Apte Laboratory

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, 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 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.

In a unique operational paradigm, several ADAMTS proteinases (ADAMTS1,4,5,9,20) cooperate physiologically in versican processing. Defective ADAMTS proteolysis of versican is involved in several major birth defects such as cleft palate, neural tube defects and congenital heart defects including ventricular septal defect, valve malformations and Tetralogy of Fallot. It is involved in fetal-maternal health via a role in umbilical cord development and myometrial activation. The laboratory devotes considerable effort to understanding versican proteolysis and the role of versican itself in morphogenesis. We are also interested in versican as a potential biomarker for human disorders.

Mutations of ADAMTS10, ADAMTS17, ADAMTSL2, ADAMTSL3 and ADAMTSL4 cause related inherited connective tissue disorders in humans and domesticated animals. Among the anomalies some of them share is disruption of the ocular zonule, a fibrillin-rich structure that suspends the lens in the optic path. This anomaly, named ectopia lentis, is commonly seen in Marfan syndrome, and it led us to investigate zonule formation and molecular mechanisms of microfibril assembly. We have shown that these ADAMTS proteins bind to fibrillins and regulate microfibril assembly. Some have a role in muscle and tendon connective tissue formation. We presently investigate the molecular mechanisms of these effects.

ADAMTS9, the most conserved of all metalloproteinases, is required for normal eye development and implicated in age-related macular degeneration. The laboratory investigates mechanisms of ocular anterior segment defects arising from ADAMTS9 deficiency that are related to the congenital disorder of glycosylation, Peters Plus Syndrome. We investigate ADAMTS9 using conditional and gene trap mutants, and misexpression or inactivation in cells.

We generate recombinant ADAMTS9, as well as other ADAMTS proteins, versican and fibrillins to study their intrinsic properties, post-translational modification, and intermolecular interactions. We are using mass spectrometry to characterize ADAMTS proteases and to identify novel ADAMTS substrates and CRISPR-Cas9 for gene editing in cells and mice.

Research in this laboratory is supported by the National Eye Institute, the NIH-NHLBI Program of Excellence in Glycosciences, Sabrina's Foundation and the Marfan Foundation.

Deborah  Hoelting
Deborah Hoelting
Research Technician

Phone:(216) 445-3284
Fax:(216) 444-9198

Dirk   Hubmacher Ph.D.
Dirk Hubmacher Ph.D.
Project Staff

Phone:(216) 444-3783
Fax:(216) 444-9198

Christopher  Koch BS
Christopher Koch BS
Graduate Student

Phone:(216) 445-3284

Timothy  Mead Ph.D.
Timothy Mead Ph.D.
Research Associate

Phone:(216) 445-3284
Fax:(216) 444-9198

Sumeda  Nandadasa Ph.D.
Sumeda Nandadasa Ph.D.
Research Associate

Phone:(216) 445-3284
Fax:(216) 444-9198

Lauren  Wang M.S.
Lauren Wang M.S.
Senior Research Technologist

Phone:(216) 445-3284
Fax:(216) 444-9198

Selected recent research articles from our laboratory:

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. 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

5. Collin GB, Hubmacher D, Charette JR, Hicks WL, Stone L, Yu M, Naggert JK, Krebs MP, Peachey NS, Apte SS, Nishina PM. Disruption of murine Adamtsl4 results in zonular fiber detachment from the lens and in retinal pigment epithelium dedifferentiation. Hum Mol Genet. 2015 Sep 24. pii: ddv399

7. 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

8. 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.


Book chapters:

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 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