The DeCaprio Lab focuses on understanding the cooperative interactions between DNA tumor viruses and cellular host proteins that conspire to transform cells. We have made numerous fundamental discoveries that form major parts of our current molecular understanding of the role of tumor suppressor genes in malignant transformation and the still complex and incompletely understood transforming mechanism of the family of polyomaviruses including SV40 and Merkel cell polyomavirus. The DeCaprio Lab’s overall strategy has been to identify cellular factors that bind specifically to the viral oncoproteins, determine their normal function, and gain insight into the biologic consequences that occur when cellular factors become mutated in cancer or perturbed by viruses.
The DeCaprio Lab has performed seminal studies that have led to a deeper understanding of the control of the mammalian cell cycle. These studies have led to a series of new insights into how cells regulate the cell cycle in both normal and malignant cells and what happens to those controls when transforming viruses are present. As part of this effort to discover cellular factors that bind to viral oncogenes, the DeCaprio Lab discovered the mammalian DREAM (DP, RB-related, E2F, and MuvB) complex and determined that DREAM serves as the master coordinator of all cell cycle-dependent gene expression. We discovered a cullin-RING-ligase complex containing CUL7, FBXW8, CUL9, and GLMN, and generated a mouse model that led to the discovery that CUL7 is mutated in the human 3-M short stature syndrome. The DeCaprio Lab revealed the molecular basis for the hereditary vascular disorder Glomuvenous Malformation (GVM). His laboratory identified FAM111A as an SV40 virus replication restriction factor, a factor mutated in the short stature Kenny-Caffey syndrome. His lab demonstrated the role of Merkel cell polyomavirus activation of the MYC paralog MYCL in Merkel cell carcinoma.