Richard Curtis Bird, PhD

R. Curtis Bird is Professor of Molecular Biology and Cancer Genetics in the Department of Pathobiology and has been at Auburn since 1985. He earned the B.Sc.(Honors) in Biology at McMaster University, Canada, in 1977, and a Ph.D. in Cellular Biology and Molecular Genetics from the Department of Zoology from the University of Toronto, Canada, in 1982. His doctoral research focused on the molecular and cellular biology of the cell cycle and the regulation of tubulin synthesis. He was awarded a Medical Research Council Post-Doctoral Fellowship in Molecular Biology, at the School of Medicine, Memorial University, St. John's, in 1981 and continued his post-doctoral training in Molecular Biology and Genetics/Microbiology, at the University of Guelph, in 1983. His post-doctoral research focused on the regulation of mRNA transcription and degradation mechanisms during myoblast development.


Research Interests

My laboratory investigates the regulatory mechanisms that control the expression and function of genes that control a cell's ability to proliferate. We are applying the knowledge gained from these investigations to better understand the mechanisms by which cancer cells evade the normal restrictions on proliferation that limit the growth of normal cells. These investigations have allowed us to design strategies for the inhibition of cancer cell proliferation through direct suppression of oncogene expression, induction of tumor suppressor gene expression and through gene therapy and modification of the immune response by recombinant autologous hybrid-dendritic cell fusion vaccine development.

We employ quantitative PCR, oncogene and tumor suppressor gene cloning and sequencing, gene transfection, selection, cloning and expression, antisense oligonucleotides, subtractive hybridization cDNA cloning, multi-parameter flow cytometry and high-speed cell sorting, as well as promoter and transcript analysis to study cell growth regulation and neoplasia.

We have identified defects in expression in canine mammary tumor cells in the oncogenes c-erbB-2 and c-myc and tumor suppressor gene mutations in both p53 and the cyclin-dependent kinase inhibitors p16/INK4A and p21/Cip1. We have also identified CDK1 promoter enhancer elements regulating induction of expression and re-entry into the cell cycle from quiescence. And, we have developed a neoplastic progression model identifying 5-7 key mutations that appear responsible for mammary carcinoma in dogs. This is based on phenotype rescue studies that have included cloning and sequencing of more than 60 canine genes/ORFs associated with cancer and cell proliferation control and are designed to explore the mechanisms by which oncogene and tumor suppressor gene products interact with regulatory activities that drive cell cycle through regulation of the cyclin/CDK complex family. The association between regulation of apoptotic cell death and disruption of the expression and the subcellular localization of these gene products has also been implicated.

We are investigating these processes in cancer cells primarily derived from breast/mammary cancer, lymphoma and malignant melanoma in canine and human models. The principle system we study is malignant canine mammary carcinoma because this cancer provides an excellent model of human disease allowing the translation of technologies between species. Development of the canine model has allowed us the opportunity to evaluate new therapeutic models against spontaneously occurring tumors in animals with intact immune systems based on advanced gene and recombinant cell therapies. As part of this analysis, we are investigating the clinical effects of retargeting viral vectors designed to deliver a lethal payload to canine lymphoma cells and the immune modulation induced by autologous hybrid dendritic cell fusion vaccines in dogs with spontaneous cancers. Our goal is to employ knowledge of cancer genetics and immunity to develop better therapies for dogs with cancer and through this effort to translate successful therapies for use in human patients.


Selected Publications

Selected Publications

Bird, R.C., Jacobs, F.A., Stein, G., Stein, J., and Sells, B.H. 1985. A Unique Subspecies of Histone H4 mRNA From Rat Myoblasts Contains Poly(A). Proc. Natl. Acad. Sci. USA 82:6760-6764.

Pai, S.R., and Bird, R.C. (1991) Growth of HeLa S3 Cells Cotransfected with plasmids containing a c-fos Gene Under the Control of the SV40 Promoter Complex, pRSVcat, and G418 Resistance, Biochem. Cell Biol., 70:316-323.

Wu, G., Su. S.P., Kung, T.-Y.T., and Bird, R.C. (1993) Molecular Cloning of G1 Phase mRNAs From a Subtractive G1 phase cDNA library, Biochem Cell Biol 71, 372-380.

Ahern T.E., Bird, R.C., Church Bird, A.E., Wolfe, L.G. (1993) Overexpression of c-erbB-2 and c-myc but not c-ras, in Canine Melanoma Cell Lines, is Associated with Metastatic Potential in Nude Mice, Anticancer Research 13, 1365-1372.

Pai, S.R., Bird, R.C. (1994) Overexpression of c-fos Induces Expression of the Retinoblastoma Tumor Suppressor Gene Rb in Transfected Cells. Anticancer Research, 14:2501-2508.

Wu, G., Su, S., Bird, R.C. (1994) Optimization of subtractive hybridization in construction of subtractive cDNA libraries. Genetic Anal Tech Applications 11, 29-33.

Bird, R.C., Su., S., Wu., G. (1994) Preparation of synchronous populations of mammalian cells in specific phases of the cell cycle by centrifugal elutriation. In Handbook of Cell Biology Volumes 1-3 (J.E. Celis, ed.), Academic Press, NY, 272-281.

Pai, S.R., Bird, R.C. (1994) c-fos expression is required during all phases of the cell cycle during exponential cell proliferation. Anticancer Res 14, 985-994.

Pai, S.R., Bird, R.C. (1995) Overexpression of c-fos induces expression of the retinoblastoma tumor suppressor gene Rb in transfected cells. Anticancer Res, 14, 2501-2508.

Silverstein, P.S., Bird, R.C., van Santen, V.L., Nusbaum, K.E. (1995) Immediate-early transcription from the channel catfish virus (CCV) genome: characterization of two immediate-early transcripts. J Virol, 69, 3161-3166.

You, J., Bird, R.C. (1995) Selective induction of cell cycle regulatory genes cdk1 (p34cdc2) cyclins A/B and the tumor suppressor gene Rb in transformed cells by okadaic acid. J Cell Phys, 164, 424-433.

Su, S., and Bird, R.C. (1995) Identification and Characterization of a Unique Human cDNA Encoding a Zinc-Finger Protein Homologous to Rat Ribosomal Protein L37, European J. Biochemistry, 232, 789-797.

Ahern, T.E., Bird, R.C., Church Bird, A.E., and Wolfe, L.G. (1995) Overexpression of the oncogene c-erbB-2 in canine mammary carcinomas and tumor-derived cell lines, Am. J. Vet. Res., 57,693-696.

Bird, R.C. (1997) The Cyclin/cdk Complex: Regulation of Cell Cycle Progression and Nuclear Disassembly. In Nuclear Structure and Gene Expression: The Nuclear Matrix and Chromatin Structure (R.C.Bird, G.Stein, J.Lian, and J.Stein, eds.), Academic Press, NY, 145-177.

Pai, S.R., and Bird, R.C. 1998. Interactions of the Rb Tumor Suppressor Protein with the c-fos Promoter in c-fos Transfected Cells Overexpressing c-fos and Rb, Anticancer Research, Anticancer Research 17:3265-3272.

Silverstein, P.S., van Santen, V.L., Nusbaum, K.E. and Bird, R.C. 1998. Characterization of Immediate Early and Early Transcripts From Channel Catfish Virus (IHV-1), J. Virology 72:3900-3906.

Bird, R.C. 1998. Synchronous Populations of Cells in Specific Phases of the Cell Cycle Prepared by Centrifugal Elutriation. In Handbook of Cell Biology Volumes 1-3, 2nd edition (J.E. Celis, ed.), Academic Press, NY, 209-217.

Bird, R.C. 1998. Cell Separation by Centrifugal Elutriation. In Handbook of Cell Biology Volumes 1-3, 2nd edition (J.E. Celis, ed.), Academic Press, NY, 205-208.

Liu, H. and Bird, R.C. 1998. Characterization of the Okadaic Acid Response Element Region of the Cyclin-Dependent Kinase 1 (p34cdc2) Promoter, Biochemical and Biophysical Research Communications, 246, 696-702.

Nusbaum, K.E., Smith, B.F., and DeInnocentes, P., Bird, R.C. (2002) Expression Kinetics of Early and Late Transcripts During the Very Fast Replication Cycle of Channel Catfish Herpesvirus (IHV-1), Veterinary Immunology & Immunopathology, 84, 151-168.

Silverstein, P., Buch, S. J., and Bird, R.C. (2002). Principles of cDNA Cloning in Genetic Library Construction and Screening (R. C. Bird and B. F. Smith, eds.), Springer-Verlag, Berlin, pp. 3-19.

Bird, R.C., and Wu, G. (2002). Subtractive Hybridization and cDNA Cloning in Genetic Library Construction and Screening (R. C. Bird and B. F. Smith, eds.), Springer-Verlag, Berlin, pp. 97-123.

Bird, R.C., and Smith, B.F. (2002). Preface and Overview to Genetic Library Construction and Screening in Genetic Library Construction and Screening (R. C. Bird and B. F. Smith, eds.), Springer-Verlag, Berlin, pp. 5-8.

Bird, R.C. (2003). Regulation of Cyclin-Dependent Kinase 1 (cdc2) Expression During the G0/G1 Phase Transition and The Consequences for Regulation of Cell Cycle Progression, in G1 Phase Progression (J. Boonstra, ed.), Landes Biosciences, Georgetown, Texas, pp. 1-18.

R. C. Bird and P. DeInnocentes (2004) Characterization of the CDP-Like/CTAS-1 Enhancer in the Okadaic Acid Response Element (OARE) of the Human cdk1(p34cdc2) Promoter, Anticancer Research 24(3), 1469-1480.

Bird, R.C., A. Church Bird and P. DeInnocentes (2005). Animal Cell Separation and Fractionation, In: Nature - Encyclopedia of Life Sciences. John Wiley & Sons, Ltd: Chichester, pp. 1-6.

Spencer, J.A., DeInnocentes, P., Moyana E.M., Guarino A.J., Ellison S.E., Bird R.C., and  Blagburn B.L. (2005) Cytokine gene expression in response to SnSAG1 in horses with equine protozoal myeloencephalitis. Clinical and Diagnostic Laboratory Immunology, Clinical & Diagnostic Lab Immunol. 12, 644-646.

Migone, F., Bird, R.C., DeInnocentes, P., Lenz, S., and Smith, B. (2005). Alterations in CDK1 Expression and Localization Following Induction in a Spontaneous Canine Mammary Cancer Model, J Cell Biochem. 2006 Jun 1;98(3):504-518.

Bird R. C. (2006) Separation of Cell Populations Synchronized in Cell Cycle Phase by Centrifugal Elutriation. In Handbook of Cell Biology Volumes 1-3, 3rd edition (J.E. Celis, ed.), Academic Press, NY, pp. 247-256.

DeInnocentes, P., Li, L.X., Sanchez, R.L., and Bird, R.C. (2006) Expression and Sequence of Canine SIRT2 and p53 Alleles in Canine Mammary Tumor Cells - Effects on Down Stream Targets Wip1 and p21/Cip1, Veterinary and Comparative Oncology, 4(3) 161-177.

Bird, R.C., DeInnocentes, P., Lenz, S., Thacker, E.E., Curiel, D.T., and Smith, B.F. (2008) Cross-presentation of a hybrid-cell fusion vaccine against canine mammary cancer, Veterinary Immunology & Immunopathology, 123 289-304.

Jayanna, P.K., Deinnocentes, P., Bird, R.C., Petrenko, V.A. (2008) Landscape phage probes for PC3 prostate carcinoma cells, Proceedings, NSTI-Nanotechnology Conference: Life Sciences, Medicine, and Bio Materials, Vol. 2, 457-460.

Fagbohun, O.A., Bedi, D., Jayanna, P.K., Deinnocentes, P., Bird, R.C., Petrenko, V.A. (2008) Landscape phage probes for PC3 breast cancer cells, Proceedings, NSTI-Nanotechnology Conference: Life Sciences, Medicine, and Bio Materials, Vol. 2, 461-464.

DeInnocentes P, Agarwal P, Bird RC. (2009) Phenotype-rescue of cyclin-dependent kinase inhibitor p16/INK4A defects in a spontaneous canine cell model of breast cancer. J Cell Biochem. 106:491-505.

Bird, R.C. (2009) Defects in Genes Regulating the Cell Cycle in Spontaneous Canine Models of Cancer, In Trends in Cell Cycle Research (K. Yoshida ed.), Research Sign Post, Kerala, India, 209-236.

Thacker, E.E., Nakayama, M., Smith, B.F., Bird R.C., Muminova, Z., Strong, T., Timares, L., Korokhov, N., O’Neill, A.M., de Gruijl, T.D., Glasgow, J.N., Tani, K., Curiel D.T. (2009) A Genetically Engineered Adenovirus Vector Targeted to CD40 Mediates Transduction of Canine Dendritic Cells and Promotes Antigen-Specific Immune Responses In Vivo. Vaccine, 27(50):7116-7124.

Jayanna PK, Bedi D, Deinnocentes P, Wang T, Torchilin VP, Bird RC, Petrenko VA. (2009) Towards Phage-Targeted Medications for Prostate Cancer, in press. New Progress and Challenges in Pharmaceutical Sciences Eds: Hincal, AA, Celebi, N, Yuksel, N), Proceedings, Third Annual BBBB International Conference on Pharmaceutical Sciences Part IV, Antalya, Turkey, pp. 178-191.

Smith, B.F., and Bird, R.C. (2010) Hematologic Neoplasia - Gene Therapy, Schalm’s Veterinary Hematology 6th Edition, pp. 550-557.

Bird, R.C., A. Church Bird and P. DeInnocentes 2011 (December 2010) Animal Cell Separation and Subcellular Fractionation. In: ENCYCLOPEDIA OF LIFE SCIENCES 2011, John Wiley & Sons, Ltd: Chichester <> [DOI: 10.1002/978047001], pp. 1-7.

Jayanna P.K., Bedi D., Gillespie J.W., DeInnocentes P., Wang T., Torchilin V.P., Bird R.C., and Petrenko V.A. (2010) Landscape Phage Fusion Protein-Mediated Targeting of Nanomedicines Enhances their Prostate Tumor Cell Association and Cytotoxic Efficiency. Nanomedicine. 6(4):538-46. [2010 Aug;6 Epub ahead of print].

Jayanna P.K., Bedi D, Deinnocentes P., Bird R.C. and Petrenko V.A. (2010) Landscape Phage Probes for PC3 Prostate Carcinoma cells. Protein Engineering, Design, and Selection, 23(6):423-30 [Epub 2010 Feb 25].

Bird, R.C., DeInnocentes, P., Church Bird A.E., van Ginkel F.W. and Smith B.F. (2011) An Autologous Dendritic Cell-Canine Mammary Tumor Hybrid-Cell Fusion Vaccine, Cancer Immunology and Immunotherapy, 60:87–97. [Epub ahead of print 2010 Nov]

Bedi, D., Musacchio, T., Fagbohun, O.A., Deinnocentesa, P., Bird, R.C., Bookbinder, L., Torchilin, V.P. and Petrenko V.A. (2011) Delivery of siRNA into Breast Cancer Cells via Phage Fusion Protein-Targeted Liposomes. Nanomedicine: Nanotechnology, Biology, and Medicine Nanomedicine,  2010 Nov 2. [Epub ahead of print].

O’Neill, A.M., Smith, A., Spangler, E., Whitley, E., Schleis, S., Bird, R.C., Curiel, D., Thacker, E., Smith, B.F. (2011) Resistance of Canine Lymphoma Cells to Adenoviral infection due to Reduced Cell Surface RGD Binding Integrins, Cancer Biology & Therapy, Cancer Biol Ther. 11(7) [2011 Apr 1;Epub ahead of print].

Xie, Z., Buschle-Diller, G., DeInnocentes, P., Bird, R.C. (2011) Electrospun poly(D,L)-lactide nonwoven mats for biomedical application: surface area shrinkage and surface entrapment, J. Applied Polymer Science, in press.

© 2009 Auburn University College of Veterinary Medicine