Project Term
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Project Summary
We investigate the biology, genetics and treatment of myeloid malignancies, including CHIP, MDS and AML. Our goal is to improve our understanding of the effect of chromatin organization on hematopoietic stem cell transformation in the context of mutations in cohesin genes and other recurrently mutated epigenetic modulators. We employ a combination of genomic, mouse modeling, biochemistry and molecular biology approaches to answer disease relevant questions to identify novel therapeutic targets.
Lay Abstract
My research program focuses on understanding the basic mechanisms that lead to blood cancer development and can be exploited therapeutically. We are specifically interested in how one particular subset of blood cancers, called myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) with cohesin mutations, develop in patients. These cancers are associated with very poor outcomes and there are currently no targeted therapies available. We have developed multiple models of cohesin-mutant blood cancers, including cell line models and primary patient cell-derived mouse models which we use to carry out our studies. Our early investigation led us to appreciate the importance of DNA damage and inflammation in development of these cancers and we are currently investigating how to best target these therapeutically. Our research program questions include the following:
1. How do mutations in the cohesin complex disrupt how DNA is folded in the nucleus?
2. What is the role of cohesin in controlling how genes are transcribed and pieced together during the process of splicing?
3. What drives increased inflammation in cohesin-mutant blood cancers and can we intercept disease development?
Program
Grant Subprogram
