Carl-Wilhelm E. Vogel, MD, PhD

Professor (Researcher ), Cancer Research Center of Hawai‘i; Clinical Professor of Pathology, John A. Burns School of Medicine; Graduate Faculty, Cell and Molecular Biology Program; Adjunct Professor, Institute for Micronesian Health and Aging Studies, University of Guam MD, University of Hamburg; PhD (Biochemistry), University of Hamburg; MS (Biochemistry), University of Hamburg; Diplomate in Clinical Pathology, American Board of Pathology; Life Fellow, College of American Pathologists cvogel@crch.hawaii.edu

Publication list via PubMed

Our laboratory studies molecular aspects of the complement system, one of the effector mechanisms of the immune system. We are particularly interested in the structure and function of the third component (C3) of the human complement system. We are studying the structural differences of C3 to a highly homologous protein that occurs in the venom in the cobra, called cobra venom factor (CVF). Whereas complement activation in serum is tightly controlled, CVF escapes control and exhaustively activates complement, leading to complement depletion. Complement plays an important biological function in host defense and the immune response; however, inappropriate complement activation is also involved in the pathogenesis of many diseases. In these diseases therapeutic complement inhibition may be warranted. CVF is by far the most potent known agent to inhibit complement (by effectively depleting it). Our laboratory has exploited the structural similarity between CVF and C3 to design derivatives of human C3 with CVF-like functions, proteins we have termed ”humanized CVF”. Humanized CVF represents a conceptually novel drug for therapeutic complement inhibition. We are studying the therapeutic potential of humanized CVF in several animal models of human diseases, including rheumatoid arthritis, reperfusion injury, macular degeneration, and monoclonal antibody therapy of lymphomas and other tumors.

Another research focus of the laboratory is to study the biological function and possible therapeutic potential of natural IgM antibodies against neuroblastoma.

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Selected Publications

Bachmann, A.S., Howard, J.P., Vogel, C.-W. Actin-binding Protein Filamin A is Displayed on the Surface of Human Neuroblastoma Cells. Cancer Science 97 (2006), 1359-1365.

Vogel, C.-W., Fritzinger, D. Humanized Cobra Venom Factor: Experimental Therapeutics for Targeted Complement Activation and Complement Depletion. Curr. Pharmaceutical Design 13 (2007), 2916-2926.

Fritzinger, D.C., Hew, B.E., Lee, J.Q., Newhouse, J, Alam, M., Gorsuch, W.B., Guikema, B.J., Stahl, G.L, Ciallella, J.R., Bowers, M., Vogel, C.-W. Derivatives of Human Complement Component C3 for Therapeutic Complement Depletion: A Novel Class of Therapeutic Agents. Adv. Exp. Med. Biol. 632 (2008), 293-307.

Fritzinger, D.C., Hew, B.E., Thorne,M., Pangburn, M.K., Janssen, J.C., Gros, P., Vogel, C.-W. Functional Characterization of Human C3/Cobra Venom Factor Hybrid Proteins for Therapeutic Complement Depletion. Dev. Comp. Immunol. 33 (2009), 105-116.

Janssen, B.J.C., Gomes, L., Koning, R.I., Svergun, D.I., Koster, A.J., Fritzinger, D.C., Vogel, C.-W., Gros, P. Insights into Complement Convertase Formation Based on the Structure of the Factor B-CVF Complex. EMBO J. (2009), in press.

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