Department of Biomedical Engineering
Suneel S. Apte, M.B.B.S., D.Phil.
Extracellular matrix, Morphogenesis and Human Disorders
Extracellular matrix (ECM) is the inanimate material between and around cells. It is the structural framework on which every tissue and organ is organized.It influences all aspects of cell behavior and fate by constituting the de facto microenvironment, i.e., it provides cells with an anchorage, regulates binding and release of growth factors and cytokines and provides bioactive ECM fragments.
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, blood vesselsneural tube 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 aortic aneurysms,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. We make extensive use of mass spectrometry for analysis of matrix proteomes and identification of matrix breakdown products. 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 focus on 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 formation of tissues and organs?
Research Support: S. Apte is presently an American Heart Association- Paul G. Allen Frontiers Group Distinguished Investigator. Research in this laboratory has also been supported by several NIH institutes, including NIAMS, NEI, NICHD and the NIH-NHLBI Program of Excellence in Glycosciences, the Marfan Foundation and Sabrina's Foundation.
Christopher Koch BS
Timothy Mead Ph.D.
Sumeda Nandadasa Ph.D.
Lauren Wang M.S.
Senior Research Technologist
A sampling of research articles from our laboratory:
1. Cikach FS, Koch CD, Mead TJ, Galatioto J, Willard BB, Emerton KB, Eagleton MJ, Blackstone EH, Ramirez F, Roselli EE, Apte SS.Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection. JCI Insight. 2018 Mar 8;3(5). pii: 97167. doi: 10.1172/jci.insight.97167.
2. Hubmacher D, Schneider M, Berardinelli S, Takeuchi H, Willard B, Reinhardt DH, Haltiwanger R, and Apte SS. Unusual life cycle and impact on microfibril assembly of ADAMTS17, a secreted metalloprotease mutated in genetic eye disease. Scientific Reports, 2017;7:41871. doi: 10.1038/srep41871.
3. Dubail, J, Vasudevan, D, Wang, LW, Earp, SE, Jenkins, MW, Haltiwanger, RS, and Apte SS. Impaired ADAMTS9 secretion: A potential mechanism for eye defects in Peters Plus Syndrome. Scientific Reports. 2016. 6:33974. doi: 10.1038/srep33974.
4. Nandadasa, S., Nelson, C.M., Apte, SS. ADAMTS9-Mediated Extracellular Matrix Dynamics Regulates Umbilical Cord Vascular Smooth Muscle Differentiation and Rotation. Cell Reports 11:1519-28, 2015
5. Hubmacher D, Wang LW, Mecham RP, Reinhardt DP, Apte SS. Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia: A novel mouse model providing insights on geleophysic dysplasia.Dis Model Mech. 8: 487-499, 2015 PMID: 25762570
6. Dubail J, Aramaki-Hattori N, Bader HL, Nelson CM, Katebi N, Matuska B, Olsen BR, Apte SS. A new Adamts9 conditional mouse allele identifies its non-redundant role in interdigital web regression. Genesis. 2014 52:702-12
7. Foulcer SJ, Nelson CM, Quintero MV, Kuberan B, Larkin J, Dours-Zimmermann MT, Zimmermann DR, Apte SS. Determinants of Versican-V1 Proteoglycan Processing by the Metalloproteinase ADAMTS5. J Biol Chem. 2014, 289(40):27859-73
Recent literature reviews, technical reports and commentaries:
1. Apte, SS. Anti-ADAMTS5 monoclonal antibodies: implications for aggrecanase inhibition in osteoarthritis. Biochem J. 2016 Jan 1;473(1):e1-e4
2. Dubail J, Apte SS. Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics.Matrix Biol. 44-46:24-37 2015
3. Foulcer SJ, Day AJ, Apte SS. Isolation and purification of versican and analysis of versican proteolysis. Methods Mol Biol. 1229:587-604, 2015
4. Nandadasa S, Foulcer S, Apte SS. The multiple, complex roles of versican and its proteolytic turnover by ADAMTS proteases during embryogenesis. Matrix Biol. 2014, 35:34-41, 2014.
1. Apte, SS. Chapter 259. Connective Tissue Structure and Function. ed. Goldman L, and Shafer, A.I., Goldman-Cecil Textbook of Medicine, Twenty-Fifth Edition, Elsevier, New York, 2016, ISBN 9781455750177
2. Apte SS. ADAMTS proteases: Mediators of physiological and pathogenic extracellular proteolysis, in Bradshaw, R., and Stahl, P, eds, Encyclopedia of Cell Biology, Elsevier, New York, 2015, ISBN 9780123944474
3. Apte, SS. Chapter 2. Overview of the ADAMTS superfamily, in Rodgers, G., ed, ADAMTS13: Biology and Disease, Springer, New York, 2015, ISBN 9783319087160
4. Traboulsi I, and Apte SS. Chapter 43. Ectopia Lentis and Associated Systemic Disease, in Traboulsi, I., ed, Genetic Diseases of the Eye, Second Edition, Oxford University Press, USA, 2012, ISBN 9780195326147
Additional publications from our laboratory are obtainable from Dr. Apte's profile on Google Scholar and at http://www.ncbi.nlm.nih.gov/pubmed/
|US Patent||Patent Title||Issue Date||First-Named Inventor|
|6,391,610||Nucleic Acids Encoding Zinc Metalloproteases||5/21/2002||Suneel S. Apte Ph.D|