T32 Training Grant [pdf]
The Parmacek laboratory examines the molecular mechanisms underlying cardiovascular development with particular focus on elucidating the transcriptional programs controlling differentiation and phenotypic modulation of muscle cell lineages. These studies are fundamentally important at a basic level and have provided important insights into the pathogenesis of atherosclerosis, congenital heart disease and cardiac hypertrophy. In the Parmacek laboratory and Penn Molecular Cardiology Center gene targeting in embryonic stem cells and mice is routinely applied to examine the molecular basis of cardiovascular development and adaptation. Members of the Parmacek laboratory characterized the GATA-4/5/6 subfamily of zinc finger transcription factors that play critical roles in the developing heart and vascular system. Gene targeting experiments in ES cells and mice revealed the critical role that GATA4 and GATA6 play in cardiovascular and pulmonary development.
The Parmacek laboratory also has elucidated the transcriptional programs and signaling mechanisms that control vascular smooth muscle cell development and differentiation. Members of the Parmacek laboratory generated transgenic mice that revealed the critical role that the MADS box transcription factor SRF plays in regulation of contractile smooth muscle cell gene expression. More recently, they demonstrated that myocardin and the two myocardin related transcription factors (MRTFs)-A and -B act as critical SRF coactivators transducing signals from the SMC cytoskeleton and modulating vascular smooth muscle cell phenotype in response to injury. In addition, the Parmacek laboratory reported that Notch signaling represses myocardin-induced vascular smooth muscle cell differentiation. Finally, in collaboration with other members of Division of Cardiovascular Medicine at the University of Pennsylvania, Dr. Parmacek has initiated a translational research program for metabolic vascular disease.
Li J., Zhu X., Chen M., Cheng L., Zhou D., Lu MM., Du K., Epstein JA., Parmacek MS.: Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development. Proceedings of the National Academy of Sciences of the United States of America 102(25): 8916-21, Jun 21 2005.
Abdullah I., Lepore JJ., Epstein JA., Parmacek MS., Gruber PJ.: MRL mice fail to heal the heart in response to ischemia-reperfusion injury. Wound Repair & Regeneration 13(2): 205-8, Mar-Apr 2005.
Lepore JJ., Cappola TP., Mericko PA., Morrisey EE., Parmacek MS.: GATA-6 regulates genes promoting synthetic functions in vascular smooth muscle cells. Arteriosclerosis, Thrombosis & Vascular Biology 25(2): 309-14, Feb 2005.
Lepore JJ., Cheng L., Min Lu M., Mericko PA., Morrisey EE., Parmacek MS.: High-efficiency somatic mutagenesis in smooth muscle cells and cardiac myocytes in SM22alpha-Cre transgenic mice. Genesis: the Journal of Genetics & Development 41(4): 179-84, Apr 2005.
Zhang SX., Garcia-Gras E., Wycuff DR., Marriot SJ., Kadeer N., Yu W., Olson EN., Garry DJ., Parmacek MS., Schwartz RJ.: Identification of direct serum-response factor gene targets during Me2SO-induced P19 cardiac cell differentiation. Journal of Biological Chemistry 280(19): 19115-26, May 13 2005.
Barron MR., Belaguli NS., Zhang SX., Trinh M., Iyer D., Merlo X., Lough JW., Parmacek MS., Bruneau BG., Schwartz RJ.: Serum response factor, an enriched cardiac mesoderm obligatory factor, is a downstream gene target for Tbx genes. Journal of Biological Chemistry 280(12): 11816-28, Mar 25 2005.
Proweller A., Pear WS., Parmacek MS.: Notch signaling represses myocardin-induced smooth muscle cell differentiation. Journal of Biological Chemistry 280(10): 8994-9004, Mar 11 2005.
Parmacek MS., Epstein JA.: Pursuing cardiac progenitors: regeneration redux. [Review] [19 refs] Cell 120(3): 295-8, Feb 11 2005.
Du, K., Chen, M., Li, J., Lepore, J.J., Mericko, P., Parmacek, M.S. : Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell differentiation from undifferentiated embryonic stem cells. J Biol Chem Vol. 279: 17578-86, 2004.
Horwitz PA., Tsai EJ., Putt ME., Gilmore JM., Lepore JJ., Parmacek MS., Kao AC., Desai SS., Goldberg LR., Brozena SC., Jessup ML., Epstein JA., Cappola TP.: Detection of cardiac allograft rejection and response to immunosuppressive therapy with peripheral blood gene expression. Circulation 110(25): 3815-21, Dec 21 2004.
Reagents and Protocols
- B-galactosidase assay
- cDNA (lambda) library prep-JML [doc]
- Colony Hybridization
- DNAsel foot print [doc]
- Ed's ES diff
- ES cell-immunoflourescent stain
- ES Cells [doc]
- GST fu protein [doc]
- High titre phage stock [doc]
- Immunoflourescence staining
- In vitro Transcription Tra copy
- In Vitro Translation
- kinase oligo-32P
- Lambda Phage DNA isol
- High titre phage stock 1 [doc]
- Maxiprep (Cs)-1992
- Northern Blot2
- LGT11 Screen-Protein
- Library screen-cDNA probe
- Nuclear extract-cardiac
- Nuclear extract-Dignam
- Oligo-gel purification
- Phage DNA prep
- Protein Deter.-Bradford
- protein quant-biorad DC
- Screening gt 11 for DNA-Protei
- Southern Blot-Alkaline 1992
- Southern Blot-single copy
- TBE Oligo Gel shift
- TGE GEL SHIFTS
- Transfection-Lipo. Card
- GH template
- Transgenic DNA Isolation
- Western Blot-1992
- X-Gal staining protocol
Michael S. Parmacek, M.D.
Chief, Division of Cardiovascular Medicine
Herbert C. Rorer Professor of Medical Sciences
University of Pennsylvania Health System
9035 W. Gates
3400 Spruce St.
Philadelphia, PA 19104
3400 Spruce Street, 9035 W. Gates
Philadelphia, PA 19104-4283
Michael Parmacek, 215-662-3140, firstname.lastname@example.org
Sauja Vadoothker, 215-417-4997, email@example.com
Jian Li, 215-898-9011, firstname.lastname@example.org
Mary Chen, 215-573-7068, email@example.com
Xiaohong Zhu, 215-573-7069, firstname.lastname@example.org
Xiaoqing Zhu, 215-573-7069
Jianhe (John) Huang, 215-898-9011, email@example.com