Research in the Capparelli Lab is centered on identifying mechanisms of drug tolerance and resistance to targeted inhibitors and immunotherapies in melanoma.

The incidence of cutaneous melanoma continues to rise, and the efficacy of FDA-approved treatments is limited by tumor heterogeneity, cellular adaptations, and resistance.  Our studies aim to understand the mechanisms underlying tumor heterogeneity and plasticity to provide new treatment strategies that improve the duration of patient responses. Intra-tumoral heterogeneity and cellular plasticity allow tumors to adapt to foreign microenvironments and tolerate therapeutic insults. It is critical to characterize the mechanisms that underlie plasticity of melanoma to overcome the onset of metastasis and drug tolerance following treatment. Our research aims to identify and target pathway dependencies and vulnerabilities in tolerant persister cells in order to prevent metastasis and improve treatment options for melanoma patients. Additional research interests include: i) characterizing alterations that occur in the Extra Cellular Matrix during the establishment of drug tolerance and ii) investigate therapies that mediate changes within the tumor immune microenvironment as an approach to improve response to immunotherapies. Understanding alterations in the tumor microenvironment could ultimately lead to the identification of novel therapeutical approaches for the treatment of melanoma.  

Overall, our studies aim to characterize the heterogeneity and plasticity of the tumor compartment and its associated tumor microenvironment during the onset of drug tolerance with the goal of identifying novel therapeutical approach for the treatment of melanoma. 

1. Determine mechanisms underlying BRAFi/MEKi tolerance in melanoma
2. Role of the tumor microenvironment in driving tolerance to targeted and immune therapies in melanoma.
3. Identify and target drug tolerant persister cell vulnerabilities to develop novel therapeutical strategies for the treatment of melanoma
4. Reinvigorate the tumor microenvironment as strategy to improve response to therapies.