Academic Background

Craig Ceol received his B.S./M.S. degree from Yale University and subsequently worked as an Associate Scientist at Eli Lilly and Company.  He received his Ph.D. from M.I.T. in 2002 and was a postdoctoral fellow at M.I.T. until 2004.  From 2004 to 2008, he was a postdoctoral fellow at Children’s Hospital Boston and Harvard Medical School where he was supported by fellowships from the Damon Runyon Cancer Research Foundation and Charles A. King Trust.  In 2009 he continued his postdoctoral studies as an Instructor in Pediatrics at Harvard Medical School with support from an NIH Pathway to Independence Award.  In 2010, Dr. Ceol joined the Program in Molecular Medicine at the University of Massachusetts Medical School.

 Genetic regulators of melanoma formation using the zebrafish      

Cancer is a genetic disease that results from mutations in genes that control cell growth, division and survival.  Our laboratory seeks to identify the genetic defects that underlie tumor initiation and maintenance and understand the aberrant cellular processes that result from cancer-promoting mutations.  We have focused on malignant melanoma, the most aggressive and deadly skin cancer.  Melanoma arises from melanocytes, which produce the melanin pigments that impart color to skin and are important in the tanning response.  Mutations in the Ras/ERK signaling pathway are involved in converting normal melanocytes into melanomas.  In particular, mutations that overactive the BRAF serine/threonine kinase, a downstream effector of Ras signaling, are found in 60-70% of all melanomas.  These mutations are also present in benign melanocytic nevi - more commonly referred to as moles - indicating that other genetic alterations cooperate with oncogenic BRAF to generate melanomas.  We aim to identify these alterations and study how they cooperate with oncogenic BRAF to promote melanoma.

We primarily utilize a zebrafish model of melanoma. Zebrafish melanocytes are externally visible, and single cells can be visualized in a living animal.  Together with a p53 mutation, human oncogenic BRAF can induce melanoma formation in zebrafish.  We developed a high-throughput method to express candidate oncogenes in zebrafish melanocytes (see figure below) and have tested whether genes that are recurrently amplified and overexpressed in human melanomas can accelerate tumor formation.  In these studies, we identified the SETDB1 histone methyltransferase as a new melanoma oncogene, highlighting the role of chromatin methylation and dysregulated transcription in tumorigenesis.  We are currently assessing additional candidates, including copy number altered genes and melanocyte lineage factors, for roles in melanoma.  In addition, we are probing how different cell subpopulations within a tumor are involved in its maintenance.  Ultimately our goal is to identify genes and cells that may serve as diagnostic and prognostic markers of disease as well as therapeutic targets.