Oscar Colegio, MD, PhD is an Assistant Professor of Dermatology at Yale University whose career goal is to become an independent investigator with expertise in the tumor immunology of skin cancers. He has developed model systems to study the role of macrophages, cells of the innate immune system, in tumor progression under the guidance of Ruslan Medzhitov, PhD. Dr. Colegio's clinical interest in immunodeficiency-associated skin cancers is complementary to his basic research interests. He directs the Yale Transplant Dermatology Clinic, the only clinic in Connecticut dedicated to post-transplant skin screenings and the primary setting for enrolling subjects for the proposed studies. More than 500,000 people have received a transplanted organ in the United States and 27,000 additional transplants are performed each year. Solid organ transplant recipients are 100-times more likely to develop cutaneous squamous cell carcinomas (SCCs) than the general population. As immunosuppression used after transplantation focuses on impairing T cell activation, a majority of studies on the etiology of post-transplant skin cancers has focused on the loss of cancer immunosurveillance. However, we have recently determined that the innate immune system is also critical in tumorigenesis. Further, increased numbers of macrophages present near tumors correlate with poor prognoses in ~80% of tumors. To date, few studies have characterized the mechanistic role of macrophages in the progression of SCCs. We have developed in vitro and murine model systems to screen and verify soluble tumor-derived factors that activate macrophages to become tumor promoting. Our objectives are to identify and verify tumor-promoting factors produced by tumor-associated macrophages isolated from human SCCs. Characterizing the core elements of these tumor-promoting pathways is critical to identifying targets and abrogating them to prevent tumor progression and metastasis of SCCs. The Yale University Departments of Immunobiology and Dermatology together have extensive scientific and clinical resources, which will enable the successful achievement of the proposed aims. Dr. Colegio will design and perform the proposed experiments under the primary mentorship of a pioneer in innate immunity, Ruslan Medzhitov, PhD, and advisory guidance of a physician scientist with expertise in SCCs, Michael Girardi, MD. In sum, this proposal will define critical components of tumor immunology while preparing the applicant for a successful independent research career as a physician scientist.

Public Health Relevance

Increased density of tumor-associated macrophages, cells of the innate immune system, within tumors correlates with a poor prognosis in most types of tumors. To date, few studies have characterized the mechanistic role of macrophages in the progression of cutaneous squamous cell carcinomas. Our objectives are to identify and characterize tumor-promoting factors produced by tumor-associated macrophages isolated from squamous cell carcinomas with the long-term goal of abrogating these factors to prevent tumor progression.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZCA1)
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Ojeifo, John O
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Yale University
Schools of Medicine
New Haven
United States
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Cyrus, Nika; Mai-Anh Bui, Christine; Yao, Xiaopan et al. (2016) Density and Polarization States of Tumor-Associated Macrophages in Human Cutaneous Squamous Cell Carcinomas Arising in Solid Organ Transplant Recipients. Dermatol Surg 42 Suppl 1:S18-23
Hanlon, A; Colegio, O R (2014) The cutting edge of skin cancer in transplant recipients: scientific retreat of international transplant Skin Cancer Collaborative and Skin Cancer in Organ Transplant Patients Europe. Am J Transplant 14:1012-5
Colegio, Oscar R; Chu, Ngoc-Quynh; Szabo, Alison L et al. (2014) Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513:559-63
Liu, L S; McNiff, J M; Colegio, O R (2014) Palmoplantar peeling secondary to sirolimus therapy. Am J Transplant 14:221-5
Colegio, Oscar R; Hanlon, Allison; Olasz, Edit B et al. (2013) Sirolimus reduces cutaneous squamous cell carcinomas in transplantation recipients. J Clin Oncol 31:3297-8
Cyrus, N; Kim, C; Arvelakis, A et al. (2013) Dialysis-associated steal syndrome. Am J Transplant 13:2768-70; quiz 2770