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Department of Pathology, Microbiology, and Immunology

 

 

  Donald  H.  Rubin, M.D.

 

 

Professor

Dept of Medicine

Dept of Pathology, Microbiology and Immunology

 

 

Contact Information

 

 

Office Location:
ACRE Building F201

VA Hospital

Phone: 615-873-7066

E-mail:  don.h.rubin@vanderbilt.edu

 

Campus Mail Address:

Dept of Medicine

MCN A-2200 (2582)

 

US Mailing Address:
Vanderbilt University School of Medicine
Department of Medicine

MCN A-2200
Nashville, TN 37232-2582

 

 

 

Education

 

 

M.D., Cornell University Medical College
B.A., SUNY at Stony Brook

 

 

Research Keywords

 

 


 

 

Research Description

 

 

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.

 

 

Publications

 

 

Ivie, SE, Fennessey, CM, Sheng, J, Rubin, DH, McClain, MS. Gene-trap mutagenesis identifies mammalian genes contributing to intoxication by Clostridium perfringens I?-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

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, 5, 32, 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

Chen, D, Rubin, D H. Mucosal T cell response to reovirus.. Immunol Res, 23(2-3), 229-34, 2001

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

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

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, 371B, 719-24, 1995

Hooper, DC, Rubin, DH, Cebra, JJ. Spontaneous proliferation of Peyer''s patch cells in vitro. Int Immunol, 6(6), 873-80, 1994

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

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

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

Taterka, JA, Cuff, CF, Rubin, DH. Viral gastrointestinal infections. Gastroenterol Clin North Am, 21(2), 303-30, 1992

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

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

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

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

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, 310, 307-15, 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

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

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

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

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

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

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

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, 24, 173-80, 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

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

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

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

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, 216A, 267-78, 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. , 1, 107-115, 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