Penn MCRC > Margulies Lab

» MCRC Home

Margulies Lab

Research

Publications

Reagents and Protocols

Contact Information

Lab Members / Contact

Useful Links

Research

Research in my laboratory focuses primarily on myocardial remodeling and myocardial responses to physiological and pathological stress with an emphasis on multilevel inquiries that balance the benefits and drawbacks of reductionism and integration.

My laboratory has had a longstanding commitment to characterizing the human myocardium through physiological and molecular analyses of tissues obtained at the time of heart transplantation and organ donation. Careful characterization of human myocardial biology permits insights into both the heterogeneity of myocardial adaptations to disease and identification of dominant mechanisms and responses. Human tissue phenotyping also allows selection and validation of appropriate models that permit more mechanistic studies and preclinical inquiries. My research program also includes patient-based in vivo inquiries allowing further validation and translation of lab-based findings.

I have had a particular interest in elucidating the responses of severely failing hearts to the mechanical unloading and neurohumoral changes that occur during circulatory assistance. This phenomenology within human hearts and appropriate animal models yields new insights into mechanisms of myocardial plasticity, load-modulated signaling, and the biology of myocardial recovery. Our long-term goal is to identify reliable biomarkers of recoverability and develop targeted therapeutic strategies to promote the recovery of failing hearts.

Recently, our tissue-based research has been extended to include examination of cardiac-derived progenitor cells (CDPCs) that we routinely isolate from human hearts at the time of heart transplantation. Co-culture studies indicate that neonatal rat cardiac myocytes can induce differentiation of a sizable proportion of the c-kit positive CDPCs isolated from human hearts. Ongoing studies are examining the biology of human CDPCs and their potential to mediate endogenous cardiac repair.

» Top

Publications

For all publications, click on

Latest Publications:

Margulies KB. Mechanisms of reversal of LV remodeling: lessons learned from LVAD experiments. J Card Fail 8:S500-S505, 2002.

Crabbe DL, Dipla K, Ambati S, Zafeiridis A, Welsh DC, Furukawa S, Houser SR, Margulies KB. Gender differences in post-infarction hypertrophy in end-stage failing hearts. J Am Coll Cardiol 41(2):300-306, 2003.

McGowan B, Scott CB, McCormick RJ, Mu A, Thomas DP, Margulies KB. Unloading-induced remodeling in the normal and hypertrophic left ventricle. Am J Physiol Heart Circ Physiol 284(6):H2061-H2068, 2003.

Houser SP, Margulies KB. Is depressed myocyte contractility centrally involoved in heart failure? Circ Res 92(4):350-358, 2003.

Rossman EI, Petre RE Chaudhary KW, Piacentino V III, Janssen PML, Gaughan JP, Houser SR, Margulies KB. Abnormal frequency-dependent responses represent the pathophysiological signature of contractile failure in human myocardium. J Mol Cell Cardiol 36:33-42, 2004.

Chaudhary KW, Eossman EI, Piacentino V III, Kenessey A, Weber C, Gaughan JP, Ojamaa K, Klein I, Bers DM, Houser SR, Margulies KB. Functionally significant reductions in sodium-calcium exchanger following mechanical circulatory support. J Am Coll Cardiol 44(4):837-45, 2004.

Jung AS, Quaile MP, Mills GD, Bednarik DP, Houser SR, Margulies KB. Pharmacological effects of AT122-107, a novel dual-pharmacophore, on myocyte calcium cycling and contractility. J Pharmacol Exp Ther 312(2):517-24, 2005.

Margulies KB, Matiwala S, Cornejo C, Olsen H, Craven WA, Bednarik D. Mixed messages: transcription patterns in failing and recovering human myocardium. Circ Res 96(5):592-9, 2005.

Jung AS, Kubo H, Wilson RM, Houser SP, Margulies KB, Modulation of contractility by myocyte-derrived arginase in normal and hypertrophied feline myocardium. Am J Physiol Heart Circ Physiol. 290(5):H1756-62, 2006.

Litvin J, Blagg A, Mu A, Matiwala S, Montgomery M, Berretta R, Houser S, Margulies KB. Periostin and periostin-like factor in the huamn heart: possible therapeutic targets. Cardiovasc Pathol. 15(1):24-32, 2006.

Petre RE, Qualie MP, Rossman EI, Ratcliffe SJ, Bailey BA, Houer SR, Margulies KB. Sex-based differences in myocardial contractile reserve. Am J Physiol Heart Circ Physiol. 2006; (ebub ahead of print).

» Top