Research Interests   Biological networks that coordinate metabolism and growth

Our lab is interested in understanding the molecular networks that coordinate nutrient metabolism and cell growth. How cells assess nutrient- or energy states and relay this information into appropriate decisions on growth is poorly understood. Coordinate regulation of nutrient metabolism and cell growth is of fundamental importance, and many human diseases, such as cancer, diabetes, and developmental disorders, are affected by alterations in this process.

Our research is focused on the mTOR signaling network that plays a crucial role in controlling cell growth in response to nutrient levels and growth factors. In spite of considerable efforts, it has not been possible to obtain a clear understanding of the molecular mechanisms by which the mTOR network is regulated by nutrient- and growth factor-signals. Utilizing novel molecular biology and biochemical tools as well as a variety of structural approaches, we will identify novel components and connectivity in the network and determine biological functions and signaling specificity thereof.

As a crucial pathway downstream of mTOR, autophagy (cellular self-eating) plays an important role for metabolic homeostasis and cellular survival. Autophagy is an evolutionarily-conserved process through which cytoplasm, organelles, or long-lived proteins or protein aggregates are sequested in a double-membrane structures and subsequently degraded in lysosomes. Through destruction of cellular organelles and proteins, autophagy provides energy for starved cells or allows for balanced regulation between biogenesis and degradation of cellular structures, thereby playing important roles in growth, survival, differentiation, and development. Dys-regulation of autophagy is associated with many human diseases including cancer, myopathies, innate immunity, and neurodegenerative diseases such as Parkinson's and Huntington's diseases. Autophagy is induced when cells are starved of nutrients or mTOR is inhibited. We investigate how nutrient starvation or mTOR inhibition leads to induction of autophagy by focusing on two protein complexes consisting of ULK, Atg13, and FIP200.

We anticipate this study will advance our understanding of the molecular bases underlying the coordinate regulation between metabolism and growth during animal development and the pathogenesis of metabolic diseases such as cancer and diabetes.

Selected Publications

Vander Haar, E., Lee, S.I, Bandhakavi, S., Griffin, T. J., Kim, D.-H. (2007) "Insulin Signalling to mTOR Mediated by Akt/PKB Substrate PRAS40." Nature Cell Biology 9, 316-23. (PDF)

Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol. 14, 1296-1302. (PDF).

Kim, D.-H., Sarbassov, D., Ali, S. M., Latek, R. R., Guntur, K. V. P., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2003) GbL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Molecular Cell 11, 895-904. (PDF)

Kim, D.-H., Sarbassov, D., Ali, S. M., King, J. E., Latek, R. R., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2002). mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110, 163-175. (PDF)

Postdoctoral positions are available in the lab. We are looking for a Ph.D or Ph.D candidate who has prior experience in molecular, cell biology, and/or structural/biochemistry. Personnel who are interested in the positions, send a CV and names of three references to the following address:

Do-Hyung Kim, Ph.D
Assistant Professor
Dept. Biochemistry, Molecular Biology, and Biophysics
University of Minnesota
6-155 Jackson Hall
321 Church Street SE
Minneapolis MN 55455
USA
 
612-626-3418 (tel)
dhkim@umn.edu