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
Analytic validation of a clinical-grade PTEN immunohistochemistry assay in prostate cancer by comparison with PTEN FISH.. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.. 2016.
ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer.. Clinical cancer research : an official journal of the American Association for Cancer Research.. 2016.
Identification of Combinatorial Genomic Abnormalities Associated with Prostate Cancer Early Recurrence.. The Journal of molecular diagnostics : JMD. 18(2):215-224.. 2016.
Expression of STAT3 in Prostate Cancer Metastases.. European urology.. 2016.
Characterizing the molecular features of ERG-positive tumors in primary and castration resistant prostate cancer.. The Prostate. 76(9):810-22.. 2016.
Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.. The New England journal of medicine.. 2016.
Docetaxel-related toxicity in metastatic hormone-sensitive and metastatic castration-resistant prostate cancer.. Medical oncology (Northwood, London, England). 33(7):77.. 2016.
Combined MYC Activation and Pten Loss Are Sufficient to Create Genomic Instability and Lethal Metastatic Prostate Cancer.. Cancer research. 76(2):283-92.. 2016.
Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations.. Molecular cancer research : MCR.. 2016.
Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology.. 2016.
Outcomes of active surveillance for the management of clinically localized prostate cancer in the prospective, multi-institutional Canary PASS cohort.. The Journal of urology. 195(2):313–320.. 2016.
Spheroid culture of LuCaP 136 patient-derived xenograft enables versatile preclinical models of prostate cancer.. Clinical & experimental metastasis. 33(4):325-37.. 2016.
High-Resolution Genomic Profiling of Disseminated Tumor Cells in Prostate Cancer.. The Journal of molecular diagnostics : JMD.. 2015.
Integrative clinical genomics of advanced prostate cancer.. Cell. 161(5):1215-28.. 2015.
ERG Activates the YAP1 Transcriptional Program and Induces the Development of Age-Related Prostate Tumors.. Cancer cell. 27(6):797-808.. 2015.
The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer.. Chemico-biological interactions. 234:332-8.. 2015.
SRRM4 Expression and the Loss of REST Activity May Promote the Emergence of the Neuroendocrine Phenotype in Castration-Resistant Prostate Cancer.. Clinical cancer research : an official journal of the American Association for Cancer Research.. 2015.