Major Areas of Research Interest
Our laboratory studies DNA base modifications and their erasure in the control of gene expression in stem cells and cancer. Our efforts extend to two distinct DNA modification systems: i) erasure of DNA cytosine methylation through Tet-oxidized 5-methylcytosine intermediates; and ii) DNA adenine N6 methylation (6mA), a previously unrecognized form of DNA modification in mammals. We are particularly interested in understanding how writers, readers and erasers of these marks modulate gene control in embryonic stem cells, and how this process goes awry in cancers such as myeloid leukemia. We use a combination of biochemistry, mouse genetics and next-generation sequencing strategies (MeDIPseq, RNA-seq, RRBS-seq) to address these questions.
Categories: Gene Control, Stem Cells, Cancer, Epigenetics, and DNA Methylation
TLR4 Signaling via NANOG Cooperates With STAT3 to Activate Twist1 and Promote Formation of Tumor-Initiating Stem-Like Cells in Livers of Mice. Gastroenterology. 2016 Mar; 150(3):707-19. View in: PubMed
NUMB phosphorylation destabilizes p53 and promotes self-renewal of tumor-initiating cells by a NANOG-dependent mechanism in liver cancer. Hepatology. 2015 Nov; 62(5):1466-79. View in: PubMed
TLR4-Dependent Tumor-Initiating Stem Cell-Like Cells (TICs) in Alcohol-Associated Hepatocellular Carcinogenesis. Adv Exp Med Biol. 2015; 815:131-44. View in: PubMed
The TBC1D15 oncoprotein controls stem cell self-renewal through destabilization of the Numb-p53 complex. PLoS One. 2013; 8(2):e57312. View in: PubMed
Pluripotency factor-mediated expression of the leptin receptor (OB-R) links obesity to oncogenesis through tumor-initiating stem cells. Proc Natl Acad Sci U S A. 2012 Jan 17; 109(3):829-34. View in: PubMed