Department of Comparative Medicine, University of Washington, T-146 Health Science Center Box 357190, Seattle, WA 98195-7190 Phone: 206-221-3932 Fax: 206-685-3006 email: biritani@uw.edu

Dr. Iritani received his D.V.M. from Washington State University and his Ph.D. in Immunology from the University of Washington. After 4 years of private veterinary practice, he pursued residency training in Laboratory Animal Medicine at the University of Washington, and then post-doctoral research training in Molecular Oncology at Fred Hutchinson Cancer Research Center. Dr. Iritani joined the faculty in Comparative Medicine in 1999.

Current Research Interests

Cancer is a complex disease caused by alterations in the expression of genes that normally control cell proliferation, development, and survival. Among the genes that are involved in neoplastic transformation, include a subset called “oncogenes”. The Iritani lab is studying the Myc oncogene family, of which there are 3 members (c-,N-, and L-Myc). Myc proteins are known to be critical for normal cell division, and their expression are deregulated in many types of cancers including breast, brain, colon cancers, and most leukemias and lymphomas. Myc genes encode for transcription factors that regulate the expression of a yet-defined set of genes that are critical for cell proliferation and growth. Myc proteins bind DNA with a related partner called Max (see figure below). Max can also bind another family of transcription factors called Mad. However, while Myc/Max dimmers stimulate transcription, Mad/Max dimers repress transcription, in part by recruiting a complex of co-repressors including Sin3 and histone deacetylases (HDAC). We are interested in understanding how Myc, and the Mad family of Myc antagonists, normally function in the development and proliferation of lymphocytes, and how these functions are altered during oncogenic activation.

Utilizing cDNA microarray technology, we have identified sets of genes that are increased and decreased by Myc in primary lymphocytes both before and after transformation. We are utilizing gene-targeting, transgenesis, retroviral gene transduction, and chromatin immunoprecipitation to understand which of these genes may be important for the ability of Myc to stimulate cell division and cancer. We are also utilizing lymphocyte-specific transgenic and knockout mice to understand how Myc and Mad normally modulate the development and function of lymphocytes.

Iritani Lab Members

Mark Tsang- Research Technician
Tania Habib, Ph.D.- Post-doctoral Fellow
Heon Park, Ph.D.- Post-doctoral Fellow

Representative publications

Fehling, H.J., Iritani, B.M., Krotkova, A., Forbush, K.A., Laplace, C., Perlmutter, R.M., and von Boehmer, H. (1997) Restoration of Early T Cell Development in pTα-deficient Mice by Anti-CDε Antibody Treatment or With Transgenes Encoding Activated Lck or Tailless pTα. Immunity, 6:703-714.

Iritani, B.M., Forbush, K.A., Farrar, M.A., and Perlmutter, R.M. (1997) Control of B Cell Development by Ras-mediated Activation of Raf. EMBO J. 16(23):7019-7031.

Iritani, B.M., Alberola-Ila, J., Forbush, K.A., and Perlmutter, R.M. (1999) Distinct Signals Mediate Maturation and Allelic Exclusion in Lymphocyte Progenitors. Immunity, 10(5):713-722.

Iritani, B.M., and Eisenman, R.N. (1999) c-Myc Enhances Protein Synthesis and Cell Size During B Lymphocyte Development. Proc. Nat. Acad. Sci. USA, 96(23):13180-13185.

Takaki, S., Sauer, K., Iritani, B.M., Chein, S., Yasuhiro Ebihara, Koh-ichiro Tsuji, Kiyoshi Takatsu, and Perlmutter, R.M. (2000) Control of B Cell Development by the Adaptor Protein Lnk: Definition of a Conserved Family of Signal Transducing Proteins. Immunity, 13: 599-609.

Queva, C., McArthur, G.A., Iritani, B.M., and Eisenman, R.N. (2001) Targeted Deletion of the S-Phase-Specific Myc Antagonist Mad3 Sensitizes Neuronal and Lymphoid Cells to Radiation-Induced Apoptosis. Molecular and Cellular Biology, 21(3):703-712.

Iritani, B.M., Delrow, J., Grandori, C., Klacking, M., Gomez, I., Carlos, L.S., and Eisenman, R.N. (2002) Modulation of T Lymphocyte Development, Growth, and Cell Size by the Myc-Antagonist and Transcriptional Repressor Mad1. EMBO J, 21(18):4820-4830.

Ruddell, A., Mezquita, P., Brandvold, K.A., Farr, A., and B.M. Iritani. (2003) B Lymphocyte Specific expression of c-myc stimulates early and functional expansion of vasculature and lymphatics in hematopoietic tissues. American Journal of Pathology, 163(6):2233-2245.

Lillian Maggio-Price, Helle Bielefeldt-Ohmann, Piper Treuting, Brian Iritani, Weiping Zeng,Andrea Nicks, Mark Tsang, Donna Shows, Phil Morrissey and Joanne Viney (2005) Co-infection with Helicobacter bilis and Helicobacter hepaticus promotes colonic dysplasia in mdr1a-/- mice. American Journal of Pathology, 166(6):1793-1806.

Cowley, S.M., Iritani, B.M., Mendrysa, S., Xu, T., Cheng, P.F., Yada, J., Liggitt, H.D., Queva, C., and Eisenman, R.N. (2005) The Sin3a Co-repressor is Essential for Embryonic Development and Determines T Cell Fate. Molecular and Cellular Biology,25(16):6990-7004.

Price, L.M., Treuting, P., Zeng, W., Tsang, M., Bielefeldt-Ohmann, H., and Iritani, B.M. (2006) A Helicobacter is Required for Inflammation and Colon Cancer in SMAD3-Deficient Mice. Cancer Research, 66(2):828-38.

Habib, T., Park, H., Tsang, M., de Alboran, I., Nicks, A., Wilson, L., Knoepfler, P., Andrews, S., Rawlings., D., Eisenman, R.N., and B.M. Iritani. (2007) Myc Stimulates B Cell Development and Amplifies Calcium Signaling. The Journal of Cell Biology, 179(4):717-731.

Gallo, E.M, Winslow, M.M., Cante-Barrett, K., Radermacher, A.M., HO, L., McGinnis, L., Iritani, B.M., Neilson, J.R., and Crabtree, G.R. (2007) Calcineurin sets the bandwidth for discrimination of signals during thymocyte development. Nature, 450(29):731-736.

Harrell, M.I., Iritani, B.M., and Ruddell, A. (2008) Lymph node mapping in the mouse. J. Immunological Methods, 332:170-174.

Ruddell, A., Harrell, M.I., Minoshima, S., Maravilla, K.R., Iritani, B.M., White, S.W., and Partridge, S.C. (2008) Dynamic Contrast-enhanced Magnetic Resonance Inaging of Tumor-induced Lymph Flow. Neoplasia, 10(7):706-713.