Carl Blobel, MD, PhD

Appointments

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

 

Selected Publications

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 (in press)

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

Zhu, W., Boachie-Adjei, O., Rawlins, B.A., Frenkel, B., Boskey, A.L., Ivashkiv, L.B., and Blobel, C.P.  2007.  A Novel Regulatory Role for SDF-1 Signaling in BMP2- Osteogenic Differentiation of Mesenchymal C2C12 Cells. Journal of Biological Chemistry 282:18676-18685

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

Horiuchi, Keisuke, Le Gall, Sylvain, Schulte, Marc, Yamaguchi, Takafumi, Reiss, Karina , Murphy, Gillian,  Toyama, Yoshiaki , Hartmann, Dieter, Saftig, Paul and Blobel, Carl P. 2007. Substrate Selectivity of Epidermal Growth Factor-Receptor Ligand Sheddases and their Regulation by Phorbol Esters and Calcium Influx. Molecular Biology of the Cell 18, 176-188.

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.  

Research Description

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.

Clinical Trials

• Osteogenic Differentiation of Human Mesenchymal Stem Cells