Research
Multimodal optical imaging of bladder cancer
A major research focus is development and translation of multimodal optical imaging technologies for detection, characterization, and resection of bladder cancer. Ongoing and past research:
1) Augmented endoscopy using artificial intelligence and computer vision
2) Molecular imaging and focal targeting therapy of CD47, an innate immunity checkpoint
3) Optical biopsy of the urinary tract using confocal laser endomicroscopy
We pioneered the urological applications of confocal endomicroscopy for bladder cancer (Sonn 2009), upper tract urothelial carcinoma (Bui 2015) and prostate cancer (Lopez 2015). This optical biopsy technology enables real-time intraoperative imaging with spatial resolution comparable to histology.
Urinary liquid biopsy and molecular diagnostics
We are identifying and validating urine-based biomarkers to inform bladder cancer diagnosis, prognosis, and treatment response. Given its abundance and non-invasive nature of sample collection, urine serves as an ideal source of liquid biopsy.
To overcome the diagnostic shortcomings of standard urine cytology, we have utilized high throughput sequencing technology as a discovery and diagnostic tool. Initially, we applied bulk RNA sequencing to urinary pellets for biomarker discovery and developed a diagnostic 3-marker urinary RNA panel (Sin 2017) and led a multi-center effort to validate another 3-marker urinary RNA panel using an integrated microfluidic cartridge (Wallace 2019). Subsequently, we identified the key biomarkers from the initial panels that could provide the highest sensitivity for bladder cancer detection and surveillance (Shkolyar 2021). We are currently working to validate this panel in a multi-site study and explore avenues to incorporate the biomarker analysis in clinical settings.
Given its abundance and ease of sample collection, urine is ideally suited as the source for development of bladder cancer molecular diagnostics. We applied high throughput sequencing and multiplex quantitative PCR to identify cancer-specific and ultrasensitive detection of tumor-derived RNA and cell-free DNA.
To overcome the diagnostic shortcomings of standard urine cytology, we have utilized high throughput sequencing technology as a discovery and diagnostic tool. Initially, we applied bulk RNA sequencing to urinary pellets for biomarker discovery and developed a diagnostic 3-marker urinary RNA panel (Sin 2017) and led a multi-center effort to validate another 3-marker urinary RNA panel using an integrated microfluidic cartridge (Wallace 2019). Subsequently, we identified the key biomarkers from the initial panels that could provide the highest sensitivity for bladder cancer detection and surveillance (Shkolyar 2021). We are currently working to validate this panel in a multi-site study and explore avenues to incorporate the biomarker analysis in clinical settings.
Medical device development - Kidney Stone Disease & Urinary Tract Infections
Our lab has strong interest in collaborative research with engineering collagues to develop medical devices for 1) retrieval of kidney stone fragments using magnetic hydrogel and 2) rapid detection of uropathogen and antimicrobial susceptibility testing.
My group has collaborated with colleagues in urology, nephrology, and engineering in clinical and translational research related to kidney stone disease. These research endeavors have established the background and impetus for our current NIDDK-funded R21 to develop new tools for kidney stone fragment removal.
