Peter S. Nelson
M.D., University of Kansas, Medicine, 1986.
B.A., University of Kansas, Chemistry/Biology/Biochemistry, 1982.
The focus of current work in the Nelson lab involves efforts to understand the process of prostate carcinogenesis with an aim toward developing diagnostic, prognostic, and therapeutic strategies.
The Major Projects are:
1. Molecular Analysis of Therapies for Early and Late Stage Prostate Carcinoma. These investigations aim to determine molecular features that associate with response and resistance mechanisms to cytotoxic chemotherapy and pathway-targeted agents. Several clinical (translational) trials are underway including a studies incorporating neoadjuvant therapies followed by radical prostatectomy. Tissue samples are acquired pre- and post-therapy and molecular correlates of direct drug effects are identified to define signatures: (a) predictive of therapeutic response and (b) predictive of disease outcome (relapse).
2. Characterization of the Prostate Androgen-Response Program. A major focus of the lab has been the identification of down-stream ''effector'' genes that are responsible for cellular events (e.g. proliferation) after androgen receptor (AR) activation. We have identified >170 genes that are regulated by androgens in the prostate. Of these, many have expression profiles restricted to the prostate. Systematic studies involving overexpression and down-regulation of these genes is in progress to determine the cellular function with the aim of identifying those genes involved in proliferation, anti-apoptosis, and differentiation. Genes with prostate-restricted expression may serve as therapeutic targets.
3. Analysis of Prostate Serine Protease Function in Metastatic Prostate Carcinoma. Prostate cancer has a high prediliction for metastasizing to bone, and often produces a ''blastic'' bone response. We hypothesize that the expression or production of prostate proteases in ectopic sites (such as bone), contribute to this disease process. The prostate produces several proteases in a highly tissue-specific fashion including several novel proteases identified in our laboratory. Current studies are designed to characterize the substrate specificities of these proteases in order to determine if they may play a role in modulating carcinogenesis (invasion/metastasis) and serve as drug targets. We are also characterizing the function of several proteases through the use of transgenic mice.
4. Determining the role of aging and cellular senescence in prostate carcinogenesis. A new direction involves studies of aging-related changes in the prostate. This work represents a logical extension of studies attempting to understand the dramatic increase in prostate cancer incidence with advanced age. We have shown that senescent prostate stromal cells develop a secretory phenotype with the potential to influence the growth and survival of adjacent epithelium. We are now extending this work to understand aging related influences in other constituents of the tumor microenvironment and determine if androgens influence senescence and aging-related paracrine effects.
5. Normal Variation. This work evolved from large-scale analyses of transcript levels in benign tissues where we found that a substantial number of genes exhibit wide fluctuations in expression levels within genetically-identical individuals. We have shown that variability in gene expression within genetically identical individuals exceeds the genome-encoded variability across different genetic backgrounds, suggesting a mechanism for maintaining variation that could contribute to natural selection. Current work is focused on determining the role of normal variation in dictating cancer phenotypes.
Honors and Awards
2009-2011, Challenge Award, Prostate Cancer Foundation
2001, Scholar Award, Damon Runyon
1998, Career Development Award, NIH
1990, Chief Resident, University of Kansas, Medicine
1989, Resident Excellence, Roy Edwards Jr. Award, University of Kansas
1981, NSF Research Award in Biochemistry, NSF, University of Kansas
1993-1996, Fellowship, University of Washington, Fred Hutchinson Cancer Center, Medical Oncology
1990-1992, Biotechnology Fellowship, National Cancer Institute
1989-1990, Chief Resident, University of Kansas, School of Medicine - KUMC
1986-1989, Intern/Resident, University of Kansas, School of Medicine - KUMC
AR variant ARv567es induces carcinogenesis in a novel transgenic mouse model of prostate cancer.. Neoplasia (New York, N.Y.). 15(9):1009-17.. 2013.
Genomic profiling defines subtypes of prostate cancer with the potential for therapeutic stratification.. Clinical cancer research : an official journal of the American Association for Cancer Research.. 2013.
Urinary TMPRSS2:ERG and PCA3 in an Active Surveillance Cohort: Results from a Baseline Analysis in the Canary Prostate Active Surveillance Study.. Clinical cancer research : an official journal of the American Association for Cancer Research. 19(9):2442-2450.. 2013.
Response of the Insulin-Like Growth Factor (IGF) System to IGF-IR Inhibition and Androgen Deprivation in a Neoadjuvant Prostate Cancer Trial: Effects of Obesity and Androgen Deprivation.. The Journal of clinical endocrinology and metabolism. 98(5):E820-8.. 2013.
PPP2R2C loss promotes castration-resistant prostate cancer growth and is associated with increased prostate cancer-specific mortality.. Molecular cancer research : MCR. 11(6):568-578.. 2013.
Development, validation and application of a stable isotope dilution liquid chromatography electrospray ionization/selected reaction monitoring/mass spectrometry (SID-LC/ESI/SRM/MS) method for quantification of keto-androgens in human serum.. The Journal of steroid biochemistry and molecular biology. 138C:281-289.. 2013.
Leveraging the species barrier to advance cancer therapy.. Nature genetics. 45(7):718-20.. 2013.
Prostate cancer cell phenotypes based on AGR2 and CD10 expression.. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.. 2013.
A model for the design and construction of a resource for the validation of prognostic prostate cancer biomarkers: the Canary Prostate Cancer Tissue Microarray.. Advances in anatomic pathology. 20(1):39-44.. 2013.
A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer.. Cell. 154(5):1074-84.. 2013.
Single cell transcriptomic analysis of prostate cancer cells.. BMC molecular biology. 14:6.. 2013.
Integrative analysis of N-linked human glycoproteomic data sets reveals PTPRF ectodomain as a novel plasma biomarker candidate for prostate cancer.. Journal of proteome research. 11(5):2653-65.. 2012.
Androgen action and metabolism in prostate cancer.. Molecular and cellular endocrinology.. 2012.
Incidence of second malignancies after external beam radiotherapy for clinical stage I testicular seminoma.. BJU international. 109(5):706-12.. 2012.
Impact of Male Hormonal Contraception on Prostate Androgens and Androgen Action in Healthy Men: A Randomized, Controlled Trial.. The Journal of clinical endocrinology and metabolism.. 2012.
Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer.. Nature genetics. 44(6):685-9.. 2012.
Editorial comment.. Urology. 80(1):180-1.. 2012.
Cellular senescence and cancer chemotherapy resistance.. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy. 15(1-2):123-131.. 2012.
Molecular States Underlying Androgen Receptor Activation: A Framework for Therapeutics Targeting Androgen Signaling in Prostate Cancer.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 30(6):644-646.. 2012.