Research

Research Description

Our laboratory focuses on understanding the molecular mechanisms that drive prostate cancer initiation, progression and recurrence with the ultimate goal of developing therapeutic strategies that target these processes. Our approach includes the genomic analysis of human tumors, cell culture studies and the use of genetically engineered mouse models. We have a strong interest in genomics and gene regulation, oncogenic kinases as potential molecular therapeutic targets and the use of in vivo lineage tracing to define the fates of specific cell populations in tumorigenesis.

Specific projects include:

The role of the oncogenic serine/threonine kinase PIM1 in prostate cancer - PIM1 is coexpressed with c-MYC and dramatically enhances c-MYC-driven prostate tumorigenesis in a kinase-dependent manner. Notably, PIM1 is induced in tumors by hypoxia, radiation and treatment with docetaxel, a common but largely ineffective option for patients with advanced castration-resistant prostate cancer. PIM1 induction by hypoxia/radiation/docetaxel promotes prostate cancer cell survival and therapeutic resistance. Therefore, PIM1 may represent a valuable therapeutic target in prostate cancer. We are using new mouse models of prostate cancer for testing the efficacy of novel PIM1 kinase inhibitors in treating prostate cancer and reversing therapeutic resistance. We have also identified novel candidate PIM1-interacting proteins in prostate epithelial cells. Among the proteins identified are a MYC transcriptional cofactor and a prostate stem cell marker/regulator. We are investigating how PIM1 promotes prostate tumorigenesis by phosphorylating these substrates involved in regulating MYC transcriptional activity and stem cell function.

Cellular and molecular determinants of prostate cancer recurrence - A major clinical problem in prostate cancer is that of tumor recurrence following initial apparently successful therapy. Recurrent tumors may arise from a small number of "cancer stem-like cells" that survive the initial therapeutic intervention and have the capacity to regenerate the tumor. We are using lineage tracing to examine the competence of specific prostate epithelial cell types to regenerate tumors following therapy in mice.

Targeting lethal prostate cancer – We are using our mouse model of lethal prostate cancer based on alterations in Myc, Pten and Tp53 to develop new targeted therapies. One current project involves the targeting of EphB4 receptor tyrosine kinase using an antagonist as a therapeutic strategy.

For more information, see Dr. Abdulkadir's faculty profile.

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Research Description

Polycomb group (PcG) proteins help to regulate gene expression in normal cells. Research shows that this family of proteins is associated with prostate cancer initiation, disease progression and metastasis. The Cao lab is particularly interested EZH2, a specific protein within the PcG family. The lab’s previous research identified EZH2 as a biomarker for aggressive breast cancer as well as characterized EZH2 as an oncogene which represses multiple tumor suppressors in breast and prostate cancer.  This work has demonstrated EZH2 as a valuable therapeutic target in cancer, and several pharmaceutical companies are developing EZH2- or BMI1- specific inhibitors for cancer therapy.

The Cao lab is also working to identify miRNAs targeting Polycomb group proteins and other oncogenes in cancer. Using bioinformatics, they identified the miRNAs, which target EZH2, EED, BMI1, and RING1B, in cancer. This research suggested that genomic loss of miR-101 leads to the overexpression of EZH2 in cancer. In addition, PRC2 complex represses a set of miRNAs, including miR-181a,b, miR-200b,c and miR-203, which, in turn, repress BMI1 and RING1B. In advanced cancer, loss or epigenetic repression of these miRNAs leads to upregulation of PRC1 proteins BMI1 and RING1B, epithelial-mesenchymal transition regulators ZEB1 and ZEB2, and histone methyltransferase MMSET. This study suggests these miRNAs may serves as therapeutic targets for advanced cancer patients.

Publications

Yi Y, Li Y, Li C, Wu L, Zhao D, Li F, Fazli L, Wang R, Wang L, Dong X, Zhao W, Chen K, Cao Q. Methylation-dependent and -independent roles of EZH2 synergize in CDCA8 activation in prostate cancer. Oncogene. 2022 Mar;41(11):1610-1621.

Yi Y, Li Y, Meng Q, Li Q, Li F, Lu B, Shen J, Fazli L, Zhao D, Li C, Jiang W, Wang R, Liu Q, Szczepanski A, Li Q, Qin W, Weiner AB, Lotan TL, Ji Z, Kalantry S, Wang L, Schaeffer EM, Niu H, Dong X, Zhao W, Chen K, Cao Q.  A PRC2-independent function for EZH2 in regulating rRNA 2'-O methylation and IRES-dependent translation. Nat Cell Biol. 2021 Apr; 23(4): 341-354.

Zhu S, Zhao D, Li C, Li Q, Jiang W, Liu Q, Wang R, Fazli L, Li Y, Zhang L, Yi Y, Meng Q, Wang W, Wang G, Zhang M, Zu X, Zhao W, Deng T, Yu J, Dong X, Chen K, Cao Q. BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. Oncogene. 2020 Jan.

Liu, Q., Wang, G., Li, Q., Jiang, W., Kim, J. S., Wang, R., Zhu, S., Wang, X., Yan, L., Yi, Y., Zhang, L., Meng, Q., Li, C., Zhao, D., Qiao, Y., Li, Y., Gursel, D. B., Chinnaiyan, A. M., Chen, K. & Cao, Q. Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer.  Int J Cancer. 2019 Jan 10.

Zhu, S., Zhao, D., Yan, L., Jiang, W., Kim, J. S., Gu, B., Liu, Q., Wang, R., Xia, B., Zhao, J. C., Song, G., Mi, W., Wang, R. F., Shi, X., Lam, H. M., Dong, X., Yu, J., Chen, K. & Cao, Q. BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1. Nat Commun. 2018 Feb 5;9(1):500.

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Research Description

For more than 25 years, Dr. Catalona’s research has contributed significantly to the areas of early detection, treatment and cures for prostate cancer. His research aims to provide genetic insights into the causes of prostate cancer. He has discovered several new regions of the human genome statistically associated with prostate cancer. His current research is studying genetic variants associated with aggressive disease in men enrolled in active surveillance protocols from around the country.

Publications

Gaylis FD, Cooperberg MR, Chen RC, Malin J, Loeb S, Witte JS, Carroll PR, Cohen ES, Dato PE, Lin DW, Zheng Y, Seibert TM, Setzler C, Wilt W, Gomez SL, Chan JML, Catalona WJ. Defining Quality Metrics for Active Surveillance: The Michigan Urological Surgery Improvement Collaborative Experience. Letter. J Urol. 2021 Jul; 206(1): 171-172.

Lopes Vendrami C, McCarthy RJ, Chatterjee A, Casalino D, Schaeffer EM, Catalona WJ, Miller FH. The Utility of Prostate Specific Antigen Density, Prostate Health Index and Prostate Health Index Density in Predicting Positive Prostate Biopsy Outcome is Dependent on the Prostate Biopsy Methods. Urology. July 2019.

Giri VN, Knudsen KE, Kelly WK, Abida W, Andriole GL, Bangma CH, Bekelman JE, Benson MC, Blanco A, Burnett A, Catalona WJ, et al.  Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017. Journal of Clinical Oncology. February 2018.

Loeb S, Shin SS, Broyles DL, Wei JT, Sanda, M, Klee G, Partin AW, Sokoll L, Chan DW, Bangma CH, van Schaik RHN, Slawin KM, Marks LS, Catalona WJ. Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer. BJU International. July 2017.

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Research Description

Dr. Kundu has successfully conducted and published on prospective evaluations of patients with urologic cancers and found that the impact of cancer treatment goes beyond physical limitations associated with treatment. The application of these findings have resulted in interventions to improve the physician-patient relationship, patient education and the health care environment overall.

Dr. Kundu is currently performing genetic studies to distinguish mechanisms that drive prostate cancer development in men with inflammatory bowel disease (IBD). His research aims to identify the specific factors underlying prostate cancer and IBD to uncover the mechanisms that may drive carcinogenesis in this inflammatory condition. In this podcast, Dr. Kundu explains approach to screening, diagnosing and treating this unique combination of conditions.

Publications

Hudnall MT, Desai AS, Tsai KP, Weiner AB, Vo AX, Ko OS, Jan S, Schaeffer EM, Kundu SD. It's all in the name: Does nomenclature for indolent prostate cancer impact management and anxiety? Cancer. 2021 Sep; 127(18): 3354-3360.

Goldberg IP, Chang SL, Kundu SD, Chung BI, Singer EA. Impact of inflammatory bowel disease on radical prostatectomy outcomes and costs of care. Prostate Int. 2021 Jun; 9(2): 66-71.

Desai AS, Sagar V, Lysy B, Weiner AB, Ko OS, Driscoll C, Rodriguez Y, Vatapalli R, Unno K, Han H, Cohen JE, Vo AX, Pham M, Shin M, Jain-Poster K, Ross J, Morency EG, Meyers TJ, Witte JS, Wu J, Abdulkadir SA, Kundu SD. Inflammatory bowel disease induces inflammatory and pre-neoplastic changes in the prostate. Prostate Cancer Prostatic Dis. 2021 May 25.

Meyers TJ, Weiner AB, Graff RE, Desai AS, Cooley LF, Catalona WJ, Hanauer SB, Wu JD, Schaeffer EM, Abdulkadir SA, Kundu SD, Witte JS. Association between inflammatory bowel disease and prostate cancer: A large-scale, prospective, population-based study. International Journal of Cancer. 2020 Jan.

Burns JA, Weiner AB, Catalona WJ, Li EV, Schaeffer EM, Hanauer SB, Strong S, Burns J, Hussain MHA, Kundu SD. Inflammatory Bowel Disease and the Risk of Prostate Cancer. European Urology. 2019 May.

Weiner AB, Tsai KP, Keeter MK, Victorson DE, Schaeffer EM, Catalona WJ, Kundu SD. The Influence of Decision Aids on Prostate Cancer Screening Preferences: A Randomized Survey Study. Journal of Urology. 2018 Nov.

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Research Description

The Meeks lab is investigating the epigenetics and genetic mutations associated with cancer biology. Specifically, he is studying how chromatin remodeling genes play a role in bladder cancer. In addition, he is investigating the “driver mutations found in bladder cancer. In the future, he hopes to develop novel systemic and intravesical therapies to improve survival of patients with bladder cancer.

In the United States, there are an estimated 72,570 new cases of bladder cancer each year. Dr. Meeks is conducting innovative research to increase our understanding of the biology of bladder cancer and to identify new therapies and technologies for bladder cancer in order to improve quality of life for our patients. In this podcast, Joshua Meeks, MD, PhD, shares how his team of scientists are involved in three active trials focused on genetic and epigenetic changes in bladder cancer, as well as immuno-oncology in bladder cancer.

Dr. Meeks is investigating the gender disparities in bladder cancer by dissecting the tumor and immune mechanisms of resistance to chemotherapy and immunotherapy. This research may translate into novel pathways and potential therapeutic targets to improve outcomes and reduce gender disparities in bladder cancer. In this video, Meeks shares details about his work.

Publications

Refer to PubMed for a full list of publications.

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Research Description

Dr. Murphy's group researches the causes and modifiable risk factors associated with prostate cancer. Their work focuses on the biological and environmental factors including serum vitamin D deficiency and prostate cancer risk. Additionally, they examine the impact of HIV infection on prostate cancer incidence and treatment. Their research also explores factors affecting prostate cancer screening accessibility, using community-based methods to improve early detection and care.

Publications

• Meza J, Babajide R, Saoud R, Sweis J, Abelleira J, Helenowski I, Jovanovic B, Eggener S, Miller FH, Horowitz JM, Casalino DD, Murphy AB. Assessing the accuracy of multiparametric MRI to predict clinically significant prostate cancer in biopsy naïve men across racial/ethnic groups. BMC Urol. 2022 Jul 18;22(1):107. 
• Murphy AB, Abern MR, Liu L, Wang H, Hollowell CMP, Sharifi R, Vidal P, Kajdacsy-Balla A, Sekosan M, Ferrer K, Wu S, Gallegos M, King-Lee P, Sharp LK, Ferrans CE, Gann PH. Impact of a Genomic Test on Treatment Decision in a Predominantly African American Population With Favorable-Risk Prostate Cancer: A Randomized Trial. J Clin Oncol. 2021 May 20;39(15):1660-1670. 

• Murphy AB, Carbunaru S, Nettey OS, Gornbein C, Macias V, Sharifi R, Kittles RA, Yang X, Kajdacsy-Balla A, Gann P, Dixon MA. A 17-Gene Panel Genomic Prostate Score Has Similar Predictive Accuracy for Adverse Pathology at Radical Prostatectomy in African American and European American Men. Urology. 2020 Jan.

• Carbunaru S, Nettey OS, Gogana P, Helenowski IB, Jovanovic B, Ruden M, Hollowell CMP, Sharifi R, Kittles RA, Schaeffer E, Gann P, Murphy AB. A comparative effectiveness analysis of the PBCG vs. PCPT risks calculators in a multi-ethnic cohort. BMC Urology. November 2019.

• Murphy AB, Nyame YA, Batai K, Kalu R, Khan A, Gogana P, Dixon M, Macias V, Kajdacsy-Balla A, Hollowell CMP, Catalona WJ, Kittles R. Does prostate volume correlate with Vitamin D deficiency among men undergoing prostate biopsy? Prostate Cancer and Prostatic Disease. October 2017.

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Research Description

Ashley Ross MD, PhD, is an active clinician and surgeon scientist with expertise in prostate cancer, genomics, immunology, targeted therapies and clinical trials.  His research is focused on improving the diagnosis and treatment of clinically significant prostate cancer, including the development of prognostic and predictive biomarkers in prostate cancer and the initiation of clinical trials. 

Dr. Ross is an expert in the design and conduct of early phase clinical trials. He has conducted clinical trials utilizing novel therapeutic approaches to lethal prostate cancer including use of immunotherapies, targeted oncogenic pathway inhibitors, and the use of more potent androgen deprivation.

In this video, Dr. Ross describes the biomarker-driven clinical trials that are showing promise for prostate cancer and other future research directions in the field.

In this podcast, Dr. Ashley Evan Ross, MD, PhD, and Brittany Szymaniak, PhD, CGC, an expert researcher in Cancer Genetics discuss Germline genetic testing and prostate cancer.

Dr. Ross and his lab team have developed nomogram MRI Risk Calculator to assess the likelihood of prostate cancer and clinically significant disease based on a combination of clinical and imaging characteristics. The nMRIsk calculator calculates the probability of a patient having clinically significant prostate cancer, which based on age, race, highest PIRADS score on prostate MRI, prostate volume, and serum markers based on their availability.

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For contact information, see the faculty profile of Ashley E Ross, MD, PhD.

Research Description

Dr. Wu's goal to better understand prostate cancer and cancer in general and to find a better treatment for the untreatable terminal diseases, her current research focuses on the following aspects:  

1. Understanding the universal mechanisms of cancer immune evasion and development of novel cancer immunotherapy with specific focus on the NKG2D signaling pathways; 
2. Understanding why immunotherapy is not effective in prostate cancer and how to make it work with understanding underlying mechanisms of resistance; 
3. Discovering biomarkers to distinguish progressive vs. indolent prostate cancer to direct clinical decision making on treatment options; 
4. Understanding mechanism underlying immunotherapy (specifically, immune checkpoint inhibitor-therapy) induced toxicity and developing mechanism-direct personalized treatment for cancer patients to alleviate toxicity and to improve clinical outcomes.  

For more information please view the faculty profile of Jennifer Wu, PhD.

Publications

Dhar P, Basher F, Ji Z, Huang L, Qin S, Wainwright DA, Robinson J, Hagler S, Zhou J, MacKay S, Wu JD. Tumor-derived NKG2D ligand sMIC reprograms NK cells to an inflammatory phenotype through CBM signalosome activation. Commun Biol. 2021 Jul; 4(1): 905-.

Basher F, Dhar P, Wang X, Wainwright DA, Zhang B, Sosman J, Ji Z, Wu JD. Antibody targeting tumor-derived soluble NKG2D ligand sMIC reprograms NK cell homeostatic survival and function and enhances melanoma response to PDL1 blockade therapy. J Hematol Oncol. June 2020.

Zhang J, Larrocha PS, Zhang B, Wainwright D, Dhar P, Wu JD. Antibody targeting tumor-derived soluble NKG2D ligand sMIC provides dual co-stimulation of CD8 T cells and enables sMIC + tumors respond to PD1/PD-L1 blockade therapy. J Immunother Cancer.  August 2019.

View a full list of publications by Jennifer Wu at PubMed.

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Research Description

The Yang laboratory is interested in the integrative analysis of large-scale, multi-dimensional genomic data to understand the initiation and progression of diseases. The research projects involve in the development of highly accurate and sensitive computational methods for analyzing large-scale genomic data, especially in the area of detecting and analyzing genetic variations and somatic mutations using next generation sequencing data. Current work in the lab is to explore the functional consequences of somatic alterations in cancer patients, to identify driver alterations, and to understand the genetic mechanisms of cancer progression and drug resistance by integrating multi-dimensional data from large-scale cancer studies such as The Cancer Genome Atlas (TCGA). Example projects span from technique-driven research that aims developing algorithms for a wide range of applications to hypothesis-driven investigation of specific biological problems where the main goal is the discovery and advancement of biological knowledge.

For more information, visit Dr. Yang's lab website.

Publications

See Dr. Yang's publications on PubMed.

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The Yu lab focuses on cancer genomics and translational cancer research.  At the current stage, our primary research interest is to understand aberrant transcriptional and epigenetic regulation of prostate cancer and to translate such knowledge into clinical applications.  We utilize high-throughput genomic techniques in combination with bioinformatics/statistical analysis to generate testable hypothesis.   We then test these hypotheses using traditional molecular and/or cellular biological approaches and examine the functional relevance of these innovative regulatory pathways in vitro and in vivo using cell lines and mouse models.  Based on the genetic and epigenetic underpinning of the disease, we pursue translational research to develop new biomarkers and novel therapeutics strategies for advanced prostate cancer.

Select Publications

Kim J, Lee Y, Lu X, Song B, Fong KW, Cao Q, Licht JD, Zhao JC, Yu J.  Polycomb- and Methylation-Independent Roles of EZH2 as a Transcription Activator.  Cell Reports. 2018 Dec 04. PMID: 30517868

Fong KW, Zhao JC, Song B, Zheng B, Yu J.  TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression.  Nat Commun. 2018 Nov 27. PMID: 30479348

Fong KW, Zhao JC, Kim J, Li S, Yang YA, Song B, Rittie L, Hu M, Yang X, Perbal B, Yu J. Polycomb-mediated disruption of an androgen receptor feedback loop drives castration-resistant prostate cancer.  CancerRes. 2016 Nov 4. PMID: 27815387

View all lab publications via PubMed.

For more information, visit the faculty profile page of Jindan Yu, MD, PhD.

Contact Us

Contact Dr. Yu at 312-503-2980 or the Yu Lab at 312-503-3041.

Lab Staff

Research Faculty

Jonathan Zhao, MD, MS, Shivani Agarwal, PhD

Postdoctoral Fellows

Ahmad Hasan Othman, PhD, Jawad Akhtar, PhD, Hongshun Shi, MD, PhD, Najma Shaheen, PhD, Wanqing Xie, PhD, Xiaodong Lu, PhD

Graduate Students

Galina Gritsina, Lourdes Brea, Qi Chu, Viriya Keo

Undergraduate Students

Edward Seo, Irina Cheng