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Travis Jerde, PhD

Associate Professor of Pharmacology and Toxicology

Research Interest 


My research focuses on studying how inflammatory and developmental signaling interplay to promote cell survival and proliferation in the inflamed microenvironment of the prostate.


Education 


1994

B.S. Bacteriology
College of Agricultural and Life Sciences, University of Wisconsin
Madison, Wisconsin

2005

PhD Pharmaceutical Sciences
University of Wisconsin School of Pharmacy  Madison, Wisconsin

2005 - 2010

Postdoctoral Fellowship
Paul P. Carbone Comprehensive Cancer Center
Cancer Biology, Urology, and Molecular and Environmental Toxicology
University of Wisconsin School of Medicine and Public Health
Mentor: Wade Bushman, M.D., PhD


Honors 


2009

Best Poster of Session
Prostate Cancer Basic Research IV
The Annual Meeting of the American Urological Association | "Interleukin-1-induced epithelial proliferation in prostate development and hyperplasia is mediated by insulin-like growth factor-1 induction"
Chicago, Illinois   

2008

Travel Award - Best Poster Submission
Society of Basic Urological Research (SBUR) 2008 Annual Fall Meeting | "Interleukin-1-induced epithelial proliferation in prostate development and hyperplasia is mediated by stromal insulin-like growth factor-1 induction."
Phoenix, Arizona  

2008   

Keystone Symposium on Signaling Pathways in Cancer and Development | Travel Award Podium Selection
"Decreased prostatic branching in interleukin receptor knockout mice reveals a key role for inflammatory mediators in prostate development."
Steamboat Springs, Colorado
  

2007 - 2009

Department of Defense
Postdoctoral Fellowship Award in Prostate Cancer Research 

2006 - 2007

NIH/NRSA Ruth L. Kirshstein Postdoctoral Fellow in Molecular and Environmental Toxicology 

2005

AUA/SBUR Summer Research Conference Travel Award
"Diseases of Inflammation of the Prostate" 

2005

Urothelium Travel Award | "Activation of Protein Kinase C and p38 MAP Kinase is necessary for Cyclooxygenase-2 induction during urothelial cell stretch." 

2004

The Dr. Razia Zaman-Dr. Shahanara Zaman Saroya Graduate Student Award for Excellence in Research and Scholarship University of Wisconsin School of Pharmacy 

2003

The Olympus Prize
Best Basic Science Research Paper - 1st Prize
World Congress and Endourology
Montreal, Canada 

2003

Members' Scientific Session Best Paper Award
Seventh European Symposium on Urogenital Radiology
London, England 


Inflammation is a complex protective action of our immune system in response to harmful substances, organisms, or events. However, unresolved inflammation can have several deleterious effects including tissue damage, chronic inflammatory pain, and the promotion of cancer. Tumorigenesis is said to result from the generation of oxygen / nitrogen radicals during inflammation, resulting in DNA damage and ultimately tumorigenesis. This, however, is only part of the story.
 

Repair and regrowth are co-regulated processes that represent a general characteristic of many cellular responses after injury, trauma, and inflammatory conditions. In order for tissue recovery to proceed, inflammation must orchestrate a precise series of events, directing damaged cells to die, inducing the proliferation of protected specialized tissue progenitors to repopulate the damaged tissue, and finally promoting the differentiation of those expanded cells into the proper cell subtypes allowing stratification of the repaired tissue layers. Errors in this process allow for expansion of damaged cells in an environment rich in growth promoting factors. This promotes not only tumorigenesis, but also a rapid expansion of the nascent tumor. Mechanisms of how inflammation directs cells to avoid death and proliferate are poorly understood.

My lab studies how inflammation reactivates the developmental process during repair and recovery associated with inflammation. It is well-known that tumor cells exhibit many physical and molecular features of cells during organ development. While studying prostate organogenesis, we made a series of discoveries that shed significant new

light on the relationship of inflammation to developmental signaling and prostate cancer and benign prostate growth. First, inflammatory mediators (in particular, interleukins) are highly expressed during normal development and play a significant role in organogenesis by promoting proliferation. 

Second, the proliferative effect of interleukin is reiterated in the adult during inflammation. Finally, the mechanism by which IL-1 induces proliferation during prostate development and inflammatory repair is the paracrine production of bona fide developmental mediators, particularly the insulin-like growth 

factors (IGFs) and transforming growth factors (TGFs). These results demonstrate clear interplay between inflammatory and developmental signaling networks.

We now seek to understand how these signaling interactions promote epithelial proliferation and allow damaged cells to escape cell death in the inflamed prostate.  Currently, the three primary specific projects in my lab are:


1.

To test the hypothesis that inflammation-induced epithelial survival and proliferation depends on insulin-like growth factor signaling.

2.

To test the hypothesis that small heat-shock chaperones promote apoptotic or autophagic escape during inflammatory reactive hyperplasia in the prostate.

3.

To test the hypothesis that androgen and IL-1 cooperatively promote prostatic growth by STAT-3 dependent IGF-1 signaling


The Prostate
 

Why study these processes in the prostate? Inflammation in the human prostate is extremely common and is diagnosed histologically from the presence of inflammatory cells infiltrating the prostatic stroma, epithelium, and/or lumen of the prostate glands. The incidence of asymptomatic prostatic inflammation is reported to be between 44 and 73%.Chronic inflammation is associated with dysplastic changes including focal disruption of the epithelium, polymorphisms of epithelial cell nuclei, cytoplasmic basophilia, and increased epithelial proliferation. The origins of inflammation in the prostate remain a subject of debate and are likely multi-factorial. Bacterial infection from culturable and non-culturable organisms causes prostatic inflammation in acute and chronic bacterial prostatitis, but these conditions are relatively uncommon.


Numerous nonbacterial potential causes of inflammation have been investigated including viruses, environmental and dietary components, changes in systemic steroid concentrations (especially estrogens) auto-immune mechanisms, oxidative stress associated with androgen action, systemic inflammation associated with the metabolic syndrome, and urinary reflux of noxious stimuli into the prostatic ducts. Though data in this area are still sparse, the number of potential chemicals in urine may represent a major inflammatory stimulus in the prostate. Whatever the causes, the study of inflammation in the prostate is of considerable importance to urological research due to its association with two of the most critical health concerns in urology: prostate cancer and BPH.

 

Prostate Cancer  

Prostate cancer is the most common malignancy and the second leading-cause of cancer-related death among men in the United States and Western Europe. Small prostatic carcinomas exist in up to 29 percent of men 30 to 40 years of age and 64 percent of men in their sixties. The risk of death due to metastatic prostate cancer is now up to 1 in 30 in western countries, and while localized disease is curable by surgery or radiation therapy, many men present with non-localized tumors or develop recurrent disease after attempted curative treatment, attesting to the urgency to prevent the development of prostate cancer, retard tumor progression, and develop new and effective therapies for non-localized disease.

 
Many potential causes of prostate cancer have been identified, including dietary factors, exposure to androgens or estrogens, acquired or inherited genetic susceptibilities, and exposure to environmental carcinogens. Of all proposed causes of prostate cancer, the most-identified characteristic associated with localization of the disease is the presence of inflammation. Recent evidence has implicated chronic inflammation as a primary contributor to the development and progression of prostate cancer. However, the mechanisms by which inflammation promotes oncogenesis and tumor growth remain obscure.


One possibility is that progenitor cell expansion associated with chronic injury and inflammation sets the stage for mutation and malignant transformation by exposing these "reserve cells" to the mutagenic effects of reactive oxygen and nitrogen species. Another possibility is that inflammatory cytokines may directly or indirectly stimulate epithelial proliferation and contribute to the expansion of pre-malignant and overtly transformed cells. This epithelial expansion resembles the developmental process in the prostate, and our preliminary data show that a reactivation of developmental mediators occurs during reactive hyperplasia of the prostate, suggesting a connection between the developmental and inflammatory processes in the prostate. This connection is supported by our recent report showing a clear role for classic inflammatory mediators in organogenesis of the prostate. Our work is based on the novel thesis that inflammatory mediators promote prostate tumor growth by inducing key developmental mediators and growth promoters of prostate epithelial cells.

 

Research in prostate biology has for years focused on cross-talk between epithelial and stromal cells during cancer or embryologic development. It is clear that such epithelial-stromal interactions drive growth of the organ during development and cancer. Our work opens an entirely new chapter in this story: epithelial-stromal-leukocytic interactions in prostate development, hyperplasia, and cancer.

Select Publications
 

  •  Jerde TJ, Bushman W.  IL-1 induces IGF-dependent epithelial proliferation in prostate development and reactive hyperplasia.  Science Signaling. 2009 2(86): 49. (cover)
  • Jerde TJ, Wong L, Wu Z, Theodorescu D, Bushman W: Bone morphogenetic signaling sustains Phosphatase and Tenson analogue (PTEN) protein expression in prostate epithelial cell lines. The Prostate, in press, 2010. 
  • Jerde TJ, Mellon WS, Bjorling DE, Checura CM, Owusu-Ofori K, Parrish JJ, Nakada SY.  Stretch induction of cyclooxygenase-2 expression in human urothelial cells is calcium- and protein kinase C zeta-dependent.  Molecular Pharmacology. 2008 73(1): 18-26. 
  • Jerde TJ, Mellon WS, Bjorling DE, Nakada SY:  Stretch-induced cyclooxygenase-2 expression in the human urothelium is regulated by transcriptional and post-transcriptional mechanisms.  Journal of Pharmacology and Experimental Therapeutics, 2006 317: 965-972.
  • Sterrett SP, Wilkinson ER, Jerde TJ, Mellon WS, Nakada SY.  Evaluation of urothelial stretch-induced cyclooxygenase-2 expression in a mouse ureteral obstruction model.  Journal of Endourology. 2009 23(3):541-4.

Our work received three best of session awards at the 2010 Annual Meeting of the American Urological Association, May 31st and June 1st, San Francisco, CA!  Work performed while a post-doc in Wade Bushman’s laboratory at the University of Wisconsin won three awards at this year’s AUA in San Francisco. Collaborators on the projects include Wade Bushman (UW), Dan Theodorescu and Zhong Wu (University of Virginia). I would like to particularly acknowledge the contributions of graduate student Sanghee Lee, and undergraduate students Christopher Loftus, Eliza McFarland, and Adam Kaye to these projects.
 

Best Poster of Session: Benign Prostatic Hyperplasia—Basic Research. The Annual Meeting of the American Urological Association “Insulin-like growth factor signaling mediates growth effects of both androgen and inflammatory signaling during prostate development, castration-regrowth, and hyperplasia.” May 31st, 2010, San Francisco, CA, USA.
 

Best Poster of Session: Prostate Cancer Basic Research-VI. The Annual Meeting of the American Urological Association “Bone morphogenetic protein signaling sustains phosphatase homologue of tensin analogue protein expression in prostate epithelial cell lines.” June 1st, 2010, San Francisco, CA, USA.
 

Best Poster of Session: Prostate Cancer Basic Research-VIII. The Annual Meeting of the American Urological Association “Insulin-like growth factors mediate inflammation-driven proliferation of the mouse prostate.” June 1st, 2010, San Francisco, CA, USA.
 

September 1, 2010: I officially begin my faculty appointment at IU School of Medicine in the Department of Pharmacology and Toxicology.


Department of Pharmacology and Toxicology | 635 Barnhill Drive, MS A401 | Indianapolis, IN 46202