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Carl P. Blobel, MD, PhD

About Dr. Blobel

Carl Blobel obtained his MD degree from the Justus-Liebig University in Giessen, Germany, and a PhD in Biochemistry and Biophysics from UCSF. He is currently a Senior Scientist and Program Director of the Arthritis and Tissue Degeneration Program at the Hospital for Special Surgery, where he holds the Virginia F. and William R. Salomon Chair in Musculoskeletal Research. He is also Professor of Medicine and of Physiology, Biophysics and Systems Biology at Weill Cornell Medicine.

In 2015, Dr. Blobel was elected to the Association of American Physicians in recognition of his outstanding contributions to medicine. In 2017, he was awarded a Distinguished Affiliated Professorship by the Technical University of Munich in 2017, which recognizes "researchers of international prominence who have not only significantly shaped their own discipline but have also inspired other areas within the scientific community." Dr. Blobel has over 13,500 citations in the Web of Science Core collection ISI citation report and an h-factor of 70.

Research

Major Focus: Uncovering the role of iRhoms and ADAM17 in development and disease, with an emphasis in autoimmune diseases such as Rheumatoid Arthritis (RA), Systemic Lupus Erythematosis Glomerulonephritis (SLE GN) and neuroinflammation.

Research in my lab is focused on elucidating the functions of cell surface metalloproteinases termed ADAMs (a disintegrin and metalloproteinase) in development and disease. ADAMs have emerged as critical modulators of cell-cell interactions because they regulate the bioavailability of membrane proteins such as the pro-inflammatory cytokine TNFalpha and ligands of the EGF-receptor (EGFR). Studies in my lab employ a synergistic combination of approaches, including biochemistry, cell biology, mouse models for development and disease and analysis of patient samples. Work in my lab has helped establish that ADAM17 is a key regulator of the EGFR signaling pathway, which is essential for maintaining the skin and intestinal barrier but can cause a variety of human pathologies when it is dysregulated. Moreover, my lab has pioneered studies on the newly discovered iRhom1 and 2 as crucial upstream regulators of ADAM17-dependent EGFR and TNFalpha-signaling. By elucidating how exactly iRhoms and ADAM17 interact, we have provided exciting new insights into the basic biology of these fascinating proteins and have identified new and attractive potential targets for treatment of autoimmune diseases and cancer.

What are the main iRhom/ADAM17-dependent signaling pathways?

The cell surface metalloprotease ADAM17 (a disintegrin and metalloprotease 17) has a crucial role in regulating several major medically relevant signaling pathways, including TNFalpha and IL-6R signaling, both established targets for treatment of autoimmune diseases, and EGF-receptor signaling, which is important for normal development and adult homeostasis, but can also promote cancer and autoimmune disease. ADAM17 is controlled by its essential partners, the seven membrane-spanning inactive Rhomboid proteins iRhom1 and 2. Together with the iRhoms, ADAM17 acts as a set of signaling scissors that cleave and release membrane proteins from cells. This process, referred to as "protein ectodomain shedding", can activate or inactivate the substrate protein, or substantially change its functional properties. Dysregulation of iRhom/ADAM17 signaling can cause Rheumatoid Arthritis, Systemic Lupus Erythematosis-Glomerulonephritis and other diseases such as neuroinflammation and defects in heart valve development. ADAM17 can be rapidly and post-translationally activated by a variety of signaling pathways, and the iRhoms have emerged as essential regulators of ADAM17 and of its substrate targeting. Work in our lab set the stage for the foundation of the biotech startup SciRhom, which has developed novel function blocking antibodies against iRhom2 in order to improve the treatment of patients suffering from autoimmune diseases. Our current knowledge of the iRhom/ADAM17 complex is just the tip of the iceberg, and many exciting questions remain regarding the regulation and function of these fascinating molecules, such as how they target and process their substrates, how these functions are controlled, and what role the iRhom/ADAM17 signaling hub has in development, autoimmune diseases, neuroinflammation and cancer.

Research Interests

Role of iRhom2/ADAM17 in regulating TNFalpha and EGFR signaling, with am emphasis on autoimmune diseases such as Rheumatoid Arthritis.

Extramural Grant Funding

NIH GM MIRA award (NIH-5R35 GM134907)
SciRhom (Biotech Startup co-founded with HSS)

Departments

Arthritis and Tissue Degeneration Program (HSS)
Depts. of Medicine and of Physiology, Biophysics and Systems Biology (WCM)

Special Expertise

Basic Biomedical Research in the area of auto-immune disease

Credentials

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

Affiliations

Distinguished Affiliated Professorship, Technical University of Munich, Munich, Germany.

Education

MD, Justus Liebig University, Giessen, Germany
PhD (Biochemistry and Biophysics), UCSF

Awards

Association of American Physicians
Distinguished Affiliated Professorship, Technical University of Munich, Germany
Hans Fischer Senior Fellowship Award, Institute of Advanced Studies, Technical University of Munich, Germany
Bayer Hemophilia Special Project Award

Languages

English, German

Publications by Dr. Blobel

Selected Publications

  • Weskamp G, 2020. ADAM17 stabilizes its interacting partner inactive Rhomboid 2 (iRhom2) but not inactive Rhomboid 1 (iRhom1). J Biol Chem. 295(13):4350-4358.
  • Qing X, 2018. iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling. J Clin Invest. 128(4):1397-1412.
  • Haxaire C, 2018. Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2/ADAM17/TNFα pathway. Blood 132(10):1064-1074
  • Issuree, P.A., 2013. Novel role for IRHOM2 in the pathogenesis of inflammatory arthritis. J. Clin. Inv. 123(2):928-32
  • Li X., 2015. iRhoms 1 and 2 are essential upstream regulators of ADAM17-dependent EGFR signaling. Proc. Natl. Acad. Sci. U S A. 112(19):6080-5.
  • McIlwain, D.R., 2012. iRhom2 regulates innate immunity via TACE/ADAM17. Science 335:229-32
  • Franzke, C.W., 2012. Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand-dependent terminal keratinocyte differentiation. J. Exp. Med. 4;209(6):1105-19.
  • Horiuchi, K., 2007. TNFalpha-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. J. Imm. 179:2686-2689
  • Blobel, C.P. 2005. ADAMs: key components in EGFR signalling and development Nature Reviews Mol. Cell. Bio. 6:32-43.
  • Sahin, U., 2004. Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR-ligands. J. Cell Biol. 164:769-779.

For more publications, please see the PubMed listing.

Selected Presentations

  • Institute for Advanced Studies, General Assembly, Technical University Munich, Germany (2018)
  • Gordon Research Conference on Protein Processing, Transport and Secretion (2018)
  • Keynote speaker, Gordon Research Seminar on Matrix Metalloproteinases, Bates College, Biddeford, ME (2017)
  • Gordon Research Conference on Notch Signaling in Development, Regeneration and Disease, Bates College, Lewiston, ME (2016)
  • Gordon Research Conference on Proteolytic Enzymes and their Inhibitors, Il Ciocco, Italy (2016)
  • Gordon Research Conference on Matrix Metalloproteinases, Newry, Maine (2015)
  • Gordon Research Conference on Notch Signaling in Development, Regeneration & Disease, Bates College, Lewiston, ME (2014)
  • Gordon Research Conference on Regulated Membrane Proteolysis, Ventura, CA (2014)
  • EULAR (The European League Against Rheumatism) Conference, Berlin, Germany (2012)
  • Keynote Speaker, Gordon Research Conference on "Regulated Proteolysis of Cell Surface Proteins, Davidson, NC (2011)

Industry Relationships

Industry Relationships

One of the goals of 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.

Below are the healthcare industry relationships reported by Dr. Blobel as of March 30, 2020.

  • Millipore - Receives Royalties
  • Kerafast - Receives Royalties
  • SciRohm - Research support, inventor, founder, advisory board member

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, the HSS Conflicts of Interest Policy does not permit payment of royalties on products developed by him/her that are used on patients at HSS.

Feel free to ask the Research staff member about their relationship(s).

Dr. Blobel in the News