My career goals as an independent researcher are: 1) to discover critical knowledge of basic prostate biology that will be used to improve the treatment and quality of life of patients with prostate disease;2) to establish myself as an independent investigator in urological/prostate research through outstanding research and the mentoring of future urology clinicians and researchers;3) improve the education process within urology through continued and expanded leadership in academic organizations in urological research, pharmacology and toxicology, and cancer biology;and 4) to become an outstanding professor of pharmacology, toxicology, and urology. My career development plan is carefully crafted to ensure that I achieve these goals. The research I will conduct for my KO1 development period is directed at understanding how inflammation promotes prostate disease by activating developmental mechanisms to promote the proliferation of specialized epithelial progenitor cells. Repair and regrowth are co-regulated processes in response to injury, trauma, and inflammatory conditions. In order for tissue recovery to proceed, inflammation must direct damaged cells to die, induce proliferation of protected specialized tissue progenitors to repopulate the damaged tissue, and promote differentiation of expanded cells into the proper cell subtypes allowing stratification of the repaired tissue layers. Errors in this process allow fr expansion of damaged cells in an environment rich in growth promoting factors, thereby promoting prostate disease. My career development plan is aimed at defining mechanistically how inflammation-generated IL-1 drives prostatic epithelial expansion through developmental growth factor induction.
Three specific aims are proposed to test the hypothesis that inflammation-induced IL-1 signaling promotes epithelial progenitor cell proliferation by inducing IGF signaling. We will determine if inflammation-induced IL-1 signaling promotes epithelial cell progenitor cell proliferation, evaluate the interrelationship of IL-1 to IGF-1 by determining if inflammation induces IGF signaling in an IL-1 dependent manner, and determine if IGF signaling expands the prostatic epithelium during inflammation by inducing progenitor cell proliferation. During my K01 training, I will adhere to my career development plan and achieve the specific professional milestones described for each award year. I will meet regularly with my mentor and advisory committee consisting of outstanding professors with expertise in progenitor cell signaling, inflammation, and prostate biology. With 42 faculty studying inflammatory signaling, 25 faculty studying tissue progenitor cell biology, and 20 faculty in prostate research, the IUSM and Simon Cancer Center is an outstanding place for my development into an independent investigator in prostate research.
Inflammation of the prostate gland is suspected to play a critical role in the development of prostate disease, including benign prostate growth and prostate cancer. The proposed research will investigate how inflammation reactivates part of the developmental process to promote proliferation of specialized progenitor epithelial cells, resulting in prostate disease.
|Wang, Liang; Zoetemelk, Marloes; Chitteti, Brahmananda R et al. (2015) Expansion of prostate epithelial progenitor cells after inflammation of the mouse prostate. Am J Physiol Renal Physiol 308:F1421-30|
|Hahn, Alana M; Myers, Jason D; McFarland, Eliza K et al. (2014) Interleukin-driven insulin-like growth factor promotes prostatic inflammatory hyperplasia. J Pharmacol Exp Ther 351:605-15|