Research Bio
Much evidence suggested that chronic inflammation is one of the causative factors in prostate tumor development involving infiltration of inflammatory cells, such as macrophages, dendritic cells and lymphocytes. The tumor lesions are often enriched with proinflammatory cytokines, which are correlated with influx of tumor-associated macrophages (TAMs), suggesting that TAMs play an important role in tumor microenvironment, cytokine secretion, as well as promoting tumor cell growth, invasion, and metastasis. Understanding the roles of TAMs and their secreted cytokines in prostate tumor development and progression will help in development of therapeutic designs against prostate tumor.
We have identified a novel role of the androgen receptor (AR) in regulating cytokine expression and chemotaxis of macrophages in a mouse wound healing model. This interesting study prompts us to link the potential regulation of AR in TAMs to prostate tumor development and progression. Therefore, we hypothesize the macrophage AR may play a key role in prostate tumor microenvironment, and promote prostate tumor development and progression through the induction of cytokine production. Objective/hypothesis: The macrophage AR may control the expression of inflammatory cytokines that may contribute to the prostate tumor development and progression.
By establishing an in vitro co-culture model between macrophages and prostate tumor cells, and generating mouse models of PTEN or TRAMP tumor/macrophage AR WT and KO mice, or PTEN or TRAMP/ cytokine WT and KO mice, we can investigate the function of macrophage AR and inflammatory cytokines in prostate tumor development and progression. From the in vitro co-culture system, we will determine the AR role in macrophages and identify which cytokine is vital for influencing prostate cancer cells. In the in vivo mouse model, we will examine whether macrophage AR and inflammatory cytokines will influence the latency of prostate tumor development and the potential of tumor invasiveness and distal metastasis.
| Travel Award | Gordon Research Conf Hormonal Carcinogenesis |
1999 |
| Predoctoral Fellowship | University of Rochester, Rochester, NY |
1998 - 2003 |
| Prostate Cancer Training Grant Postdoctoral Fellowship | Princess Margaret Hospital | Toronto, Ontario, Canada |
2004 |
| Aug, 2004 Heart & Stroke/ Richard Lewar Center of Excellence Fellowship Award | Canada |
2004 |
| Postdoctoral Training Grant (2006-2008) | Department of Defense Prostate Cancer Program (PCRP) | USA |
2005 |
| New investigator Award (2010-2013) | Department of Defense Prostate Cancer Program (PCRP) | USA |
2009 |
2013 Apr 6
Izumi K, Mizokami A, Lin WJ, Lai KP, Chang C. "Androgen Receptor Roles in the Development of Benign Prostate Hyperplasia (BPH)." The American journal of pathology. 2013 Apr 6; Epub 2013 Apr 06. |
2012 Oct
Lu T, Lin WJ, Izumi K, Wang X, Xu D, Fang LY, Li L, Jiang Q, Jin J, Chang C. "Targeting androgen receptor to suppress macrophage-induced EMT and benign prostatic hyperplasia (BPH) development." Molecular endocrinology (Baltimore, Md.). 2012 Oct 0; 26(10):1707-15. Epub 2012 Aug 21. |
2012 May 25
Wang X, Lin WJ, Izumi K, Jiang Q, Lai KP, Xu D, Fang LY, Lu T, Li L, Xia S, Chang C. "Increased infiltrated macrophages in benign prostatic hyperplasia (BPH): role of stromal androgen receptor in macrophage-induced prostate stromal cell proliferation." The Journal of biological chemistry. 2012 May 25; 287(22):18376-85. Epub 2012 Apr 02. |
2012
Fang LY; Izumi K; Li L; Lai KP; Liang L; Miyamoto H; Lin WJ*; and Chang C*. "A Critical Role for AR/CCL4 axis in promotion of prostate tumorigenesis. Paper in revision to Cancer Research. co-corresponding author." 2012; . |
2012
Izumi K, Fang LY, Mizokami A, Namiki M, Li L, Lin WJ*, and Chang C*. "Targeting Androgen Receptor-induced CCL2 Expression by STAT3 Activation Contributes to Prostate Cancer Metastasis. Paper in submission to EMBO Mol Medicine. co-corresponding author." EMBO Mol Medicine. 2012; . |
