Three cores support Prostate SPORE research and development projects:
Jill Miller, Administrator
The University of Michigan (UM) Prostate SPORE Administration Core is responsible for leadership, guidance and management. The Administration Core oversees all aspects and performs numerous duties across the expansive scope of the SPORE to support the translational goals of the investigators. The 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.
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 maintain a robust SPORE infrastructure and facilitate the progress of translational objectives.
Specific Aim 3: Identify, support, and facilitate scientific collaborations. The Administration Core is charged with creating a culture of collaboration through fostering and helping to establish and maintain successful collaborations.
Specific Aim 4: Facilitate communication between investigators and groups within the Prostate SPORE as well as with other 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.
Specific Aim 6: Coordinate patient advocacy and 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 will develop and maintain an advocacy portal to prostate cancer patient community.
Arul M. Chinnaiyan, MD, PhD, serves as principal investigator of the Administrative Core and provides overall scientific oversight. Kathleen Cooney, MD, continues to serve as a co-director to oversee all of the developmental programs, patient advocacy efforts, as well as the Biostatistics and Tissue Cores. Ganesh Palapattu, M.D., serves as a co-director responsible for the translational science of the UM Prostate SPORE as Director of the Clinical Applications Committee. Ms. Jill Miller has served as UM Prostate SPORE administrator since 1998 and will continue in this role. This core provides the framework to support the success and mission of the UM Prostate SPORE as a cohesive group of investigators committed to supporting translational research in prostate cancer.
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
- Tomlins SA, Palanisamy N, Brenner JC, Stall JN, Siddiqui J, Thomas DG, Lucas DR, Chinnaiyan AM, Kunju LP. Usefulness of a Monoclonal ERG/FLI1
Antibody for Immunohistochemical Discrimination of Ewing Family Tumors. Am J Clin Pathol 2013 Jun;139(6):771-9. PMID:23690120 / PMCID:PMC3662488.
- Cheng HH, Mitchell PS, Kroh EM, Dowell AE, Chéry L, Siddiqui J, Nelson PS, Vessella RL, Knudsen BS, Chinnaiyan AM, Pienta KJ, Morrissey C, Tewari M. Circulating
microRNA profiling identifies a subset of metastatic prostate cancer patients with evidence of cancer-associated hypoxia. PLoS One 2013 8(7):e69239. PMID:
23935962 / PMCID:PMC3730015.
- Warrick JI, Tomlins SA, Carskadon SL, Young AM, Siddiqui J, Wei JT, Chinnaiyan AM, Kunju LP, Palanisamy N. Evaluation of tissue PCA3 expression in prostate
cancer by RNA in situ hybridization-a correlative study with urine PCA3 and TMPRSS2-ERG. Mod Pathol 2014 Apr;27(4):609-20. PMID: 24072184 / PMCID: PMC3968238.
- Prensner JR, Iyer MK, Sahu A, Asangani IA, Cao Q, Patel L, Vergara IA, Davicioni E, Erho N, Ghadessi M, Jenkins RB, Triche TJ, Malik R, Bedenis R, McGregor N,
Ma T, Chen W, Han S, Jing X, Cao X, Wang X, Chandler B, Yan W, Siddiqui J, Kunju LP, Dhanasekaran SM, Pienta KJ, Feng FY, Chinnaiyan AM.
The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nat Genet 2013 45(11):1392-8. PMID: 24076601 /
- Han S, Brenner JC, Sabolch A, Jackson W, Speers C, Wilder-Romans K, Knudsen KE, Lawrence TS, Chinnaiyan AM, Feng FY. Targeted radiosensitization of ETS fusion-
positive prostate cancer through PARP1 inhibition. Neoplasia 2013 15(10): 1207-1217. PMID: 24204199 / PMCID: PMC3819636.
- Cao Q, Wang X, Zhao M, Yang R, Malik R, Qiao Y, Poliakov A, Yocum AK, Li Y, Chen W, Cao X, Jiang X, Dahiya A, Harris C, Feng FY, Kalantry S, Qin ZS,
Dhanasekaran SM, Chinnaiyan AM. The central role of EED in the orchestration of polycomb group complexes. Nat Commun. 2014 Jan 24;5:3127. PMID: 24457600 /
- Prensner JR, Chen W, Iyer MK, Cao Q, Ma T, Han S, Sahu A, Malik R, Wilder-Romans K, Navone N, Logothetis CJ, Araujo JC, Pisters LL, Tewari AK, Canman CE,
Knudsen KE, Kitabayashi N, Rubin MA, Demichelis F, Lawrence TS, Chinnaiyan AM, Feng FY. PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous
recombination in cancer. Cancer Res. 2014 Mar 15;74(6):1651-60. PMID: 24473064 / PMCID: PMC4009928.
- Asangani IA, Dommeti VL, Wang X, Malik R, Cieslik M, Yang R, Escara-Wilke J, Wilder-Romans K, Dhanireddy S, Engelke C, Iyer MK, Jing X, Wu YM, Cao X, Qin ZS,
Wang S, Feng FY, Chinnaiyan AM. Therapeutic Targeting of BET Bromodomain Proteins in Castration-Resistant Prostate Cancer. Nature. 2014 2014;510(7504):278-82.
PMID: 24759320 / PMCID:PMC4075966.
- Smith SC, Palanisamy N, Zuhlke KA, Johnson AM, Siddiqui J, Chinnaiyan AM, Kunju LP, Cooney KA, Tomlins SA. HOXB13 G84E-related Familial Prostate Cancers: A Clinical, Histologic, and Molecular Survey. Am J Surg Pathol. 2014 May: 38(5): 615-626. PMID: 24722062 / PMCID: 3988475.
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.