Current Projects
The Obesity Paradox In Melanoma
Immune checkpoint blockade (ICB) and BRAF-targeted therapy have significantly extended the life expectancy of melanoma patients. However, despite these treatment successes, a substantial 40-65% of those with metastatic melanoma do not survive beyond five years. Recent research has uncovered a perplexing phenomenon: obese patients receiving ICB and BRAF-targeted therapy show improved survival rates compared to their normal-weight counterparts. This unexpected discovery, known as the "obesity paradox," contradicts the establish thinking regarding obesity. In our research project, we aim to unravel this paradox by investigating how obesity-associated changes affect the efficacy of melanoma treatment.
The Genomic Landscape of In-Transit Melanoma
In-transit melanoma (ITM) metastases are cutaneous or subcutaneous deposits of melanoma cells in the drainage area between the primary tumor and the first regional lymph node. ITM is a distinct clinical entity that can be difficult to treat because the tumors can be multiple and encompass a very large area. The mechanisms underlying ITM metastases are not fully understood. While ITM often occurs in the presence of distant metastasis some patients exhibit only aggressive locoregional disease with delayed or no progression to distant sites. Our lab is looking at the unique mutational landscape of ITM metastases to determine if we can determine the underlying mechanism for this unique clinical behavior and possibly find therapeutic targets.
Endoplasmic Reticulum Stress in Obesity and the Effect on Melanoma
Endoplasmic Reticulum (ER) stress is caused by an accumulation of unfolded proteins within the ER. The increased inflammation associated with obesity increases the amount of ER stress within cells. Cancer cells utilize the unfolded protein response (UPR) to compensate to avoid undergoing cell death. We are investigating how melanoma cancer cells in obesity may have higher ER stress and are overall more susceptible to treatment as a result.
