Forward and reverse degradomics of cardiovascular extracellular matrix

Extracellular matrix (ECM) surrounds all cells and modifies all signals received by cells. It is thus not purely mechanical and hardly a static entity. Its turnover by proteases is a key element in its regulation, yet little is known about the global landscape of ECM breakdown, or proteolysis. Suneel Apte, M.B.B.S., D. Phil, will investigate how ECM is broken down in the cardiovascular system, both the physiological breakdown that occurs during heart development, and excess breakdown which may contribute to vascular disease. Too much breakdown is harmful because it weakens tissue structure and cells may react inappropriately to it. Apte and his team will use protein mass spectrometry to study all the changes in the extracellular matrix of the heart and blood vessels in a high-throughput approach intended to define the entire landscape of proteolysis. In addition to yielding a fundamental understanding of the biology of extracellular matrix breakdown, the work may uncover new cardiovascular disease biomarkers, disease pathways and targets for drug development.

Affiliated Investigators

Suneel Apte, M.B.B.S., D. Phil.

Cleveland Clinic Lerner Research Institute

Suneel Apte has a staff appointment at the Cleveland Clinic. He graduated from medical school at Bombay University and trained at first in orthopedic surgery. During clinical training, he moved to the University of Oxford, where he was supported by a Rhodes Scholarship and obtained a D.Phil under the mentorship of John Kenwright, Ph.D. He subsequently undertook post-doctoral training with Bjorn Olsen, Ph.D., at Harvard Medical School. During this period, he made the decision to switch to a career as a full-time scientist. His training experiences resulted in a long-term commitment to investigating connective tissues and ECM at a fundamental level. His laboratory discovered and characterized several ECM-degrading proteases with widespread relevance to embryogenesis and human disease. He utilizes genetic, molecular, cellular and proteomic approaches to investigate proteolytic turnover of ECM in cellular phenotype regulation, mammalian embryogenesis and inherited and acquired disorders. He has served the ECM community as President of the American Society for Matrix Biology and Chair of the Gordon Research Conference on Matrix Metalloproteinases.