Boston University Department of Biology

Faculty Profiles

Current Research

One of our areas of study focuses on dissecting the in vivo role of the myocyte enhancer factor-2 (MEF2) family of transcription factors in muscle development. The four mammalian mef2 genes—mef2a, mef2b, mef2c, and mef2d—are co-expressed in cardiac and skeletal muscle. Loss-of-function studies in mice have revealed important yet distinct functions for the vertebrate mef2 genes in the heart. Inactivation of the mef2c gene results in defective cardiac morphogenesis in developing embryos. In contrast, inactivation of the mef2a and mef2d genes results in perinatal cardiomyopathy and altered stress-dependent cardiac remodeling, respectively. Exploring the downstream cellular pathways controlled by the various mef2 genes will help us understand the genetic pathways in muscle development and disease.

Another area of investigation relates to the role of scaffolding proteins, i.e. proteins that bind signaling enzymes, in muscular dystrophy. Muscular dystrophy is a severe muscle degenerative disease and one form of this disease is the result of a deficiency in dystrophin. Significantly, we have identified a muscle-specific scaffolding protein, myospryn, that interacts with protein kinase A (PKA) and dystrophin. Because the signaling pathways involved in muscular dystrophy are still poorly understood, we are looking into the potential role for myospryn in this process.

Courses Taught

• BI 553 Molecular Biology 2

Selected Publications

• Reynolds JG, McCalmon SA, Donaghey JA, Naya FJ. (2008). Deregulated PKA signaling and myospryn expression in muscular dystrophy. J Biol Chem, 283(13):8070-4.
• Reynolds JG, McCalmon SA, Tomczyk T, Naya FJ. (2007). Identification and mapping of protein kinase A binding sites in the costameric protein myospryn. Biochim Biophys Acta. 1773(6), 891-902.
• Parsons SA, Millay DP, Sargent MA, Naya FJ, McNally EM, Sweeney HL, Molkentin JD. (2007). Genetic disruption of calcineurin improves skeletal muscle pathology and cardiac disease in a mouse model of limb-girdle muscular dystrophy. J Biol Chem. 282(13), 10068-78.
• Huang HT, Brand OM, Mathew M, Ignatiou C, Ewen EP, McCalmon SA, Naya FJ. (2006). Myomaxin is a novel transcriptional target of MEF2A that encodes a Xin-related alpha-actinin-interacting protein. J Biol Chem; 281(51), 39370-9.
• Durham JT, Brand OM, Arnold M, Reynolds JG, Muthukumar L, Weiler H, Richardson JA, Naya FJ. (2006). Myospryn is a direct transcriptional target for MEF2A that encodes a striated muscle, alpha-actinin-interacting, costamere-localized protein. J Biol Chem. 281(10), 6841-9.
• Talmadge RJ, Otis JS, Rittler MR, Garcia ND, Spencer SR, Lees SJ, Naya FJ. (2004). Calcineurin activation influences muscle phenotype in a muscle-specific fashion. BMC Cell Biol. 5, 28.
• Naya FJ, Black BL, Wu H, Bassel-Duby R, Richardson JA, Hill JA, Olson EN. (2002). Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Nat Med 8(11), 1303-9.