CANCER RESEARCH CENTER OF HAWAII, Honolulu, HI (2000 – Present)
Principal Investigator—The ***** Laboratory
Director, Laboratory Support Shared Resource (*****)
University of Hawaii, Cancer Research Center of Hawaii, Natural Products and Cancer Biology Program
Associate Specialist (Non-tenure Track Professor)
Served as principal investigator of a laboratory delivering leading-edge and novel work in the field of complement depletion and creation of hybrid molecules that can form C3 convertases with unique properties. Provided basic services for research laboratories while functioning as Director of the Laboratory Support Shared Resource.

Area of Research: Structure/function studies on the multifunctional protein, human complement factor C3; invention and development (molecular biology) of novel human C3/CVF hybrid C3 complement*****plement protein C3 plays a central role in all the activation pathways of the complement system, a major component of the innate immune system. Protein engineering studies are being conducted by replacing portions of the C3 sequence with sequences from a C3 homolog, cobra venom factor (CVF). CVF acts much in the same manner as C3; however, it forms a much more stable C3 convertase (activating enzyme) than does the C3b-containing enzyme. Studying the properties of these novel, chimeric proteins increases understanding of the molecular biology of complement protein activation and allows creation of novel, potential drug candidates and biotechnology products. A number of human C3/CVF hybrid proteins have been constructed that are able to form stable, active C3 convertases.

Key Achievements:
• Demonstrated that the lead drug candidate, HC*****, effectively depletes or modulates complement in mice, rats, and monkeys and has been efficacious in vivo in multiple animal disease models spanning autoimmune, retinal, and ischemia-reperfusion conditions.
• Directly contributed to the successful formation of a private biotechnology firm, Incode Bio-pharmaceuticals, Inc. funded by Avalon Ventures, LLC of San Diego, California.
• As PI in InCode-University of Hawaii Research Collaboration, played key role in enabling HC***** to be modified and to be successfully expressed in CHO expression system, paving a manufacturing path towards human clinical testing.

DAVID C. *****, PHD
Page 2 of 6

PROFESSIONAL EXPERIENCE

CANCER RESEARCH CENTER OF HAWAII, Honolulu, HI (2000 – Present)
• Published ten papers in highly cited, premier peer-reviewed journals including the Journal of Biological Chemistry.
• Presented findings at major clinical meetings and submitted work to leading specialty journals.
• Successfully partnered with leading global laboratories, including Professor of Piet Gros’ at Utrecht University in the Netherlands.

MYRIAD GENETICS, INC., Salt Lake City, UT (1997 – 2000)
Head, Core Production Sequencing and Genotyping Facility / Scientist III
Directed DNA sequencing and genotyping operations including overseeing core sequencing and genotyping facilities. Supervised a 25-person team of technicians, managed a $1.5 million budget, and administered a $5 million capital investment.

Key Achievements:
• Drove core changeover to reagent tracking and 64 lane gels.
• Managed and developed robotics for a high throughput genomic sequencing facility.

SRA TECHNOLOGIES, INC., Rockville, MD (1994 – 1996)
Senior Scientist
Guided a molecular biology group charged with automated DNA sequencing, mutation analysis and DNA synthesis consisting of four technicians and two part-time employees. Oversaw quantitative RT-PCR assays to determine viral load and detection of mutations in the HIV-1 reverse transcriptase gene. Designed new assay for detection of point mutations. Resolved fluorescent differential display assay. Actively contributed to multiple research and development projects.

UNIVERSITY OF MASSACHUSETTS, Amherst, MA
PhD, Biochemistry
National Institutes of Health (NIH) Pre-doctoral Trainee

PURDUE UNIVERSITY, West Lafayette, IN
BS, Chemistry

• Four patents obtained relating to the structure and expression of Cobra Venom Factor (U.S. patent numbers *****, *****, and *****).
• Two patents applied for relating to human C3/Cobra Venom Factor hybrid proteins with novel functional activities (WO***** (A2), and MXPA***** (A)).
• One provisional patent application on the use of human C3/CVF hybrid proteins to improve the efficacy of monoclonal antibody treatment of lymphoma.
• One provisional patent application on the use of human C3/CVF proteins to modulate the immune system and deplete complement.

AFFILIATIONS

• Faculty Senate, University of Hawaii, *****
• American Society for Biochemistry and Molecular Biology, 2008-Present
• American Association for the Advancement of Science, 1990-Present

• *****, D.C., Dean, R., Meschter, C., Wong, K., Halter, R., Borlak, J., St. John, W.D., and Vogel, C.-W. (2010) “Complement Depletion with Humanized Cobra Venom Factor in a Mouse Model of Age-related Macular Degeneration.”, Adv. Exp. Med. Biol., 703: *****.
• Vogel, C.-W., and ***** D.C. (2010) “Cobra venom factor: Structure, function, and humanization for therapeutic complement depletion.” Toxicon 56, *****.
• Wang, S.-Y., Veeramani, S., Racila, E., Cagley, J., *****, D., Vogel, C.-W., St. John, W., and Weiner, G.J. (2009) “Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model.” Blood, 114, *****.
• Gorsuch, W.B., Guikema, B.J., *****, D.C., Vogel, C.-W., and Stahl, G.L. (2009) “Humanized cobra venom factor decreases myocardial ischemia reperfusion injury.” Mol. Imm. 47, *****.
• Janssen, B.J.C., Gomes, L., Koning, R.I., Svergun, D.I., Koster, A.J., *****, D.C., Vogel, C.-W., and Gros, P. (2009) “Insights into complement convertase formation based on the structure of the factor B–CVF complex.” EMBO J. 28, *****.
• *****, D.C., Hew, B.E., Thorne, M., Pangburn, M.K., Janssen, B.J., Gros, P., and Vogel, C.-W. (2009) “Functional characterization of human C3/cobra venom factor hybrid proteins for therapeutic complement depletion.”*****p. Immunol. 33, *****.
• *****, D.C., Hew, B.E., Lee, J.Q., Newhouse, J., Alam, M., Ciallella, J.R., Bowers, M., Gorsuch, W.B., Guikema, B.J., Stahl, G.L., and Vogel, C.-W. (2008) “Derivatives of Human Complement Component C3 for Therapeutic Complement Depletion: A Novel Class of Therapeutic Agents.”, Adv. Exp. Med. Biol. 632, *****.).