Faculty Spotlight: Exploring Sex Differences in LUTS With Jason Van Batavia, MD

Editor’s Note: Meet the diverse, dedicated, and distinctive faculty who are discovering and developing pediatric life-changing solutions at Children’s Hospital of Philadelphia Research Institute, in our monthly Faculty Spotlight series. This year, we’re celebrating our internal grant recipients who are pursuing new avenues of research with this dedicated funding support. Although we cannot feature all the award recipients in this series, we congratulate their continued hard work and scientific contributions to pediatric research. In this Q&A, we meet Jason Van Batavia, MD, recipient of the Foerderer Fund for Excellence. Stay tuned for more from our Faculty Spotlight series throughout the year.

How long have you been at CHOP, and what is your research specialty?

I came to CHOP more than eight years ago when I started my pediatric urology fellowship in July 2015, finishing it in June 2017. I then joined the Division of Urology faculty as a clinical instructor while completing my Master of Science in Translational Research (MSTR) at the University of Pennsylvania under a KL2 grant from the Institute for Translational Medicine and Therapeutics.

For two years, this provide me with protected time for research, which was crucial for me to build a foundation in the Urology Basic Science Laboratory under the mentorship of Stephen Zderic, MD. After completing the MSTR program, I was lucky enough to secure an NIH K08 career development award, and I joined CHOP’s faculty as an assistant professor in July 2019.

As a pediatric urologist and physician-scientist, my lab focuses on deciphering the neuro-urologic pathways that control normal and abnormal voiding and translating these findings into clinical improvement for children. The overall theme of my research, both clinical and basic science, has been on lower urinary tract symptoms (LUTS), specifically on how volitional voiding occurs in normal conditions and what changes in disease states. In my lab, we use state-of-the-art neuroscience techniques, such as optogenetics and fiber photometry, to understand the role of specific neuronal subpopulations in the brainstem region that controls voiding.

Overall, I consider myself a neuro-urologist, which works well because often when I tell people I am a urologist, they think I say neurologist, so either way they are correct. My long-term career goal is to become an expert and leader in the field of neuro-urology.

Why did you choose to focus on this specialty?

Serendipity led me to a career that has been centered on neuro-urology and pediatric neurogenic and non-neurogenic lower urinary tract (LUT) dysfunction. My early career mentors, Kenneth Glassberg, MD, and Dr. Zderic, instilled in me an interest in the clinical aspects of LUT dysfunction as well as a fascination for basic science research into the pathophysiology of LUT dysfunction working with animal models.

Interestingly, LUT dysfunction and bladder dysfunction are among the most common reasons for referral to pediatric urologists and affect approximately 20% of school-aged children. Despite this prevalence, these conditions are often neglected by pediatric urologists because they are time consuming to manage, rarely lead to surgical intervention, and can be frustrating for patients and families.

Many pediatric urologists refer treatment of LUTS to non-physician providers and prefer not to invest clinical time in non-surgical causes. I foresee myself as an advocate for these children, bringing change to a field that has seen little therapeutic development in decades.

What is a new avenue of research you’re able to explore as result of the Foerderer Fund for Excellence?

LUTS decreases quality of life and increases social humiliation and isolation in both children and adults. Sex differences are associated with specific LUT conditions, such as voiding postponement and overactive bladder. Despite the potential importance of sex-dependent mechanistic differences in LUTS, most basic science research has focused on male animal models.

Sex differences in the pathophysiology of LUTS may have implications for diagnosis and treatment of these conditions. Chronic social defeat stress (CSDS) is a translationally relevant psychosocial stress model that has already been shown in animal models to increase expression of the stress neuropeptide corticotropin releasing hormone (CRH) in the brain’s voiding “control center,” the Barrington’s nucleus (BN). CRH signaling components and neuronal responses are sex-dependent.

My Foerderer grant allows me to further collaborate with two CHOP neuroscientists, Amelia Eisch, PhD, and Sanghee Yun, PhD, to explore:

• The effects of a novel chronic non-discriminatory social defeat stress (CNDSD) model on the voiding phenotype and bladder wall, and CRH expression in BN neurons in female and male animal models
• Optogenetic inhibition of CRH BN neurons to reverse psychosocial stress-induced voiding dysfunction in freely moving female and male animal models. Our hypothesis is this inhibition of CRH BN neurons will more effectively reverse the psychosocial-induced voiding phenotype (larger, less frequent voids) and thus return the voiding pattern toward normal in females versus males.

This would provide the first direct evidence that sex-difference in psychosocial stress-induced LUTS and brainstem manipulation can reverse a voiding dysfunction and would highlight the potential targeting of the brain for LUTS. 

Can you tell us about a current research project that you are excited about?

I am also exploring the effects of sex hormones on the development of CSDS phenotypes. There is little understanding of the role sex hormones play in the development of stress-induced altered voiding phenotypes, so we will explore the role of these hormones in our CNDSD model. 

The third aim of my career development award utilizes single cell nuclear RNA-sequencing to identify and characterize the neuronal subpopulations that reside in and around Barrington’s nucleus in the pons. We have begun to isolate nuclei in this brain region and will be working in the next few months with CHOP’s Single Cell Technology Core to begin sequencing these nuclei.

What are the long-term research questions you hope to answer?

Ultimately, I believe this research will have translational potential to help us better understand how potential differences in responses to treatment options based on sex could affect how we treat our pediatric patients with LUT dysfunction.