Our research is currently funded by National Institutes of Health Grants U54DK104310, RC2DK129994, and other sources.

Project 1: Determine how the urethra fights infections

• The urethra isn’t just a tube; it actively helps fight off urinary tract infections.
• Special cells called neuroendocrine cells can sense bacteria and release serotonin, a chemical signal. This signal may tell nearby cells to contract and push bacteria out or trigger other defenses
• We’re figuring out which cells are involved and how they respond — to improve UTI diagnosis and treatment in both people and pets.
  

  Specialized serotonin-producing neuroendocrine cells (white) signal to nearby serotonin receptor positive cells (red) and other cells in the adult human female urethra

This time-lapse video shows fluorescent beads moving through a mouse urethra. By watching how the beads move, we can test whether drugs or chemicals change the speed or direction of flow. It helps us understand how the urethra works, and how we might control it to treat disease.

Project 2: Determine how the urethra causes male lower urinary tract symptoms

• Millions of men deal with lower urinary tract symptoms (LUTS), like not fully emptying the bladder or needing to pee often at night.
• These problems are often linked to prostate inflammation, which might cause neuroendocrine cells to release too much serotonin.
• Instead of helping, serotonin may tighten the urethra or prostate, making it harder to urinate.
• We’re studying this pathway to find new ways to stop it — and to help men avoid invasive treatments.

Project 3: Remap the cellular anatomy of the prostate and urinary tract.

• Advanced molecular biology methods allow us to visualize organs in ways that were not previously possible
• We partnered with the Strand Lab at the University of Texas Southwestern to visualize the urinary tract at the cellular and subcellular level
• We are examining how aging, inflammation, and other processes influence prostate and urinary tract cellular composition, trajectories of cell differentiation, and physiological function

Prostate cells are identified by fluorescent staining. We are determining how aging, inflammation, benign enlargement and cancer influence the prostate’s cellular composition

Project 4: Identify new ways to combat prostate collagen accumulation.

• Collagen increases stiffness and reduces efficiency of many aging organs
• Collagen accumulates in prostates of some aging men, impairing passage of urine
• Collagen accumulates during development of some prostate cancers, potentially enabling tumor growth and metastasis
• We are identifying which prostate cells make collagen and testing new therapies to reduce collagen

The left image shows collagen (red) in the prostate of a young adult man. The right image shows expansive collagen in the prostate of an older man. We are measuring collagen abundance and determining how it changes during aging and in response to inflammation, which occurs frequently as men age

Project 5: Determine how the early life environment influences urinary health in adulthood.

• Why some men and male dogs develop symptoms at an early age or in a severe form is unknown
• Our seminal work demonstrated that adult male voiding function is not only shaped by the adult environment, but also by the fetal and neonatal environments
• We are currently unraveling how environmental chemicals program urinary tract anatomy and physiology to make males more susceptible to aging-related urinary dysfunction

We have evidence that environmental chemicals reprogram prostate neuroanatomy, causing prostate smooth muscle to contract excessively and obstructing urine flow through the urethra.

Nerve axons are detected as green fluorescence (urethral epithelial cells are white and cell nuclei are blue). We are counting axons and testing whether they become more numerous after environmental chemical exposures

Calcium is released when prostate smooth muscle contracts and is detected as red, green, and blue fluorescence. Contracted smooth muscle can interfere with urine flow through the urethra and prevent the bladder from emptying. We are testing whether environmental chemicals increase prostate muscle contraction