A group photo of the Michael Ittmann Lab members.
About Us
Research in the Michael Ittman Laboratory is focused on the molecular genetics of human prostate cancer and the pathobiology of benign prostatic hyperplasia. In particular, we are interested in role of Fibroblast Growth Factors in these two diseases.
Current Studies
We are carrying out a number of studies to determine the role of FGFs in prostate cancer including:
Direct analysis of human prostate cancers by Western blotting, immunohistochemistry, ELISA, quantitative RT-PCR and Northern blotting to determine quantitatively the content of FGFs in prostate cancer, the tissues (epithelial or stromal) expressing specific FGFs and the tissue specific expression of FGF receptors and their isoforms.
Use of dominant negative and activated receptors to determine the biological effects of FGF receptor activation and inactivation in prostate cancer cell lines and analysis of the signal transduction pathways mediating these effects.
Evaluation of the role of FGFs in tumor progression in vivo using transgenic and knockout mouse models.
Examining the effect of aging and tissue senescence on prostate cancer initiation and progression via the effect of these processes on FGF expression in vivo.
Benign Prostatic Hyperplasia
Benign Prostatic Hyperplasia is an extremely common disease of older men that causes significant morbidity in this group. The abnormal growth of the transition zone of the prostate leads to the outflow obstruction characteristic of this disease. Our recent work has identified an important role of increased expression of FGFs in this abnormal growth. We are now exploring the role of paracrine regulators of FGF expression in the increased expression of FGFs in BPH and the role of tissue senescence in mediating expression of FGFs and cytokines in BPH.
Yu W, Feng S, Dakhova O, Creighton CJ, Cai Y, Wang J, Li R, Frolov A, Ayala G, Ittmann M. FGFR-4 Arg(3)(8)(8) enhances prostate cancer progression via extracellular signal-related kinase and serum response factor signaling. Clin Cancer Res. 2011;17(13):4355-66. PMCID: 3131485.
Kannan K, Wang L, Wang J, Ittmann MM, Li W, Yen L. Recurrent chimeric RNAs enriched in human prostate cancer identified by deep sequencing. Proc Natl Acad Sci U S A. 2011;108(22):9172-7. PMCID: 3107329.
Wang J, Cai Y, Shao LJ, Siddiqui J, Palanisamy N, Li R, Ren C, Ayala G, Ittmann M. Activation of NF-{kappa}B by TMPRSS2/ERG Fusion Isoforms through Toll-Like Receptor-4. Cancer Research. 2011;71(4):1325-33. PMCID: 3041849.
Choi N, Zhang B, Zhang L, Ittmann M, Xin L. Adult murine prostate basal and luminal cells are self-sustained lineages that can both serve as targets for prostate cancer initiation. Cancer Cell. 2012;21(2):253-65. PMCID: 3285423.
Valdez JM, Zhang L, Su Q, Dakhova O, Zhang Y, Shahi P, Spencer DM, Creighton CJ, Ittmann MM, Xin L. Notch and TGFbeta form a reciprocal positive regulatory loop that suppresses murine prostate basal stem/progenitor cell activity. Cell Stem Cell. 2012;11(5):676-88. PMCID: 3490134.
Shao L, Tekedereli I, Wang J, Yuca E, Tsang S, Sood A, Lopez-Berestein G, Ozpolat B, Ittmann M. Highly specific targeting of the TMPRSS2/ERG fusion gene using liposomal nanovectors. Clinical Cancer Research. 2012;18(24):6648-57. PMCID: 3525716.
Feng S, Shao L, Yu W, Gavine P, Ittmann M. Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression. Clinical Cancer Research. 2012;18(14):3880-8.
Cai Y, Wang J, Ren C, Ittmann M. Frequent heterogeneous missense mutations of GGAP2 in prostate cancer: implications for tumor biology, clonality and mutation analysis. PLoS One. 2012;7(2):e32708. PMCID: 3289671.
Kwon OJ, Zhang L, Ittmann MM, Xin L. Prostatic inflammation enhances basal-to-luminal differentiation and accelerates initiation of prostate cancer with a basal cell origin. Proceedings of the National Academy of Sciences of the United States of America. 2013.
Ittmann M, Huang J, Radaelli E, Martin P, Signoretti S, Sullivan R, Simons BW, Ward JM, Robinson BD, Chu GC, Loda M, Thomas G, Borowsky A, Cardiff RD. Animal models of human prostate cancer: the consensus report of the New York meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee. Cancer Research. 2013;73(9):2718-36. PMCID: 3644021.
Qin J, Wu SP, Creighton CJ, Dai F, Xie X, Cheng CM, Frolov A, Ayala G, Lin X, Feng XH, Ittmann MM, Tsai SJ, Tsai MJ, Tsai SY. COUP-TFII inhibits TGF-beta-induced growth barrier to promote prostate tumorigenesis. Nature. 2013;493(7431):236-40.
Feng S, Dakhova O, Creighton CJ, Ittmann M. Endocrine fibroblast growth factor FGF19 promotes prostate cancer progression. Cancer Research. 2013;73(8):2551-62. PMCID: 3630260.
Dakhova O, Rowley D, Ittmann M. Genes upregulated in prostate cancer reactive stroma promote prostate cancer progression in vivo. Clinical Cancer Research. 2014;20(1):100-9.
Kwon OJ, Valdez JM, Zhang L, Zhang B, Wei X, Su Q, Ittmann MM, Creighton CJ, Xin L. Increased Notch signalling inhibits anoikis and stimulates proliferation of prostate luminal epithelial cells. Nature Communications. 2014;5:4416.
Vital P, Castro P, Tsang S, Ittmann M. The senescence-associated secretory phenotype promotes benign prostatic hyperplasia. The American Journal of Pathology. 2014;184(3):721-31. PMCID: 3936307.