Department of Biomedical Engineering
The Apte Laboratory
To determine the molecular basis of tissue function, the biological basis of disease and pathways to cures.
Our laboratory conducts fundamental research on extracellular matrix and the proteases that remodel it. Why? Because extracellular matrix is the basis for existence of multicellular life forms. It provides the structural scaffold of every tissue and is a major regulatory influence on cells. We study it at the tissue, cell and molecular scale.
Matrix is continuously remodeled by balanced matrix production and removal by matrix degrading proteases. The ADAMTS proteases, which we study, are important participants in this process. Matrix remodeling is crucial for tissue repair and regeneration and is abnormal in inflammation, cancer, fibrosis, and degenerative disorders such as arthritis.
Laboratory members have diverse backgrounds and expertise and explore a variety of individual interests related to extracellular matrix.
Dirk Hubmacher PhD, Project Scientist, obtained his PhD from the University of Lübeck in Germany, and trained as a post-doctoral fellow with Dieter Reinhardt at McGill University (Montreal, Canada). His research interests are matrix assembly, the function of a subgroup of ADAMTS proteases and ADAMTS-like proteins, and their relationship to fibrillin microfibrils using biochemistry, cell culture studies, and mouse models. Human mutations affecting this subgroup of ADAMTS/ADAMTSL proteins phenocopy all or several aspects of genetic disorders caused by mutations in the fibrillin-1 gene itself, suggesting a functional relationship. He is currently the recipient of a grant from the Marfan Foundation.
Lauren Weiping Wang, MS, Lead Research Technologist, has expertise in protein purification, intermolecular interactions and developmental biology. Her current interests are in defining the role of ADAMTS10 in congenital eye defects, and understanding the post-translational modifications of ADAMTS proteins.
Sumeda Nandadasa, PhD, Post-doctoral Fellow (Morgenthaler Fellow), has a career interest in developmental biology. He completed his PhD at Cincinnati Children’s Hospital with Chris Wiley and Janet Heasman. He currently investigates versican in early embryogenesis, the participation of ADAMTS cleavage of versican in extraembryonic vasculature, and the role of ADAMTS9 in embryogenesis.
These images represent some of the research done in this laboratory
EXTRACELLULAR MATRIX and PROTEASES in MORPHOGENESIS and HUMAN DISORDERS
Extracellular matrix (ECM)is the inanimate material that surrounds cells and provides a scaffold for tissue and organ architecture. ECM and cell-ECM interactions have widespread relevance to human disease.
We study the effects of abnormal ECM in birth defects affecting the neural tube, eyes, face, limbs, heart and blood vessels. Our work is relevant to several inherited connective tissue disorders such as Marfan syndrome and to acquired disorders such as aortic aneurysms, arthritis, fibrosis, cancer and glaucoma. We also conduct fundamental research using genetics, biochemistry, cell biology and proteomics to define mechanisms of ECM assembly and turnover and their effects on cell behavior.
Brief Bio-data and Research Support:
Suneel Apte graduated from medical school at Bombay University. He interrupted his clinical training as an orthopaedic surgeon to obtain the D. Phil degree at the University of Oxford (mentor: John Kenwright), where he was a Rhodes Scholar. He subsequently trained as a post-doctoral fellow with Bjorn Olsen at Harvard Medical School.
The laboratory has received support from several NIH institutes, including NIAMS, NEI, NICHD and the NIH-NHLBI Program of Excellence in Glycosciences, the Marfan Foundation, Arthritis Foundation and Sabrina's Foundation. Our current research is supported by the NIH and the Allen Distinguished Investigator Program, through support made by The Paul G. Allen Frontiers Group and the American Heart Association
Research articles (2018):
Mead TJ, Du Y, Nelson CM, Gueye N-A, Drazba J, Dancevic CM, Vankemmelbeke M, Buttle DJ, Apte SS.ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation.Cell Reports.2018, 23; 2, 485-498.
MeadTJ, McCulloch DR, Ho JC, Du Y, Adams SM, Birk DE,ApteSS.The metalloproteinase-proteoglycans ADAMTS7 and ADAMTS12 provide an innate, tendon-specific protective mechanism against heterotopic ossification.JCI Insight.2018 April5;3(7). pii: 92941. doi: 10.1172/jci.insight.92941
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.
Prins, B. , Mead, T.J. (joint first authors) et al.Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.Genome Biol 2018, 19:87.https://doi.org/10.1186/s13059-018-1457-6
Wang LW, Kutz WE, Mead TJ, Beene LC, Singh S, Jenkins MW, Reinhardt DP,Apte SS.Adamts10 inactivation in mice leads to persistence of ocular microfibrils subsequent to reduced fibrillin-2 cleavage. Matrix Biol. 2018.Sep 7. pii: S0945-053X(18)30253-1. doi: 10.1016/j.matbio.2018.09.004. [Epub ahead of print]
Schnellmann R, Sack R, Hess D, Annis DS,MosherDF,ApteSS, Chiquet-Ehrismann R.A selective extracellular matrix proteomics approach identifies fibronectin proteolysis by ADAMTS16 and its impact on spheroid morphogenesis.Mol Cell Proteomics.2018 Apr 18. pii: mcp.RA118.000676. doi: 10.1074/mcp.RA118.000676. [Epub ahead of print]
Aviram R, Zaffryar-Eilot S, Hubmacher D, Grunwald H, Mäki JM, Myllyharju J,Apte SS, Hasson P.Interactions between lysyl oxidases and ADAMTS proteins suggest a novel crosstalk between two extracellular matrix families. Matrix Biol. 2018 May 11. pii: S0945-053X(17)30448-1. doi: 10.1016/j.matbio.2018.05.003. [Epub ahead of print]
Current BioRxiv preprints:
Hubmacher,D, Thacker,S, Adams SM, Birk, D, Schweitzer,R, Apte, S.Limb- and tendon-specificAdamtsl2deletion identifies a soft tissue mechanism modulating bone length.http://biorxiv.org/cgi/content/short/307496v1;doi:https://doi.org/10.1101/307496
Please click on the publications tab at the top of this page for earlier publications or visit Dr. Apte's profile on Google Scholar and at http://www.ncbi.nlm.nih.gov/pubmed/
Other Recent Laboratory Activities:
Timothy Mead was selected to attend the 2018 Neonatal Cardiopulmonary Biology Young Investigators Forum in Chicago IL. Sept. 6-9th2018, where he was awarded a 2018 Excellence in Research Grant.
Chris Koch attended the 2018 American Association for Clinical Chemistry National Meeting in Chicago, IL. He recieved a travel grant and was selected to participate in the student oral presentation competition. For his talk “Assay Development and Evaluation of Serum Aggrecan and Versican as Novel Biomarkers for Thoracic Aortic Aneurysm and Dissection” he was awarded first place.
Sumeda Nandadasa's abstract was selected for a podium presentation at the Gordon Research Conference on Protein Processing, Trafficking and Secretion in New Hampshire, July 15-20, 2018
Chris Koch presented his work at the Gordon Research Conference on Proteoglycans in New Hampshire,July 8-13 2018.
Sumeda Nandadasa received a travel award from The Histochemical Society to present his work at the 2018 American Society for Matrix Biology Conference, Las Vegas, October 14-17, 2018. Tim Mead, Chris Koch and Debbie Hoelting will also present their work at this conference.
Christopher Koch BS
Timothy Mead Ph.D.
Sumeda Nandadasa Ph.D.
Lauren Wang M.S.
Senior Research Technologist
A sampling of research publications from 2017 and earlier:
1. 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.
2. 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.
3. 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
4. Enomoto, H., Nelson, C., Somerville, R.P.T., Mielke, K., Dixon, L., Powell, K., Apte, S.S. Cooperation of two ADAMTS metalloproteases in closure of the mouse palate identifies a requirement for versican proteolysis in regulating palatal mesenchyme proliferation. Development, 2010, 37:4029-38.
5. McCulloch, D.R., Nelson, C.M., Dixon, L.J., Silver D.L., Wylie, J.D., Lindner, V., Sasaki, T., Cooley, M.A., Argraves, W.S. and Apte, S.S. ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression. Developmental Cell 2009, 17:687-98. PMCID:PMC2780442.
Recent literature reviews, technical reports and commentaries:
2. Apte, SS. Anti-ADAMTS5 monoclonal antibodies: implications for aggrecanase inhibition in osteoarthritis. Biochem J. 2016 Jan 1;473(1):e1-e4
3. Dubail J, Apte SS. Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics.Matrix Biol. 44-46:24-37 2015
4. Foulcer SJ, Day AJ, Apte SS. Isolation and purification of versican and analysis of versican proteolysis. Methods Mol Biol. 1229:587-604, 2015
5. 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/
Suneel S. Apte, M.B.B.S., D.Phil.
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 445-3278
Fax: (216) 444-9198