Welcome to Lee Labs at OHSU

"Genius is one per cent inspiration and ninety-nine per cent perspiration. Accordingly, a 'genius' is often merely a talented person who has done all of his or her homework"  Thomas Edison

 
 

The CNS consists of myriads of cell-types with diverse morphology and functionality. These anatomical, cellular and molecular complexities present a challenge for mechanistic studies of CNS development. One of the most fundamental questions in neuroscience is how an amazing number of neural cell-types are produced at specific time and space, acquire their specialized connections and functions, and form neural circuits.

Our long-term research goal is to understand processes governing generation of diverse neural cell-types and formation of neural circuits and how disruption of these processes lead to various CNS developmental disorders. Our lab has been unraveling the important molecular and cellular mechanisms to generate cellular diversity in developing CNS. Using integrated experimental tools, we have made pivotal contributions to the understanding of gene regulatory networks underlying cell-fate specification and maturation in the developing spinal cord and forebrain. More recently, we have also started to dissect the gene regulatory network for cell-fate specification and postnatal metabolic function of two critical neurons in feeding circuitry, arcuate AgRP- and POMC-neurons.

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.

The FoxG1 gene 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’. 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.

Gene Networks in CNS Development and Disorders, Metabolism and Tumorigenesis