The K05 candidate is a senior faculty member (professor) who has been actively involved in cancer research and mentoring for over two decades. She is an independent investigator who has developed and sustained a vigorous research and training program in cancer prevention. The candidate has over 270 scientific publications and is recognized nationally and internationally for her prostate cancer (PCa) research (e.g., epidemiology, biomarkers, prevention, outcomes). The candidate's research program has been instrumental in building a robust environment and infrastructure that will provide critical support, resources, and opportunities for young investigators during the proposed K05 award. This award would provide needed support for the candidate to devote substantially more time and effort toward career development goals and successful launching of the next generation of young investigators in cancer prevention. The K05 proposal has 3 components: 1) Career Plan; 2) Research Plan; and, 3) Mentoring Plan. Dr. Stanford's Career Plan includes: 1) advancing knowledge of genomics, epigenomics, and molecular biology; 2) augmenting her research skills, particularly related to analyses of high-throughput data; and, 3) enhancing her mentoring skills. The career plan is strongly tied to the proposed research and mentoring plans, and will encompass academic courses, conferences, heading a new journal club, and teaching in the research ethics program. The Research Plan is aimed to expand knowledge of biomarkers for PCa, and will test the hypothesis that epigenomic and genetic alterations influence PCa progression to its aggressive phenotype. The research plan will: 1) determine whether genome-wide DNA methylation and gene expression profiles in PCa tumor tissue are associated with recurrent and lethal PCa; and, 2) combine top-ranked genes from the methylation and expression profiles with genetic variants associated with PCa-specific mortality to build an integrated panel of biomarkers for stratification of patients (indolent vs. aggressive tumors) who may benefit most from novel therapy and prevention approaches. The research plan will take advantage of a population-based cohort of PCa patients (n=1,458) with available data and biospecimens. The Mentoring Plan is built upon the candidate's experience gained from working with graduate students, fellows, and junior faculty, and will include both individual and group interactions aimed at inspiring and building the research and career skills of K05 mentees (e.g., study design and methodology, data analyses, writing scientific papers and grant proposals, presenting at scientific meetings). Trainees will be identified and supported through training and other grants and awards within the candidate's research-academic environment. All data, biospecimens, and resources from the candidate's research program will be made available for training these young scientists.

Public Health Relevance

The K05 proposal involves career development, research, and mentoring plans that are clearly tied together for synergy and to meet the overall goal of advancing the candidate's career and mentoring skills for training the next generation of young researchers in cancer prevention and control. The research plan focuses on epigenomic and genetic biomarkers for aggressive prostate cancer (PCa). The intellectual ability and research expertise that these young, well-trained investigators will bring to the fight against PCa, which i a major cause of human suffering and death, may lead to development of novel therapy and prevention approaches.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Award (K05)
Project #
5K05CA175147-05
Application #
9392896
Study Section
Subcommittee I - Transistion to Independence (NCI)
Program Officer
Perkins, Susan N
Project Start
2014-01-09
Project End
2019-06-30
Budget Start
2018-01-01
Budget End
2019-06-30
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Dai, James Y; Wang, Bo; Wang, Xiaoyu et al. (2018) Vigorous physical activity is associated with metastatic-lethal progression in prostate cancer and differential tumor DNA methylation in the CRACR2A gene. Cancer Epidemiol Biomarkers Prev :
FitzGerald, L M; Zhao, S; Leonardson, A et al. (2018) Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases. Prostate Cancer Prostatic Dis 21:228-237
Zhao, Shanshan; Leonardson, Amy; Geybels, Milan S et al. (2018) A five-CpG DNA methylation score to predict metastatic-lethal outcomes in men treated with radical prostatectomy for localized prostate cancer. Prostate :
Geybels, Milan S; Fang, Min; Wright, Jonathan L et al. (2017) PTEN loss is associated with prostate cancer recurrence and alterations in tumor DNA methylation profiles. Oncotarget 8:84338-84348
Geybels, Milan S; McCloskey, Karen D; Mills, Ian G et al. (2017) Calcium Channel Blocker Use and Risk of Prostate Cancer by TMPRSS2:ERG Gene Fusion Status. Prostate 77:282-290
Jhun, Min A; Geybels, Milan S; Wright, Jonathan L et al. (2017) Gene expression signature of Gleason score is associated with prostate cancer outcomes in a radical prostatectomy cohort. Oncotarget 8:43035-43047
Rubicz, Rohina; Zhao, Shanshan; Wright, Jonathan L et al. (2017) Gene expression panel predicts metastatic-lethal prostate cancer outcomes in men diagnosed with clinically localized prostate cancer. Mol Oncol 11:140-150
Zhao, Shanshan; Geybels, Milan S; Leonardson, Amy et al. (2017) Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer. Clin Cancer Res 23:311-319
Shui, Irene M; Kolb, Suzanne; Hanson, Christi et al. (2016) Trichomonas vaginalis infection and risk of advanced prostate cancer. Prostate 76:620-3
Wright, J L; Chéry, L; Holt, S et al. (2016) Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2:ERG fusion status. Prostate Cancer Prostatic Dis 19:53-6

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