Curtis R. Brandt, Ph.D.
Professor
6630 Medical Sciences Center
1300 University Ave.
Madison, WI 53706-1532
(608) 262-8054
| Degrees: | B.S. 1975, Washington State University, Pullman, WA M.S. 1977, Washington State University, Pullman, WA M. Phil. 1983, Columbia University, College of Physicians and Surgeons, NY, NY Ph.D. 1984, Columbia University, College of Physicians and Surgeons, NY, NY |
| Appointments: | Department of Ophthalmology & Visual Sciences Medical Microbiology and Immunology Waisman Center Paul Carbone Comprehensive Cancer Center |
| Fellowships: | Postdoctoral Fellowship, 1983-86, Fred Hutchinson Cancer Research Center, Seattle, WA |
| Research: | Research in my laboratory focuses on four areas. Gene Delivery: 1) Injection of viral gene delivery vectors into the eye triggers an inflammatory response. We are trying to identify the trigger so we can block it. Currently we are looking at several pro-inflammatory cytokines such as IL-6. In addition we are making viral delivery vectors for several labs on campus. 2) Herpes simplex virus (HSV) causes blinding keratitis (inflammation of the cornea) and we are interested in identifying genes in the virus that contribute to severe infection. Recently, we demonstrated that multiple genes are involved and have identified a number of novel mutations in several viral proteins. New sequencing technology allows us to rapidly sequence an entire HSV genome in about a week. This allows us to directly compare virulence characteristics in animal models with the sequence of several strains to identify disease associated markers. 3) We have an active program of antiviral drug discovery and development and have worked with several companies. We have also identified novel antivirals. One was isolated from an edible mushroom that grows in Wisconsin. This novel protein appears to block several previously unknown steps in viral infection. The second group of antivirals is a series of peptides that block virus entry into cells. The peptides block HSV, Papillomavirus, HIV, and vaccinia virus. We have also shown one peptide blocks Influenza including bird flu strains. We are also using peptide based strategies to study protein function. We are currently developing the peptides as novel microbicides to block sexually transmitted viral infections. The peptides are also being used to study the poorly-understood process of viral entry. 4) One of our antiviral peptides binds to sialic acid residues on HSV-1 envelope proteins that form the fusion/entry complex. Enzymatic removal of sialic from virus particles renders them non-infectious. We now know that this is because the formation of the fusion complex is triggered by desialylation. Thus sialic acid regulates fusion complex formation. We are working to identify how this occurs. |
| Publications: | Bultmann H, Busse JS, Brandt CR. A modified FGF4 signal peptide inhibits entry of Herpes simplex Type I virus. J Virol 75:2634-2645, 2001. Spencer B, Agarwala S, Gentry L, Brandt CR. HSV-1 vector-delivered FGF2 to the retina is neuroprotective, but does not preserve functional responses. Mol Ther 3:746-756, 2001. Bultmann H, Brandt CR. Peptides containing membrane transiting motifs inhibit virus entry. J Biol Chem 277:36018-36023, 2002. Brandt CR, Kolb AW, Shah DD, Pumfery AM, Kintner RL, Jaehnig E, Van Gompel JJ. Multiple determinants contribute to the virulence of HSV ocular and CNS infection and identification of serine 34 of the US1 gene as an ocular disease determinant. Invest Ophthalmol Vis Sci 44:2657-2668, 2003. Liu, X, Hu, Y, Filla, M, Gabelt, BT, Peters, DM, Brandt, CR, and Kaufman, PL. 2005. The effect of C3 transgene expression on actin and cellular adhesions in cultured human trabecular meshwork cells and on outflow facility in organ cultured monkey eyes. Mol. Vision 11:1112-1121. PMID: 16379023. molvis.org. Jones, JC, Turpin, EA, Bultmann, H, Brandt, CR, and Schultz-Cherry, S. 2006. Inhibition of influenza virus infection by a novel antiviral peptide that targets viral attachment to cells. J. Virol. 80:11960-11967. PMCID: PMC1676284. Teuton, JR and Brandt, CR. 2007. Sialic acid on herpes simplex virus type 1 envelope glycoproteins is required for efficient infection of cells. J. Virol. 81:3731-3739. PMCID: PMC1866119. Bultmann, H, Teuton, J, and Brandt, CR. 2007. Addition of a c-terminal cysteine improves the anti-herpes simplex virus activity of a peptide containing the HIV-1 TAT protein transduction domain. Antimicrobial. Agents Chemother. 51:1596-1607. PMCID: PMC1855575. Brandt, CR, Akkarawongsa, R, Altmann, S, Jose, G, Kolb, AW, Waring, AJ, and Lehrer, RI. 2007. Evaluation of a θ-defensin in a murine model of herpes simplex virus type 1 keratitis. Invest. Ophthalmol. Vis. Sci. 48:5118-5124. PMID: 17962464. iovs.org. |