Steven S. Segal, PhD

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.

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