Gene Networks in Metabolism, Tumorigenesis & FoxG1 Syndrome


Our long-term goal is to understand the transcriptional regulatory network in metabolism, tumorigenesis and FoxG1 syndrome.

1. MLL3/4 complexes in transcription, metabolism and cancer: Our lab purified the first mammalian transcriptional coactivator complex that methylates histone H3-lysine 4 (H3K4). This complex contains either MLL3, a H3K4-methyltransferase, or its paralogue MLL4. We have discovered that MLL3/4 complexes selectively target genes involved in diverse metabolic processes, such as adipogenesis and glucose/lipid homeostasis. Our recent effort has been directed at characterizing roles of MLL3/4 complexes in bile acid homeostasis. MLL3/4 complexes also function as major tumor suppressors, and MLL3 and MLL4 have been shown to be mutated in diverse human cancers. Our MLL3 mutant mice develop kidney and intestinal tumors. The major hypothesis that we are currently investigating is: MLL3/4 complexes play important roles in the interface of tumor suppression and metabolism. For this line of work, we also collaborate with Seunghee Lee’s group at Seoul National University, Korea.   

2. Central roles of glucocorticoid in metabolism: We wish to understand how the central nervous system (CNS) processes peripheral metabolic cues at gene regulation levels. For this effort, we picked glucocorticoid, a peripheral orexigenic cue, as a model. Our current efforts include genome-wide analyses to identify metabolic target genes of glucocorticoid in the hypothalamus.

3. FoxG1 syndrome: The gene, FoxG1, encodes a transcription factor that plays critical roles in forebrain development. Mutations or duplication of this gene result in ‘FoxG1 syndrome’, also known as ‘congenital Rett-like syndrome’. In collaboration with Soo Lee’s lab, we have recently initiated a major effort to understand the molecular basis of this syndrome in a hope to find treatment for this devastating neurodevelopmental disorder.

Jae went to Texas A&M Univ for his Ph.D. degree. After postdoctoral training at Harvard and bioventure life, he established his own group in academia. He made numerous seminal discoveries in the area of mammalian transcriptional regulation, including the first cloning of ligand-dependent coregulators of nuclear receptors using the yeast two  hybrid system, the first purification of mammalian coactivator complex containing histone H3-lysine 4 methyltransferases (H3K4MTs), and the first demonstration for critical metabolic function of H3K4MTs, MLL3 and MLL4.  

Welcome to Jae W. Lee’s Lab