Dr. Bhatia is an Assistant Professor (CHS) in the Department of Urology at the School of Medicine and Public Health. Her mentors are Drs. Heidi Wendell Brown, Marisa Hilliard, and Kris Penniston.
The title of Dr. Bhatia’s work is Transforming Care for Youth with Hypospadias: The Patient-Prioritized Care Plan. Hypospadias (HS) is one the most common congenital urological birth defects worldwide, affecting 1 in 200 male live births. This condition often requires multiple genital surgeries in childhood, all of which exhibit significant complication rates. While ample literature reports the technical outcomes and complication rates in HS, limited research on psychosocial outcomes demonstrates that people with HS experience challenges, including difficulty seeking social support, depression and anxiety, and fear of using public restrooms and change rooms.
The ability to understand and attend to these concerns in tandem with functional concerns, could guide individualized follow-up and referral strategies to improve outcomes in HS. Health-related quality of life (HRQOL) is an important patient-reported outcome construct that captures all positive and negative aspects of life that affect health; however it has not been studied in HS. To facilitate understanding of patient priorities and care needs in HS, we developed the HS-Specific HRQOL Framework, which identified five inter-related components8 and identified a battery of HRQOL measures that could be used to obtain a comprehensive understanding of HS-Specific HRQOL.
A care plan tool for patients with HS could help practitioners incorporate functional and HRQOL data into a personalized follow-up plan for youth with HS. Emerging data suggest that indefinite follow-up may be needed to identify both QoL and surgical issues requiring intervention. In other chronic pediatric health conditions requiring life-long follow-up, care plans have been used to improve patient health knowledge, engagement with self-care, and communication with providers. A care planning tool for youth with HS could advance the treatment of HS by ensuring that patients receive early psychosocial support. In addition, such a tool could allow physicians to accurately evaluate the outcomes of different surgical techniques, and, accordingly, routinely incorporate HRQOL into care decision-making for HS. This approach could then be expanded to the care of youth with other complex genitourinary anomalies.
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Andrew Wentland, MD, PhD
Dr. Wentland is an Assistant Professor in the Department of Radiology, School of Medicine and Public Health. His co-mentors are Scott Reeder, MD, PhD, Professor, Departments of Radiology, Medical Physics, Biomedical Engineering, &
Medicine and Walid Farhat, MD, Professor and Chief of Pediatric Urology, Department of Urology, School of Medicine and Public Health.
The title of Dr. Wentland’s research is Quantitative Magnetic Resonance Urography: Non-Invasive Evaluation of Per-Kidney Urinary Output. This work will focus on developing improved non-invasive measurement of urine output from individual kidneys. Technetium-99m-MAG3 (99mTc-MAG3) scintigraphy is commonly performed in pediatric urology to diagnose ureteral obstruction, duplicated collecting systems, and congenital kidney abnormalities, including crossed-fused renal ectopia, dysplastic kidneys, ectopic kidneys, and horseshoe kidney. However, nuclear scintigraphy has a number of limitations. Scintigraphy requires administration of ionizing radiation, which is particularly problematic in pediatric patients. Furthermore, scintigraphy provides poor anatomic detail, with limited ability to assess bifid versus duplicated ureters or the independent function of renal moieties in conditions such as crossed-fused renal ectopia, horseshoe kidney, and duplicated collecting systems. Magnetic resonance urography (MRU) is a promising technique with the potential to overcome limitations of other imaging modalities. MRU provides excellent anatomic detail and yields valuable information for surgical planning even in complicated renal or urinary systems. Furthermore, novel MRU techniques provide information on renal function.
Dr. Wentland’s career goals include development of an independent program of research that will advance the precision of use of MRI to assess the urinary tract. This work has the potential to significantly decreases exposure of pediatric patients to ionizing radiation. His work will test the hypothesis that a quantitative MRU (qMRU) technique can provide measurements of urinary excretion similar to, or more accurate than, measurements obtained with 99mTc-MAG3 nuclear scintigraphy.
Aim 1 of Dr. Wentland’s research will test the hypothesis that a novel velocity-sensitive MRI technique can accurately measure low flow states. Aim 2 will test the hypothesis that a quantitative MRU technique can detect changes in urinary excretion in a swine model and provide an accurate assessment of urinary excretion compared to 99mTc-MAG3 nuclear medicine scintigraphy. It is anticipated that this novel quantitative MRU technique will provide both functional evaluation of urinary excretion as well as more accurate anatomic information compared to 99mTc-MAG3 nuclear scintigraphy. qMRU will more accurately guide surgical management of pediatric patients with renal or urinary tract abnormalities. This technology lays the groundwork for an unprecedented means of assessing urinary excretion across patient populations.
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Lauren Baker, DVM, PhD
Dr. Baker is an Assistant Scientist in the School of Veterinary Medicine and the Department of Urology, School of Medicine and Public Health. Her mentors are Dr. Corinne Engelman and Dr. Stephen Nakada.
The title of Dr.Baker’s research is Discovering genetic drivers of calcium oxalate urinary stone disease through multi-omics dissection in the spontaneous dog model. Kidney stone disease is a common, life-altering diagnosis causing significant patient morbidity. Over 75% of kidney stones are composed of calcium oxalate (CaOx), and recurrence is common. Genetic predisposition plays a large role in disease initiation. The complexity of the disease and human genetic diversity have limited the success of genetic studies in human beings.
The Miniature Schnauzer dog is an excellent spontaneous animal model for genetic study of CaOx urinary stones. Miniature Schnauzers are 12 times more likely to develop CaOx stones compared to the general canine population, and reduced genetic diversity within the breed increases statistical power to detect genetic associations. Previous epidemiological research shows that the majority of Miniature Schnauzers with CaOx stones are hypercalciuric, which is the most common metabolic abnormality in humans. One third of these dogs also have disorders of vitamin D metabolism, indicating that there are multiple drivers of hypercalciuria within the breed. Therefore, the dog model provides the advantage of reduced genetic complexity while maintaining disease complexity that is applicable to the human condition.
Aim 1 of Dr. Baker’s work will pursue the complexity of CaOx stone disease through metabolomics analysis to define molecular phenotypes before genetic association analysis to discover genetic drivers of metabolic abnormalities. Aim 2 will follow up on preliminary evidence that a long intergenic non-coding RNA (lincRNA) is driving regulation of the calcium sensing receptor (CASR), causing absorptive hypercalciuria in stone formers. This work will expand this analysis to discover additional RNA biomarkers, and utilize network analysis to define core genes and genetic pathways that are involved in disease pathogenesis. A similar RNA sequencing analysis in human beings will be performed to construct a consensus network to formally define genes and genetic pathways that are shared between dogs and humans, which will guide future research.
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Matthew D. Grimes, MD
Dr. Grimes is an Assistant Professor (CHS) in the Department of Urology at the School of Medicine and Public Health. His mentors are Drs. Wade Bushman and Chad Vezina.
The title of Dr. Grimes’ work is loss of CD44 expression drives altered collagen structure in lichen sclerosus. Lichen sclerosus (LS) is a poorly understood chronic inflammatory condition of the genital skin with an estimated prevalence of 1:300. Approximately 20% of men with LS develop urethral stricture disease (USD). These patients commonly develop profound fibrosis of the entire anterior urethra requiring complex and morbid surgical reconstruction with low success rates. The mechanisms by which LS leads to USD are unknown and represent a critical knowledge gap in benign urology.
Dr. Grimes’ long-term career goal is to develop minimally invasive and nonsurgical treatments of LS and USD through improved understanding of its molecular pathogenesis. This proposal focuses on the principal hyaluronic acid receptor CD44. Human LS skin lesions are characterized by a loss of CD44 and an overabundance of extracellular hyaluronic acid. Lichen sclerosus skin lesions and associated stricture are characterized by prominent collagen fibrosis in the extracellular matrix. A mouse model of genetic epithelial CD44 depletion recapitulates this pattern of increased hyaluronic acid abundance and collagen fibrosis. The proposed research plan will directly test the overarching hypothesis that loss of CD44 expression in patients with lichen sclerosus triggers extracellular hyaluronic acid accumulation, TGF-β pathway activation, and collagen accumulation.
While conducting this work, Dr. Grimes will complete a Certificate Program in the Foundations of Clinical Research and be mentored by a diverse team with expertise in advanced microscopy, image analysis, and utilization of transgenic animal and in vivo functional testing to link molecular mechanisms to physiological outcomes. The proposed research will provide preliminary data for a subsequent K23 application, and the proposed training plan will prepare Dr. Grimes to achieve his long-term goals as an independent researcher. By defining the mechanisms driving fibrosis in LS he will identify putative therapeutic targets and alter the current “surgery first” treatment of LS and related USD.
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LaTasha Crawford, VMD, PhD, Diplomate American College of Veterinary Pathologists
Dr. Crawford is an Assistant Professor in the School of Veterinary Medicine and Department of Patholbiological Sciences. Her mentors are Drs. Dale Bjorling and Chad Vezina.
Dr. Crawford’s research focuses on chronic pain. Chronic pain associated with urologic disease affects millions of people in the U. S. alone, yet is exceedingly challenging to treat. There is an unmet therapeutic need that extends beyond the opioid crisis, as many existing therapies often lead to addiction, cause unwanted side effects, or prove inadequate for managing pain in many patients. Deficits in the ability to diagnose or effectively treat pain patients stem from a lack of understanding of pain mechanisms; this is particularly true for bladder pain. For example, in interstitial cystitis, it is still unknown what causes pain symptoms and why comorbid disease in other organ systems is so frequent. Recent studies indicate that many patients with bladder disease have comorbid changes in somatosensory neurons that are diagnostic for neuropathic pain. This suggests that somatosensory neurons may play a role in referred pain, challenging the existing dogma that referred somatic pain is due to spinal cord mechanisms. Somato-visceral crosstalk within the peripheral nervous system comprises a substantial gap in our knowledge of bladder pain mechanisms. Dr. Crawford’s research will test the hypothesis that there is peripherally-mediated crosstalk between somatosensory and bladder sensory neurons that contributes to comorbid pain in distinct organs systems and provides a mechanism for dysregulation of bladder function. To test this hypothesis, she will determine the cell type-specific molecular, anatomic, and neurophysiologic underpinnings of somato-visceral crosstalk in mouse models of cystitis and hindlimb nerve injury. This project will optimize an innovative neurophysiology approach, provide experience in transcriptomics, and develop Dr. Crawford’s expertise in biomarkers of bladder pain, propelling her career as a clinician-scientist. Her findings will have significant benefits for urologic disease research by highlighting potential diagnostic features of comorbidities in bladder pain patients and providing a mechanistic rationale to guide selection of existing anti-pain therapies as well as development of novel therapeutics.
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