Donald H. Rubin, M.D.
Professor of Medicine, Pathology, Microbiology & Immunology
Vanderbilt University Medical Center
Nashville, TN 37232-2582
- M.D. - Cornell University, 1974
- Fellowship - Brigham and Women's Hospital, 1979
- Residency - Mount Sinai Medical Center, 1977
- Internship - Mount Sinai Medical Center, 1975
Molecular Genetics of the Pathogen-Host Interaction, Mechanism of Mucosal Immunity
Research has focused on understanding cellular and molecular aspects of viral infection in the GI tract and liver using reovirus. This work has led to the development of an exciting technology to sort out cellular genes that participate in cellular infection. Gene-trap retroviruses are used to select cells that are resistant to lytic reovirus infection. One hundred twenty cell lines have been established with a reovirus resistant phenotype and the genes disrupted are being characterized. Of the 120 genes disrupted, 20 of the genes are known. Many of these known genes are part of the endocytic pathway and 50% have been associated with virus infections. This work has been expanded to include the study of cellular genes involved in Trypanosoma cruzi infection. In addition, the laboratory is currently pursuing studies to elucidate the mechanisms of generating effective mucosal immunity. Recent studies have found that there is an oligoclonal response of the host to reovirus and that mucosal CD8+ that express the aa homodimer do not signal via NfkB.
- Ivie, SE, Fennessey, CM, Sheng, J, Rubin, DH, McClain, MS Gene-trap mutagenesis identifies mammalian genes contributing to intoxication by Clostridium perfringens Îµ-toxin. PLoS One, 6(3), e17787, 2011.
- Murray, JL, Mavrakis, M, McDonald, NJ, Yilla, M, Sheng, J, Bellini, WJ, Zhao, L, Le Doux, JM, Shaw, MW, Luo, CC, Lippincott-Schwartz, J, Sanchez, A, Rubin, DH, Hodge, TW Rab9 GTPase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus. J Virol, 79(18), 11742-51, 2005.
- Organ, EL, Sheng, J, Ruley, HE, Rubin, DH Discovery of mammalian genes that participate in virus infection. BMC Cell Biol, 5(1), 41, 2004.
- Organ, EL, Nalbantyan, CD, Nanney, LB, Woodward, SC, Sheng, J, Dubois, RN, Price, J, Sutcliffe, M, Coffey, RJ, Rubin, DH Effects of transforming growth factor-alpha (TGF-alpha) in vitro and in vivo on reovirus replication. DNA Cell Biol, 23(7), 430-41, 2004.
- Sheng, J, Organ, EL, Hao, C, Wells, KS, Ruley, HE, Rubin, DH Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection. BMC Cell Biol, 532, 2004.
- Chen, D, Rubin, D H Mucosal T cell response to reovirus.. Immunol Res, 23(2-3), 229-34, 2001.
- Saragovi, HU, Rebai, N, Di Guglielmo, GM, Macleod, R, Sheng, J, Rubin, DH, Greene, MI A G1 cell cycle arrest induced by ligands of the reovirus type 3 receptor is secondary to inactivation of p21ras and mitogen-activated protein kinase. DNA Cell Biol, 18(10), 763-70, 1999.
- Mora, A L, Chen, D, Boothby, M, Rubin, D H Lineage-specific differences among CD8+ T cells in their dependence of NF-kappa B/Rel signaling.. Eur J Immunol, 29(9), 2968-80, 1999.
- Major, AS, Rubin, DH, Cuff, CF Mucosal immunity to reovirus infection. Curr Top Microbiol Immunol, 233(Pt 2), 163-77, 1998.
- Chen, D, Lee, F, Cebra, JJ, Rubin, DH Predominant T-cell receptor Vbeta usage of intraepithelial lymphocytes during the immune response to enteric reovirus infection. J Virol, 71(5), 3431-6, 1997.
- Taterka, J, Cebra, JJ, Rubin, DH Characterization of cytotoxic cells from reovirus-infected SCID mice: activated cells express natural killer- and lymphokine-activated killer-like activity but fail to clear infection. J Virol, 69(6), 3910-4, 1995.
- Cuff, CF, Rubin, DH, Cebra, JJ Development, function, and trafficking of mucosal leukocytes in immunodeficient mice. Adv Exp Med Biol, 371B719-24, 1995.
- Taterka, J, Sutcliffe, M, Rubin, DH Selective reovirus infection of murine hepatocarcinoma cells during cell division. A model of viral liver infection. J Clin Invest, 94(1), 353-60, 1994.
- Hooper, DC, Rubin, DH, Cebra, JJ Spontaneous proliferation of Peyer''s patch cells in vitro. Int Immunol, 6(6), 873-80, 1994.
- Cuff, CF, Cebra, CK, Rubin, DH, Cebra, JJ Developmental relationship between cytotoxic alpha/beta T cell receptor-positive intraepithelial lymphocytes and Peyer''s patch lymphocytes. Eur J Immunol, 23(6), 1333-9, 1993.
- Rubin, DH, Wetzel, JD, Williams, WV, Cohen, JA, Dworkin, C, Dermody, TS Binding of type 3 reovirus by a domain of the sigma 1 protein important for hemagglutination leads to infection of murine erythroleukemia cells. J Clin Invest, 90(6), 2536-42, 1992.
- Williams, WV, Weiner, DB, Borofsky, MA, Rubin, DH, Yui, K, Greene, MI Modulation of T cell responses with MHC-derived peptides. Immunol Res, 11(1), 11-23, 1992.
- Rubin, DH, Weiner, DB, Dworkin, C, Greene, MI, Maul, GG, Williams, WV Receptor utilization by reovirus type 3: distinct binding sites on thymoma and fibroblast cell lines result in differential compartmentalization of virions. Microb Pathog, 12(5), 351-65, 1992.
- Taterka, JA, Cuff, CF, Rubin, DH Viral gastrointestinal infections. Gastroenterol Clin North Am, 21(2), 303-30, 1992.
- Williams, WV, Kieber-Emmons, T, Weiner, DB, Rubin, DH, Greene, MI Contact residues and predicted structure of the reovirus type 3-receptor interaction. J Biol Chem, 266(14), 9241-50, 1991.
- Cuff, CF, Cebra, CK, Lavi, E, Molowitz, EH, Rubin, DH, Cebra, JJ Protection of neonatal mice from fatal reovirus infection by immune serum and gut derived lymphocytes. Adv Exp Med Biol, 310307-15, 1991.
- Cebra, JJ, Cuff, CF, Rubin, DH Relationship between alpha/beta T cell receptor/CD8+ precursors for cytotoxic T lymphocytes in the murine Peyer''s patches and the intraepithelial compartment probed by oral infection with reovirus. Immunol Res, 10(3-4), 321-3, 1991.
- London, SD, Cebra-Thomas, JA, Rubin, DH, Cebra, JJ CD8 lymphocyte subpopulations in Peyer''s patches induced by reovirus serotype 1 infection. J Immunol, 144(8), 3187-94, 1990.
- Cuff, CF, Lavi, E, Cebra, CK, Cebra, JJ, Rubin, DH Passive immunity to fatal reovirus serotype 3-induced meningoencephalitis mediated by both secretory and transplacental factors in neonatal mice. J Virol, 64(3), 1256-63, 1990.
- George, A, Kost, SI, Witzleben, CL, Cebra, JJ, Rubin, DH Reovirus-induced liver disease in severe combined immunodeficient (SCID) mice. A model for the study of viral infection, pathogenesis, and clearance. J Exp Med, 171(3), 929-34, 1990.
- Rubin, DH, Morrison, AH, Witzleben, CL, Guico, CJ, Piccoli, DA Site of reovirus replication in liver is determined by the type of hepatocellular insult. J Virol, 64(9), 4593-7, 1990.
- Piccoli, DA, Witzleben, CL, Guico, CJ, Morrison, A, Rubin, DH Synergism between hepatic injuries and a nonhepatotropic reovirus in mice. Enhanced hepatic infection and death. J Clin Invest, 86(4), 1038-45, 1990.
- Williams, WV, London, SD, Weiner, DB, Wadsworth, S, Berzofsky, JA, Robey, F, Rubin, DH, Greene, MI Immune response to a molecularly defined internal image idiotope. J Immunol, 142(12), 4392-400, 1989.
- London, SD, Cebra, JJ, Rubin, DH Intraepithelial lymphocytes contain virus-specific, MHC-restricted cytotoxic cell precursors after gut mucosal immunization with reovirus serotype 1/Lang. Reg Immunol, 2(2), 98-102, 1989.
- Weisenthal, RW, Sinclair, SH, Frank, I, Rubin, DH Long-term outpatient treatment of CMV retinitis with ganciclovir in AIDS patients. Br J Ophthalmol, 73(12), 996-1001, 1989.
- Cebra, JJ, Cebra-Thomas, JA, Cuff, CF, George, A, Kost, SI, London, SD, Rubin, DH Reoviruses as probes of the gut mucosal T cell population. Immunol Invest, 18(1-4), 545-58, 1989.
- Rubin, DH, Bauman, LJ, Lauby, JL The relationship between knowledge and reported behavior in childhood asthma. J Dev Behav Pediatr, 10(6), 307-12, 1989.
- London, SD, Cebra, JJ, Rubin, DH The reovirus-specific cytotoxic T cell response is not restricted to serotypically unique epitopes associated with the virus hemagglutinin. Microb Pathog, 6(1), 43-50, 1989.
- Kaljot, KT, Shaw, RD, Rubin, DH, Greenberg, HB Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis. J Virol, 62(4), 1136-44, 1988.
- Weiner, DB, Girard, K, Williams, WV, McPhillips, T, Rubin, DH Reovirus type 1 and type 3 differ in their binding to isolated intestinal epithelial cells. Microb Pathog, 5(1), 29-40, 1988.
- Williams, WV, Guy, HR, Rubin, DH, Robey, F, Myers, JN, Kieber-Emmons, T, Weiner, DB, Greene, MI Sequences of the cell-attachment sites of reovirus type 3 and its anti-idiotypic/antireceptor antibody: modeling of their three-dimensional structures. Proc Natl Acad Sci U S A, 85(17), 6488-92, 1988.
- Cebra, JJ, Cebra, ER, Cebra-Thomas, JA, George, A, Lebman, DA, London, SD, Rubin, DH, Schweitzer, PA Specific and nonspecific perturbations of B- and T-cell subsets in Peyer''s patches. Monogr Allergy, 24173-80, 1988.
- London, SD, Rubin, DH, Cebra, JJ Gut mucosal immunization with reovirus serotype 1/L stimulates virus-specific cytotoxic T cell precursors as well as IgA memory cells in Peyer''s patches. J Exp Med, 165(3), 830-47, 1987.
- London, SD, Rubin, DH, Cebra, JJ Murine Peyer''s patches are capable of generating a cytotoxic T cell (CTL) response to nominal antigens. Adv Exp Med Biol, 216A267-78, 1987.
- Rubin, DH Reovirus serotype 1 binds to the basolateral membrane of intestinal epithelial cells. Microb Pathog, 3(3), 215-9, 1987.
- Rubin, DH, Costello, T, Witzleben, CL, Greene, MI Transport of infectious reovirus into bile: class II major histocompatibility antigen-bearing cells determine reovirus transport. J Virol, 61(10), 3222-6, 1987.
- Rubin, DH, Eaton, MA, Anderson, AO Reovirus infection in adult mice: the virus hemagglutinin determines the site of intestinal disease. Microb Pathog, 1(1), 79-87, 1986.
- Rubin, DH, Eaton, MA, Costello, T Reovirus type 1 is secreted into the bile. J Virol, 60(2), 726-8, 1986.
- Anderson AO, MacDonald TT, Rubin DH "Effect of orally administered avridine on enteric antigen uptake and mucosal immunity." Int. J. Immunother. , 1107-115, 1985.
- Twist, EM, Kolonich, K, Rubin, DH Propagation of rotaviruses in the presence of chicken serum. J Gen Virol, 65 ( Pt 7)1207-10, 1984.
- Abramczuk, J, Vorbrodt, A, Rubin, DH, Fields, BN, Koprowski, H Interactions of preimplantation mouse embryos with reovirus serotypes 1 and 3. Infect Immun, 42(1), 301-7, 1983.
- Hrdy, DB, Rubin, DH, Fields, BN Molecular basis of reovirus neurovirulence: role of the M2 gene in avirulence. Proc Natl Acad Sci U S A, 79(4), 1298-302, 1982.
- Offit, PA, Rubin, DH Viral diseases: infections of the gastrointestinal tract. Compr Ther, 8(8), 21-6, 1982.
- Rubin, D, Weiner, HL, Fields, BN, Greene, MI Immunologic tolerance after oral administration of reovirus: requirement for two viral gene products for tolerance induction. J Immunol, 127(4), 1697-701, 1981.
- Wolf, JL, Rubin, DH, Finberg, R, Kauffman, RS, Sharpe, AH, Trier, JS, Fields, BN Intestinal M cells: a pathway for entry of reovirus into the host. Science, 212(4493), 471-2, 1981.
- Rubin, DH, Fields, BN Molecular basis of reovirus virulence. Role of the M2 gene. J Exp Med, 152(4), 853-68, 1980.