Suneel S. Apte,  M.B.B.S., D.Phil.

Suneel S. Apte, M.B.B.S., D.Phil.


Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 445-3278

Apte Laboratory


Extracellular matrix (ECM) is the inanimate material that surrounds cells and provides a scaffold for tissue and organ architecture. ECM undergoes constant remodeling by enzymes called proteases. We have discovered that several protease mutations can lead to common birth defects. In addition, abnormal activity of proteases is a major contributor to adult-onset disorders such as osteoarthritis, cancer and aortic aneurysms, to name only a few. This relevance to pediatric and adult disorders has motivated our broad interest in proteases and ECM.

Research on the ADAMTS proteases is a major emphasis of the laboratory because of their high significance for embryonic development and adult diseases. We investigate how their mutations lead to birth defects affecting the heart, blood vessels, brain, eyes, face and limbs. Our research is also relevant to maternal-fetal health and inherited human connective tissue disorders such as Marfan syndrome and the acromelic dysplasias. Among acquired human disorders, we investigate osteoarthritis, aortic aneurysms, cancer and heart failure. The laboratory makes intensive use of proteomics to identify protease substrates and to define the proteolytic landscape of diseased human tissues.

To access our work, please click on the publications tab at the top of this page for publications or visit Dr. Apte's profile on Google Scholar and at

Lay Summary

Our lab studies extracellular matrix, the mesh-like substance that determines the structure of tissues and organs. We are especially interested in how proteases, which are enzymes that break down proteins, affect the extracellular matrix. Proteolytic breakdown of the matrix is necessary for normal organ function, but when inadequate or in excess, it leads to a variety of disorders. We are applying the discoveries we make to illnesses such as osteoarthritis, cancer, and heart disease, and to birth defects involving the heart, eyes, and limbs.

View publications for Suneel S. Apte, M.B.B.S., D.Phil.

Publications in 2021

Martin DR, Santamaria S, Koch CD, Ahnström J, Apte SS. Identification of novel ADAMTS1, ADAMTS4 and ADAMTS5 cleavage sites in versican using a label-free quantitative proteomics approach. Proteomics. 2021 Aug 24:104358. doi: 10.1016/j.jprot.2021.104358. Online ahead of print.

Santamaria S, Martin DR, Dong X, Yamamoto K, Apte SS, Ahnström J. Post-Translational Regulation And Proteolytic Activity Of The Metalloproteinase Adamts8. J Biol Chem. 2021 Oct 20:101323. doi: 10.1016/j.jbc.2021.101323. Online ahead of print.

Rypdal KB, Erusappan PM, Melleby AO, Seifert DE, Palmero S, Strand ME, Tønnessen T, Dahl CP, Almaas V, Hubmacher D, Apte SS, Christensen G, Lunde IG. The extracellular matrix glycoprotein ADAMTSL2 is increased in heart failure and inhibits TGFβ signalling in cardiac fibroblasts. Sci Rep. 2021 Oct 5;11(1):19757. doi: 10.1038/s41598-021-99032-2.

Apte SS. The Pivotal Role of Versican Turnover by ADAMTS Proteases in Mammalian Reproduction and Development. In Proteoglycans in Stem Cells. From Development to Cancer. Götte, M, Forsberg-Nilsson, K (Eds.), Springer 2021, ISBN 978-3-030-73452-7.

Nandadasa S, Burin des Rozier C, Koch C, Tran-Lundmark K, Dours-Zimmermann MT, Zimmermann DR, Valleix S, Apte SS. A new mouse mutant with cleavage-resistant versican and isoform-specific versican mutants demonstrate that proteolysis at the Glu441-Ala442 peptide bond in the V1 isoform is essential for interdigital web regression. Matrix Biology Plus, 2021, May 14;10:100064. doi: 10.1016/j.mbplus.2021.100064. 

Nandadasa S, O'Donnell A, Murao A, Yamaguchi Y, Midura RJ, Olson L, Apte SS. The versican-hyaluronan complex provides an essential extracellular matrix niche for Flk1+ hematoendothelial progenitors. Matrix Biol. 2021  Mar;97:40-57. doi: 10.1016/j.matbio.2021.01.002. 

Arechederra M, Bazai SK, Abdouni A, Sequera C, Mead TJ, Richelme S, Daian F, Audebert S, Dono R, Lozano A, Gregoire D, Hibner U, Allende DS, Apte SS, Maina F. ADAMTSL5 is an epigenetically activated gene underlying tumorigenesis and drug resistance in hepatocellular carcinoma. J Hepatol. 2021 Apr;74(4):893-906. doi: 10.1016/j.jhep.2020.11.008. 

Witten JC, Tan CD, Rodriguez ER, Shrestha NK, Gordon SM, Hussain ST, Apte SS, Unai S, Blackstone EH, Pettersson GB. Invasive Aortic Valve Endocarditis: Clinical and Tissue Findings from a Prospective Investigation. Ann Thorac Surg. 2021 Apr 8;S0003-4975(21)00651-2. doi: 10.1016/j.athoracsur.2021.03.072.

Foulcer SJ, Day AJ, Apte SS. Isolation and Purification of Versican and Analysis of Versican Proteolysis. Methods Mol Biol. 2022;2303:559-578. doi: 10.1007/978-1-0716-1398-6_43

Balic Z, Misra S, Willard B, Reinhardt DP, Apte SS, Hubmacher D. Alternative splicing of the metalloprotease ADAMTS17 spacer regulates secretion and modulates autoproteolytic activity. FASEB J. 2021 Feb;35(2):e21310. doi: 10.1096/fj.202001120RR.

Publications in 2020

Nandadasa S, Szafron JM, Pathak V, Murtada S-I, Kraft CM, O ’ Donnell A, Norvik C, Hughes C, Caterson B, Domowicz MS, Schwartz NB, Tran-Lundmark K, Veigl M, Sedwick D, Philipson EH, Humphrey JD, Apte SS. Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth.  Elife. 2020 Sep 10;9:e60683. doi: 10.7554/eLife.60683. Accompanying Commentary:

Martin DR, Witten JC, Tan CD, Rodrigues ER, Pettersson GB, Seifert DE, Willard BB, Apte SS. Proteomics identifies a convergent innate response to infective endocarditis and extensive proteolysis in vegetation components. JCI Insight 2020 Jun 16;135317. doi: 10.1172/jci.insight.135317

Ataca D, Aouad P, Constantin C, Laszlo C, Beleut M, Shamseddin M, Rajaram RD, Jeitziner R, Mead TJ, Caikovski M, Bucher P, Ambrosini G, Apte SS, Brisken C. The secreted protease ADAMTS18 links hormone action to activation of the mammary stem cell niche. Nat Commun. 2020 Mar 26;11(1):1571. doi: 10.1038/s41467-020-15357-y.

Zhang A, Berardinelli SJ, Leonhard-Melief C, Vasudevan D, Liu TW, Taibi A, Giannone S, Apte SS, Holdener BC, Haltiwanger RS. O-Fucosylation of ADAMTSL2 is required for secretion and is impacted by geleophysic dysplasia-causing mutations. J Biol Chem. 2020 Sep 10:jbc.RA120.014557. doi: 10.1074/jbc.RA120.014557. Online ahead of print.

Evans DR, Green JS, Fahiminiya S, Majewski J, Fernandez BA, Deardorff MA, Johnson GJ, Whelan JH, Hubmacher D, Apte SS; Care4Rare Canada Consortium, Woods MO. A novel pathogenic missense ADAMTS17 variant that impairs secretion causes Weill-Marchesani Syndrome with variably dysmorphic hand featuresSci Rep. 2020 Jul 2;10(1):10827. doi: 10.1038/s41598-020-66978-8

Koch CD, Lee CM, Apte SS. Aggrecan in Cardiovascular Development and Disease. J Histochem Cytochem. 2020 Sep 1:22155420952902. doi: 10.1369/0022155420952902.

Koch CD, Apte SS. Characterization of Proteoglycanomes by Mass Spectrometry. In, S. Ricard-Blum (ed.) Extracellular Matrix Omics, In the series, Biology of Extracellular Matrix, pp69-82. ISBN 978-3-030-58329-3 7. SpringerNature Switzerland AG 2020.

Apte SS. ADAMTS Proteins: Concepts, Challenges, and Prospects. Methods Mol Biol. 2020;2043:1-12. doi: 10.1007/978-1-4939-9698-8_1. Review.

Mead TJ, Apte SS.Visualization and Quantification of Pericellular Matrix. Methods Mol Biol. 2020;2043:261-264. doi: 10.1007/978-1-4939-9698-8_21.

Mead TJ, Apte SS.Expression Analysis by RNAscope™ In Situ Hybridization. Methods Mol Biol. 2020;2043:173-178. doi: 10.1007/978-1-4939-9698-8_14.

Publications in 2019

Wang LW, Nandadasa S, Annis DS, Dubail J, Mosher DF, Willard BB, Apte SS. A disintegrin-like and metalloproteinase domain with thrombospondin type 1 motif 9 (ADAMTS9) regulates fibronectin fibrillogenesis and turnover. J Biol Chem, 2019,294:9924-9936. doi: 10.1074/jbc.RA118.006479

Hubmacher, D, Thacker, S, Adams SM,  Birk, D,  Schweitzer, R, Apte, SS. Limb- and tendon-specific   Adamtsl2   deletion identifies a soft tissue mechanism modulating bone length. Matrix Biology, 2019. pii: S0945-053X(18)30372-X. doi: 10.1016/j.matbio.2019.02.001. 

Nandadasa, S, Kraft, CM, O’Donnell, A, Wang, LW, O’Donnell, A, Patel, R, Gee HY, Grobe, K, Cox, TC, Hildebrandt F and Apte, SS. Secreted metalloproteases   ADAMTS9 and ADAMTS20 have a non-canonical role in ciliary vesicle growth   during ciliogenesis. Nature Communications, (2019) 10:953 |

Choi YJ, Halbritter J, Braun DA, Schueler M, Schapiro D, Rim JH, Nandadasa S, Choi WI, Widmeier E, Shril S, Körber F, Sethi SK, Lifton RP, Beck BB, Apte SS, Gee HY,Hildebrandt F. Mutations of ADAMTS9 Cause Nephronophthisis-Related Ciliopathy. Am J Hum Genet. 2019 104:45-54. doi: 10.1016/j.ajhg.2018.11.003.

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. 2019, 77:117-128.  pii: S0945-053X(18)30253-1. doi: 10.1016/j.matbio.2018.09.004. 

Jensen LD, Hot B, Ramsköld D, Germano RFV, Yokota C, Giatrellis S, Lauschke VM, Hubmacher D, Li MX, Hupe M, Arnold TD, Sandberg R, Frisén J, Trusohamn M, Martowicz A, Wisniewska-Kruk J, Nyqvist D, Adams RH, Apte SS, Vanhollebeke B, Stenman JM, Kele J. Disruption of the Extracellular Matrix Progressively Impairs Central Nervous System Vascular Maturation Downstream of β-Catenin Signaling. Arterioscler Thromb Vasc Biol. 2019 39:1432-1447. doi: 10.1161/ATVBAHA.119.312388. 

Santamaria S, Yamamoto K, Teraz-Orosz A, Koch C, Apte SS, de Groot R, Lane DA, Ahnström J. Exosites in Hypervariable Loops of ADAMTS Spacer Domains control Substrate Recognition and Proteolysis. Sci Rep. 2019 Jul 29;9(1):10914. doi: 10.1038/s41598-019-47494-w

Holdener BC, Percival CJ, Grady RC, Cameron DC, Berardinelli SJ, Zhang A, Neupane S, Takeuchi M, Jimenez-Vega JC, Uddin SMZ, Komatsu DE, Honkanen R, Dubail J, Apte SS, Sato T, Narimatsu H, McClain SA, Haltiwanger RS. ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in a mouse model of Peters Plus Syndrome.  Hum Mol Genet. 2019 Oct 10. pii: ddz225. doi: 10.1093/hmg/ddz225. [Epub ahead of print]

Graae AS, Grarup N, Ribel-Madsen R, Lystbæk SH, Boesgaard T, Staiger H, Fritsche A, Wellner N, Sulek K, Kjolby M, Backe MB, Chubanava S, Prats C, Serup AK, Birk JB, Dubail J, Gillberg L, Vienberg SG, Nykjær A, Kiens B, Wojtaszewski JFP, Larsen S, Apte SS, Häring HU, Vaag A, Zethelius B, Pedersen O, Treebak JT, Hansen T, Holst B.ADAMTS9 Regulates Skeletal Muscle Insulin Sensitivity Through Extracellular Matrix Alterations. Diabetes. 68(3):502-514. doi: 10.2337/db18-0418.

Publications in 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.

Mead TJ, McCulloch DR, Ho JC, Du Y, Adams SM, Birk DE, Apte SS. 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.

Schnellmann R, Sack R, Hess D, Annis DS, Mosher DF, Apte SS, 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. 

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.


Apte SS. ADAMTS proteins: Concepts, Challenges and Prospects. Methods Mol Biol. 2020;2043:1-12. doi: 10.1007/978-1-4939-9698-8_1.

Reviews, technical reports and commentaries

1. Mead TJ, Apte SS. ADAMTS proteins in human disorders.Matrix Biol. 2018 Jun 6. pii: S0945-053X(18)30179-3. doi: 10.1016/j.matbio.2018.06.002.

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.

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 from Dr. Apte's profile on Google Scholar and at

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

10/01/2020 |  

New Study Unveils the Cellular Mechanism of Umbilical Cord Vessel Closure Following Delivery

Researchers have discovered that umbilical cord arteries contain components that naturally promote narrowing at birth, and ensure a sequence in which the arteries close before the vein, supporting delayed cord clamping following delivery in most uncomplicated deliveries.

08/12/2020 |  

Identifying Protein Makeup of Valvular Vegetations Can Help Diagnose Infective Endocarditis

A team of researchers, led by the Department of Biomedical Engineering, found that differences in the protein makeup of vegetations may help to identify the pathogen of infective endocarditis and cast new light upon the deadly disease.