Hay-Oak Park

Focus

Regulation of Cell Growth and Oriented Cell Division; Oxidative Stress Response and Oxidant-induced Cell Death

Research interests

Our research addresses two main questions in cell biology: How do cells achieve polarized organization of the cytoskeleton in response to spatial cues?  How do cells respond to oxidative stress caused by cellular metabolism and other environmental stresses?  Specifically, our current research focuses on the GTPase signaling networks — one controlling polarity establishment and another involved in oxidant-induced cell death.  

Spatial and Temporal Control of Cell Polarity          

One of the fundamental problems in cell biology is how asymmetry and polarity within a cell are established, resulting in oriented cell divisions or a functionally specialized cell fate.  We are using budding yeast as a model system to understand spatial and temporal control of polarity development. Selection of a growth site in budding yeast determines the axis of cell polarity and the cell division plane. Proper choice of cell division plane is critical for the growth of many cell types including epithelial tissues and for the prevention of cancer. Budding yeast is a particularly attractive model system because it displays pronounced cell polarity in response to intracellular and extracellular cues. Our goal is to delve deeper into the molecular mechanisms underlying polarity development during yeast budding, and ultimately to understand general principles underlying cell polarization in all eukaryotes and what is unique to yeast.

Bud5-GFP localization during the cell cycle

     Kang et al., Science 2001

 

 

Oxidative Stress Response & Oxidant-Induced Cell Death

Most eukaryotic cells are constantly exposed to reactive oxygen species (ROS), which are produced as byproducts of metabolism and upon exposure to diverse environmental stresses. The increased production of ROS also leads to the induction of defense mechanisms to avoid molecular damage, but the redox balance is disturbed under excessive stress. ROS pose a constant threat to cells by causing severe damage to DNA, proteins, and lipids. When the stress level is too high, cells undergo either apoptotic or necrotic cell death . We recently found that the Rho5 GTPase is necessary for apoptotic cell death induced by oxidants.  To elucidate the mechanism by which Ras and Rho GTPases regulate cell fate determination under stress, we undertake multi-directional appraoches by combining methods in genetics, functional genomics, biochemistry as well as live cell imaging.

Bimolecular Fluorescence Complementation

     Singh et al., PNAS 2008

 

 

PARK LAB MEMBERS:

Pil Jung Kang, Ph.D.; Chan-Hun Jung, Ph.D.; Mid-eum Lee; Dominik Berdysz; Bryanta Spencer; Andrew Gruenzel; Sooyeon Lee; Victoria Mason

 

 

Publications

• Singh, K., P. J. Kang, and H.-O. Park* (2008) The Rho5 GTPase is necessary for oxidant-induced cell death in budding yeast. Proc. Natl. Acad. Sci. USA 105: 1522-1527
• Park, H.-O.* and E. Bi (2007) Central roles of small GTPases in the development of cell polarity in yeast and beyond. Microbiology & Molecular Biology Reviews, 71: 48-96
• Kang, P. J., B. Lee, and H.-O. Park * (2004) Specific residues of the GDP/GTP exchange factor Bud5p are involved in the cell-type-specific budding pattern in yeast. J. Biol. Chem., 279: 27980-27985 . (Epub 2004 May 10).
• Kang, P. J., E. Angerman , K. Nakashima, J. R. Pringle, and H.-O. Park* (2004) Interactions among Rax1p, Rax2p, Bud8p, and Bud9p in Marking Cortical Sites for Bipolar Bud-site Selection in Yeast. Mol. Biol. Cell, 15: 5145-5157 (Epub. 2004 Sept 08).
• Kozminski, K. G.@, L. Beven@, E. Angerman, A. Tong, C. Boone, & H.-O. Park* (2003) Interaction between a Ras-like and a Rho-like GTPase couples the selection of a growth site to the development of cell polarity. Mol. Biol. Cell 14: 4958-4970. - received the "MBC Paper of the Year" Award in 2003.
• Park, H.-O.*, P. J. Kang, and A. W. Rachfal (2002) Localization of the Bud1/Rsr1 GTPase involved in selection of a proper growth site in yeast. J. Biol. Chem. 277: 26721-26724. (Epub 2002 Jun 10).
• Kang, P. J., A. Sanson, B. Lee, & H.-O. Park* (2001) A GDP/GTP exchange factor involved in linking a spatial landmark to cell polarity. Science 292:1376-1378. (Science Express, 19 April, 2001) - reviewed in Curr. Biol. (2001) 11:R610-R612