Assistant Professor    309 Mudd Hall Johns Hopkins University 3400 N. Charles Street Baltimore, MD  21218-2685   Email: ylee99@jhu.edu Office: 410 516-4147 Lab: Mudd Hall 312 Departmental fax 410 516-5213   B.S. Seoul National Univ., Korea Ph.D. University of Chicago (Chemistry) Postdoctoral Research Harvard University (Molecular & Cellular Biology)

Research Interests

Mechanisms of nutritional homeostasis

For all living organisms, adaptation to different nutritional conditions is essential for survival and proliferation. When nutritional conditions change, cells adapt to different nutritional demands by changing the way they utilize nutrients (metabolic reprogramming). We are interested in how cells recognize different nutritional demands and in the molecular mechanism coordinating the metabolic reprogramming to cell growth/proliferation.

Currently our main focus is the discovery of cellular metabolites regulating nutrient-regulated proteins and characterize the role of these metabolite-protein interactions in vitro and in cells (mammalian/yeast/bacteria).  Many proteins involved in nutritional homeostasis have been suggested, based on indirect evidence, to be regulated by endogeneous metabolites (recommended short review articles: Wilson and Roach and Lindsley and Rutter). Often times, identities of these protein-regulating metabolites are unknown, hampering further studies. Our initial goal is to identify cellular metabolites regulating selected proteins of our interests. Once metabolites regulating target proteins are defined, the regulation will be characterized in vitro and also in model organisms (mostly yeasts and cultured mammalian cells).

Our initial protein of interest is human pyruvate kinase M2 (PKM2), an isozyme of pyruvate kinase abundant in proliferating cells. Because this PKM2 (but not normal cell counterparts PKM1 and PKL) has been shown to be essential for the metabolic reprogramming of cancer cells and for the growth of tumor, we searched for cellular metabolites that binds to PKM2 in isozyme-specific manner. In addition to previously known ligand fructose-1,6-bisphosphate, we identified an additional metabolite selectively binding to and stimulating PKM2 in vitro and in cancer cells. We are evaluating the function of this new PKM2 regulator in vitro and in vivo. We are also expanding our approach to discover additional metabolites regulating other proteins of our interest.

The outcome of our research projects has potential implication for both basic and applied life sciences. Many chemicals currently being used to treat these pathological conditions are either directly or indirectly targeting nutrient-regulated proteins. However, often times, we do not know how nutrient conditions regualte these 'nutrient-regulated' proteins. Detailed understanding of these regulations may provide additional routes toward treatments of these pathological conditions. For additional information, please check our lab website.

Representative Publications