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Neal A. Rubinstein, MD, PhD

Neal A. Rubinstein, MD, PhD

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Associate Professor of Cell and Developmental Biology
Department: Cell and Developmental Biology

Contact information
1112 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-6058
Office: 215-898-4162
Fax: 215-898-9871
Education:
B.A.
Dartmouth College, Hanover, NH, 1969.
M.D.
University of Pennsylvania, Philadelphia, PA, 1974.
Ph.D. (Dept. of Anatomy)
University of Pennsylvania, Philadelphia, PA, 1975.
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Description of Research Expertise

Control of contractile protein synthesis in the extraocular muscles: Although oculomotor disorders such as strabismus or nystagmus can have marked, deleterious effects on the development of vision, little is known about the final common pathway of oculomotor control: the extraocular muscles (EOMs).

The unusual properties of EOMs are defined by their diverse and unique fiber types. We have previously demonstrated that a layer of skeletal muscle cells in the EOMs demonstrate a longitudinal variation in their myosin heavy chain (MyHC) isoforms.

At the neuromuscular junction, an EOM-specific MyHC isoform is present, while a distinct isoform is found proximal and distal to the neuromuscular junction and sharply excluded from the junctional area. We are currently investigating the neural mechanisms responsible for this synapse specific synthesis of one isoform and the extra-synapse specific synthesis of another.

Diaphragmatic adaptations elicited by severe COPD: Patients with severe chronic obstructive pulmonary disease (COPD) do not exhibit diaphragmatic fatigue even when they are exercised to exhaustion. We have demonstrated that this resistance to fatigue results from global changes in contractile protein isoforms and metabolic pathways during the progression of COPD. We are currently investigating the signal transduction pathways that may be involved in this global transformation.



Figure 1. Relationship of EO-MyHC and acetylcholine receptors on postpartum day 11. A whole mount of rat EOM at age 11 days was stained with antibody to the EO-MyHC (red) and antibody to the acetylcholine receptors (AChRs; green). Figures a and b show that these are essentially coextensive. In c and d, a composite showing both antibodies concurrently, can be seen at progressively higher powers. The EO-MyHC is initially found, therefore, only in the immediate vicinity of the AChRs.



Figure 2. Development of longitudinal variation in MyHC isoforms of the rat EOMs. Whole mounts of rat EOMs stained with antibody specific to the embryonic MyHC isoform (green) or with antibody specific to the extraocular muscle MyHC isoform (EO-MyHC) at specific days postpartum. Initially, the embryonic isoform occupies the entire length of the fibers; with development, however, it becomes excluded from the area of the neuromuscular junction. The EO-MyHC isoform initially appears as a double in the center of the fibers. It gradually fills the entire central area of the fibers, an area corresponding to the neuromuscular junction.

Selected Publications

Levine, S., C. Gregory, T. Nguyen, J. Shrager, L. Kaiser, RUBINSTEIN, N.A., and G. Dudley: Bioenergetic adaptation of individual human diaphragmatic myofibers to severe COPD. J Appl Physiol. 92(3): 1205-1213, March 2002.

Fischer MD, Gorospe JR, Felder E, Bogdanovich S, Pedrosa-Domellof F, Ahima RS, RUBINSTEIN, NA, Hoffman EP, Khurana TS: Expression profiling reveals metabolic and structural components of extraocular muscles. Physiol Genomics 9(2): 71-84, 2002.

Levine, S., T. Nguyen, J. Shrager, L. Kaiser, V. Canasamudren, and RUBINSTEIN, N.A.: Diaphragm adaptations elicited by sever chronic obstructive pulmonary disease: lessons for sports science. Exenc. Sport Sci. Rev. 29: 71-75, 2001.

Nguyen, T. J. Shrager, L. Kaiser, MEI, L., M. Daood, J. Watchko, N. RUBINSTEIN, and S. Levine: Developmental myosin heavy chains in the adult human diaphragm: coexpression patterns and effect of COPD. J. Appl. Physiol. 88: 1446-1456, 2000.

Shrager, J., P. Desjardins, J. Burkman, S. Konig, D. Stewart, M. Shah, M. Tewari, R. Hoffman, M. Rickels, E. Jullian, N. RUBINSTEIN, and H. Stedman: Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-IIb-perinatal-extraocular. J. Muscle Res. And Cell Motility 21: 345-355, 2000.

RUBINSTEIN, N.A. and J.F.Y. Hoh: The distribution of myosin heavy chain isoforms among rat extraocular muscle fiber types. Investigative Ophthalmology Vis. Sci 41: 3391-3398, 2000.

Myers, J., D. Li, N. RUBINSTEIN, and C. Clark: Up-regulation of type XIX collagen in rhabdomyosarcoma cells accompanies myogenic differentiation. Experimental Cell Res. 253: 587-598, 1999.

Lefaucheur, L., R. Hoffman, D. Gerrard, C. Okamura, N. RUBINSTEIN, and A. Kelly: Evidence for three adult fast myosin heavy chain isoforms in type II skeletal muscle fibers in pigs. J. Anim. Sci. 76: 1584-1593, 1998.

Lefaucheur, L., Hoffman, R., Okamura, C., Gerrard, D., Leger, J., RUBINSTEIN, N., and Kelly, A: Transitory expression of alpha cardiac myosin heavy chain in a subpopulation of secondary generation muscle fibers in the pig. Dev Dynamics 210: 106-116, 1997.

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Last updated: 10/15/2012
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