Bruce F. Smith, VMD, PhD

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), as well as an autosomal recessive muscular dystrophy (aka ARMD, PTPLA deficeincy, Labrador Retriver Myopathy) are being studied.

The laboratory has identified the gene defects in several DMD models and is working on identifying the pathogenic effects of the gene defects in ARMD. The laboratory will then use these models to develop gene therapy approaches to the muscular dystrophies, as well as DNA based testing programs to eliminate these diseases from the canine population.

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 is currently funded by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) and 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.

• 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. [Epub 2008 Sep 30] 2008 Dec; 16(12):1944-52.
• 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.
• Martin D.R., Rigat B.A., Foureman P., Varadarajan G.S., Hwang M., Krum B.K., Smith B.F., Callahan J.W., Mahuran D.J., Baker H.J.., Molecular consequences of the pathogenic mutation in feline GM1 gangliosidosis, Molecular Genetics and Metabolism. 2008 Jun; 94(2): 212-21.
• Wang CY. and Smith B. F. Development of quantitative polymerase chain reaction assays for allelic discrimination of gangliosidoses in cats. American Journal of Veterinary Research. 68(3):231-5, 2007 Mar.
• 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 B. F. and Siegal GP. Adenovirus-mediated p53 tumor suppressor gene therapy of osteosarcoma. Laboratory Investigation. 86(8):748-66, 2006 Aug.
• Migone F. DeInnocentes P. Smith B. F. 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 B. F. 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 B. F. Siegal GP. Curiel DT. Productive replication of human adenovirus type 5 in canine cells.  Journal of Virology. (Jan) 79(2):1308-11, 2005.
• Martin, D.R., Krum, B.K., Varadarajan,  G.S., Hathcock, T.L., Smith, B. F., Baker, H.J.,  An inversion of 25 base pairs causes feline GM2 GangliosidosisVariant 0.  Experimental Neurology, 187:30-37, 2004.
• 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.
• 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), 2003.
• 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.
• 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), January 2003.
• Whitley E.M. Sellins K.S. Ewald SJ. Smith B. F. Yang S. Sartin EA. Wolfe LG. Canine mammary tumor cells transfected with B7-1 or B7-2 stimulate proliferation of peripheral blood mononuclear cells. Anticancer Research. 22(5):2567-74, 2002 Sep-Oct.
• Wang, C-Y. J.,  Giambrone, J. J., Smith, B.F., Detection of duck hepatitis b virus DNA on filter paper by PCR and SyBr green dye-based quantitative PCR.  Journal of Clinical Microbiology, 40(7): 2584-2590, 2002.
• Wang, C-Y. J.,  Giambrone, J. J., Smith, B.F., Comparison of cell culture systems for duck hepatitis B virus using SyBr green quantitative PCR.  Journal of Virological Methods 106(2), 175-184, 2002.
• Wang, C-Y. J.,  Giambrone, J. J., Smith, B.F., Development of viral disinfectant assays for duck hepatitis B virus using cell culture / PCR.  Journal of Virological Methods, 106(1), 39-50, 2002. 
• Samoylov, A. M., Samoylova, T. I., Hartell, M. G., Pathirana, S. T., Smith, B. F., Vodyanoy, V. J.  Recognition of cell-specific binding of phage display derived peptides using an acoustic wave sensor. Biomolecular Engineering, 18(6):269-272, 2002. 
• Wernette, C. M., Smith, B. F., Barksdale, Z. M., Hecker, R., Baker, H. J.  CpG oligodexoynucleotides stimulate canine and feline immune cell proliferation.  Veterinary Immunology and Immunopathology, 84:223-236, 2002.
• Nusbaum, K. E., Smith, B. F., DeInnocentes, P., Bird, R. C.  DNA vaccination of channel catfish against early and late transcripts of the channel catfish herpesvirus (IHV-1).  Veterinary Immunology and Immunopathology, 84:151-168, 2002. 
• Skibild, E. Dahlgaad, K. Rajpurohit, Y. Smith, B.F. Giger, U. Haemolytic anaemia and exercise intolerance due to phosphofructokinase deficiency in related springer spaniels. Journal of Small Animal Practice, 42 (6) p. 298-300, 2001.
• Samoilova, T. and Smith, B. F.  Flow microsphere immunoassay based method of virus quantitation.  BioTechniques, 27(2):356-361, 1999.
• Samoilova, T. and Smith, B. F.  Elucidation of muscle binding peptides by in vivo phage display screening.  Muscle and Nerve, 22:460-466, 1999.
• Lockaby, S.B., Hoerr, F.J., Lauerman, L.H., Smith, B. F., Samoylov, A.M., Toivio-Kinnucan, and Kleven, S.H.  Factors associated with virulence of Mycoplasma synoviae.  Avian Diseases, 43:251-261, 1999.
• Smith, B. F., Baker. H. J., Curiel, D.T., Jiang, W., and Conry, R.M. Humoral and cellular immune responses of dogs immunized with a nucleic acid vaccine encoding human carcinoembryonic antigen.  Gene Therapy, 5:865-868, 1998. 
• Jiang, W., Baker, H.J., Swango, L.J., Schorr, J., Self, M.J., and Smith, B.F. Nucleic acid immunization protects dogs against challenge with virulent canine parvovirus.  Vaccine, 16(6), pp.601-607, 1998.

Book Chapters:

1. Smith, B.F. and Wrighten, R., Animal Models for Inherited Muscle Disease, in Muscle Gene Therapy, Dongsheng Duan, Editor, Springer-Verlag, 2010.
2. Smith, B.F. and Bird R.C., Gene Therapy, in Schalm’s Veterinary Hematology, 6th Edition, Wiley, 2010.
3. Curiel, D.T., Zhu, Z.B, Smith, B.F., Siegal, G.P., Adeno-Virotherapy, in The Encyclopedia of Cancer, 2nd edition, Springer Verlag, 2009.
4. Smith, B.F. and Wrighten, R., Animal Models for Inherited Muscle Disease, in Muscle Gene Therapy, Dongsheng Duan, Editor, Springer-Verlag, New York, 2010.
5. Smith, B.F. and Bird R.C., Gene Therapy, in Schalm’s Veterinary Hematology, 6th Edition, Wiley, in press, 2010.
6. Curiel, D.T., Zhu, Z.B, Smith, B.F., Siegal, G.P., Adeno-Virotherapy, in The Encyclopedia of Cancer, 2nd edition, Springer Verlag, 2009.
7. Bird, R. C. and Smith, B. F., co-editors, Genetic Library Construction and Screening: Advanced Cloning Techniques and Applications, Springer-Verlag, 2002.
8. Samoilova, T. and Smith, B. In vivo phage display screening, in Genetic Library Construction and Screening: Advanced DNA Cloning Techniques and Applications, Springer-Verlag, 2002.
9. Jiang, W. and Smith, B. Homemade TA cloning, in Genetic Library Construction and Screening: Advanced DNA Cloning Techniques and Applications, Springer-Verlag, 2002.
10. Baker, H. J., Smith, B. F. , Martin, D. R. and Foureman, P. Molecular Diagnosis of the Feline Gangliosidoses: A Model for Elimination of Inherited Diseases in Pure Breeds. In August, J. Consultations in Feline Internal Medicine, Volume 4, W.B. Saunders, Co, Orlando, Florida, 2001.

Recent Refereed Journal Articles

1. 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]
2. 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]
3. 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.
4. 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).
5. 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.
6. 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.
7. 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.