research overview
- My lab has had a long-standing interest in understanding the molecular mechanisms that regulate human gene expression. Our primary focus is the human Pre-Initiation Complex (PIC), which consists of Mediator, RNA polymerase II (RNAPII), TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH and is approximately 4.0 MDa in size. Broadly speaking, the PIC functions to regulate the activity of the RNAPII enzyme, which transcribes all protein-coding genes and most non-coding RNAs in the human genome. Within the PIC, the 1.4 MDa Mediator complex, the 1.3 MDa TFIID complex, and the 0.5 MDa TFIIH complex help regulate RNAPII activity in ways that remain poorly understood. At a basic level, TFIIH regulates transcription initiation and post-initiation steps (e.g. RNA processing), whereas Mediator and TFIID function by converting biological inputs (communicated by sequence-specific, DNA-binding transcription factors) into physiological responses (via changes in gene expression). Our lab uses an array of experimental approaches, ranging from basic biochemistry, transcriptomics, metabolomics, proteomics, biophysics and molecular biology, to study regulatory mechanisms that govern human gene expression.