Fundamental research on ADAMTS proteins and morphogenesis: Several ECM-modifying ADAMTS proteases and the related ECM molecules named ADAMTS-like proteins were first discovered by our laboratory. We investigate their fundamental characteristics by asking: 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, i.e., how do they participate in formation of tissues and organs?
ADAMTS proteins in birth defects: The laboratory has implicated defective ADAMTS proteolysis of versican in birth defects such as cleft palate, syndactyly, abnormal skin pigmentation, and congenital heart defects such as ventricular septal defect and Tetralogy of Fallot. Studies on cardiovascular and vascular defects are supported by an award from the NIH-NHLBI Program of Excellence in Glycosciences.
Inherited eye defects and development of the eye: Mutations of ADAMTS10, ADAMTS17 and ADAMTSL4 affect development of the ocular zonule, a fibrillin-rich structure that suspends the lens in the optic path. This anomaly, named ectopia lentis, is also common in Marfan syndrome. We investigate formation of the zonule and ectopia lentis with support from an award from the NIH-NEI. An understanding of microfibril biogenesis is important for many other organs as well.
A second project on eye development that is potentially related to an inherited disorder called Peters Plus syndrome, investigates how ADAMTS9 regulates development of the anterior half of the eye. This research is supported by awards from the NIH-NEI and the Knight Templar Eye Foundation (to Johanne Dubail, post-doctoral fellow).
The laboratory has a constantly evolving portfolio of projects based on individual member’s interests and new findings. Some of the topics currently pursued by the laboratory include development of extra-embryonic tissues and vascular biology of the fetal-maternal axis (supported by a grant from Sabrina’s Foundation) and musculoskeletal developmental anomalies (supported by an NIH F32 training award to Timothy Mead). We appreciate past support from the KTEF and Marfan Foundation that launched some of the laboratory’s current projects.
We welcome inquiries regarding collaborations, studentships, fellowships or sabbaticals.
Extracellular matrix (ECM) is the dynamic, hierarchical network of proteins, proteoglycans and glycans around cells. It provides them an anchorage, and influences every aspect of their behavior and fate. ECM provides the structural framework on which every tissue and organ is built. It stores and regulates growth factors, and is a source of bioactive fragments. ECM and cell-ECM interactions are relevant to every organ system and all human diseases. ECM is easy to overlook, challenging to investigate, and impossible to live without.
Our laboratory studies ECM in embryogenesis (developmental biology) and birth defects involving the face, eye, heart, brain, blood vessels and limbs. Our work is relevant to several human connective tissue disorders as well as to fetal-maternal health and acquired conditions such as arthritis, cataracts, cancer and vascular disorders. The fundamental and translational laboratory activities that span these interests use genetics, biochemistry and cell biology tools.
Much of our current work revolves around ADAMTS metalloproteinases, which interact with or clip a variety of ECM molecules. Among these targets, the macromolecules fibrillin and versican are prominent, and functionally crucial in their own right, which has prompted us to investigate them more closely. After all, the biology of proteases is really the biology of its substrates.
|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|
Selected recent research articles:
1. Nandadasa, S., Nelson, C.M., Apte, SS. ADAMTS9-Mediated Extracellular Matrix Dynamics Regulates Umbilical Cord Vascular Smooth Muscle Differentiation and Rotation. Cell Reports 11, 1–10, June 16, 2015
2. 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. 2015 Mar 11. [Epub ahead of print] PMID: 25762570
3. Beene, LC, Wang, LW, HubmacherD, Keene DR, Reinhard DP, Annis, DS, Mosher, DF, Mecham, RP, Traboulsi, EI, and Apte SS. Non-selective assembly of fibrillin-1 and fibrillin-2 in the rodent ocular zonule and in cultured cells: Implications for Marfan syndrome. Invest Ophthal Visual Sci 2013, 54(13):8337-44
4. 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
5. 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 reviews, technical reports and perspectives:
1. Dubail J, Apte SS. Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics.Matrix Biol. 2015 Mar 11, ePub.PMID: 25770910
2. Apte SS, Parks WC. Metalloproteinases. A parade of functions in matrix biology and an outlook for the future. Matrix Biol. 2015, April 23, ePub. PMID 25916966
3. Foulcer SJ, Day AJ, Apte SS. Isolation and purification of versican and analysis of versican proteolysis. Methods Mol Biol. 2015;1229:587-604
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.
Recent 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
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, In Press
3. Apte, SS. Chapter 2. Overview of the ADAMTS superfamily, in Rodgers, G., ed, ADAMTS13: Biology and Disease, Springer, New York, 2015, In Press
Additional publications can be obtained at http://www.ncbi.nlm.nih.gov/pubmed/