Bruce F. Smith, VMD, PhD

Education

PhD, University of Pennsylvania, Molecular Biology and Genetics, 1993
VMD, University of Pennsylvania, 1988

Biography

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. Over his career, Dr. Smith has made significant discoveries in the identification of canine models of Duchenne Muscular Dystrophy (DMD), nucleic acid immunization, CpG based immunomodulation, and Oncolytic virus therapy for cancer. Dr. Smith’s current work focuses on understanding the molecular cascades involved in DMD and developing next-generation oncolytic viral vectors for a variety of cancers.

Research Interests

Dr. Smith’s current 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 three of these models and is working to develop gene therapy approaches to the muscular dystrophies. Of particular interest is understanding and subsequently addressing the cardiac defects seen in this disease.

Dr. Smith’s research program on immunologic and gene therapy for cancer is currently focused on developing novel oncolytic viruses, using canine cancer as both a target and a model of human cancer. This work utilizes RNA Sequencing to understand the gene expression profiles of individual tumors, which in turn drives development of personalized viral vectors, designed to specifically replicate in and attack individual tumors. Projects have initially employed canine adenovirus, however additional viruses are being evaluated. In order to produce custom oncolytic viruses in a time frame that will allow treatment, the laboratory is utilizing synthetic biology approaches to create entire novel adenovirus genomes. Among the tumors of interest to the laboratory are osteosarcoma, hemangiosarcoma, lymphoma, melanoma, and mammary cancer.

In addition, Dr. Smith has multiple investigators from Auburn University, Washington University, St. Louis and the University of Alabama, Birmingham.

Publications and Links

Book Chapters (4 of 7)

Shrader, S.M., Smith, B.F. and Wrighten, R., Animal Models for Inherited Muscle Disease, in Muscle Gene Therapy, 2^nd Edition, Dongsheng Duan, Editor, Springer-Verlag, 2019.

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 Scientifi 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.

Recent Refereed Journal Articles (past 10 years)

Bird, R.C., DeInnocentes, P., Church Bird, A., Kabir, F.M.L.,  Martinez-Romero, E.G., Smith^, A.N., Smith, B.F., Autologous Hybrid Cell Fusion Vaccine in a Spontaneous Intermediate Model of Breast Carcinoma, Journal of Veterinary Science, accepted 2019.

Ahmad H. Alhowail, Jenna Bloemer, Mohammed Majrashi, Priyanka D. Pinky, Subhrajit Bhattacharya, Zhang Yongli, Dwipayan Bhattacharya, Matthew Eggert, Lauren Woodie, Manal A. Buabeid, Nathaniel Johnson, Alyssa Broadwater, Bruce Smith, Muralikrishnan Dhanasekaran, Robert D. Arnold & Vishnu Suppiramaniam, Doxorubicin-induced neurotoxicity is associated with acute alterations in synaptic plasticity, apoptosis, and lipid peroxidation, Toxicology Mechanisms and Methods, June 18, 2019, DOI: 10.1080/15376516.2019.1600086

Stephanie Shrader, Bruce F. Smith, SeungWoo Jung, Thomas S. Denney, Characterization of Australian Labradoodle Dystrophinopathy, Neuromuscular Disorders, Neuromuscul Disord. 2018 Nov;28(11):927-937. doi: 10.1016/j.nmd.2018.08.008. Epub 2018 Aug 29. PMID: 30286978.

Agarwal P, Gammon EA, Sajib AM, Sandey M, Smith BF., Cell-Surface Integrins and CAR Are Both Essential for Adenovirus Type 5 Transduction of Canine Cells of Lymphocytic Origin. PLoS One. 2017 Jan 9;12(1). PMID: 28068367

Grimes JA, Prasad N, Levy S, Cattley R, Lindley S, Boothe HW, Henderson RA, Smith BF., A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs. BMC Vet Res. 2016 Dec 3;12(1):272. PMID: 27912752

Pondugula, S.R., Ferniany, G., Ashraf, F., Abbott, K. Smith, B.F., Coleman, E. Mansour, M., Bird, R.C., Smith, A. Karthikeyan, C., Trivedi, P., Tiwari, A., Stearidonic acid, a plant-based dietary fatty acid, enhances the chemosensitivity of canine lymphoid tumor cells. Biochemical and Biophysical Research Communications (BBRC), 2015, May 15;460(4).PMID:25847597

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.  PMID: 25740329

Hakim CH, Yue Y, Shin JH, Williams RR, Zhang K, Smith BF, 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 Mar 5;1:14002. PMID: 25105153

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. 2014 Aug 15;547(1):23-33. PMID: 24865935

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 March, 23(3), 287-294.

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. 2012 Feb, 23(2), 202-209.

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.

Dr. Smith bibliography