I direct the Ludwig Collaborative Laboratory and the Swim Across America Laboratory at Memorial Sloan Kettering. I also lead the biorepository for the Melanoma Service at MSK.
My research projects focus on investigating the means for developing immune-based therapies to treat cancer. In addition, some of my work aims to study the pathogenesis and treatment of melanoma and is directed in part at developing tools to study melanoma and immune responses in multiple cancers. My projects are heavily collaborative in nature, within the Wolchok lab and across different disciplines at MSK.
My projects can be divided into the following categories:
Overcoming resistance to checkpoint blockade therapy by modulating the immune system. This work is focused on combining checkpoint blockade with other immune modulatory molecules that inhibit components of the immune suppressive tumor microenvironment (such as IDO and TGFb) or activate effector immune cells that can directly recognize and kill tumor cells (such as OX40 and GITR).
Using the immune modulatory properties of modalities that target and kill tumor cells directly. We have been exploring targeted oncogenic pathway inhibitors such as MEK inhibitors, conventional therapies such as radiation therapy and chemotherapy, adoptive T cell therapy, and oncolytic viruses such as NDV and MVA. We have also been combining these modalities with checkpoint blockade and costimulation.
Defining biomarkers and genetic determinants of response to immune therapy. We recently started exploring the genetic determinants of response to immune therapy and have demonstrated the importance of tumor burden in tumor immunity. We are now exploring the relationship between the genetic determinants of antitumor immune response and other factors such as expression of tumor-associated antigens, T cell repertoire diversity, and the immune tumor landscape. We are also exploring means to develop vaccine therapies based on neoantigens defined by these approaches.
Developing a tissue repository for the immunotherapy and melanoma groups. We have developed a system for the routine collection, processing, and analysis of samples that have been collected as part of multiple clinical trials. We have tested and optimized standard operating procedures for multiple integrated techniques that will enable us to characterize surgical resections or biopsies. These samples can then be uniquely interrogated for functionality and biomarkers of response to therapy. We have also established means to develop cell lines and PDX models using these samples. We have worked with multiple investigators across several services at MSK that are interested in immunotherapy and melanoma biology.