Cardiovascular disease (CVD) is the leading cause of pregnancy-related mortality in the US, accounting for 26.5% of maternal deaths; yet most of these deaths are preventable, stemming from delayed recognition of warning signs, missed diagnoses, and gaps in prenatal or postpartum care. Despite clinical advances, a critical gap remains in understanding the patient experience in cardio-obstetric care. Many women with CVD are incorrectly told they cannot or should not become pregnant, underscoring the need for patient empowerment through education and engagement. This study aims to identify barriers to patient involvement and inform strategies that foster effective provider-patient communication. We developed evidence-based educational materials on CVD, contraception, and pregnancy, distributed at the UCLA Cardio-Obstetrics clinic. To evaluate patient attitudes, we conducted stratified focus groups with pregnant and postpartum cardio-obstetric patients and employed a mixed-methods approach, combining qualitative thematic analysis with quantitative maternal and neonatal clinical data. Analysis is in progress; initial insights illuminate both shared and divergent themes across subgroups, providing a more holistic understanding of the patient experience and impact of educational intervention. By obtaining a deeper understanding of these perspectives, we hope to encourage patient-provider relationships that prioritize advocacy, improving maternal and neonatal outcomes for cardio-obstetric patients globally.

Cerebral palsy (CP) is the leading cause of physical disability in childhood. Spastic CP, the most common form, is characterized by progressive skeletal muscle impairment, often culminating in fixed contractures. Previous research has shown muscular differences between CP patients and control patients. However, none of these studies have compared the intracellular structure of myofibrils or measured its mechanical properties. This project compares the architecture of myofibrils between CP muscle and control muscles, specifically vastus lateralis. Longitudinal cross-sections (50μm) were prepared for imaging. A 2-Photon (2P) microscope imaged the autofluorescence of collagen and elastin in muscle sections. Subsequently, Fluorescent Lifetime Imaging (FLIM) produced better resolution images of the elastin channel by breaking down the lifetimes of components. AI Visualization Image Analysis (AIVIA) quantified the differences in myofibril length. These processes produced a three-dimensional reconstruction of the sarcomere for the first time in CP muscle. Preliminary results found a significant difference in distance between individual myofibrils. The average distance between myofibrils in CP tissue was 1.15μm, while only 0.76μm in control tissue. CP myofibrils were approximately 34% farther away from other myofibrils than control myofibrils, which could explain the lack of force transmission in CP muscles. Further research aims to compare myofibril alignment with ryanodine receptors (RYR-1) and its part in the T-tubule network.

Neurodevelopmental disorders (NDDs) are a group of conditions that arise from abnormalities in brain development, often associated with delays in motor, behavioral and cognitive functions, including communication and social interactions. MACF1-related neurodevelopmental disorder is a serious life-changing pediatric condition caused by mutations in the MACF1 gene which encodes Microtubule-Actin Cross-Linking Factor 1 protein. This protein plays a critical role in neuronal migration and axonal function. There are currently no targeted therapeutics for this disorder, as its underlying mechanisms remain poorly understood. In this study, we used patient-derived induced pluripotent stem cells (iPSCs) to develop an in vitro model of the disease. We generated cortical organoids from control and MACF1 iPSCs to investigate the role of MACF1 in early brain development, including neuronal cell maturation and migration. Our studies show stem cell-based in vitro modeling MACF1-related neurodevelopment disorder can be used to serve as a patient-specific platform to better understand the processes of this disease and help advance therapeutics.

Pancreatic ductal adenocarcinoma (PDAC) accounts for >80% of pancreatic cancers and has a poor ~12% 5-year survival rate. Although radiation therapy (RT) is a cornerstone of cancer treatment, PDAC is notably radioresistant, partly due to metabolic adaptations that buffer oxidative stress. In this project, I investigated the role of the serine metabolism axis in PDAC radioresistance. Radiation induces cancer cell death primarily through reactive oxygen species (ROS), while glutathione (GSH) neutralizes ROS. We hypothesized that serine availability enhances GSH production and radioresistance, and that NRF2 regulates serine uptake and utilization in response to RT. We examined NRF2’s role in regulating the serine transporter SLC1A5 and the mitochondrial enzyme SHMT2, which converts serine to glycine and supports GSH synthesis via serine-glycine one-carbon metabolism (SGOM). Using doxycycline-inducible CRISPR-Cas9, we knocked out NRF2 in MiaPaCa cells to study its role under serine deprivation and radiation. SHMT2 expression increased with radiation and serine deprivation, but this effect was eliminated with NRF2 knockout, indicating NRF2 is a key regulator of SHMT2 following radiation. SLC1A5 expression also increased with radiation but showed less NRF2 dependence. Overall, our findings suggest NRF2 promotes SGOM in PDAC after radiation by upregulating SHMT2, highlighting NRF2 as a potential target to sensitize PDAC to RT by limiting serine metabolism and overcoming radioresistance.

Hepatocellular carcinoma (HCC) accounts for 80-90% of primary liver cancers and remains the fifth most common cancer worldwide. The five-year survival rate is 22% as of 2026, primarily due to late-stage diagnosis and high recurrence rates following treatments like thermal ablation. Tumor recurrence within sublethal zones remains a significant challenge, and the efficacy of adjuvant immunotherapy of natural killer (NK) cells in these zones is not yet fully characterized. This project investigated how HCC cell lines respond to primary natural killer (NK) cells following sublethal heat exposure. The experimental design utilized four groups of tumor cells: . Cell lines were subjected to 45 degrees Celsius for 10 minutes and given 24 hours to recover and be plated the next day. Human NKs were negatively selected from whole blood and activated with IL-2 or IL-2 and αCD16 before co-incubation with HCC tumor cells. Cytotoxicity was monitored in real-time using eSight to measure cell index via electrical impedance. NK cell cytotoxicity was validated through ELISAs for cytokines IFN-ɣ and TNF-α. This research sought to determine if combinatorial NK cell activation enhances the immune response against heat-stressed HCC. This study provided a detailed characterization of immunotherapy effectiveness post-ablation, offering insights that could optimize clinical protocols to prevent HCC recurrence and improve patient survival.