Hay-Oak Park

Professor
Faculty

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)

     

Negative signaling of Cdc42 polarization at the current and old cell division sites  Negative signaling of Cdc42 polarization at the current and old cell division sites (Miller et al. Mol Biol Cell 2017)

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. 

 

PARK LAB MEMBERS:

Pil Jung Kang (PhD), Kristi E. Miller, Kendra Lian, Jack Fioretti, Grant Leever, Sarah Johnson

We welcome highly motivated students to join our group. Our research projects provide interdisciplinary training including genetics, biochemistry, quantitative microscopy, and mathematical modeling. For any questions, please contact Hay-Oak Park (park.294@osu.edu).

 

SELECTED PUBLICATIONS since 2007  (*Corresponding Author):

 

 

 

Areas of Expertise
  • Regulation of polarized cell growth
  • Cellular aging and stress response
Dr. Hay-Oak Park
Phone:
614-688-4575
Fax:
614-292-4466
226 Biological Sciences Building
484 West 12th Avenue
Columbus, OH 43210-1292