Senior Scientist, Hospital for Special Surgery
Program Director of the Arthritis and Tissue Degeneration Program, Hospital for Special Surgery
Professor in the Department on Medicine, Weill Medical College of Cornell University
Professor in the Department of Physiology & Biophysics, Weill Medical College of Cornell University
Virginia F. and William R. Salomon Chair in Musculoskeletal Research
Member, Association of American Physicians (AAP)
David R. McIlwain, Philipp A. Lang, Thorsten Maretzky, Koichi Hamada, Kazuhito Ohishi, Sathish Kumar Maney, Thorsten Berger, Aditya Murthy, Duncan, G., Xu, H.C., Lang, K.S., Häussinger, D., Wakeham, A., Youten, A.I., Khokha, R., Ohashi, P.S., Blobel, C.P. and Mak, T.W. 2012. iRhom2 regulates innate immunity via TACE/ADAM17. Science 335(6065):229-32
Glomski, K., Monette, S., Manova, K., De Strooper, B., Saftig, P., and Blobel, C.P. 2011. Deletion of ADAM10 in endothelial cells leads to defects in organ-specific vascular structures. Blood 118(4):1163-74
Maretzky, T., Evers, A., Zhou, W., Swendeman, S.L., Wong, P.-M., Rafii, S., Reiss, K., and Blobel, C.P. 2011. Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17. Nature Comm. 2:229
Brandl, K., Sun, L., Neppl, C., Siggs, O.M., Le Gall, S.M., Tomisato, W., Li, X., Du, X., Maennel, D.N., Blobel, C.P., Beutler, B. 2010. MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. Proc. Natl. Acad. Sci. USA. 107:19967-72.
Le Gall, S.M., Maretzky, T., Issuree, P.D.A., Niu, X-D, Reiss, K., Saftig, P., Khokha, R., Lundell, D., Blobel, C.P. 2010. ADAM17 is regulated by a rapid and reversible mechanism that controls access to its catalytic site. J. Cell Science. 23(Pt 22):3913-22
Weskamp G., Mendelson K., Swendeman S., Le Gall S., Ma Y., Lyman S., Hinoki A., Eguchi S., Guaiquil V., Horiuchi K., Blobel C.P. 2010. Pathological Neovascularization Is Reduced by Inactivation of ADAM17 in Endothelial Cells but Not in Pericytes. Circ. Research 106:932-940
Le Gall, S.M.; Bobé, P.; Reiss, K.; Horiuchi, K.; Niu, X-D.; Lundell, D.; Gibb, D.R.; Conrad, D.; Saftig, P.; and Blobel, C.P. 2009. ADAMs 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as TGFa, L-Selectin and TNFa. Molecular Biology of the Cell 20:1785-1794.
Swendeman, S., Mendelson, K., Weskamp, G., Horiuchi, K., Deutsch, U., Scherle, P., Hooper, A., Rafii, S., Blobel, C.P. 2008. VEGF-A Stimulates ADAM17-Dependent Shedding of VEGFR2 and Crosstalk Between VEGFR2 and ERK Signaling. Circulation Research, 103:916-918.
Overall, C.M. and Blobel, C.P. 2007. In search of partners: linking extracellular proteases to substrates. Nature Reviews in Molecular and Cellular Biology 8:245-257
Horiuchi, K., Kimura, T., Miyamoto, T., Takaishi. H., Okada, Y., Toyama, Y., and Blobel, C.P. 2007. TNFa-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. Journal of Immunology 179:2686-2689
Weskamp, Gisela, Ford, Jill W, Sturgill, Jamie, Martin, Steve, Docherty, Andrew J P, Swendeman, Steven, Broadway, Neil, Hartmann, Dieter, Saftig, Paul, Umland, Shelby, Sehara-Fujisawa, Atsuko , Black, Roy A, Ludwig, Andreas, Becherer, J David, Conrad, Daniel H and Blobel, Carl P. 2006. ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23. Nature Immunology 7, 1293 - 1298.
Blobel, C.P. 2005. ADAMs: key components in EGFR signaling and development Nature Reviews in Molecular and Cellular Biology 6:32-43
Sahin, U., Weskamp, G., Zhou, H., Higashiyama, S., Peschon, J., Hartmann, D., Saftig, P., and Blobel, C.P. Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR-ligands. 2004. J. Cell Biol., 164:769-779.
For more publications, please see the PubMed listing.
Metalloprotease-disintegrins (ADAMs): key players in growth factor signaling, angiogenesis and arthritis
Studies in my lab are focused on a family of membrane-anchored metalloproteases named ADAMs (a disintegrin and metalloprotease) with an emphasis on their role in tissue degeneration and regeneration, rheumatoid arthritis and angiogenesis. ADAMs are membrane-anchored glycoproteins that can function as molecular signaling switches by cleaving and releasing other membrane proteins from cells. This process, which is referred to as “protein ectodomain shedding”, can activate or inactivate the substrate protein, or substantially change its functional properties. Examples of membrane proteins whose function is regulated by ADAMs are the pro-inflammatory cytokine TNF alpha, the main target of drugs for treatment of rheumatoid arthritis, and several ligands of the epidermal growth factor receptor (EGFR), a receptor with important roles in development, cancer and wound healing.
We are taking three complementary approaches to study the function of ADAMs and their role in ectodomain shedding. The first is to create and analyze mice lacking specific ADAMs (“knockout mice”), which are essential for evaluating the function of these proteins during development and in mouse models for human diseases. The second is to use cells from these knockout mice to uncover the molecular mechanism underlying the function of different ADAMs, for example by identifying defects in ectodomain shedding in cells that lack one or more ADAMs. The third is to biochemically characterize recombinant ADAMs and determine their substrate specificity and inhibitor profile. Results obtained from studies in vitro can be extended and verified in vivo in cell culture and whole animals, and vice versa.
Currently the lab is focused on understanding how ADAMs regulate the activity of ligands of the epidermal growth factor receptor (EGFR), on elucidating the mechanism underlying the recently discovered roles of ADAMs in angiogenesis, and on their involvement in rheumatoid arthritis and healing of bone fractures and skin wounds. We anticipate that our studies will provide interesting new insights into the role of these proteins in cell-cell interactions and signaling and hope that they will help devise new approaches to fighting autoimmune disease and tissue degeneration and to stimulating tissue growth and regeneration.
One of the goals of Hospital for Special Surgery (HSS) is to advance the science of orthopedic surgery, rheumatology, and related disciplines for the benefit of patients. Research staff at HSS may collaborate with outside companies for education, research and medical advances. HSS supports this collaboration in order to foster medical breakthroughs; however, HSS also believes that these collaborations must be disclosed.
As part of the disclosure process, this website lists Research staff collaborations with outside companies if the Research staff member received any payment during the prior year or expects to receive any payment in the next year. The disclosures are based on information provided by the Research staff and other sources and are updated regularly. Current ownership interests and leadership positions are also listed. Further information may be available on individual company websites.
As of March 26, 2015, Dr. Blobel reported no financial interest relationships with healthcare industry.
By disclosing the collaborations of HSS Research staff with industry on this website, HSS and its Research staff make this information available to patients and the public, thus creating a transparent environment for those who are interested in this information. Further, HSS’ Conflicts of Interest Policy does not permit payment of royalties on products developed by him/her that are used on patients at HSS.