B.S., Rutgers University
Ph.D., Mount Sinai School of Medicine
Postdoctoral fellow, Johns Hopkins University School of Medicine
Without the extracellular matrix (ECM), any multicellular organism would just be a ball of cells with no structure. Therefore, the ECM is essential for life. The ECM is known to act as a scaffold to provide structural integrity to tissues and organs. However, this matrix is a highly dynamic structure that also provides a suitable environment for cell migration and tissue morphogenesis, and serves as a reservoir for growth factors, presenting and modifying signals that guide cell behavior. Thus, the ECM is as essential for cell behavior as the cell itself. How the ECM carries out these multiple functions is still poorly understood. A deeper understanding of how this dynamic matrix is modified and remodeled for its different functions will provide insight into how the ECM regulates cell behavior during both development and disease.
Among the extracellular enzymes that modify and remodel the ECM is the ADAMTS family of metalloproteases (Zinc metal-dependent), secreted proteases that cleave specific ECM molecules. The ADAMTS proteases are key players in ECM remodeling, and highly conserved among higher eukaryotes. The ADAMTS family in mammals is quite large, consisting of 19 members, each with distinct expression patterns, molecule(s) they cleave, and modes of action. ADAMTSs are required for both a wide array of developmental processes as well as diverse disease states; thus, this family of proteases can tell us much about how the ECM gets remodeled for different cellular processes. To help clarify how these proteins function in different developmental and disease contexts, I am using a simpler model organism Drosophila to study the roles of ADAMTS proteases in ECM remodeling, focusing specifically on cell migration and tissue morphogenesis. The Drosophila genome encodes only three ADAMTS metalloproteases: AdamTS-A, AdamTS-B, and stl. These three genes have distinct expression patterns during embryogenesis, and throughout the lifetime of the fly. Projects in my lab will focus on the characterization of each of these three proteases during cell migration and tissue morphogenesis.
Ismat, A., Cheshire, A.M., and Andrew, D.J. (2013), The secreted AdamTS-A metalloprotease is required for collective cell migration, Development 140, 1981-1993.
Chen, Y-C., Lin, Y., Banerjee, S., Venken, K., Li, J., Ismat, A., Chen, K., Duraine, L., Bellen, H.J., and Bhat, M.A. (2012), Drosophila Neuroligin 2 is required presynaptically and postsynaptically for proper synaptic differentiation and synaptic transmission, The Journal of Neuroscience 32, 16018-16030.
Reim, I., Hollfelder, D., Ismat, A., and Frasch, M. (2012), The FGF8-related signals Pyramus and Thisbe promote pathfinding, substrate adhesion, and survival of migrating longitudinal gut muscle founder cells, Developmental Biology 368, 28-43.
Ismat, A., Schaub, C., Reim, I., Kirchner, K., Schultheis, D., and Frasch, M. (2010), HLH54F is required for the Specification and Migration of Longitudinal Gut Muscle Founders from the Caudal Mesoderm of Drosophila, Development 137, 3107-3117.
Inaki, M., Shinza-Kameda, M., Ismat, A., Frasch, M., and Nose, A. (2010), Drosophila Tey represses transcription of a repulsive cue Toll and generates neuromuscular target specificity, Development 137, 2139-2146.
Watford, M., Chelleraj, V., Ismat, A., Brown, P., and Raman, P. (2002), Hepatic glutamine metabolism, Nutrition 18, 301-303.