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Suneel S. Apte, MD, PhD

Associate Professor, Biomedical Engineering

aptes@ccf.org 216.445.3278 (o) 216.444.9198 (f)

Member, Molecular Oncology Program

 

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Extracellular matrix, Morphogenesis and Human Disorders

Extracellular matrix (ECM) is the inanimate material between and around cells. It provides cells with anchorage, and influences every aspect of their behavior and fate. It is the structural framework on which every tissue and organ is built. It stores and regulates growth factors, is a source of bioactive fragments, and provides the appropriate microenvironment for stem cells. ECM and cell-ECM interactions are relevant to almost every human disease. ECM of the embryo is quite different from the specialized ECM found in adult tissues, and it is provisional, meaning that it is impermanent and rapidly remodeled. Our laboratory studies provisional ECM in embryogenesis and birth defects involving the face, eye, heart, neural tube, blood vessels and limbs. This work is relevant to several human inherited connective tissue disorders as well as to fetal-maternal health and acquired conditions such as arthritis, fibrosis, cataracts, cancer and vascular disorders. We use genetics, biochemistry and cell biology techniques to define mechanisms of ECM assembly and turnover, and to understand how ECM controls cell behavior.

Current laboratory activities:
At its core, the laboratory is interested in how secreted metalloproteinases modify the provisional ECM, and how this, in turn, regulates morphogenesis and influences human disease. We investigate proteinases of the ADAMTS family. Several ADAMTS proteinases and ADAMTS-like proteins were discovered in this laboratory, and we have been investigating their fundamental characteristics and functions for over a decade. We ask: What do they look like? What post-translational modifications render them fully functional? What are their interacting partners and substrates? What are the consequences of their deficiency or excess? How do they participate in the formation of tissues and organs? The laboratory benefits from collaboration with several groups around the world to bring diverse expertise to bear on these specific questions.