Associate Adjunct Professor, Medicine
Ph.D., University of Manitoba, Winnipeg MB Canada; PDF, University of California, San Diego, CA USA
My specific research focus lies in understanding the mechanisms underlying biomechanical stress responses in the heart, which play a central role in the pathophysiology of heart disease and arrhythmias. Little is known about how mechanical stress is sensed by cardiac cells, transduced into intracellular signals and how dysfunction of these pathways lead to heart disease and arrhythmias. Our research interests are in uncovering new pathway(s) mediating biomechanical stress responses in cardiac cell biology and disease, with a specific focus on sarcomeric and cardiac cell-cell junction proteins, which have specific importance in mechanical stress driven genetic based cardiomyopathies, such as dilated and arrhythmogenic right ventricular cardiomyopathy as well as cardiac arrhythmias. Our laboratory uses a multi-disciplinary approach, which combines molecular, cellular, developmental and physiological techniques as well as establishes genetic mouse and human stem cell model systems to provide a platform to translate, validate and test therapeutic approaches identified through our research.
BMS Focus Areas:
R.C. Lyon, V. Mezzano, A. Wright, E. Pfeiffer, J. Chuang, K. Banares, A. Castaneda, K. Ouyang, L. Cui, Y. Gu, S. Evans, J. Omens, K.L. Peterson, A. McCulloch and F. Sheikh (2014) Connexin Defects Underlie Arrhythmogenic Right Ventricular Cardiomyopathy In a Novel Mouse Model. Hum Mol Genet 23: 1134-1150. PMID: 24108106
V. Mezzano, J. Pellman and F. Sheikh (2014) Cell Junctions In the Specialized Conduction System of the Heart. Cell Commun Adhes 21:149-159. PMID: 24738884
F. Sheikh§, R.C. Lyon and J. Chen§ (2014) Getting the Skinny on Thick Filament Regulation in Cardiac Muscle Biology and Disease. Trends Cardiovasc Med 24: 133-141. PMID: 23968570 §co-corresponding authors. (Journal Cover)
F. Zanella, R.C. Lyon and F. Sheikh (2014) Modeling Heart Disease in a Dish: From Somatic Cells to Disease-Relevant Cardiomyocytes. Trends Cardiovasc Med 24: 32-44. PMID: 24054750
R.C. Lyon, S. Lange and F. Sheikh (2013) Breaking down protein degradation mechanisms in cardiac muscle: Therapeutic outlooks for disease. Trends Mol Med 19: 239-249. PMID: 23453282
A. Raskin, S. Lange, K. Banares, R.C. Lyon, A. Zieseniss, L. Lee, H. Granzier, C.C. Gregorio, A.D. McCulloch, J.H. Omens and F. Sheikh. (2012) A Novel Mechanism Involving Four and a Half LIM Domain Protein-1 and Extracellular Signal Regulated Kinase-2 Mediates Titin Phosphorylation and Mechanics. J Biol Chem 287: 29273-29284. PMID: 22778266 (Journal Cover)
J.A. DeQuach, J.E. Lin, C. Cam, D. Hu, M.A. Salvatore, F. Sheikh and K.L. Christman (2012) Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model. Eur Cell Mater 5:400-412.
F. Sheikh*§, K. Ouyang*, S. Campbell*, R.C. Lyon, J. Chuang, D. Fitzsimons, J. Tangney, C.G. Hidalgo, C.S. Chung, H. Cheng, N.D. Dalton, Y. Gu, H. Kasahara, M. Ghassemian, J.H. Omens, K.L. Peterson, H.L. Granzier, R.L. Moss, A.D. McCulloch§ and J. Chen§ (2012) Mouse and computational models link MLC2v dephosphorylation to altered myosin kinetics in early cardiac disease. J Clin Invest 122:1209-1221. *co-first authorship, §co-corresponding authors
V. Mezzano and F. Sheikh (2012) Cell-Cell Junction Remodeling in the Heart: Possible Role in Cardiac Conduction System Function and Arrhythmias? Life Sci 90:313-21.
H. Cheng , M. Zheng, A.K. Peter, K. Kimura, X. Li, K. Ouyang, T. Shen, L. Cui, D. Frank, N.D. Dalton, Y. Gu, N. Frey, K.L. Peterson, S.M. Evans, K.U. Knowlton, F. Sheikh, J. Chen. (2011) Selective deletion of long but not short Cypher Isoforms Leads to Late Onset Dilated Cardiomyopathy. Hum Mol Genet 20:1751-1762.
J.A. DeQuach, V. Mezzano, A. Miglani, S. Lange, G.M. Keller, F. Sheikh and K.L. Christman (2010) Simple and high yielding method for preparing tissue specific extracellular matrix coatings for cell culture. PLoS One 27:e13039.
J. Pellman, R.C. Lyon and F. Sheikh (2010) Extracellular matrix remodeling in atrial fibrosis: Mechanisms and implications in atrial fibrillation. J Mol Cell Cardiol 48:461-467.
F. Sheikh, R.S. Ross and J. Chen (2009) The Cell-Cell Connection to Cardiac Disease. Trends Cardiovasc Med. 19:182-190.
F. Sheikh, A. Raskin, P.H. Chu, S. Lange, A.A. Domenighetti, M. Zheng, X. Liang, T. Zhang, T. Yajima, Y. Gu, N.D. Dalton, S.K. Mahata, G.W. Dorn II, J. Heller-Brown, K.L. Peterson, J.H. Omens, A.D. McCulloch and J. Chen. (2008) An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice. J Clin Invest 118: 3870-3880.
F. Sheikh, M.L. Bang, S. Lange and J. Chen. (2007) “Z”eroing in on the Role of Cypher in Striated Muscle Function, Signaling and Human Disease. Trends Cardiovasc Med 17: 258-262. PMID: 18021935
F. Sheikh and J. Chen. (2007) Mouse models for cardiomyopathy research. Prog Pediatric Cardiol 24: 25-32.
F. Sheikh, Y. Chen, X. Liang, A. Hirschy, A.E. Stenbit, Y. Gu, N.D. Dalton, T. Yajima, Y. Lu, K.U. Knowlton, K.L. Peterson, J.C. Perriard, J. Chen (2006) alpha-E catenin inactivation disrupts the cardiomyocyte adherens junction resulting in cardiomyopathy and susceptibility to wall rupture. Circulation 114:1046-1055.