distinguished Professor (2017)

Professional Societies

• American Physiological Society (1985 - present)
• The Microcirculatory Society, Inc. USA (1985 - present)
• European Society for Microcirculation (1990 - present)

Selected Publications

• Kapela A, Behringer EJ, Segal SS and Tsoukias N. Biophysical properties of microvascular endothelium: Requirements for initiating and conducting electrical signals. Microcirculation (accepted manuscript online 11/08/2017) DOI: 10.1111/micc.12429
• Sinkler SY and Segal SS. Rapid versus slow ascending vasodilatation: Intercellular conduction versus flow-mediated signalling with tetanic versus rhythmic muscle contractions. J Physiol 595.23: 7149-7165, 2017. DOI: 10.1113/JP275186
• Behringer EJ, Scallan JP, Jafarnejad M, Castorena Gonzalez JA, Moore Jr. JE, Davis MJ and Segal SS. Calcium and Electrical Dynamics in Lymphatic Endothelium. J Physiol 595.24: 7347-7368, 2017. DOI:  10.1113/JP274842
• Behringer EJ and Segal SS. Impact of aging on calcium signaling and membrane potential in endothelium of resistance arteries: A role for mitochondria. J Gerontol A Biol Sci Med Sci 72: 1627-1637, 2017. DOI: 1093/gerona/glx079
• Boerman EM and Segal SS. Depressed perivascular sensory innervation of mouse mesenteric arteries with advanced age. J Physiol 594.8:2323-2338, 2016. PMID: 26010764
• Boerman EM, Everhart JE and Segal SS. Advanced age decreases local calcium signaling in endothelium of mouse mesenteric arteries in vivo. Am J Physiol Heart Circ Physiol 310: H1091-H1096, 2016. PMID: 26945073
• Fernando CA, Liu Y, Sowa G and Segal SS. Attenuated rapid onset vasodilation with greater force production in skeletal muscle of caveolin-2^-/- Am J Physiol Heart Circ Physiol 311: H415-H425, 2016. PMC5008651
• Sinkler SY, Fernando CA and Segal SS. Differential adrenergic modulation of rapid onset vasodilatation along resistance networks of skeletal muscle in old versus young mice. J Physiol 594: 6987-7004, 2016. PMID: 27501249
• Segal SS.  Special Circulations.  In: WF Boron and EL Boulpaep: Medical Physiology (3^rd Ed). Elsevier, Philadelphia, 2016. pp. 556-587.  ISBN: 978-1-4557-4377-3
• Segal SS.  Exercise Physiology and Sports Science.  In: Boron WF and Boulpaep EL: Medical Physiology (3^rd Ed). Elsevier, Philadelphia, 2016. pp. 1204-1222. ISBN: 978-1-4557-4377-3
• Socha MJ, Boerman EM, Behringer EJ, Shaw RL, Domeier TL and Segal SS. Advanced age protects microvascular endothelium from aberrant Ca²⁺ influx and cell death induced by hydrogen peroxide. J Physiol 593.9: 2155–2169, 2015. PMC4422569
• Behringer EJ and Segal SS. Membrane potential governs calcium influx into microvascular endothelium: Integral role for muscarinic receptor activation. J Physiol 293.20: 4531-4548, 2015. PMC26260126
• Segal, SS. Integration and Modulation of Intercellular Signaling Underlying Blood Flow Control.   J Vasc Res 52:136-157, 2015. PMC4670584
• Sinkler SY and Segal SS. Aging alters reactivity of microvascular resistance networks in mouse gluteus maximus muscle. Am J Physiol Heart Circ Physiol 307: H830-H839, 2014. PMC4166744
• Westcott EB and Segal SS. Ageing alters perivascular nerve function of mouse mesenteric arteries in vivo. J Physiol5:1251-1263, 2013. PMC3607869
• Behringer EJ, Shaw RL, Socha MJ, W and Segal SS. Aging impairs electrical conduction along endothelium of resistance arteries through enhanced Ca²⁺-activated K⁺ channel a Arterio Thromb Vasc Biol 33:1892-1901, 2013. PMC3769416
• Socha MJ and Segal SS. Isolation of Microvascular Endothelial Tubes from Mouse Resistance Arteries. J Vis Exp 81: e50759, 2013. http://www.jove.com/video/50759   PMC3992011
• 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⁺ 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