Prostate Cancer Center of Excellence
About Us
Our Mission
The mission of the Prostate Cancer Center of Excellence (PC-COE) is to provide superior clinical care and conduct multidisciplinary research on prostate cancer to improve outcomes in both quantity and quality of life for men affected by prostate cancer and in doing so, benefit both prostate cancer patients and their families.
Our Goals
The Prostate Cancer Center of Excellence:
1. Increases outstanding collaborative multi-disciplinary research.
2. Promotes excellence in providing superior clinical care for patients.
3. Increases the number of clinical trials offered to patients.
4. Creates a distinct training program for the next generation of scientists.
5. Strengthens fundraising for prostate cancer research.
6. Promotes community outreach & research to decrease racial disparities.
7. Increases name recognition of the care and research at MCW.
Meet Our Team
Center Leadership
The Prostate Cancer Center of Excellence is directed by nationally renowned and respected prostate cancer researchers and clinicians who work together to provide excellent clinical care, conduct multidisciplinary research and train the next generation of prostate cancer researchers.
Marja Nevalainen, MD, PhD, Director of the Prostate Cancer Center of Excellence
Dr. Nevalainen is an internationally recognized leader in the field of cytokine and steroid hormone signaling in prostate cancer. The focus of her laboratory is on translational prostate cancer research to develop and improve diagnostics and therapy for prostate cancer. Dr. Nevalainen holds the title of Eminent Scholar at MCW. She is also Director of Prostate Cancer Center of Excellence at MCW Cancer Center, which is a multi-disciplinary hub for prostate cancer research with an international collaborative network. Dr. Nevalainen serves as Assistant Dean for Research at MCW, and Associate Director of Education for the MCW Cancer Center. Her primary appointment is in the Department of Pathology, and a secondary appointment in the Department of Pharmacology and Toxicology. Dr. Nevalainen has extensive experience in collaborative research, mentoring and leadership from her previous roles at Sidney Kimmel Cancer Center at Thomas Jefferson University as Associate Director of Education and Vice Chair of Education in the Department of Cancer Biology.
Dr. See serves as co-director for the Prostate Cancer Center of Excellence. Based upon his 30-year career as an academic urologic oncologist and his prior research efforts focused on urologic cancers, he is uniquely positioned to assist with the PC-COE. As a surgeon-scientist, it has been his objective to direct his research efforts in order to advance scientific knowledge, while simultaneously building a foundation for clinical translation and patient benefit. He has served as an investigator on over 30 clinical trials in prostate cancer and has published extensively on both clinical and basic research aspects of prostate cancer. Dr. See has extensive clinical experience in the diagnosis and treatment of prostate cancer, including open, laparoscopic and robotic prostatectomy, as well as experience with cryosurgical ablation of the prostate. One of his most recent research projects includes collaboration with Dr. Nevalainen, Co-Director of the PC-COE, for optimization of the 3D tumor explant culture system of patient-derived prostate cancer. Dr. See is committed to the fulfillment of his goal to improving treatment outcomes for patient with prostate cancer and establishing a world class urologic cancer research program in the PC-COE.
The External Advisory Board for the Prostate Cancer Center of Excellence provides strategic and scientific direction, identifies opportunities for cross-institutional collaboration, provides assessments and feedback, and helps review grant applications.
Howard Soule, PhD
Executive Vice President
Chief Science Officer
Prostate Cancer Foundation
Howard R. Soule, PhD, since 1997 and as Chief Science Officer, coordinates global academic, government and biopharmaceutical sector research activity and is responsible for the implementation of the Prostate Cancer Foundation global research strategies. He is also a member of the Department of Defense Prostate Cancer Research Program Integration Panel.
Dr. Soule has been with the Foundation for 20 years. Prior to joining PCF in 1997, Dr. Soule was a senior R&D executive for nine years at Corvas International, Inc., a public biotechnology company. He was responsible for the discovery and development of innovative products for the treatment of life-threatening cardiovascular diseases. Dr. Soule has considerable experience in medical diagnostic and device industries as well. Dr. Soule received a PhD from Baylor College of Medicine in Virology and Epidemiology and was a Post-Doctoral Fellow in Immunology and Vascular Biology at the Scripps Research Institute.
Gail Prins, PhD
Professor of Urology and Physiology
Director of University Andrology Laboratory
University of Illinois at Chicago College of Medicine
Gail S. Prins, PhD is the Michael Reese Professor of Urology in the Departments of Urology, Pathology and Physiology, University of Illinois at Chicago. She is the Director of the University Andrology Laboratories and co-Director of the NIEHS-funded P30 Chicago Center on Health and Environment. She is Past-President of Society for Basic Urologic Research (SBUR) and the American Society of Andrology (ASA).
Dr. Prins’ basic research program focuses on prostate gland development, prostate stem and progenitor cells, steroid receptors, hormonal carcinogenesis, BPH and endocrine disrupting chemicals (EDCs). She has published 180 manuscripts and 22 book chapters on her research which has been NIH funded for > 30 years. Dr. Prins received the 2009 Excellence in Urologic Research Award from the SBUR/SWIU, the 2011 UIC Researcher of the Year Award and the 2014 Distinguished Andrologist Award from the ASA. She has served on the DoD Integration Panel for the Prostate Cancer Research Program, and as member of multiple NIH Study Sections. She currently serves as Associate Editor of Environmental Health Perspectives and Journal of Clinical & Experimental Urology and as Editorial Board member of multiple scientific journals.
Angelo DeMarzo, MD, PhD
Professor of Pathology
Associate Director of Cancer Research Pathology
Johns Hopkins University School of Medicine
Dr. De Marzo has published more than 320 papers, reviews and book chapters, and, he and colleagues described a potential new prostate cancer precursor/risk factor lesion for prostate cancer, proliferative inflammatory atrophy. His laboratory continues to study the role of inflammation in prostate carcinogenesis as well as the role of the MYC oncogene and the PTEN tumor suppressor in prostate cancer early disease development and progression. Along with colleagues, his lab is also heavily engaged in genomic studies of early prostate cancer and precursor lesions.
In addition, his lab also has a number of ongoing translational research efforts focused largely on using immunohistochemistry against PTEN and other biomarkers, where such markers might aid in diagnosis, prognosis, treatment stratification and disease resistance monitoring. Recently, his lab has also been performing extensive studies using multiplex immunofluorescence staining for inflammatory and other cell types, in situ hybridization for a number of different nucleic acid targets, as well as biospecimen science investigations related to optimizing methods of tissue handling for molecular studies.
Jan Lennon
Member of the Board of Directors
Wisconsin Breast Cancer Showhouse (WBCS)
Chair, WBCS Scientific Review Committee
Jan's focus as a volunteer and donor has always been on research and education, supporting avenues for advancement in these broad areas. She became involved with WBCS in 1998 when it was a fledgling nonprofit. Jan was honored to work closely with founder Nance Kinney and the early supporters and volunteers to facilitate basic breast cancer and prostate cancer research at the Medical College of Wisconsin. WBCS is now a major supporter of the Prostate Cancer Center of Excellence at the MCW Cancer Center.
From the beginning WBCS has defined success by the partnerships and collaborations created among donors and scientists, and MCW and WBCS leadership, who together invest in promising research at an early stage. This success has been leveraged to grow and develop this small but mighty nonprofit into a force to advance discoveries and inspire all involved to make a difference for prostate cancer patients, families and the entire community.
Center Accomplishments at the 2019 Scientific Retreat
PC-COE members and trainees played a significant role at the 2019 MCW Cancer Center Scientific Retreat, giving scientific talks, siting on panels, presenting and judging posters, mentoring and collaborating. PC-COE member Dr. Kirsten Beyer was presented with the Directors' Award for Highly Promising Peer Reviewed Research - a grant given to those who received near-fundable scores on a recent R01 submission. Congratulations to everyone who attended, presented and participated.
Other Member and Trainee Accomplishments
Kenneth Iczkowski, MD, Professor of Pathology and Urology, has been elected president-elect of the International Society of Urological Pathology for a two-year term. The International Society of Urological Pathology (ISUP) is an international program that issues guidelines for the practice of uropathology and offers educational opportunities for pathologists worldwide. The ISUP has more than 1,400 members from 81 countries in 6 continents.
The ISUP is also sponsoring the 2019 Prostate Cancer Grading Conference in France, for which Dr. Iczkowski is co-chairing. This year's conference will likely address and resolve several outstanding issues related to prostate cancer grading and ongoing changes in the diagnostic pathway of prostate cancer.
John Bukowy, postdoctoral fellow in Dr. Peter LaViolette’s lab, gave a presentation in early April on “Accurate Segmentation of Prostate Cancer Histomorphometric Features Using a Weakly Supervised Convolutional Neural Network,” at the 2019 Experimental Biology Conference in Orlando, Florida.
Marja Nevalainen, MD, PhD, Professor of Pathology, will serve as an ad-hoc member for the American Cancer Society Institutional Research Grants Committee this June in Atlanta, Georgia. Dr. Nevalainen is also serving as an ad-hoc reviewer for the Department of Defense Prostate Cancer Research Program (PCRP) Idea Development Award Pre-application in June-July 2019.
Back in February, Dr. Nevalainen served as a member of the Second Tier Reviewer Panel for the Department of Defense Prostate Cancer Programmatic Review. She also served as session chair at the March 2019 European Association of Urology Conference in Barcelona, Spain.
PC-COE Clinical Co-Director, William See, MD, was awarded the 2019 Christy Foote Fighter Award from WBCS, Inc. for his work as both a distinguished prostate cancer surgeon and his research efforts. Congratulations, Dr. See!
Center Impact: Prostate Cancer Screening for Underserved Men in MKE
Mark your calendars for the 3rd annual Prostate Health Education Event (PHEE) at Pilgrim Rest Missionary Baptist Church on Saturday, November 2 at 8 a.m. Free PSA screening for eligible men, plus education, discussion, a survivors' panel and more!
Wisconsin has extremely high rates of prostate cancer incidence, late-stage incidence and death, particularly in our African American communities and rural populations.
African American men in Wisconsin are almost twice as likely to develop prostate cancer and die from their disease.
These disparities cry out for immediate action. The MCW Cancer Center and PC-COE along with faith-based partners, has committed to providing free early screening and prostate health education for underserved men in Milwaukee. Our annual Prostate Health Education Symposium provides education and discussion from prostate cancer doctors and researchers and free on-site PSA testing, with the results sent directly to the men.
Center Events
The PC-COE brings together researchers, clinicians and trainees through regular monthly meetings, working groups, guest speakers and retreats.
Research Highlights
Available clinical trials, select publications and peer reviewed research grants from members of the Prostate Cancer Center of Excellence.
View additional prostate cancer research publications from 2014-2019.
SELECTED PUBLICATIONS
JAMA Oncology, 2019
PC-COE Author: William Hall
Quality of Life in Patients With Low-Risk Prostate Cancer Treated With Hypofractionated vs onventional Radiotherapy: A Phase 3 Randomized Clinical Trial.
Cell, 2018
PC-COE Author: Liang Wang
Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus.
Nature Communications, 2018
PC-COE Author: Liang Wang
High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing.
Lancet Oncology, 2018PC-COE Author: Elizabeth Gore
Sequence of hormonal therapy and radiotherapy field size in unfavorable, localized prostate cancer (NRG/RTOG 9413): long-term results of a randomized, phase 3 trial.
Clinical Cancer Research, 2018
PC-COE Authors: Marja Nevalainen (Last Author), Carmen Bergom, William See
STAT5A/B Blockade Sensitizes Prostate Cancer to Radiation through Inhibition of RAD51 and DNA Repair.
Clinical Cancer Research, 2018
PC-COE Author: Liang Wang
Synergistic Interaction of and Predisposes to Aggressive Prostate Cancer.
Center Researchers
The PC-COE provides the collaborative and supportive framework for a cross-disciplinary team of talented and innovative researchers and physician scientists who work together for the benefit of patients, families and our community. This team includes:
- An up and coming physicist and imaging researcher who uses 3-D printing technology to model individual prostate cancers from patients for clinicians to improve diagnosis and surgical treatment of prostate cancer.
- A researcher who has improved a specific type of a non-invasive liquid biopsy to help gauge treatment efficacy, giving physicians greater agility and precision in treating aggressive prostate cancers.
-A researcher who has identified and validated a novel therapeutic target for a clinical trial starting to treat patients with advanced prostate cancer.
- A cancer health geographer who designed a special adaptive mapping system to pinpoint areas where prostate cancer disparities are worse than expected and help other researchers target areas for interventions and investments.
- An expert in designing effective clinical trials to evaluate the efficacy of new therapies for prostate cancer.
- A clinical researcher who adapts MR-Linac technology for more effective radiation treatment of prostate cancer.
- A researcher investigating how dietary and physical activity changes affect body composition, biomarkers of general health and prostate cancer recurrence risk, and quality of life among prostate cancer survivors.
Kirsten Beyer, PhD, MPH, MS is an Assistant Professor in the Institute for Health & Equity, Division of Epidemiology at MCW and holds an adjunct appointment in Geography at the University of Wisconsin-Milwaukee. She is Associate Director of the PhD Program in Public and Community Health and Co-Associate Director of the Global Health Pathway at MCW and serves on the MCW Cancer Center Community Advisory Board. Dr. Beyer received her PhD in Geography and her MPH in Global Health from the University of Iowa in Iowa City and an MS in Clinical and Translational Science, with a focus on epidemiology, from MCW.Dr. Beyer is a health/medical geographer interested in the ways in which environments and place-based systems contribute to patterns of health and disease. Her work includes disease mapping, social and spatial epidemiology, and mixed methods approaches that aim to identify spatial patterns of disease, understand the complex human-environment processes that create them, and intervene to improve health and reduce disparities. Dr. Beyer’s current projects focus on cancer disparities, housing, and environmental justice both at home and abroad. Dr. Beyer’s current research focuses on the impacts of neighborhood environmental characteristics such as residential racial segregation and green space on cancer outcomes, particularly through pathways that include stress, time spent outdoors, social interaction, and food and physical activity behaviors. Her primary research project (NIH R01CA214805) is focused on the contemporary problems of institutional racism and residential racial segregation and investigates whether these social structures contribute to the magnitude of racial and ethnic cancer survival disparities. The project uses a community engaged research framework that draws upon existing partnerships with community organizations in Milwaukee, WI, which often tops the list of America’s most segregated cities. Dr. Beyer has worked with her team to create maps of prostate cancer incidence, late-stage diagnosis, and mortality in Wisconsin, revealing clear spatial patterns of disparity. In addition, she is currently a consultant on a large, NIH/NCI P01 project based in California called RESPOND (Research on Prostate Cancer in Men of African Ancestry: Defining the Roles of Genetics, Immunity and Stress). She will assist in an examination of the relationship between social stressors and prostate cancer aggressiveness and contribute novel measures of housing discrimination and segregation to the project.
Dr. Weiguo Cui was originally trained as an MD in Tianjin Medical University, China. He pursued his graduate study through an exchange program at Yale University and obtained his PhD in 2004. After his postdoctoral research in immunology at Yale, Dr. Cui joined the Versiti Blood Center of Wisconsin as an independent investigator since 2013. Dr. Cui aims to understand how T cells develop into an “exhausted” state during chronic viral infection and tumorigenesis. His lab has been a leader in using single-cell transcriptomics and epigenetic to identify the genes and signaling molecules involved in T cell exhaustion. Dr. Cui is also interested in how to restore the function of exhausted T cells and use them to combat viruses during chronic infection or tumor cells as a means of cancer immunotherapy. Memory T cell Biology
During an acute viral or bacterial infection, naïve T cells can differentiate into multiple types of effector and memory T cells that help to mediate pathogen clearance and provide long-term protective immunity. The main goal of our research in the lab is to elucidate how TCR and cytokine signaling and their downstream transcriptional programs regulate pathogen-specific T cells to proliferate, differentiate into either short-lived effector cells or long-lived memory cells.
Activated T cells receive and integrate a myriad of signals from their microenvironment. These signals differ in type, quality, quantity and duration, and could have significant impact on T cell activation, differentiation and survival. One area of our research interest is to study how these different signals cooperate with each other to regulate T cell expansion and acquisition of their effector function, and concurrently differ in their activities to control the short- or long-term fate decision. We aim to further investigate where and when these signals are produced and emanated, which will help to better understand how the distinct cellular niches influence effector and memory T cell fate decision and functional maturation.
JAK-STAT pathways are the important mediators to transmit extracellular signals into transcriptional programs that ultimately regulate effector and memory T cell differentiation, survival and homeostasis. Our recent work has demonstrated that STAT4 and STAT3 largely promote distinct cell fate commitment, and terminal effector versus memory cells respectively. A major focus in the lab currently is to better define how these different STAT pathways act in a synergistic or divergent fashion to regulate both terminal cell-fate commitment and permit plasticity in effector and memory T cells.
Jennifer Doll, PhD, is a well-established investigator in prostate cancer research. Her research group focuses on basic and translational studies to elucidate the mechanistic contributions of obesity / high fat diets and altered lipid metabolism to prostate cancer progression. Dr. Doll is a member of the Cancer Center and a member of the Prostate Cancer Center of Excellence at MCW. She is an Associate Professor and the Chairperson of the Biomedical Sciences Department at the University of Wisconsin-Milwaukee where her research lab is located. Dr. Doll’s research group has focused on two tumor suppressor proteins, which have potent anti-angiogenic activity, pigment epithelium derived factor (PEDF) and thrombospondin-1 (TSP-1). Both TSP-1 and PEDF are expressed in the normal prostate but, in PCa patient tissues, expression is decreased or absent, thus suggesting a role in disease progression. Initial studies elucidated the roles of the proteins in prostate tumor angiogenesis; however, additional studies led to the observations that these proteins also function in regulating metabolic pathways, such as lipid and energy metabolism, particularly in an obese setting. With over 30% of U.S. adults considered to be obese, an obesity contributing the incidence and progression of many types of cancer, understanding how obesity and a high fat diet impact cancer metabolism and progression is essential. Her current studies are aimed to identify the specific molecular pathways through which an obese microenvironment alters cellular metabolism and specifically to elucidate the roles of PEDF and TSP-1 in these functions in prostate cancer. The ultimate goal of these studies is to identify druggable targets for obese prostate cancer patient therapy development.
I am a board certified radiation oncologist with a passion for research in prostate cancer and radiological sciences. I balance a busy clinical practice treating primarily prostate and GI malignancies with an active research career. Thus far, in the early portion of my career, I have devoted my efforts to understanding novel biomarkers of radiation therapy treatment response. In addition I have focused on the integration of advanced imaging modalities, including MRI, into radiation treatment planning. Moreover, I have published several peer-reviewed articles devoted to the optimal use of radiation therapy for prostate cancer. Such articles have specifically related to radiation therapy technological advances, MRI incorporation into radiation planning, and the optimal radiation therapy dosing strategy. My future research goals are focused on developing and improving our ability to identify novel metrics of response to radiation therapy using both serum biomarkers and imaging biomarkers. In addition, I hope to develop MRI strategies that would use novel and unique MRI sequences to enable precise delineation of the most malignant portions of a tumor. My aspiration is to work closely with collaborators to refine our ability to accurately identify malignant tissue and direct intensification of local radiation therapy.
My ongoing research in prostate cancer focuses on two main areas: 1. serum inflammatory cytokines and their association with response to radiation therapy and 2. advanced imaging modalities to guide treatment with highly precise radiation therapy. In this regard I have recently completed a validation study measuring the serum inflammatory cytokines in patients with high risk prostate cancer. In this study, we examined the influence of C-reactive protein (CRP) serum levels on treatment outcomes after radiation therapy using serum samples from a large phase III clinical trial that recently completed. In addition we examined an array of serum cytokines for their correlations with response to treatment with radiation therapy. We found that pre-treatment levels of IL-10 appear to correlate with response to treatment with radiation. In addition, we found that several pre-treatment serum cytokine levels appear to correlate with the development of toxicity. In addition to this translational work I also have a strong interest in MR guided radiation therapy, along with advance imaging techniques to improve prostate radiation therapy. In this regard I am conducting a prospective observational trial collecting MRI’s during a treatment course with radiation therapy. We have recently shown some changes in the rectal wall that occur during treatment with radiation when closely examined using MR guidance. If expanded to a larger cohort, these results could be used as potential novel metrics of toxicity monitoring in men with prostate cancer being treated with curative radiation therapy.
Dr. Iczkowski was trained in anatomic pathology and completed fellowships in surgical and cytologic pathology at University of Kansas followed by urologic (GU) pathology at Mayo Clinic Rochester (1998). In addition to being a surgical and urologic pathologist, he also ran an extramurally funded research laboratory from 2002-2010, focused on the role of CD44 and cell adhesion in prostate cancer invasion and growth.
Dr. Iczkowski’s current research effort in prostate cancer is focused on inflammatory biomarkers NF-kappa B and GDF-15. These molecules in the prostate are involved in carcinogenesis and tumor development. They also appear to be deferentially expressed between African-American men’s and Caucasian men’s prostates.
Dr. Iczkowski has also published extensively on the various growth patterns of prostate cancer. Dr. Iczkowski was the first in his field to publish the finding that cribriform growth pattern of Gleason grade 4 prostatic adenocarcinoma has a particularly worse outcome than the identically-graded Gleason grade for non-cribriform prostatic adenocarcinoma. He has published work including PTEN and p27 expression as they relate to patterns of prostate cancer growth.
For the past several years, Dr. Iczkowski has collaborated with Dr. Peter LaViolette (Radiology) on a project to perform correlation of prostate cancer grades and patterns of growth with findings on magnetic resonance imaging. These studies included machine-learning of prostate cancer grading based on expert digital 'annotation' of prostate cancer foci in scanned whole-mount slides. This collaboration has resulted in several publications.
Finally, Dr. Iczkowski collaborates with Dr. Marja Nevalainen’s group (Pathology) in harvesting prostate cancer from prostatectomy specimens. The few-millimeter piece of tissue is examined by frozen section to determine the presence of cancer, so that the tissue can be used for establishing and running 3D tumor explant cultures and xenografts of patient-derived prostate cancer. He also works with Dr. Nevalainen on studying cancers with predominant neuroendocrine/ small cell differentiation and their expression of STAT5 and related markers of prognosis.
Iczkowski Lab:
Danny Abbot
Amrou Abdelkader
Huiya Huang
Oleksandr Kravtsov
Mohamed Mostafa
Shira Ronen
Kenneth Jacobsohn, MD is fellowship trained in minimally-invasive urologic oncology and board-certified in urology. He is the Director of Minimally Invasive Urologic Surgery at MCW and Associate Professor of Urology. Dr. Jacobsohn specializes in robotic surgery for malignant and benign urologic diseases. He has pioneered many technical advances and firsts in robotic urologic surgery and is a dedicated clinician who focuses intensely on balancing his patients oncologic and quality of life outcomes. He has been instrumental in the development and use of MRI for prostate cancer imaging at Froedtert & MCW. Dr. Jacobsohn has emerging interests in prostate cancer prevention and the role of nutrition in prostate cancer development on and progression.
Dr. Jacobsohn collaborates with Dr. Nevalainen for optimization of the 3D tumor explant culture system of patient-derived prostate cancers. He partners with Dr. Laviolette on his innovative MRI-based prostate cancer imaging techniques. Other current efforts include development of the Functional Anatomy Sparing Technique for Prostatectomy (FAST-P), and retzius-sparing prostatectomy.
Dr. Karan’s research focuses on cancer immunology and immunotherapy, and to understand the role of inflammation in the development and progression of prostate cancer. Overall emphasis of his research is based on harnessing the power of immune system to improve its preventive and therapeutic efficacy against cancer cells using antigen-specific immunotherapy, natural compounds, and chemotherapy drugs. His laboratory addresses the role of immune system in antitumor therapy, activation of antitumor responses and characterization of antitumor effector mechanisms specific to prostate cancer. Dr. Karan’s lab developed an adenovirus (Ad5)-based vaccine for a simultaneous targeting of prostate-specific antigens and demonstrated its superior therapeutic efficacy in preclinical studies. Dr. Karan’s immediate goal is to translate this dual antigen-specific prostate cancer immunotherapy approach into clinics.These studies will provide a strong rationale to test the bivalent vaccine in combination with other therapies such as androgen deprivation therapy, chemotherapy, radiation therapy, and checkpoint inhibitors in future clinical settings.To better understand the success or failure of immunotherapyin prostate cancer, Dr. Karan and his lab are focused in identifying immune cell-basedbiomarkers. His lab performed global gene expression analysis with a primary object to discover and validate differentially expressed immunologic biomarkers that may have clinical predictive/ prognostic significance in patients undergoing immunotherapy treatment. Based on his preliminary studies, Dr. Karanproposedto validate the clinical significance and determine the mechanistic regulation of the identified markers. This study will help to establish the concept that molecules of immune cells selected for tumor cell killing can serve as a useful biomarker(s) predicting the therapeutic efficacy of an immunotherapy approach.Dr. Karan’s lab is focused in understanding the biology of prostate cancer associated with disparity between African American and Caucasian men. Genetic and epigenetic changes are known as tumorigenic drivers because epigenetic editing precludes mounting of host antitumor response necessary for tumor cell clearance. DNA methylation, catalyzed by DNA methyltransferase, is the best-characterized epigenetic modification in prostate cancer, and racial disparities in DNA methylation are associated with cancer prognosis and survival. Dr. Karan’s goal is to determine the impact of antitumor immunity following DNA methylation targeting in prostate cancer cells.To manipulate the immune system in tumor-microenvironment, Dr. Karan’s studies are utilizing a dietary agent withaferin-A (WA). His lab has demonstrated that WA significantly induces the activation of natural killer (NK) cells and inhibited the growth of established tumors. Studies are focused to determine WA-induced functional activity of NK cells using in vitro and in vivo mouse model for prostate cancer; and to determine the molecular mechanism by which WA augments NK cells function. Additionally, effect of WA on macrophages showed a differential regulation of multiple cytokines/chemokines associated with cancer cell growth and immune cells regulation. So far, Dr. Karan’s lab has demonstrated a dual mechanism of WA inhibiting NF-B and disintegration of inflammasome complex proteins regulating inflammatory cytokines-chemokines. These studies are investigating the role of inflammatory cytokines/chemokines via inflammasome modulation in growth and development of cancer cells.
Dr. Kilari practices at the Froedtert & Medical College of Wisconsin Clinical Cancer Center where he specializes in the management of patients with genitourinary malignancies. Dr. Kilari moved back to the United States after finishing medical school in India to finish his internal medicine training at New York Methodist Hospital. During his residency, he developed an interest in Oncology during his rotations at the Memorial Sloan Kettering Cancer Center in New York. Subsequently he completed a fellowship in hematology and oncology at the University of Rochester, where he also served as a Chief Fellow. He received the ASCO foundation Merit award in 2013. He currently practices at the Froedtert and Medical College of Wisconsin and Zablocki VA hospital.Research Dr.Kilari’s research interests includes development of novel therapeutic options for patients with genitourinary malignancies.He also has an interest in geriatric oncology. He currently leads a Phase 2 study evaluating the role of Enzalutamide and 5 alpha reductase inhibitors as upfront treatment for men with systemic prostate cancer. The trial is unique in several ways due to the inclusion of men only who are at a high risk of adverse effects with androgen deprivation therapy and incorporating comprehensive geriatric assessment into the study. He also leads a trial evaluating the role of exosomal micro-RNAs to predict duration of response to androgen deprivation therapy. He has led several other translational studies both in prostate and urothelial carcinoma. He is the site -PI of several clinical trials for patients with genitourinary malignancies.
Colleen A. F. Lawton, MD is an internationally recognized Genitourinary Radiation Oncologist who has gained this recognition through her research in prostate cancer. She has worked for several decades focusing on clinical research in all aspects of prostate cancer from localized disease to locally advanced. In addition, Dr. Lawton has served as the president of the American Society of Radiation Oncology (ASTRO) where prior to becoming president, she served on the board working on educational programs in prostate cancer. She has also served as the program director for the Medical College of Wisconsin Radiation Oncology Residency Program for approximately 25 years and as such received the Association of Residents of Radiation Oncology Educator of the Year Award. Dr. Lawton is also a nationally recognized leader in total body irradiation for stem cell transplant. She has given national educational courses on the topic and was awarded an American Cancer Society Career Development Award for research in this arena. Dr. Lawton currently serves as the Vice Chair of the Medical College of Wisconsin Department of Radiation Oncology.
Dr. Lawton’s research in total body irradiation for stem cell transplant was the first to show a renal toxicity issue that could be addressed via partial shielding of the kidneys and subsequently the same issue with the lungs and liver. She began her focus on prostate cancer clinical research with her involvement in the Radiation Therapy Oncology Group (RTOG now NRG) national cooperative clinical trial group in the early 1990’s with two trials. The first RTOG 94-13 established that there was a clear role for radiation to the pelvic lymph nodes in addition to the prostate for locally advanced prostate cancer patients. The next trial RTOG 98-05 was the first multi institutional trial demonstrating the ability to successfully treat localized prostate cancer with LDR (low dose rate) I131 seeds in a cooperative group setting. This trial stemmed from a similar successful MCW single institution trial. Her next trial RTOG 00-19 proved that for intermediate risk prostate cancer patients, LDR brachytherapy in addition to external beam radiation added toxicity but no clear improvement in prostate cancer control compared to LDR brachytherapy alone.
Her most recent completed RTOG/NRG trial was 09-38 which has shown the ability to treat localized prostate cancer with hypofractionation. This trial was designed to show whether prostate cancer treated in 12 fractions over 2.5 weeks verses 5 fractions over 2.5 weeks was equal in terms of cancer control and toxicity. Early results suggest equivalency in terms of both.
Finally she is continuing her work within the NRG cooperative group with the development of trial NRG-GU1817 which will address locally advanced/lymph node positive prostate cancer patients with local regional radiation in addition to newer systemic agents looking at improving the outcomes for this group of patients thought to be incurable.
Marja Nevalainen, MD, PhD is an internationally recognized leader in the field of cytokine and steroid hormone signaling in prostate cancer. The focus of her laboratory is on translational prostate cancer research to develop and improve diagnostics and therapy for prostate cancer. Dr. Nevalainen holds the title of Eminent Scholar at MCW. She is also Director of Prostate Cancer Center of Excellence at MCW Cancer Center, which is a multi-disciplinary hub for prostate cancer research with an international collaborative network. Dr. Nevalainen serves as Assistant Dean for Research at MCW, and Associate Director of Education for the MCW Cancer Center. Her primary appointment is in the Department of Pathology, and a secondary appointment in the Department of Pharmacology and Toxicology. Dr. Nevalainen has extensive experience in collaborative research, mentoring and leadership from her previous roles at Sidney Kimmel Cancer Center at Thomas Jefferson University as Associate Director of Education and Vice Chair of Education in the Department of Cancer Biology.
Research
- Jak-Stat signaling
- Prostate cancer progression
- Therapy development
- Companion diagnostics
- Predictive Factors
- DNA repair
- Radiation therapy
- In vitro and in vivo models
- 3D tumor explant culture
- Epithelial-mesenchymal transition
- Cancer stem-like cell properties
- Metastases models
- Small molecule therapeutics
Dr. Nevalainen’s group provided the initial proof-of-concept that Jak2-Stat5-axis is a therapeutic target in prostate cancer. Dr. Nevalainen’s group made the seminal finding of Stat5 as a critical factor for prostate cancer cell viability and growth in vitro, in vivo in xenograft tumor models and ex vivo in patient-derived clinical prostate cancers. Her group further established the concepts of: 1) Stat5 as a critical inducer of castrate-resistant prostate cancer growth, 2) Stat5 as a predictive factor of early prostate cancer recurrence and disease-specific death after radical prostatectomy, 3) Stat5 as a inducer of prostate cancer stem cell properties, epithelial-to-mesenchymal transition and metastatic disease, 4) Stat5 as a regulator of homologous recombination DNA repair and radiation response of prostate cancer. In recent work, using medicinal chemistry Dr. Nevalainen and collaborators have identified a family of novel small molecule Stat5 inhibitors with high efficacy in both PC and Bcr-Abl-driven leukemias. Dr. Nevalainen’s research accomplishments include development of an androgen-dependent human PC cell line which mimics the course of human disease when grown as xenograft tumors in nude mice.
Specifically, the tumors response to androgen deprivation by regression but regrow eventually back as castrate-resistant tumors.Dr. Nevalainen is further recognized in her field for early development of a long-term 3D tumor explant culture system for normal and malignant prostate tissue for efficacy testing of experimental biologics and small-molecules ex vivo in clinical PCs from patients and as an experimental model system for identification of growth factor and drug modulated signaling proteins in prostate tissue.Recent work from her laboratory demonstrated a novel role for Stat5 as regulator of radiation response of prostate cancer through control of Rad51 levels and homologous recombination DNA repair. Current work focuses on Jak-Stat signaling in anti-androgen resistance of prostate cancer, Stat5 regulation of BRCAness of prostate cancer, optimization of the lead compound Stat5 inhibitor and interaction of Jak2-Stat5 signaling with androgen receptor signaling network in prostate cancer.
Nevalainen Lab:
Savita Devi
Cristina Maranto
Sara Schmitt
Vindhya Udhane
Dr. Park’s basic science research is supported by the NIH-National Cancer Institute. He also participates in clinical cancer research by serving the NCI-MATCH Precision Medicine Cancer Trial as the Translational Chair of the Dabrafenib & Trametinib combination therapy arm, which targets BRAF-driven cancer. He was an American Cancer Society Research Scholar and a member of the ACS MEN2 Thyroid Cancer Consortium.
Dr. Park’s areas of interest in prostate cancer include the role of MAPK pathways in PCa. Previously, Dr. Park’s lab demonstrated that ERK1/2 has a role in regulating androgen receptor and neuroendocrine differentiation of PCa and that a cross-talk is established between AKT and B-Raf under androgen-deprived conditions.
Publications:
Hong SK, Kim JH, Lin MF, Park JI (2011) The Raf/MEK/extracellular signal-regulated kinase 1/2 pathway can mediate growth inhibitory and differentiation signaling via androgen receptor downregulation in prostate cancer cells. Exp Cell Res 317: 2671-82
Hong SK, Jeong JH, Chan AM, Park JI (2013) AKT upregulates B-Raf Ser445 phosphorylation and ERK1/2 activation in prostate cancer cells in response to androgen depletion. Exp Cell Res 319: 1732-4
Dr. Sarah Patch received her BS in Mathematics & Computational Sciences from Stanford University in 1989 and her PhD in Applied Math from UC Berkeley in 1994. She then obtained a National Science Foundation Postdoctoral Fellowship in Mathematical Sciences and worked at the Institute for Mathematics and its Applications from 1994 to 1995. In 1995, she was awarded a Humboldt Postdoctoral Fellowship to work at the University of Muenster, Germany. The following year Patch went back to Stanford University. From 1997 to 1999 Patch held a position GE’s Corporate Research and Development Center; in 2005 she joined GE Medical Systems’ Applied Science Lab in Milwaukee. Since 2005, she has been working at University of Wisconsin-Milwaukee. Professor Patch is inventor on more than 10 patents, as well as author on numerous publications. Her work has been supported by NIH, NSF, and DARPA.
Thermoacoustic Range Verification During Particle Therapy
A controversial application of proton therapy is prostate cancer treatment. To spare radiosensitive rectal tissue the standard prostate cancer protocol treats only with horizontal beams, which travel through thick bony structures before reaching the prostate. Bone degrades the proton beam’s energy spectrum, minimizing the advantage of proton therapy over intensity modulated x-ray radiation therapy. Horizontal-only delivery maximizes proton path length through hip and thighbones. Accurate range verification could enable delivery using oblique beams that avoid large bones and maintain a sharp Bragg peak, taking full advantage of the potential of particle therapy. Therefore, we performed a Monte Carlo simulation study and developed a two-step method for accurately estimating the Bragg peak location from thermoacoustic emissions measured by receivers that could be embedded onto the form factor of a transrectal ultrasound imaging array (Fig. 1,MedPhys45(2):783-793).
Fig. 1. Monte Carlo simulations of oblique beam and range estimates from SNR=0 dB signals overlaid on planning CT.“+” indicate locations of low frequency receive elements projected orthogonally onto each CT plane. Axial, sagittal, and coronal planes through true Bragg peak location in (a) through (c), respectively. White line in (a) and (d) indicates beamline. Magenta dot is true Bragg peak location. Yellow triangle and circle indicate orthogonal projections of beamformed and final estimates. (d) Zoomed image of axial plane near Bragg peak. CT display window is [-200, +200] HU.
Fig. 2. Bragg peak locations for “control” beams and “measured” beam are plotted with magenta squares and dot, respectively. Dotted yellow lines connect the transducer locations to the beamformed estimate (yellow triangle). A dashed line connects the beamformed estimate to the nearest control point, and a solid yellow line connects the control point to the final estimate (yellow circle).
Dr. See serves as co-director for the Prostate Cancer Center of Excellence. Based upon his 30-year career as an academic urologic oncologist and his prior research efforts focused on urologic cancers, he is uniquely positioned to assist with the PC-COE. As a surgeon-scientist, it has been his objective to direct his research efforts in order to advance scientific knowledge, while simultaneously building a foundation for clinical translation and patient benefit. He has served as an investigator on over 30 clinical trials in prostate cancer and has published extensively on both clinical and basic research aspects of prostate cancer. Dr. See has extensive clinical experience in the diagnosis and treatment of prostate cancer, including open, laparoscopic and robotic prostatectomy, as well as experience with cryosurgical ablation of the prostate. One of his most recent research projects includes collaboration with Dr. Nevalainen, Co-Director of the PC-COE, for optimization of the 3D tumor explant culture system of patient-derived prostate cancer. Dr. See is committed to the fulfillment of his goal to improving treatment outcomes for patient with prostate cancer and establishing a world class urologic cancer research program in the PC-COE.
Dr. Stolley is a clinical psychologist by training and has established a reputable portfolio of research in cancer prevention and survivorship in minority populations. Her research focuses on health behaviors and health behavior change with the goal of improving patient reported and cancer outcomes. In addition, her work examines the impact of lifestyle change on biomarkers that link adipose tissue to cancer. Dr. Stolley also has expertise in the recruitment and retention of cancer survivors across multi-site studies, as well as translating research-based interventions to practical, community-based settings. Relevant to this work are the nearly 20 years Dr. Stolley has spent as a behavioral scientist developing, implementing and examining the efficacy and effectiveness of lifestyle change interventions. She recently completed an NCI funded R01 intervention study of a community-based weight loss program with 246 African-American breast cancer survivors. This study included behavioral, psychosocial, quality of life and biological outcomes. Currently, she is conducting three new behavioral interventions: 1) targeting plant-based eating and exercise in women with metastatic breast cancer; 2) targeting weight loss in Latina breast cancer survivors who have completed initial treatment; and 3) a recently funded R01 to examine the efficacy of a plant-based eating and exercise intervention on biological, behavioral, and psychosocial outcomes among African-American prostate cancer survivors. As the Associate Director of Cancer Prevention and Control at the Medical College of Wisconsin (MCW) Cancer Center, Dr. Stolley works closely with clinicians and research scientists to increase the breadth and depth of MCW’s cancer center scientific agenda through inter and intra-programmatic collaborations. She also leads the MCW Community Outreach and Engagement program which focuses on community-based efforts to reduce medical mistrust, improve cancer prevention and control behaviors and increase minority accrual to clinical trials. Finally, Dr. Stolley is engaged with a number of training initiatives including a public high school-based cancer health education program, a summer cancer disparities training program for undergraduates and first year medical students,and mentoring post-doctoral fellows and junior faculty.
Demin Wang, PhD is a nationally and internationally recognized leader in the field of hematopoiesis and immunology. His scientific interests focus on studying the signal regulation of hematopoietic stem cells and B lymphocytes. Dr. Wang’s research program aims to understand the molecular pathogenesis of various hematological and immunological diseases and cancers, and to suggest new approaches to prevention and treatment of these disorders.He is the recipient of American Cancer Society Research Award and the recipient of Leukemia and Lymphoma Society Scholar Award, USA. Presently, and holds the John B and Judith A Gardetto Endowed Chair for Cancer Research. Dr. Wang’s primary appointment is in the Versiti Blood Research Institute and a secondary appointment in the Department of Microbiology & Immunology, Medical College of Wisconsin. He is also an editorial board member of the peer-reviewed medical journal Blood.
Hematopoietic stem cells (HSCs) give rise to all blood cells, including erythroid, myeloid and lymphoid lineages. The self-renewal and hematopoietic differentiation of HSCs are strictly controlled by both extrinsic and intrinsic signals. B cells, a subtype of lymphoid cells,are critical to the immune defense, and their development and function are also highly regulated by signals derived from a variety of cell surface receptors. Abnormal signals from the receptors often lead to multiple diseases, including malignancies, and immunodeficiency and autoimmune diseases. Dr. Wang’s research focuses on identifying and functionally characterizing signaling pathways that control B cell development from HSCs. His research employs multiple cutting-edge approaches, including targeted gene disruption,transgenic,bone marrow transplantation and high-throughput DNA/RNA sequencing technologies. Dr. Wang has identified a number of important molecular components, including PLC1, PLC2, Bcl10, TAK1, Stat5, et al,of the signaling pathways that play critical roles in regulating hematopoiesis/lymphopoiesis. His research findings have significantly advanced our understanding of the regulation of hematopoiesis and lymphopoiesis.
Cytokine receptors regulate a variety of cellular responses, including cell growth, survival, differentiation, and function. Engagement of cytokine receptors induces the activation of the JAK family of protein tyrosine kinases. In turn, Jaks activate components of diverse signal transduction pathways, including members of the Signal Transducers and Activators of Transcription (Stat). Dysregulation of JAK/Stat pathway is implicated in the pathogenesis of numerous diseases. Stat5is activated by the prolactin receptor and is critical for prostate cancer cell viability, growth, metastasis and dissemination. Constitutively activated Stat5is associated with high grade prostate cancers, and prostate cancer recurrence and metastasis. Inhibition of stat5 activity induces rapid prostate cancer cell death and prevents prostate tumor growth in mice. One of Dr. Wang’s current research projects studies the regulation and function of Stat5 protein. He has identified a naturally occurring C-terminal truncated Stat5 that lacks the transcription activation domain and thus acts as a dominant negative form. His recent work discovered a novel mechanism underlying the down regulation of Stat5 in tumor cells. Dr. Wang’s laboratory is exploring this novel down regulation of Stat5 signaling pathway for inhibiting prostate cancer cell proliferation and survival, and thus preventing prostate cancer progression.
Dr. Wang is a Professor of Pathology and Genetics at Medical College of Wisconsin. He has extensive experiences on genetic/epigenetic biomarker study and sequencing data analysis. His research interest is to identify biomarkers that are associated with genetic susceptibility, early diagnosis, treatment efficacy and prognosis. His research work has been published in over 100 articles including publications in Nature Genetics, Lancet Oncology, Gastroenterology, European Urology and Nature Communications. Dr. Wang’s research is currently supported by grants from NCI and other funding agencies.
Dr.Wang’s lab has been focused on genome variations and human cancers. Specifically, the lab is interested in understanding the genetic contributions to human cancers. It is well known that cancer is associated with a cascade of changes in human body’s genetic materials. Molecular characterization of these genetic changes will facilitate discovery of new biomarkers for cancer risk assessment, early detection, and outcome prediction. Although most cancer types are involved, Dr. Wang’s primary interest has been prostate cancer, the most commonly diagnosed cancer in US men.
To identify the genetic variants causing prostate cancer, Dr. Wang’s lab is collaborating with a wide variety of experts,including medical oncologist, biostatistician, biomedical informatician, and molecular biologist. The lab applies state-of-art research technologies,such as genome sequencing and gene editing,to determine functional role of genetic variations in prostate cancer initiation and progression.
One example of the research efforts currently being carried out include a large-scale RNA sequencing project that aims to analyze RNA sequences in over 500 prostate cancer patients. The goal is to identify genes and genetic variants that contribute to aggressive forms of prostate cancer. Dr. Wang’slab is also interested in the development of prostate cancer biomarkers with high diagnostic values. By examining tumor nucleic acid components in blood stream, the lab has developed a PGA (plasma genomic abnormality) score algorithm to estimate tumor burden and predict treatment response and clinical outcome in advanced prostate cancer patients. The lab is now testing unique genetic changes in peripheral blood of over 400 clinical trial cohort patients. This liquid biopsy study has been recently funded by National Cancer Institute and will determine genetic changes for more accurate prediction of treatment response.Success of this study will not only help clinicians in selecting the most effective treatment options, but also provide important clues regarding mechanisms that underlie prostate cancer progression and recurrence.
Liang Wang Lab:
Jing Jia
Yijun Tian
Meijun Du L. Wang
Fankai Xiao
Wenbin Yue
Peng Zhang
Clinical Cancer Researchers and Clinicians
These Prostate Cancer Center of Excellence physicians, who are faculty at the Medical College of Wisconsin and practice at the Froedtert and MCW Clinical Cancer Center, are some of the most innovative, compassionate, and successful prostate cancer clinicians in our region and around the country. Patients in the greater Milwaukee area, and throughout Wisconsin and the upper Midwest have the best prostate cancer care right here in their own backyards.
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