Osteoarthritis (OA) is a degenerative joint disease characterized by pain and reduced mobility. Current treatments like physical therapy and corticosteroids do not modify disease progression, while autologous platelet-rich plasma (PRP) injections offer a promising alternative due to their platelet and growth factor content. However, PRP’s effectiveness in reducing knee OA pain varies, and the specific therapeutic components remain unclear. In this study, PRP samples from 30 patients with knee OA (Kellgren & Lawrence grades 2-3) were analyzed to identify biomarkers associated with treatment response. Blood samples were drawn and PRP was prepared; one set was used for therapy and the other, analysis. Comprehensive profiling included cell counts, immune cell characterization via mass cytometry, and proteomic analysis using mass spectrometry. Pain was assessed using KOOS pain scores at baseline and 6 weeks post-injection. Results showed that PRP therapy improved pain in 19 of 30 patients. While platelet type analysis revealed no differences between responders and non-responders, distinct immune cell clusters (CD4 T cells, CD8 T cells, and NKT cells) and differentially expressed proteins, several differentially expressed proteins correlated with pain outcomes. In patients who responded to PRP, levels of the proteins CD47, ILK, and GPX1 were low, while the proteins CTSG, S100A8, and LCP1 were high. These findings suggest that specific biomarkers within PRP may predict treatment success, guiding personalized therapeutic strategies.

Fibroblast growth factor 21 (FGF21) is a metabolic cytokine that is synthesized in the liver, secreted into the bloodstream, and signals through other tissues, namely the brain and adipose, thereby regulating systemic energy homeostasis. Obesity is caused by imbalances in energy homeostasis and affects 39.6% of U.S. adults, making it one of the most pressing public health crises in modern history. The zinc finger protein 36 (ZFP36) family of RNA binding proteins (RBPs) are post-transcriptional regulators that degrade their mRNA targets by binding to AU-rich elements. These proteins are involved in the post-transcriptional regulation of FGF21. Deletion of the ZFP36 proteins in the livers of adult male mice led to significant upregulation of Fgf21 mRNA and dramatic weight loss, while deletion in female mice led to lower Fgf21 mRNA upregulation but comparable weight loss. To investigate the discrepancy between Fgf21 mRNA upregulation and weight loss in males and females, we conducted qPCR on the livers of male and female mice lacking the ZFP36 proteins for 2 or 20 days to directly compare Fgf21 mRNA expression between the sexes. Female mice have higher basal levels of hepatic Fgf21, elucidating why the fold change in Fgf21 mRNA expression in females lacking the ZFP36 proteins is less than that observed in males. This expands on our current knowledge of FGF21, its role in diet-induced obesity, and how sex differences in Fgf21 mRNA expression may influence the development and efficacy of targeted therapies for metabolic diseases.

Acute lymphoblastic leukemia (ALL) has worse clinical outcomes in patients with obesity. Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors, such as dapagliflozin, are effective in treating obesity and have shown anticancer activity in several malignancies. However, the effects of SGLT2 inhibitors on ALL remain unexplored. My project aims to determine the extent to which dapagliflozin affects ALL cell viability and to explore mechanisms of SGLT2i (Sodium-Glucose Cotransporter-2 inhibitor) with ALL. I hypothesize that dapagliflozin will reduce ALL cell proliferation and viability by limiting glucose availability, preventing cancer cells from acquiring the high concentrations of glucose they need to survive and rapidly divide. Our lab has already found that SGLT2i decreases viability in cell culture with 8093 mouse leukemia in a dose-dependent manner and shows synergy with the common chemotherapy vincristine. I have also examined the effect of dapagliflozin on human ALL cell lines (RS4;11 and BV173) in cell culture, finding that dapagliflozin and vincristine decreased cell count and cell viability in a dose dependent manner. Our lab will continue to investigate dapagliflozin's effect molecularly, specifically on pro-inflammatory genes known to boost tumor proliferation. These findings will provide insight into the role of SGLT2 in ALL metabolism and explore the potential of dapagliflozin as a therapeutic strategy either by itself or supplement to chemotherapies, paving the way for improved outcomes in ALL treatment.

Brown adipose tissue (BAT) is characterized by its distinct ability to expend energy through thermogenesis, a mechanism that carries therapeutic potential for metabolic disorders. Glycogen metabolism, a primary regulator of energy homeostasis, is an emerging area of interest in BAT functionality. Despite low basal levels, glycogen turnover increases under metabolic shifts like thermogenic activation, though this mechanism remains incompletely understood. Glycogenesis is primarily regulated by the rate-limiting enzyme glycogen synthase (GYS1). Importantly, Gys1 deletion in adipose tissue impairs its capacity for adaptive thermogenesis, suggesting its role as a key enzyme in coordinating energy expenditure. However, the regulatory mechanisms of GYS1 remain poorly defined in BAT. To address this gap, we adopted an unbiased, proteomics-based approach to explore GYS1 regulation in brown adipocytes. As the complete GYS1 interactome has not yet been characterized in BAT, we utilized proximity labeling via the TurboID system to identify interacting partners with GYS1. Unexpectedly, pathway analysis of identified interactors revealed enrichment in processes related to lipid metabolism and mitochondrial dynamics, suggesting previously unrecognized roles for GYS1. CoIP analysis will be conducted to experimentally validate interactions and explore their regulation during metabolic shifts. These findings will further elucidate the mechanisms that regulate glycogen metabolism in brown adipocytes.