Thomas P. Stricker, M.D., Ph.D.

Assistant Professor of Pathology, Microbiology and Immunology
Director, CALDx - Center for Advanced Lab Diagnostics
MCN CC-3309A
1161 21st Avenue South
(615) 343-4008

Cancer, breast cancer, genomics, ChIP-seq, RNAseq, mutations, chromatin, transcription, epigenetics

Research Information

One of the surprising findings coming out of large cancer re-sequencing studies, such as The Cancer Genome Atlas (TCGA), was the large number of recurrent mutations in transcriptional regulators and chromatin remodeling enzymes. Research in my lab is focused on understanding how mutations in these genes contribute to the malignant phenotype. Projects in the lab analyze large, publicly available datasets, such as TCGA, with a focus on integrative analyses, as well as ChIPseq and RNAseq datasets generated in house in manipulatable cell line models. 

Currently, research in the lab is focusing on mutation of chromatin remodeling enzymes in breast cancer. In particular, KMT2C/MLL3, which is mutated in about 7% of all estrogen receptor positive breast cancers, is a histone methyltransferase that creates the H3K4me1 mark at enhancers. We hypothesize that loss of MLL3/KMT2C function leads to a shift in the enhancer landscape, altering the sites available for estrogen receptor binding and thus changing gene transcription in breast cancer. A second project focuses on sequence-specific transcription factors that are recurrently mutated in breast cancer, such as FOXA1, GATA3, and TBX3. Evidence from mouse knockout models and human mendelian disorders suggest that these transcription factors have a function in determining cell identify in the developing breast. We are currently testing the hypothesis that these transcription factors form a genomic regulatory network, and disruption of that network by mutation destabilizes gene expression programs, contributing to malignancy.

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