When
Monday, December 1, 2025, 12:00 p.m.
Keating 103 | Zoom link
Hosts: Swarna Ganesh and Kellen Chen
Romi Castillo
PhD Candidate, Tardiff Lab
"A Novel TR-F Based High Throughput Screen to Identify Small Molecules that Modulate Diastolic Performance"
Abstract: Hypertrophic cardiomyopathy is a genetic cardiac disorder of the sarcomere that affects approximately 1/250-1/500 individuals globally. One of the earliest manifestations of the disease is impaired myocardial relaxation. This is an observable trait of preclinical HCM patients where impaired relaxation can be identified prior to the development of left ventricular hypertrophy. Here we develop a time-resolved fluorescence-based high throughput screening platform to identify small molecules that can enhance myocardial relaxation. Our optimized screening system yielded a hit rate of 3% and identified 360 small molecules that bind to the cardiac thin filament and produce a structural change in the N-terminus of cardiac troponin I, a region of the thin filament that is known to regulate cardiac relaxation. We proceeded with these small molecules for secondary screening and found that many alter the rate of thin filament deactivation. The small molecules that accelerated thin filament deactivation were moved forward with for tertiary screening using murine myofibril ATP-ase. Small molecules from this screen restored ATP-ase rates in myofibrils isolated from our HCM disease model. Future work will include scaling up the testing of the small molecules in more complex systems such as cardiomyocytes or the whole organ level. Altogether, this work provides a novel screening method to identify small molecules that can modulate diastolic performance with the potential to treat HCM or diseases of diastolic dysfunction more broadly.
Dilara Long
MD/PhD Candidate, Barton Lab
"Quantitative Analysis of Collagen Architecture in the Human Uterotubal Junction Using Optical Coherence Tomography Imaging"
Abstract: The uterotubal junction (UTJ) refers to the narrow intramural segment of the fallopian tube that is thought to regulate the precisely timed, bidirectional transport of gametes and embryos and provide protection against retrograde menstruation. Abnormal UTJ structure and function is implicated in the pathogenesis of endometriosis and tubal factor infertility; however, this relationship remains poorly characterized. Our objective was to map the architecture of collagen fibers in the UTJ using optical coherence tomography (OCT). UTJ tissue from 9 individuals undergoing hysterosalpingectomy were acquired and longitudinally opened to expose the luminal surface. Non-overlapping volumetric OCT images (FOV: 3 x 1 x 2.5 mm) were acquired from proximal (uterine), middle and distal (isthmic) UTJ segments using a benchtop OCT system. To reliably locate and map collagen fiber networks, we developed a preprocessing pipeline to improve tissue contrast and minimize tissue-mimicking artifacts. Enhanced en face images were divided into subregions and local fiber orientation and alignment strength was extracted from Sobel-filtered intensity gradients to generate depth-resolved fiber orientation maps for each volume.
Across all patients, we characterized transitional changes in two smooth muscle layers along the proximal-distal UTJ axis: an inner layer of strongly aligned longitudinal muscle and an outer muscular ring (weakly aligned oblique and highly aligned orthogonal fibers). Our findings provide the first quantitative, depth resolved profile of UTJ smooth muscle architecture, which could be used to establish diagnostic markers of structural abnormalities linked to endometriosis.
Accessibility: Persons with a disability may request a reasonable accommodation by contacting the Disability Resource Center at 621-3268 (V/TTY).