At Roswell Park Comprehensive Cancer Center, my clinical practice and research is focused on immunodeficiency-associated skin cancers and skin disorders associated with solid organ transplantation. My research has centered on defining the role of immune cells called macrophages in tumor progression. The focus of these studies has been to identify pathways of tumorigenesis critical to a variety of murine tumor types including lung carcinoma, melanoma, colon carcinoma and cutaneous squamous cell carcinoma. Parallel studies in identifying tumor-promoting pathways induced by infiltrating macrophages in human cutaneous squamous cell carcinomas from immunosuppressed versus non-immunosuppressed patients is the current focus of our lab.
I am a member of several professional organizations related to my clinical and research interests. Specifically, I am the president-elect of the International Transplant Skin Cancer Collaborative, the largest international organization dedicated to studying and treating skin diseases that develop after solid organ transplantation. Further, I am also a member of the American Academy of Dermatology, Society for Investigative Dermatology and American Dermatologic Association.
As a native Texan, I graduated from The University of Texas, where I earned a BS in Pharmacy in 1995, and of Yale University where I earned a PhD in Cell Biology in 2003 and an MD, with election to Alpha Omega Alpha medical honor society, in 2004. I completed an Internship in Internal Medicine and a Residency in Dermatology at Yale-New Haven Hospital. In 2015, I was honored to receive the Young Physician-Scientist Award of the American Society for Clinical Investigation and the 2017 Young Investigator Award of the American Academy of Dermatology.
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, my colleagues and I 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 approximately 80% of tumors. To date, few studies have characterized the mechanistic role of macrophages in the progression of SCCs. Our group has developed in vitro and murine model systems to screen and verify soluble tumor-derived factors that activate macrophages to become tumor promoting. Their objectives are to identify and verify tumor-promoting factors produced by tumor-associated macrophages isolated from human SCCs from immunosuppressed transplant recipients and non-immunosuppressed patients. 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 both in this high-risk population as well as for the general population.
1: Cheng JY, Li FY, Ko CJ, Colegio OR. Cutaneous Squamous Cell Carcinomas in
Solid Organ Transplant Recipients Compared With Immunocompetent Patients. JAMA
Dermatol. 2018 Jan 1;154(1):60-66. doi: 10.1001/jamadermatol.2017.4506. PubMed
PMID: 29167858; PubMed Central PMCID: PMC5833573.
2: Mittal A, Colegio OR. Skin Cancers in Organ Transplant Recipients. Am J
Transplant. 2017 Oct;17(10):2509-2530. doi: 10.1111/ajt.14382. Epub 2017 Sep 14.
Review. PubMed PMID: 28556451.
3: Colegio OR, Chu NQ, Szabo AL, Chu T, Rhebergen AM, Jairam V, Cyrus N,
Brokowski CE, Eisenbarth SC, Phillips GM, Cline GW, Phillips AJ, Medzhitov R.
Functional polarization of tumour-associated macrophages by tumour-derived lactic
acid. Nature. 2014 Sep 25;513(7519):559-63. doi: 10.1038/nature13490. Epub 2014
Jul 13. PubMed PMID: 25043024; PubMed Central PMCID: PMC4301845.
4: Eisenbarth SC, Williams A, Colegio OR, Meng H, Strowig T, Rongvaux A,
Henao-Mejia J, Thaiss CA, Joly S, Gonzalez DG, Xu L, Zenewicz LA, Haberman AM,
Elinav E, Kleinstein SH, Sutterwala FS, Flavell RA. NLRP10 is a NOD-like receptor
essential to initiate adaptive immunity by dendritic cells. Nature. 2012 Apr
25;484(7395):510-3. doi: 10.1038/nature11012. Erratum in: Nature. 2016 Feb
25;530(7591):504. PubMed PMID: 22538615; PubMed Central PMCID: PMC3340615.
5: Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, Flavell RA. Crucial role
for the Nalp3 inflammasome in the immunostimulatory properties of aluminium
adjuvants. Nature. 2008 Jun 19;453(7198):1122-6. doi: 10.1038/nature06939. Epub
2008 May 21. PubMed PMID: 18496530; PubMed Central PMCID: PMC4804622.