Projects

IGFBP-3 and PDAC-induced Skeletal Muscle Wasting

Recently, our lab discovered new experimental evidence that is both consistent with the established paradigm of a pro-inflammatory tumor microenvironment in PDAC, and novel findings that associated SMW is mediated by the induction of IGFBP-3 and adipogenesis in affected skeletal muscle. Taken together with the literature, we propose a unifying hypothesis of PDAC-related SMW pathogenesis in which pro-inflammatory cytokines, and potentially IGFBP-3 itself, act as paracrine factors to promote M2 myelopoiesis, in which IGFBP-3 expressing macrophages infiltrate skeletal muscle and mediate myofiber catabolism and lipid accumulation.

Validation of Dual Energy X-ray Absorptiometry to Quantify Tumor Burden

Noninvasive imaging is central to preclinical, in vivo models of pancreatic ductal adenocarcinoma (PDAC). While bioluminescent imaging (BLI) is a gold standard, its signal is dependent on the metabolic activity of tumor cells. In contrast, dual energy X-ray absorptiometry (DEXA) is a direct measure of body composition. Findings from our lab support the use of BLI for initial tumor engraftment and persistence but demonstrate the superiority of DEXA for longitudinal tumor burden studies. As tumor detection by DEXA is not restricted to luciferase expressing models, future studies to assess its value in various cancer models and as an in vivo outcome measure of treatment efficacy are warranted.

IGFBP-3 and PDAC Tumor Progression

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths and metabolic dysfunction is understood to be a driving mechanism in disease progression. Our lab recently identified insulin-like growth factor binding protein 3 (IGFBP-3) as a possible key regulatory molecule and publicly available human TCGA data indicates that IGFBP-3 is significantly upregulated in PDAC tumors and correlates strongly with poor survival. The lab is currently investigating the role that increased IGFBP-3 expression plays in PDAC tumor progression.

Rheumatoid Arthritis, Wheel Running, and Skeletal Muscle Wasting

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, swelling, and joint destruction that decreases mobility. RA patients also suffer from pulmonary disease (PD) and sarcopenia, which decrease strength and endurance for physical activity. Remarkably, the ACR just released its first guidelines on the use of 4 distinct exercises in conjunction with disease-modifying anti-rheumatic drugs (DMARDs) as an integrative management approach for RA. However, the risk: benefit ratio of exercise on inflamed joints remains a major concern, although the most recent clinical studies demonstrate long-term benefits. Recently, we showed that ad libitum wheel running is effective in improving lean mass in the male TNF-Tg mouse model of RA.