Basic & Translational Research Program
Urologic Research at the University of Chicago
The Section of Urology at the University of Chicago has a strong legacy and rich tradition of basic science and translational research in urologic oncology. Our objectives are to improve the understanding of urologic cancer biology through which improved treatments for cancer can be developed. Our focus is on the patients and how we, as scientists, can improve their lives.
Much akin to our clinical programs, the Basic Urology Laboratory is committed to promoting newer and more innovative approaches to cancer treatment. Our research efforts are directed towards improving the quality of life of patients with cancer by developing, advancing, and subsequently offering state-of-the-art treatments to patients with urologic cancers by developing improved therapies and treatment paradigms that incorporate novel anti-cancer agents and technologies as a compliment to conventional surgical therapy.
The Basic Urology Research Laboratory at the University of Chicago
The Basic Urology Research Laboratory is comprised of several state-of-the art research laboratories totally over 3,000 square feet of space. It is equipped for state of the art molecular and cellular biology studies, development and maintenance of stable cell lines and primary cultures, biochemical and immunochemical studies, and molecular analysis of clinical specimens.
Research is directed by four Principal Investigators. This includes Drs. Carrie Rinker-Schaeffer, , Walter Stadler, and Diane Yamada. Each of these faculty members has his or her own research agenda and area of expertise, all founded on improving our understanding and treatment of metastatic disease.
Metastasis Gene Discovery and Function
Metastatic disease remains the predominant cause of death for cancerpatients. Understanding the cellular and molecular mechanisms that regulate the metastatic process is critical to improved diagnosis and treatment. To this end, my laboratory research focuses on the functional identification of genes that specifically inhibit metastasis (e.g. metastasis-suppressor genes). During the past seven years, my laboratory has led the effort to identify prostate cancer metastasis-suppressor genes on human chromosomes 17 and 12.
Chromosome 17 was chosen for our initial studies because its loss is associated with the progression of prostate cancers (1-3). We have recently identified the mitogen-activated protein kinase kinase 4/stress-activated protein/Erk kinase 1/JNK-activating kinase 1 (MKK4/SEK1/JNKK1 hereafter referred to as MKK4) gene as a metastasis-suppressor gene encoded by chromosome 17 (4). This gene stands as one of five known metastasis suppressor genes (reviewed in 4). In animal models, MKK4 suppresses the growth of cancer cells at the metastatic site, a step known as metastatic colonization. MKK4 expression is decreased in high-grade primary human prostate cancers and metastases, supporting a role for its down-regulation in human disease. We are currently conducting mechanistic studies to discern how MKK4 functions to suppress metastasis.
In 1998, we initiated a second line of research on chromosome 12, since its loss is associated with the development of prostate cancer and bands 12pter-12q13 suppress tumorigenesis in human prostate cancer models (5). Initially, we identified a metastasis-suppressor activity encoded by an ~70 cM portion region and have now narrowed the region to an ~3 megabase (Mb) region on the q terminus. We are using positional cloning approaches to identify the metastasis-suppressor gene encoded by this region. Studies from animal models suggest that the candidate gene suppresses growth of the cells at the metastatic site. In contrast to MKK4, expression of the gene encoded by the ~3 Mb region results in death of the disseminated cells. This observation suggests that it works through a different mechanism than MKK4.
As genes are identified in our prostate cancer model system, we envision translating our work into other cancer cell types, including the most prevalent and deadly cancers (lung, breast, colon). To this end, we have established a wide array of basic science and clinical collaborators. Thus, the basic and translational impact of our work may radiate beyond prostate cancer. For example, we have recently shown that MKK4 can function as a metastasis suppressor gene in ovarian cancers (6) Studying the basic biological and biochemical functions of metastasis-suppressor genes has already provided some surprising insights into fundamental mechanisms regulating metastasis (4). All in all it is an exciting time in metastasis research and we are excited about the potential for our studies to identify new targets for anti-metastatic therapies.
Dietary Polyunsaturated Fatty Acid Studies
The incidence of prostate cancer in Jamaican men is among the highest in the world. The Jamaican diet is high in fatty food, especially omega-6 (?6) PUFAs. Omega-6 PUFAs have been shown to promote prostate cancer development.
We have demonstrated a significant association between increased?6 and decreased ?3 PUFAs and serum PSA and risk of prostate cancer in Jamaican men.
Current studies are being undertaken to evaluate tissue levels of these ?6 and decreased ?3 PUFA in benign and malignant prostate tissue and to identify specific components of the Jamaican diet which may predispose these men to prostate cancer. Ackee fruit, a staple of the Jamaican diet, is rich in Omega-6 polyunsaturated fatty acids (?6 PUFAs) and is one potential factor.
Walter Stadler, M.D.
Medical Oncology Research
Diane Yamada, M.D.
Gynecologic Oncology Research