Division of Laboratory Research in the Department of Urology
The Laboratory Division within the Department of Urology comprises 10 faculty who spend all or most of their time directing laboratory research. Participating faculty are largely senior, tenured investigators with appointments at the full or associate professor levels. All of these faculty direct successful, well-funded, productive research programs that provide a rich environment for the training of both pre-doctoral students, post-doctoral fellows, urology residents and medical students.
The general areas of research focus provided by these faculty include: 1) The application of genomic, proteomic, and bioinformatic approaches to understanding urologic disease; 2) Identification of the biological/physiological mechanisms underlying pelvic floor dysfunction and urinary incontinence, or consequent to bladder outlet obstruction; 3) Elucidation of the biology of cancer metastasis, including mechanisms that disrupt cell-cell adhesion or that guide the establishment of distant metastases; 4) Defining the mechanisms that guide development of the genitourinary system; 5) Identifying and manipulating normal and malignant stem cells in the bladder and prostate; 6) Developing new therapeutics, surgical instrumentation and imaging modalities useful in the management of urologic disease; 7) Examination of the role of hormone and hormone receptor dysfunction in the development of urologic disease, and 8) Identification of genetic and other risk factors for the development of urologic disease. Together, these areas of research provide a comprehensive mechanism to provide optimal training experiences in diverse aspects of normal or abnormal genitourinary development and function, and urologic disease.
The Macoska Laboratory
Jill Macoska, Ph.D. (Division Head)
Dr. Jill Macoska is the Chief of the Laboratory Research Division and directs the Urology Research Training Program as well as the Cancer Center Affymetrix and cDNA Microarray Core. The Macoska Laboratory focuses on aging-associated changes in the prostate tissue microenvironment that promote benign and malignant cellular proliferation. The laboratory recently published papers in the Journal of Biological Chemistry, The Prostate, and Neoplasia, detailing how particular chemokines secreted through paracrine and/or autocrine mechanisms consequent to aging promote benign (BPH) and malignant (PCa) proliferation in the prostate. This work may lead to diagnostic markers and new therapeutic targets to delay or abrogate the development of BPH and/or PCa, and recently received substantial funding from the National Institutes of Health (NIH). Dr. Sathish Kasina, a Macoska laboratory post-doctoral fellow, recently received a two-year award from the American Urological Association Foundation to continue aspects of this work. A project accomplished in collaboration with Dr. Cheryl Lee showed that the anti-Bcl2 compound, gossypol, promotes apoptosis and synergizes with other commonly used chemotherapeutic agents (carboplatin, gemcitabine, or taxol) to promote apoptosis of bladder cancer cells. cultures.
The Day Laboratory
Several recent publications from the Day laboratory report the important role(s) of particular pro-teins, generally termed disintegrins, on pros-tate cancer development and metastasis. Another area of research in the Day laboratory concerns the role epigenetic changes, particularly those affecting DNA methylation, in the development of prostate tumors. Dr. Day has also successfully trained several graduate students who now pursue independ-ent research in prostatic disease.
The Keller Laboratory
Dr. Evan Keller directs a multi-million dollar NIH-funded program project award on prostate cancer metastasis to bone. The Keller Laboratory investi-gates mechanisms that contribute to bone metastasis. A recently accepted publication in Prostate explores the expres-sion of DKK-1 in prostate cancers on tissue microarrays. Another publication accepted to the same journal highlights how a metastasis suppressor gene identified in the Keller laboratory, RKIP, promotes radiation-induced apoptosis. Dr. Keller also has an active interest in the contribution of aging to the development of genitourinary disease, and employs several animal models (including zebrafish!) to pursue these studies.
The Roberts Laboratory
The Roberts Histotripsy Lab continues to focus on developing histotrispy, based on the phenome-non of cavitational ultrasound, for noninvasive debulking of the prostate as treat-ment for BPH and prostate cancer. Tim Hall, PhD, recently joined the laboratory as a postdoctoral fellow after pursuing dissertation research with Dr. Roberts and collaborators in the School of Engineering. Dr. Roberts recently received significant funding from the NIH to continue and expand this exciting research program.
The Park Laboratory
The Park Laboratory continues to focus on the pathophysiology of urinary tract ob-struction, a prevalent clinical problem in pediatric urology. The laboratory continues to examine the bio-logical role and mechanism of bladder smooth muscle cell response to obstruction and mechanical stretch using both in vivo and in vitro models. A nice collaboration with Victor Thannickal of Internal Medicine (Pulmonary) permits examination of the role of anti-oxidants in the obstruction-induced changes in the blad-der, while collaborations with Steve Feinberg and Monica Liebert are focused on the development of surgical tissue replacement alternatives using both urothelium and oral keratinocytes. Another area of interest is the potential role of urinary E-cadherin cleavage in the obstructive uropathy in both diagnosis and novel mechanism of tissue alterations. And the laboratory is excited over Dr. Park’s recent induction as the first Chang professor.
The Chinnaiyan Laboratory
The Chinnaiyan Laboratory celebrates the significant achievement of Howard Hughes Foundation sponsorship, placing it among only a few other such research laboratories nationwide. Recent publications have shown that fusions between the androgen-regulated TMPRSS gene and ETS- family genes are commonly identified in prostate tumors. These findings have generated intense interest in the scientific community and have spawned multiple studies in other laboratories examining the role(s) of TMPRSS/ETS family gene fusions in tumorigenesis.
The Pienta Laboratory
Dr. Kenneth Pienta directs the multi-million dollar NIH-funded Prostate SPORE, which supports several translational projects focused on the development of interventions against prostate cancer. The Pienta Laboratory is investigating tumor-interactive chemokines and the associated insights into the molecular and cellular basis of tumor-microenvironment interac-tions. These insights have stimulated the development of targeted cancer therapeu-tics -most recently the identification of an antibody (anti-monocyte chemoattractant protein -1) as a novel therapeutic agent for prostate cancer that is now in Phase I trials. Another focus of the laboratory is on the role of autophagy in the development and progression of prostate cancer.
The Cooney Laboratory
Dr. Kathleen Cooney is the Principal Investigator of the University of Michigan Prostate Cancer Genetics Project which is a large (over 3,000 participants) family-based study of inherited prostate cancer susceptibility. Recent work from her lab has focused on genes on chromosome 17q, including the BRCA1 gene, and potential molecular contributions to prostate cancer. The Cooney lab, in collaboration with Dr Julie Douglas from Human Genetics, has also created a novel study of brothers with and with-out prostate cancer that has led to interesting genetic and behavioral observations.
The Smith Laboratory
The Gary Smith Laboratory continues to make groundbreaking progress towards successful oocyte cryo-preservation and nano-fluidics platforms for successful sperm sorting. In collaboration with Dr. Shu Takayama, the Smith laboratory is extending the use of nano-fluidics to study sub-cellular signaling, in vitro fertilization on a chip, the effects of physiological and pathological fluid mechanical stresses on airway epithelial cells, microfluidic flow cytometry, cancer cell culture, and microfluidic embryonic stem cell cultures.