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The Knoepfler Lab is interested in epigenetics and chromatin, and the cellular machinery that regulates these states normally in stem cells and aberrantly in cancer particularly brain tumors. What are the shared and distinct molecular events in normal and cancer stem cells? What role does Myc play?
We were the first to argue for the new paradigm of the Myc protein, which has important roles in cancer and pluripotency, fulfilling a global chromatin function in addition to being a gene-specific transcription factor.
We have followed that up with functional genomics and other studies over the last several years. Our 2011 paper on Miz-1 and Myc achieved three milestones. It was the first functional genomics study of Miz-1, it was the first paper to study Myc genomic function in human ESC (interestingly all the other studies were in mouse ESC), and it was the first to study in parallel the genomic function of Myc and a cofactor. Our recent 2012 paper on the similarities between iPS cells and cancer cells was a first in the field as well. We are also interested in basic chromatin and epigenomics events.
In 2013 we published the first paper reporting a knockout of a histone H3.3 encoding gene, H3f3b. The relatively few surviving knockout mice exhibit a number of phenotypes including sterility and knockout cells have chromosome segregation defects, karyotypic abnormalities, epigenomic and transcriptomic changes, and alterations in chromatin.
Our big picture goal is to impact human health through discoveries in cancer and stem cell biology.