Carl P. Blobel, MD, PhD, Hospital for Special Surgery

Dr. Blobel
Carl P. Blobel, MD, PhD

Studies in the Blobel 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. Their current focus is 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. A main goal is to elucidate the role of these proteins in cell-cell interactions and signaling in order to develop new approaches to fighting autoimmune disease and tissue degeneration and to stimulating tissue growth and regeneration.

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References

  1. Weskamp G, Krätzschmar J, Reid MS, Blobel CP. MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains. J Cell Biol. 1996 Feb;132 (4):717-26.
  2. Roghani M, Becherer JD, Moss ML, Atherton RE, Erdjument-Bromage H, Arribas J, Blackburn RK, Weskamp G, Tempst P, Blobel CP. Metalloprotease-disintegrin MDC9: intracellular maturation and catalytic activity. J Biol Chem. 1999 Feb 5;274(6):3531-40.
  3. Peduto L, Reuter VE, Shaffer DR, Scher HI, Blobel CP. Critical function for ADAM9 in mouse prostate cancer. Cancer Res. 2005 Oct 15;65(20):9312-9.
  4. Guaiquil V, Swendeman S, Yoshida T, Chavala S, Campochiaro PA, Blobel CP. ADAM9 is involved in pathological retinal neovascularization. Mol Cell Biol. 2009 May;29 (10):2694-703.
  5. Inoue, D.; Reid, M.; Lum, L.; Krätzschmar, J.; Weskamp, G.; Myung, Y. M.; Baron, R.; Blobel, C. P. Cloning and initial characterization of mouse meltrin beta and analysis of the expression of four metalloprotease-disintegrins in bone cells. J. Biol. Chem. 1998, 273, 4180-4187.
  6. Krätzschmar, J.; Lum, L.; Blobel, C. P. Metargidin, a membrane-anchored metalloprotease-disintegrin protein with an RGD integrin binding sequence. J. Biol. Chem. 1996, 271, 4593-4596.
  7. Lum L.; Reid, M. S.; Blobel, C. P. Intracellular maturation of the mouse metalloprotease disintegrin MDC15. J. Biol Chem. 1998, 273, 26236-26247.
  8. Horiuchi K, Weskamp G, Lum L, Hammes HP, Cai H, Brodie TA, Ludwig T, Chiusaroli R, Baron R, Preissner KT, Manova K, Blobel CP. Potential role for ADAM15 in pathological neovascularization in mice. Mol Cell Biol. 2003 Aug;23(16):5614-24.
  9. Maretzky T, Yang G, Ouerfelli O, Overall CM, Worpenberg S, Hassiepen U, Eder J, Blobel CP. Characterization of the catalytic activity of the membrane-anchored metalloproteinase ADAM15 in cell-based assays. Biochem J. 2009 Apr 28;420(1):105-13.
  10. Maretzky T, Le Gall SM, Worpenberg-Pietruk S, Eder J, Overall CM, Huang XY, Poghosyan Z, Edwards DR, Blobel CP. Src stimulates fibroblast growth factor receptor-2 shedding by an ADAM15 splice variant linked to breast cancer. Cancer Res. 2009 Jun 1;69(11):4573-6.
  11. Horiuchi, K.; Weskamp, G.; Lum, L.; Hammes, H. P.; Cai, H.; Brodie, T. A.; Ludwig, T.; Chiusaroli, R.; Baron, R.; Preissner, K. T.; Manova, K.; Blobel, C. P. Potential role for ADAM15 in pathological neovascularization in mice. Mol. Cell. Biol. 2003, 23, 5614-5624.
  12. Schlöndorff, J.; Becherer, J. D.; Blobel, C. P. Intracellular maturation and localization of the tumour necrosis factor alpha convertase (TACE). Biochem J. 2000, 347, 131-138.
  13. Zheng, Y.; Schlondorff, J.; Blobel, C. P. Evidence for regulation of the tumor necrosis factor alpha-convertase (TACE) by protein-tyrosine phosphatase PTPH1. J. Biol. Chem. 2002, 277, 42463-42470.
  14. Horiuchi, K.; Kimura T.; Miyamoto T.; Takaishi H.; Okada Y.; Toyama, Y., Blobel, C. P. Cutting edge: TNF-alpha-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. J. Immunol. 2007, 179, 2686-2689.
  15. Le Gall, S. M., Maretzky, T., Issuree, P. D., Niu, X. D.; Reiss, K., Saftig, P., Khokha, R., Lundell, D., Blobel, C. P. ADAM17 is regulated by a rapid and reversible mechanism that controls access to its catalytic site. J. Cell. Sci. 2010, 123, 3913-3922.
  16. Maretzky, T., Evers, A., Zhou, W., Swendeman, S. L., Wong, P. M., Rafii, S., Reiss, K., Blobel C. P. Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17. Nat. Commun. 2011, 2, 1-25.
  17. Chesneau, V.; Becherer, J. D.; Zheng, Y.; Erdjument-Bromage, H.; Tempst, P.; Blobel, C. P. Catalytic properties of ADAM19. J. Biol. Chem. 2003, 278, 22331-22340.
  18. Zhou, H. M.; Weskamp, G.; Chesneau, V.; Sahin, U.; Vortkamp, A.; Horiuchi, K.; Chiusaroli, R.; Hahn, R.; Wilkes, D.; Fisher, P.; Baron, R.; Manova, K.; Basson, C. T.; Hempstead, B.; Blobel, C. P. Essential role for ADAM19 in cardiovascular morphogenesis. Mol. Cell. Biol. 2004, 24, 96-104.
  19. Kawaguchi, N.; Horiuchi, K.; Becherer, J. D.; Toyama, Y.; Besmer, P.; Blobel, C. P. Different ADAMs have distinct influences on Kit ligand processing: phorbol- ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19. J. Cell. Sci. 2007, 120, 943-952.
  20. Howard, L.; Maciewicz R. A.; Blobel C. P. Cloning and characterization of ADAM28: evidence for autocatalytic pro-domain removal and for cell surface localization of mature ADAM28. Biochem J. 2000, 348, 21-27.
  21. Howard, L.; Zheng, Y.; Horrocks, M.; Maciewicz, R. A.; Blobel, C. Catalytic activity of ADAM28. FEBS Lett. 2001, 498, 82-86.
  22. Howard, L., Nelson, K.K., Maciewicz, R.A., and Blobel, C.P. 1999. Interaction of the metalloprotease-disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1. J. Biol. Chem. 274:31693-31699.
  23. McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K, Maney SK, Berger T, Murthy A, Duncan G, Xu HC, Lang KS, Häussinger D, Wakeham A, Itie-Youten A, Khokha R, Ohashi PS, Blobel CP, Mak TW. iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science. 2012 Jan 13;335(6065):229-32.