Travis J. Jerde, PhD

Research in Dr. Jerde’s laboratory is focused on elucidating the cellular signaling mechanisms and cell-to-cell communication networks in the inflamed prostate and bladder microenvironments that result in diseases such as hyperplasia and cancer. Specifically, our lab studies how inflammation reactivates elements of developmental biology as part of its repair and recovery function, and how these elements go awry, resulting in chronic diseases. Repair and regrowth are co-regulated processes in response to inflammatory conditions. In order for tissue recovery to proceed, inflammation must coordinate a precise series of events that directs damaged cells to die, induces proliferation of protected specialized tissue progenitors to repopulate the damaged tissue, and promote differentiation of 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, thereby promoting disease. Inflammation in tissue microenvironments provides many of the necessary components for rapid proliferation of prostate epithelium and stroma: production of oxygen and nitrogen radicals and other DNA damaging agents; an environment rich in growth promoting cytokines, growth factors, and lipid mediators; and a reactive stroma.

Our laboratory is highly collaborative with several IUSM and Purdue University colleagues, and together we have developed numerous methodologies for the study of inflammation-induced signal transduction mechanisms in the prostate and urinary bladder, the study of expanding tissue progenitor cells, proliferation mechanisms, and cell survival mechanisms. These include our E.coli-induced mouse model of prostatic inflammation that results in neoplastic formation in aged animals, our first-of-its-kind systemic Toxoplasma gondii model of reactive microglandular hyperplasia that mimics epithelial nodule formation in advanced BPH in men, and orthotopic tissue-specific growth models of hyperplasia, and cancer of the prostate and urinary bladder in vivo. These models and others are employed in our laboratory to study several key projects:

1. To determine how inflammation-induced interleukin-1 (IL-1) signaling promotes epithelial progenitor cell survival and proliferation. This project involves studying how IL-1 regulates critical signaling in the prostate via two IL-1 effectors: Insulin-like Growth Factor -1 (IGF-1), and the androgen receptor. This work involves side-by-side collaboration with Dr. Timothy Ratliff’s laboratory at Purdue University.

2. To determine how the multifunctional protein Apurinic/apyrimidinic endonuclease/Redox factor-1 (APE1/Ref-1) regulates urinary bladder cancer cellular proliferation and cell survival. This project is a collaboration with Dr. Melissa Fishel and Dr. Mark Kelley, both affiliate faculty in the Department of Pharmacology and Toxicology. A second component of this work is determining if inhibition of this protein results in reducing the debilitating side effect of neuropathies associated with bladder cancer treatments, via a collaboration with fellow IUSM Pharmacology professor Dr. Jill Fehrenbacher.

3. Through collaboration with Professor Dr. Gustavo Arrizabalaga, we have found that the intracellular parasite Toxoplasma gondii infects and encysts in the prostate and induces microglandular hyperplasia similar to epithelial nodules present in men with advancing benign prostatic hyperplasia (BPH). We have optimized this model, and are studying the effect of infection in men, through collaboration with Dr. Douglas Strand at the University of Texas Southwestern. In addition, we are using this model to study the signaling mechanisms for microglandular hyperplasia formation, and the urinary tract symptoms that result in mice via a collaboration with Dr. Dale Bjorling at the University of Wisconsin-Madison and the O’Brien Center.