Professor of Medicine and Chief, Cardiovascular Division of Department of Medicine
812 Stellar Chance
9123 Founders Pavilion
3400 Spruce Street
Philadelphia, PA 19104-4283
Phone: (215) 662-3140
Fax: (215) 349-8017
Vertebrate muscle is composed of three functionally distinct mesodermally derived cell lineages: cardiac, skeletal and smooth muscle. The diverse functional capacities of these three lineages are determined by the expression of distinct sets of tissue-specific genes, including those encoding myofibrillar isoforms, cell surface receptors and lineage-specific enzymes. The tissue-specific pattern of expression of many muscle genes is controlled at the level of transcription. Therefore, an understanding of muscle cell development and adaptation must at some level be based upon elucidating the molecular mechanisms that control lineage-specific gene expression. Our laboratory has focused on defining the transcriptional pathways that control cardiac- and smooth muscle-specific gene expression, utilizing both in vitro and in vivo murine model systems. While primarily basic in nature, these studies are directly relevant to understanding such pathophysiological processes as cardiac hypertrophy, cardiomyopathy, atherosclerosis, and restenosis following percutaneous balloon angioplasty.
- Parmacek MS, Ip HS, Jung F, Shen T, Martin JF, Vora AJ, Olson EN, Leiden JM (1994) A novelmyogenic regulatory circuit controls slow/cardiac troponin C gene transcription in skeletal muscle. Mol Cell Biol 14:1870-1885.
- Ip HS, Wilson DB, Heikinheimo M, Tang Z, Ting C-N, Simon MC, Leiden JM, Parmacek MS (1994) The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells. Mol Cell Biol 14:7517-7526.
- Chang, M.W., Barr, E., Seltzer, J., Lu, M.M., Nabel, G.J., Nabel, E.G., Parmacek, M.S. and Leiden, J.M. Cytostatic gene therapy for vascular proliferative disorders using a constitutively active form of Rb. Science 267:518-522, 1995.
- Solway, J., Seltzer, J., Samaha, F.F., Kim, S., Alger, L.E., Niu,Q., Morrisey, E.E., Ip, H.S., and M.S. Parmacek. Structure and expression of a smooth muscle cell-specific gene, SM22alpha. J. Biol. Chem. 270:13460-13469, 1995.
- Morrisey, E.E., Ip, H.S., Lu, M.M., and M.S. Parmacek. GATA-6: a zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm. Dev. Biol. 177:309-322, 1996.