Kymora B. Scotland, MD, PhD

2023–2028 Award Winner

Assistant Professor, Department of Urology
Director of Endourology Research
Associate Director, Endourology Fellowship Program
University of California, Los Angeles

Research Project: "Elucidating the Role of Biofilm-Forming Bacteria in Nephrolithiasis"

Sponsor: Frank and Marion Hinman Urology Research Fund

Abstract:
The goal of Dr. Scotland’s proposal is to determine the role of bacteria in the growth of calcium-based kidney stones and thus the significance of bacteria to kidney stone disease. Nephrolithiasis (kidney stone disease) is increasingly prevalent, affecting over 35 million (11%) North Americans per year, and remains a serious health concern due to its association with severe pain, life-threatening infection, and potential damage to kidneys. Moreover, the rate of recurrence is high, with approximately 50% of patients experiencing another stone episode within 5 years of their first treatment. Thus, kidney stones pose a substantial financial burden on the medical system, with the annual direct and indirect costs estimated at more than $5 billion in the United States. Approximately 80% of kidney stones are composed of calcium oxalate. Successful prevention requires a clear understanding of the mechanisms involved in stone formation. However, the actual process of calcium stone formation is not well understood. Emerging data suggest that bacteria may play a critical role in stone formation. Recent studies have identified bacteria in calcium stones collected from patients who had no evidence of urinary tract infection, suggesting that these bacteria are not simply bystanders but may in fact influence stone formation. Dr. Scotland’s research hypothesizes that bacteria interact with calcium stones and that this interaction plays a key role in the propagation of the stones. During the 5-year Rising Stars in Urology Research Award, Dr. Scotland will investigate stone biofilm formation from bacteria to see whether this process contributes to kidney stone layering. The project will explore the role of surface sensing in the bacteria-kidney stone interaction, evaluating whether known pathways are involved in triggering stone formation. Lastly, the project will investigate how bacteria respond to calcium oxalate crystals and kidney stone propagation in urine using a three-dimensional kidney model that Dr. Scotland’s lab has developed. Successful completion of this research will provide valuable insight into future strategies to treat kidney stone disease.

Ryan K. Flannigan, MD

2022–2026 Award Winner

Assistant Professor, Department of Urological Sciences
Director of Male Reproduction and Sexual Medicine Research Program
University of British Columbia

Research Project: "Leveraging Computational Modelling and 3-D Bioprinting in Pursuit of a Regenerative Therapeutic Approach for Male Infertility"

Sponsor: Astellas Pharma, US, Inc.

Abstract:
Leveraging computational modelling and 3-D bioprinting in pursuit of a regenerative therapeutic approach for male infertility, Dr. Flannigan aims to develop technology toward establishing a regenerative therapy platform to grow sperm from a patient's stem cells in a laboratory setting. His project proposes to utilize state-of-the-art single cell sequencing and associated computational technologies to reveal molecules that are key regulators of developing sperm from stem cells. Since the production of sperm from a stem cell involves several stages of changes to the cell, his lab has uniquely segmented this process into well described stages, so that each stage can be studied independently and precisely. Stage-specific findings will then be screened with small molecules and growth factors to identify the most critical molecules that promote stem cells to mature into sperm. Lab-grown patient testis cells will be 3D bio printed into tubular structures similar to those found within the human testis that naturally coordinate sperm production. Results from this study will contribute to developing the understanding and technology to regenerate sperm for males lacking any ability to father biological children. This technology is particularly salient considering the pervasiveness of infertility in prepubertal men surviving cancer treatment and among 15% of couples globally, with male factors contributing to 50% of infertility cases.

A. Lenore Ackerman, MD, PhD

2021–2024 Award Winner

Assistant Professor, Urology
Director of Research, Division of Female Pelvic Medicine and Reconstructive Surgery
University of California, Los Angeles

Research Project: "The Urinary Microbiota and Host Inflammation in Lower Urinary Tract Symptoms"
Sponsor: Frank and Marion Hinman Urology Research Fund

Abstract:
Focusing on the roles that urinary microbes (the “urobiome”) play in the lower urinary tract, Dr. Ackerman will examine urinary bacterial and fungal communities in different types of voiding dysfunction to identify patterns in the urobiome associated with specific lower urinary tract symptoms. Her studies will include an exploration of the co-occurring patterns of urinary inflammation as well as an investigation of human genes that may confer an increased risk of disease. The application of large-scale systems biology approaches to voiding dysfunction and the integration of these data with detailed patient symptomatic phenotyping will facilitate a deeper understanding of the mechanistic foundations of these syndromes. The integration of this kind of multi-“omic” data will help allow the discovery of clinically useful disease markers, both microbial and inflammatory, that may provide needed prognostic information for patient care. It will also help to explore the molecular mechanisms underlying different forms of voiding dysfunction to aid in the future development of new management and therapeutic approaches.