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Marion J. Siegman, PhD

Contact Dr. Siegman

1020 Locust Street
Philadelphia, PA 19107

(215) 503-3975
(215) 503-2073 fax

Expertise & Research Interests

In disease states, such as hypertension, the primary defect may be traced to the regulation of the mechanisms for maintenance of tone in smooth muscle. The basic mechanisms controlling tone are not well understood. A unique and important characteristic of all smooth muscles is the ability to vary the energy cost of force production and maintenance during the time course of isometric contractions. It has become obviousthat there are many similarities among the mechanical and energetic properties of mammalian smooth muscles during the 'latch' state and molluscan muscles during 'catch,' yet the molecular basis of these states and their regulation is not well understood. A unique feature of catch muscle is the operation of a mechanism that appears to control the detachment rate of the crossbridge. Such a mechanism has not yet been identified in mammalian muscle, but would be of great importance as a means of regulating tone and consequently physiological functions, such as blood pressure. The elucidation of such a mechanism in catch thus has the potential to provide important insights into normal and abnormal function of the cardiovascular, pulmonary, digestive, and reproductive systems. We have discovered that the mini-titin 'twitchin' is key to the regulation of force production and catch. Twitchin is associated with myosin and is an integral part of the thick contractile filament. The overall goal of our research is to define the state of the myosin crossbridge and its kinetics of turnover at rest and during phasic and catch contractions in the anterior byssus retractor muscle ABRM of Mytilus edulis, and to identify the molecular mechanisms by which the phosphhorylation state of twitchin regulates transition of the crossbridge into and out of the catch state.

Other Expertise

Electron Microscopy
Muscle Mechanical Properties

Keywords

Actin; Myosin; cAMP; Energetics of Contraction; Muscle Contraction; Muscle Relaxation; Myosin; High energy phosphates; Mollusca; Regulation of Smooth Muscle; Catch; Anterior byssus retractor muscle (ABRM); Twitchin; Ultrastructure of Muscle; Shortening;