Hakryul Jo Ph.D.

Associate Research Scientist in Epidemiology (Environmental Health)

Research Interests

Natural and synthetic chemicals; Cancer; Age-related macular degeneration; neuroinflammation and neurodegeneration; mitochondrial diseases

Research Summary

I am interested in interactions between genetic predisposition and environmental factors as they realate to development and progression of human diseases. Using cell culture system, I am employing pharmacological approaches to screen for small synthetic and natural compounds that interfere with the key cellular pathways responsible for disease pathogenesis. Eventually, such compounds and their derivatives will be tested in pre-clinical animal models of human diseases.

Extensive Research Description

Previously, I employed a chemical screening approach to study and to modulate the PI3K/Akt signaling pathway, which is a key regulator of cell proliferation, survival, migration, and metabolism. The image-based high content chemical screening approach identified a series of activators as well as suppressors of this signaling pathway, which subsequently led to in vivo animal studies in the context of cancer cell death and neuronal survival. My experience in chemical genetics approach encompasses all disciplines that include the development of high throughput assay, screening of chemicals, characterization of candidate compounds, and elucidation of their biological effects in cell culture and in vivo.

The current interests include elucidation of physiological functions of HtrA family of serine proteases. The members of this protease family have been linked to various human diseases, such as age-related macular degeneration (AMD), neurodegeneration, and cancer. I am interested in pharmacological rescue of various neurological symptoms of mutant mice caused by loss a mitochondrial protease. The mutant mice display several clinical features of human basal ganglia diseases including Huntington's and Parkinson’s as well as human mitochondrial diseases.

Selected Publications

  • Jo H*, Mondal, Subhanjan M*, Tan D, Nagata E, Sharma AK, Hou Q, Shanmugasundaram K, Tung J, Tejeda AO, Man H, Rigby AC, and Luo HR. Small molecule-induced cytosolic activation of Akt rescues ischemia-elicited neuronal death. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10581-6 (*equal contribution)
  • Jo H* and Luo HR*. Exploiting Effectors of Rac GTPase. Chem Biol. 2012 Feb 24;19 (2):169-71 (*Corresponding author)
  • Jo H, Lo P, Li Y, Loison F,Green S,Wang J, Silberstein LE, Ye K, Chen H, and Luo HR. Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination. Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6486-91
  • Jo H, Loison F, Hattori H, Silberstein LE, Yu H, Luo HR. Natural product Celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs. PLoS One. 2010 Apr 23;5(4):e10318.
  • Jo H., Jia Y. Subramanian KK. Hattori H, Luo HR Cancer cell-derived clusterin modulates the phosphatidylinositol 3'-kinase-Akt pathway through attenuation of insulin-like growth factor 1 during serum deprivation. Mol Cell Biol. 2008 Jul;28(13):4285-99.
  • Hattori H, Subramanian KK, Sakai J, Jia Y, Li Y, Porter TF, Loison F, Sarraj B, Kasorn A, Jo H, Blanchard C, Zirkle D, McDonald D, Pai SY, Serhan CN, Luo HR. Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3546-51.

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