DOD, NIH Funding Allows for Innovative Approaches to Prostate Cancer Research

From left: immunology grad student Edwin Reyes chats with prostate cancer researchers Don Vander Griend, PhD; and Russell Szmulewitz, MD, in their lab at the University of Chicago Surgery Brain Research Institute (SBRI) lab Monday, Feb. 24, 2014.    (Robert Kozloff/The University of Chicago)

From left: immunology grad student Edwin Reyes chats with prostate cancer researchers Don Vander Griend, PhD; and Russell Szmulewitz, MD, in their lab at the University of Chicago Surgery Brain Research Institute (SBRI) lab Monday, Feb. 24, 2014. (Robert Kozloff/The University of Chicago)

By Donald Vander Griend, PhD

I’ve dedicated the last 10 years of my lab research, including the past five at the University of Chicago, to targeting various aspects of prostate cancer, including the role of stem cells and development in cancer initiation and progression, which is the leading cause of cancer death in men.

Now with generous funding from the National Institutes of Health and, most recently, the Department of Defense, my lab can continue its creative and innovative approach to prostate cancer research.

One project that’s in its infancy is based upon our comparative study of the seminal vesicles and prostate gland. The seminal vesicles and the prostate are functionally and developmentally similar, yet the seminal vesicles rarely become diseased while the prostate is highly prone to enlargement and cancer.

Our work utilized a global expression analyses approach to compare prostate and seminal vesicle, in order to highlight key differences between these organs and identify new gene targets that we can modulate for prevention and therapy.

We are looking at all the genes expressed between the two reproductive organs to elucidate what could be determining these innate qualities.

My theory is that the prostate becomes diseased because of how it develops and, likewise, the seminal vesicles do not become diseased because of how they develop at the cellular level.

The work of Vander Griend and Russell Szmulewitz, MD, assistant professor of medicine, was profiled in the most recent edition of Medicine on the Midway.

The DOD has made the future of the project possible by awarding me a young investigator grant of $75,000 over three years to study one pathway involved in organ patterning and control of gene expression: the Hox gene family of transcription factors. Interestingly, members of this pathway have been found to be mutated in a number of cancers, but it’s unclear how they function in both normal and cancer cells.

Another research project, which my lab has spent the better part of three years investigating, deals with an embryonic stem cell regulator, named Sox2. This spring the NIH awarded me an R01 research project grant of $1.5 million over five years to further the study of Sox2

Several genes are involved in embryonic stem cell identity and function to dictate what the cells will become in the body. Of a small group of stem cell genes that control embryonic stem cells, we discovered the Sox2 gene has a particularly important role in how the prostate forms and develops, and also has a role in prostate cancer initiation and progression.

For example, we have found that expression of Sox2 enables a prostate cancer cell to become resistant to hormone therapy. Our goal is to understand how Sox2 works in order to identify new drug targets to help our fight against prostate cancer.

Studying the prostate has driven me to keep asking the important questions: Why do so many men develop prostate cancer? When it forms, why is it aggressive in some men and not in others? Can we somehow discern indolent tumors from aggressive ones by using stem cell gene expression? Sox2 regulates other genes; what is it regulating in the prostate? Does Sox2 have unique and novel functions in the prostate that we can exploit for therapeutic benefit?

For example, if we can target Sox2 in prostate cancer cells, we could block the ability of cells to acquire resistance to hormone therapy and thus increase the efficacy of hormone therapy.

Cancer research is crucial to identifying key causes of disease development. Once we know more about the mechanisms of cancer development in the prostate, we can ultimately work to prevent prostate cancer from developing in the first place and taking its toll on the lives of men worldwide.

Donald Vander Griend, PhD, is an Assistant Professor in the Department of Surgery’s Section of Urology, and Director of Urological Stem Cell Research at the University of Chicago

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