Ohio State nav bar

Hay-Oak Park

Hay-Oak Park

Hay-Oak Park

Professor

park.294@osu.edu

614-688-4575

226 Biological Sciences Building
484 West 12th Avenue
Columbus, OH
43210-1292

Google Map

Areas of Expertise

  • Cell Polarity and Asymmetry
  • Cellular Aging
  • Stress Response and Cell Death

Living cells are often polarized with a distinct front and back or top and bottom. Cell asymmetry and polarity are critical for cell proliferation and development. Indeed, the loss of cell polarity and asymmetry has been implicated in many diseases including cancer and cellular aging. Our current research has two main focuses: 1) spatial and temporal regulation of cell polarization; and 2) regulation of cellular lifespan. Some of our recent work is highlighted below.

Spatial and Temporal Control of Cell Polarity          

In yeast and animal cells, signaling pathways involving small guanosine triphosphatases (GTPases) regulate cell polarization. In budding yeast, selection of a bud site directs polarity establishment and subsequently determines the plane of cell division. 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. We discovered how two different proteins Bud3 and Cdc24 sequentially activate the Cdc42 GTPase to ensure yeast form a bud at the right place. Bud3 stimulated nucleotide release from Cdc42 in vitro and activated Cdc42 in Cdc24-deficient cells. Live imaging of wild-type cells revealed that Cdc42 normally undergoes two waves of activation: a Bud3-dependent wave in late mitosis/early G1 followed by a Cdc24-dependent activation phase in late G1 (Kang et al., J Cell Biol 2014). Such biphasic activation of Cdc42 is necessary for spatial cue–directed polarity establishment in haploid budding yeast in the correct time in the cell cycle. While the positive signaling of polarity establishment is important, we found that negative GTPase signaling involving Rga1, a Cdc42 GTPase activating protein, is also critical for establishing a proper axis of cell polarization (Miller et al., Mol Biol Cell 2017). Rga1 inhibits Cdc42 at all previously used cell division sites so that Cdc42 polarization and thus bud growth is directed to a new unused site. Live cell imaging and mathematical modeling suggests that strict spatial control of Rga1 in coordination with G1 progression is critical for establishing a proper axis of cell polarization.
 

 

 

Biphasic activation of the Cdc42 GTPase in G1

Biphasic activation of the Cdc42 GTPase in G1  (Kang et al., J Cell Biol 2014; see also–  “In This Issue” of the J Cell Biol. July 7, 2014)

Research

Dynamics of Bem1-GFP at the division site at two temporal steps in the G1 phase in wild type and rsr1 mutants (Miller et al. 2019 Mol Biol Cell)

Research
Research

Modeling and simulations of Cdc42 polarization in wild type and rsr1 mutants. Miller et al. (2019) Mol Biol Cell 15; 30(20): 2543-2557. https://www.molbiolcell.org/doi/full/10.1091/mbc.E19-02-0106?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Cellular Aging and Stress Response

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. We discovered that the Rho5 GTPase is necessary for apoptotic cell death induced by oxidants (Singh et al., PNAS 2008). We investigate how asymmetric cell division and cell polarity are involved in maintaining cellular damage in mother cells and what limits cellular lifespan. 

Research

A microfluidics-based imaging platform to image yeast cells for their entire lifetime. A single “trap” with a yeast cell expressing red and green fluorescent protein is enlarged. From P. J. Kang & H.-O. Park.

Research in cellular aging and stress response

The screen of VN fusion library for Rho5 interacting proteins by bimolecular fluorescence complementation (BiFC) assays. Singh et al. (2019) G3, 7;9(3):921-931. https://www.g3journal.org/content/9/3/921.long

 

SELECTED PUBLICATIONS since 2007   (*Corresponding Author):