PROJECT SUMMARY/ABSTRACT Candidate: I am a postdoctoral fellow in the laboratory of Dr. Richard White at Memorial Sloan Kettering Cancer Center. My research career has focused on how cells interact and communicate, beginning with my PhD research into how skin cells coordinate rapid wound healing in the embryonic epidermis, and continuing into my postdoctoral research on how tumor and microenvironment cells interact during melanoma invasion. My recent publication uncovered a novel “interface” cell state adopted by both tumor and microenvironment cells at the tumor boundary, distinguished by upregulation of cilia. The objective of this proposal is to determine the contribution of the cilia-enriched interface cell state to melanoma invasion. Ultimately, my long-term goal is to lead an independent group studying how tumor and microenvironment cells cooperate to promote melanoma progression. To accomplish these goals, I have developed a career plan to: (1) develop new scientific and technical skills; (2) become an effective leader and mentor; (3) extend my professional network of advisors and collaborators; (4) successfully transition to an independent role. Research: Recent advances in treating melanoma, including targeted therapies and immunotherapy, demonstrate how an understanding of the molecular mechanisms of melanoma progression and the role of the tumor microenvironment (TME) can lead to novel therapeutics. Interactions between tumor and TME cells often promote melanoma progression. My recent work identified a novel cilia-enriched “interface” cell state adopted by tumor and microenvironment cells at the tumor boundary, and found that cilia are required for melanoma invasion. This indicates that the interface cell state may have a critical role in melanoma progression. To investigate the role of the interface in invasion, I will accomplish the following specific aims: (1) determine the mechanism by which cilia promote invasion; (2) investigate how cilia gene expression is regulated; (3) identify the mechanisms that establish the interface cell state. Environment: During the mentored phase, the proposed work will be completed at Memorial Sloan Kettering Cancer Center (MSKCC), one of the world’s leading cancer centers with a history of major discoveries in cancer biology. The research will be performed in the White laboratory within Sloan Kettering Institute, the research arm of MSKCC, led by Dr. Joan Massagué. The White laboratory is a member of the Cancer Biology and Genetics Program within Sloan Kettering Institute, a program led by my co-mentor Dr. Scott Lowe. Between my mentor, co-mentor, advisory committee, and collaborators, I have assembled an outstanding team of experts in basic and translational cancer research who will guide this work and assist with achieving my scientific and professional goals during the transition to independence.

PROJECT NARRATIVE Tumor and microenvironment cells often interact to promote cancer progression, but gaps remain in our understanding of how these interactions occur. My recent publication uncovered a novel cilia-enriched “interface” cell state adopted by both tumor and microenvironment cells in melanoma, indicating that the interface may have a critical role in melanoma progression. My proposed work will investigate how the interface is established and how it contributes to invasion, and could provide novel therapeutic targets to prevent melanoma progression.