Prostate Specialized Programs of Research Excellence (SPORE)
Three cores support Prostate SPORE research and development projects:
Jill Miller, Administrator
The University of Michigan Comprehensive Cancer Center (UMCCC) Prostate SPORE administrative core is responsible for leadership, guidance and management. The administrative core oversees all aspects and performs numerous duties across the expansive scope of the SPORE to support the translationalgoals of the investigators. The Prostate SPORE Administration Core is guided by the following Specific Aims:
Specific Aim 1: Provide scientific, programmatic and administrative leadership to all aspects of the SPORE. Effective Administration Core leadership is essential to the success of the SPORE. The Administration Core is the central decision-making group designed to encourage research productivity, promote interaction and collaboration and set direction and priorities for the SPORE.
Specific Aim 2: Develop, facilitate and monitor progress of translational aims with project co-leaders. The Clinical Applications Committee, the annual review with the External Advisory Board and Steer Committee and the monthly meetings between project leaders and the SPORE PI all function to keep the SPORE robust and move the translational objectives forward. All of these interactions are facilitated by the Administration Core.
Specific Aim 3: Identify, support, and facilitate scientific collaborations. The Administration Core is charged with creating a culture of collaboration through initiating and implementing successful collaborations. Formal horizontal and vertical collaborations are encouraged to accomplish research progress and move promising SPORE projects to the next step on the translational / clinical development pathway.
Specific Aim 4: Facilitate communication. Thorough communication is crucial to the SPORE's success. The Administration Core is responsible for facilitating communication between investigators and groups within the Prostate SPORE as well as with UM SPOREs, the SPORE network outside UM, NCI and investigators across the spectrum of translational cancer research.
Specific Aim 5: Perform fiscal and data management functions. The Core performs financial management for each project, core and development project. The Core also oversees data management, an essential component of excellent clinical research.
Specific Aim 6: Provide functional and ethical oversight to projects and cores. The Core provides support and oversight to ensure that all investigators have IRB and animal approvals in place to conduct research. The Core coordinates quality assurance between the tissue banks and clinical databases.
The Administration Core (AC) Director, Dr. Kenneth Pienta, guides and facilitates overall direction of the SPORE and oversees the research projects. Dr. Kathleen Cooney, as co-leader, oversees all cores and developmental programs. During this period of transition, Drs. Montie and Palapattu in the role as co-leader oversee the translational components and assures the translational objectives are met. They also direct the Clinical Applications Committee. Jill Miller as Administrative Director coordinates the day-to-day SPORE operations. Dr. Evan Keller assists with core management and facilitates project progress.
Core 2: Biostatistics Core
Statistical expertise through experimental design, data collection, analysis and interpretation.
The goal of the Biostatistics Core is to collaborate with SPORE investigators and other core resource scientists to enhance the quality of the research undertaken in the University of Michigan Prostate SPORE. The Core personnel have been chosen because of their expertise in relevant areas of Biostatistics and Bioinformatics that is specifically required for the SPORE projects to succeed. Support will be provided in all stages of the research, beginning with the formulation of the research question, through the experimental design stage and data collection stage, to data analysis and interpretation, to the writing of reports and dissemination of results. It will be apparent from this proposal that Core personnel have played a significant role in designing the proposed experiments and in planning the data analysis. The exact nature of the collaboration will depend on the specifics of the science and the needs of the project. In addition to direct support of the projects and other cores, senior statisticians will also focus on statistical methodology development related to the needs of prostate cancer research in this SPORE. Thus the Specific Aims of the Core are:
- Assist investigators in the design of clinical and laboratory experiments;
- Assist investigators in the analysis and interpretation of data from clinical and laboratory experiments and in writing of manuscripts relaying prostate cancer SPORE results to the scientific community; and
- Undertake translational biostatistics research to develop methodology and software implementation relevant to prostate cancer.
Recent Representative Collaborative Publications:
Ren G, Baritaki S, Marathe H, Feng J, Park S, Beach S, Bazeley PS, Beshir AB, Fenteany G, Mehra R, Daignault S, Al Mulla F, Keller E, Bonavida B, de la Serna I, Yeung KC. "Polycomb protein EZH2 regulates tumor invasion via the transcriptional repression of the metastasis suppressor RKIP in breast and prostate cancer." Cancer Res. 2012 Jun 15;72(12):3091-104. doi: 10.1158/0008-5472.CAN-11-3546.
Roca H, Craig MJ, Ying C, Varsos ZS, Czarnieski P, Alva AS, Hernandez J, Fuller D, Daignault S, Healy PN, Pienta KJ. "IL-4 induces proliferation in prostate cancer PC3 cells under nutrient-depletion stress through the activation of the JNK-pathway and survivin up-regulation." J Cell Biochem. 2012 May;113(5):1569-80.
Jung Y, Shiozawa Y, Wang J, McGregor N, Dai J, Park SI, Berry JE, Havens AM, Joseph J, Kim JK, Patel L, Carmeliet P, Daignault S, Keller ET, McCauley LK, Pienta KJ, Taichman R. "Prevalence of Prostate Cancer Metastases Following Intravenous Inoculation Provides Clues into the Molecular Basis of Dormancy in the Bone Marrow Microenvironment." Neoplasia 2012 May; 14(5):429-439.
Park SI, Liao J, Berry JE, Li X, Koh AJ, Michalski ME, Eber MR, Soki FN, Sadler D, Sud S, Tisdelle S, Daignault SD, Nemeth JA, Snyder LA, Wronski TJ, Pienta KJ, McCauley LK "Cyclophosphamide creates a receptive microenvironment for prostate cancer skeletal metastasis." Cancer Res. 2012 May 15;72(10):2522-32.
Sottnik JL, Daignault-Newton S, Zhang X, Morrissey C, Hussain MH, Keller ET, Hall CL. Integrin alpha(2)beta(1) (? (2)? (1)) promotes prostate cancer skeletal metastasis. Clin Exp Metastasis. 2013 Jun;30(5):569-78. doi: 10.1007/s10585-012-9561-6.
Hamstra DA, Conlon AS, Daignault S, Dunn RL, Sandler HM, Hembroff AL, Zietman AL, Kaplan I, Ciezki J, Kuban DA, Wei JT, Sanda MG, Michalski JM; PROSTQA Consortium Study Group.. Multi-institutional Prospective Evaluation of Bowel Quality of Life After Prostate External Beam Radiation Therapy Identifies Patient and Treatment Factors Associated With Patient-Reported Outcomes: The PROSTQA Experience. Int J Radiat Oncol Biol Phys. 2013 Jul 1;86(3):546-53. doi: 10.1016/j.ijrobp.2013.01.036.
Brady, J. J., Li, M., Suthram, S., Jiang, H., Wong, W. H., Blau, H. M., (2013) Early role for IL6 signaling in iPS generation revealed by heterokaryon RNA-Seq. Nature Cell Biology Nat Cell Biol. 2013 Oct;15(10):1244-52. doi:10.1038/ncb2835. Epub 2013 Sep 1. PubMed PMID: 23995732. PMCID in process.
Russo N, Wang X, Liu M, Banerjee R, Goto M, Scanlon C, Metwally T, Inglehart R, Tsodikov A, Duffy S, van Tubergen E, Bradford C, Carey T, Wolf G, Chinnaiyan AM, and D'SilvaNJ. (2013) A novel approach to biomarker discovery in head and neck cancer using an autoantibody signature. 2013 Oct 17;32(42):5026-37. Doi: 10.1038/onc.2012.532. Epub 2012 Nov 19. PubMed PMID: 23160375. PMCID in process.
Lee, F., Badalament, R., Hu, C., Bousho, I., Tsodikov, A. (2012) Prostate cancers detected during 5?-reductase inhibitor use are smaller, dedifferentiated, but confined when compared to controls, Journal of Cancer, 3, 122-8, PMCID:PMC3297839
The continued goal of Prostate SPORE Tissue/Informatics Core is to collect biological material with associated clinical information to facilitate translational research. The Tissue Core places patient confidentiality and clinical care as a top priority. As a coordinated effort between pathology, urology, medical oncology, and SPORE researchers, the Core has a developed a unified bioinformatics infrastructure that provides researchers a wide range of annotated samples. To date, detailed information exists on over 4200 radical prostatectomy patients operated on at the Univ. of Michigan between 1994-present. The specific goals of the Tissue Core include:
(1) Protection of patient welfare. The highest priority is given to assure that no research protocol compromises pathology diagnosis or tumor staging.
(2) Acquisition and processing of prostate tissues for research. The Core assures that the widest range of prostate tissues and derived biomolecules (i.e., protein, DNA and RNA) are available from several established and new sources. These include benign prostate tissue from patients without any known prostatic disease (cystoprostatectomy specimens and transplant donor prostates), clinically localized prostate cancer, and metastatic hormone refractory prostate cancer (Rapid Autopsy Program).
(3) Maintenance of clinical and pathology data with links to molecular studies. The Tissue/Informatics Core will continue to expand the detailed clinical and pathology database conforming to the NCI's Common Data Elements (CDE) guidelines, permitting queries between molecular findings and clinically relevant outcomes.
(4) High quality pathologic review of prostate tissues. Expert GU pathologists assure uniform review of prostate tissue samples.
(5) Pathology consultation for the purpose of designing translational research projects. This service focuses on determining the types of tissues and amount required for the successful completion of the projects.
(6) Quality assessment of prostate tissues and clinical data. The Tissue Core staff regularly evaluates frozen and formalin fixed tissues for adequacy.
(7) Development of technology appropriate for pathology based translational research. New technologies such as genome and transcriptome sequencing to identify causative, driving mutations are being introduced. The Tissue Core will continue to be integral to the sample preparation, analysis of biopsy tissue tumor content and long-term storage of all these patient samples. In summary, the Tissue Core will provide SPORE investigators with a wealth of carefully annotated samples for translational research, while maintaining the highest level of clinical care and patient confidentiality.
- Collins CC, Volik SV, Lapuk A, Wang Y, Gout PW, Wu C, Xue H, Cheng H, Haegert A, Bell RH, Brahmbhatt S, Anderson S, Fazli L, Hurtado-Coll A, Rubin MA, Demichelis F, Beltran H, Hirst M, Marra MA, Maher CA, Chinnaiyan AM, Gleave ME, Bertino JR, Lubin M, Wang Y. Next generation sequencing of prostate cancer from a patient identifies a deficiency of methylthioadenine phosphorylase (MTAP), an exploitable tumor target. Mol Cancer Ther 2012, 11(3): 775-783. PMID: 22252602. NIHMSID:352379.
- Beltran H, Rickman DS, Park K, Chae SS, Sboner A, Macdonald TY, Wang Y, Sheikh KL, Terry S, Tagawa ST, Dhir R, Nelson JB, de la Taille A, Allory Y, Gerstein MB, Perner S, Pienta KJ, Chinnaiyan AM, Wang Y, Collins CC, Gleave ME, Demichelis F, Nanus DM, Rubin MA. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov 2011, 1(6):487-495. PMCID:PMC3290518
- Prensner JR, Rubin MA, Wei JT, Chinnaiyan AM. Beyond PSA: The next generation of prostate cancer biomarkers. Sci Trans Med 2012, 4(127):127rv3. PMID: 22461644
- Grasso CS, Wu Y-M, Robinson DR, Cao X, Dhanasakaran SM, Khan AP, Quist MJ, Jing X, Lonigro RJ, Brenner JS, Asangani IA, Ateeq B, Chun SY, Siddiqui J, Sam L, Anstett M, Mehra R, Prensner JR, Palanisamy N, Ryslik GA, Vandin F, Raphael BJ, Kunju LP, Rhodes DR, Pienta KJ, Chinnaiyan AM, Tomlins SA. The mutational landscape of lethal castrate resistant prosate cancer. Nature 2012, 487(7406): 239-243. PMCID:PMC3396711
- Poisson LM, Sreekumar A, Chinnaiyan AM, Ghosh D. Pathway-directed weighted testing procedures for the integrative analysis of gene expression and metabolomics data. Genomics 2012, 99(5):265-274. PMID: 22497771 / PMCID:PMC3525328
- Lapuk AV, Wu C, Wyatt AW, McPherson A, McConeghy BJ, Brahmbhatt S, Mo F, Zoubeidi A, Anderson S, Bell RH, Haegert A, Shukin R, Wang Y, Fazli L, Hurtado-Coll A, Jones EC, Hach F, Hormozdiari F, Hajiresouliha I, Boutros PC, Bristow RG, Zhao Y, Marra MA, Fanjul A, Maher CA, Chinnaiyan AM, Rubin MA, Beltran H, Sahinalp SC, Gleave ME, Volik SV, Collins CC. From sequencing to molecular pathology, and a mechanism driving he neuroendocrine phenotype in prostate cancer. J Pathol 2012, 227(3):286-297. PMID: 22553170
- Kalyana-Sundaram S, Kumar-Sinha C, Shankar S, Robinson DR, Wu Y-M, Cao X, Asagani, IA, Kothari V, Prensner JR, Lonigro RJ, Iyer M, Barrette T, Shanmugam A, Dhanasakaran SM, Palanisamy N, Chinnaiyan AM. Expressed pseudogenes in the transcriptional landscape of human cancers. Cell 2012, 149(7):1622-1634. NIHMSID: 381120
- Kumar-Sinha C, Kalyana-Sundaram S, Chinnaiyan AM. SLC45A3-ELK4 chimera in prostate cancer: Spotlight on cis-splicing. Cancer Discov 2012, 2(7):582-585. PMID: 22787087
- Tomlins SA, Palanisamy N, Siddiqui J, Chinnaiyan AM, Kunju LP. Antibody-based detection of ERG rearrangements in prostate core biopsies, including diagnostically challenging cases: ERG staining in prostate core biopsies. Arch Pathol Lab Med 2012, 136(8):935-946. PMID: 22849743
- Prensner JR, Chinnaiyan AM, Srivastava S. Systematic, evidence-based discovery of biomarkers at the NCI. Clin Exp Metastasis 2012 Aug 7 [Epub ahead of print]. PMID: 22868876
- Kalyana-Sundaram S, Shankar S, DeRoo S, Iyer MK, Palanisamy N, Chinnaiyan AM, Kumar-Sinha C. Gene fusions associated with recurrent amplicons represent a class of passenger aberrations in breast cancer. Neoplasia 2012, 14(8):702-708. PMID: 22952423. PMCID:PMC3431177.
- Young A, Palanisamy N, Siddiqui J, Wood DP, Wei JT, Chinnaiyan AM, Kunju LP, Tomlins SA. Correlation of urine TMPRSS2:ERG and PCA3 to ERG+ and total prostate cancer burden. Am J Clin Pathol 2012, 138(5):685-696. PMID:23086769
- Wang R, Asangani IA, Chakravarthi BV, Ateeq B, Lonigro RJ, Cao Q, Mani RS, Camacho DF, McGregor N, Schumann TE, Jing X, Menawat R, Tomlins SA, Zheng H, Otte AP, Mehra R, Siddiqui J, Dhanasekaran SM, Nyati MK, Pienta KJ, Palanisamy N, Kunju LP, Rubin MA, Chinnaiyan AM, Varambally S. Role of transcriptional corepressor CtBP1 in prostate cancer progression. Neoplasia 2012, 14(10):905-914. PMID:23097625 / PMCID:PMC3479836
- Asangani IA, Ateeq B, Cao Q, Dodson L, Pandhi M, Kunju LP, Mehra R, Lonigro RJ, Siddiqui J, Palanisamy N, Wu Y-M, Cao X, Kim JH, Zhao M, Qin ZS, Iyer MK, Maher CA, Kumar-Sinha C, Varambally S, Chinnaiyan AM. Characterization of the EZH2-MMSET Histone Methyltransferase Regulatory Axis in Cancer. Mol Cell 2012, Oct. 14 [Epub ahead of print]. NIHMSID: 416141