Bruce F. Smith, V.M.D, Ph.D.20130717, Dr. Bruce Smith, Scott-Ritchey Research Center, College of Veterinary Medicine, OCM,

Professor, Department of Pathobiology
Director – Auburn University Research Initiative in Cancer (AURIC)

smithbf@auburn.edu

Dr. Smith is the Director of the Auburn University Research Initiative in Cancer (AURIC), a Professor in the Department of Pathobiology and Scientist in the Scott-Ritchey Research Center.  He earned the V.M.D. degree from the University of Pennsylvania in 1988, where he was appointed a Kleberg Fellow in Medical Genetics. He received a Ph.D. in Molecular Biology and Genetics from the University of Pennsylvania in 1993. His long-range research interests are in gene therapy of inherited muscle diseases such as Duchenne muscular dystrophy, gene therapy of cancer and nucleic acid immunization.

Research Interests:

Dr. Smith’s research focuses in two areas of genetic therapy, gene therapies for inherited muscular dystrophies, and genetic approaches to therapy for cancer.

Dr. Smith’s research program in muscular dystrophies is currently focused on identifying canine models of these diseases and applying novel genetic therapies to their treatment. Currently, four models of X-linked Duchenne-like muscular dystrophy (DMD) are being studied.

The laboratory has identified the gene defects in several DMD models and is working to develop gene therapy approaches to the muscular dystrophies.

Dr. Smith’s research program on immunologic and gene therapy for cancer is part of a large collaborative program involving multiple investigators from Auburn University, Washington University, St. Louis and the University of Alabama, Birmingham. This includes the following areas:

    • Conditionally replicative adenoviruses (CRADs) for canine osteosarcoma.  These viruses have been tested and encouraging results were seen in a small clinical trial.  Additional clinical trials in dogs with this tumor are being pursued.
    • Tumor cell targeted suicide gene therapy in canine lymphoma.  This work involves specifically targeting viral verctors to lymphoma cells and delivery to genes that may be induced to kill the tumor cells.
    • Dendritic cell fusion vaccines in canine mammary cancer (Dr. R. Curtis Bird, PI).  These vaccines use autologous dendritic cells fused with canine breast cancer cell lines to create anti-tumor immune responses.

Book Chapters (4 of 7)

Lutful Kabir, F, *O’Neill, AM, Smith, BF, Bird, RC, Canine breast cancer and lymphoma as models in cancer research,  in Animal Models of Cancer Research, SA Murray Editor, Nova Scientific Publishers, 2013, pp. 69-86.=

Smith, B.F. and Wrighten, R., Animal Models for Inherited Muscle Disease, in Muscle Gene Therapy, Dongsheng Duan, Editor, Springer-Verlag, 2010.

Smith, B.F. and Bird R.C., Gene Therapy, in Schalm’s Veterinary Hematology, 6th Edition, Wiley, 2010.

Curiel, D.T., Zhu, Z.B, Smith, B.F., Siegal, G.P., Adeno-Virotherapy, in The Encyclopedia of Cancer, 2nd edition, Springer Verlag, 2009.

Recent Refereed Journal Articles

Duan D, Hakim CH, Ambrosio CE, Smith BF, Sweeney HL. Early loss of ambulation is not a representative clinical feature in Duchenne muscular dystrophy dogs: remarks on the article of Barthélémy et al., Dis Model Mech. 2015 Mar;8(3):193-4. doi: 10.1242/dmm.019216. PMID: 25740329 .

Sandey M, Bird RC, Das SK, Sarkar D, Curiel DT, Fisher PB, Smith BF,.Characterization of the canine mda-7 gene, transcripts and expression patterns, Gene, Volume 547, Issue 1, 15 August 2014, Pages 23-33.

Foote JB, Kabir FM, Graff EC, Cattley RC, DeInnocentes P, Smith BF, Bird RC. Engraftment of canine peripheral blood lymphocytes into nonobese diabetic-severe combined immune deficient IL-2R common gamma chain null mice. Vet Immunol Immunopathol. 2014 Feb 15;157(3-4):131-41.

Hakim C, Yue Y, Shin JH, Williams R, Zhang K, Smith BF and Duan D. Systemic gene transfer reveals distinctive muscle transduction profile of tyrosine mutant AAV-1, -6 and -9 in neonatal dogs. Molecular Therapy – Methods & Clinical Development, 2014 March 5, 1, doi:10.1038/mtm.2014.2.

Boudreaux B, Smith A,. Lee H, Boothe D, Higginbotham ML, Whitley EM, Smith BF, Behrend EN, In vitro Evaluation of ABCB1 After Exposure to Prednisilone and Enrofloxacin in Two Canine Lymphoid Cell Lines: A pilot Study. J. of Appl. Res Vet Med, 2013, vol 10, 31-41.

Foote JB, Kabir FM, Graff EC, Cattley RC, Deinnocentes P, Smith BF, Bird RC. Engraftment of canine peripheral blood lymphocytes into nonobese diabetic-severe combined immune deficient IL-2R common gamma chain null mice. Vet Immunol Immunopathol. 2014 Feb 15;157(3-4):131-41. doi: 10.1016/j.vetimm.2013.11.007. Epub 2013 Dec 1. PMID: 24368085

Shin JH, Yue Y, Smith B, Duan D Humoral Immunity to AAV-6, 8, and 9 in Normal and Dystrophic Dogs. Hum Gene Ther. 2012 Jan 11. [Epub ahead of print]

Shin JH, Yue Y, Srivastava A, Smith B, Lai Y, Duan D., A Simplified Immune Suppression Scheme Leads to Persistent Micro-dystrophin Expression in Duchenne Muscular Dystrophy Dogs. Hum Gene Ther. 2011 Dec 14. [Epub ahead of print]

Fine DM, Shin JH, Yue Y, Volkmann D, Leach SB, Smith BF, McIntosh M, Duan D., Age-matched comparison reveals early electrocardiography and echocardiography changes in dystrophin-deficient dogs. Neuromuscul Disord. 2011 Jul;21(7):453-61. Epub 2011 May 13.

O’Neill AM, Smith AN, Spangler EA, Whitley EM, Schleis SE, Bird RC, Curiel DT, Thacker EE, Smith BF, Resistance of canine lymphoma cells to adenoviral infection due to reduced cell surface RGD binding integrins. Cancer Biol Ther. 2011 Apr 1;11(7).

Smith, B.F., Yue, Y., Woods, P.R., Kornegay, J.N., Shin,, J-H, Williams, R.R., Duan, D. An intronic LINE-1 element insertion in the dystrophin gene aborts dystrophin. Journal of Laboratory Investigation. 2011 Feb;91(2):216-31. Epub 2010 Aug 16.

Bird, R.C., DeInnocentes, P., Church-Bird, A.E., van Ginkel, F.W., Lindquist, J., Smith, B.F., An Autologous Dendritic Cell-Canine Mammary Tumor Hybrid-Cell Fusion Vaccine, Cancer Immunology Immunotherapy, 2011 Jan;60(1):87-97. Epub 2010 Nov 11.

DiGangi BA, Griffin B, Levy JK, Smith BF, Baker HJ, Use of a commercially available relaxin test for detection of pregnancy in cats. J Am Vet Med Assoc. 2010 Dec 1;237(11):1267-74.

Thacker EE, Nakayama M, Smith BF, Bird RC, Muminova Z, Strong TV, Timares L, Korokhov N, O’Neill AM, de Gruijl TD, Glasgow JN, Tani K, Curiel DT., A genetically engineered adenovirus vector targeted to CD40 mediates transduction of canine dendritic cells and promotes antigen-specific immune responses in vivo. Vaccine. 2009 Nov 23;27(50):7116-24.

Yue Y., Ghosh A., Long C., Bostick B., Smith B.F., Kornegay J.N., Duan D., A Single Intravenous Injection of Adeno-associated Virus Serotype-9 Leads to Whole Body Skeletal Muscle Transduction in Dogs. Molecular Therapy. 2008 Sep 30. [Epub ahead of print]

Bird R.C., Deinnocentes P., Lenz S., Thacker E.E., Curiel D.T., Smith B.F., An allogeneic hybrid-cell fusion vaccine against canine mammary cancer. Veterinary Immunology and Immunopathology. 2008 Jun 15;123(3-4):289-304.

Smith, B.F., Curiel, D.T., Ternovoi, V.V., Borovjagin, A.V., Baker, H.J., Cox, N., and Siegal, G.P. Administration of a conditionally replicative oncolytic canine adenovirus in normal dogs, Cancer Biotherapy & Radiopharmaceuticals Dec 2006, Vol. 21, No. 6: 601-606.

Ternovoi VV. Curiel DT. Smith BF. Siegal GP. Adenovirus-mediated p53 tumor suppressor gene therapy of osteosarcoma. Laboratory Investigation. 86(8):748-66, 2006 Aug.

Migone F. Deinnocentes P. Smith BF. Bird RC. Alterations in CDK1 expression and nuclear/nucleolar localization following induction in a spontaneous canine mammary cancer model. Journal of Cellular Biochemistry. 98(3):504-18, 2006 Jun 1.

Le LP. Rivera AA. Glasgow JN. Ternovoi VV. Wu H. Wang M. Smith BF. Siegal GP. Curiel DT. Infectivity enhancement for adenoviral transduction of canine osteosarcoma cells. Gene Therapy. 13(5):389-99, 2006 Mar.

Ternovoi, VV. Le LP. Belousova N. Smith BF. Siegal GP. Curiel DT. Productive replication of human adenovirus type 5 in canine cells. Journal of Virology. (Jan) 79(2):1308-11, 2005.

Spencer, J.A., Smith, B.F., Gaurino, A.J., Blagburn, B.L., Baker, H.J. The use of CpG as an adjuvant to Toxoplasma gondii vaccination.  Parasitology Research, 92:313-316, 2004.

Hemminki, A., Kanerva, A., Kremer, E.J., Bauerschmitz G.J., Smith, B.F., Liu, B., Wang, M., Desomd, R.A., Keriel, A., Barnett, B, Baker, H.J., Siegal G.P., Curiel, D.T. A Canine Conditionally Replicating Adenovirus for Evaluating Oncolytic Virotherapy in a Syngeneic Animal Model.  Molecular Therapy, 7(2)163-173, 2003.

Smith, B.F., Migone, F.K., Cox, N.R., Baker, H.J. An In Utero Allotransplantation Model of Metastatic Breast Cancer in the Cat. In Vivo, 17(1):35-40, 2003.

Jiang, W., Baker H.J., Smith, B.F. Mucosal Immunization with Helicobacter, CpG DNA and Cholera Toxin is Protective. Infection and Immunity, vol 71(1):40-46, 2003.

Whitley E.M., Sellins K., Ewald S.J., Sartin E.A., Smith B.F., Yang, S., Sartin, E. A., Wolfe L.G.:- Canine mammary tumor cells transfected with B7-1 or B7-2 stimulate the proliferation of peripheral blood mononuclear cells.  Anticancer Research, 22:2567-2574, 2002.