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Jen-Tsan Ashley Chi

Associate Professor
Molecular Genetics and Microbiology
(919)668-4759
Research Interest: 
Genetics
Microbiology and virology
Research Summary: 
Use of genomic tools to enhance understanding of human diseases and disease-related biological questions.
Research Description: 

My research focus is on how mammalian cells interact with outside environmental changes. These changes are also referred as “stresses” and play important physiological and pathological roles in many human diseases. We have analyzed the short-term response and somatic mutations which have resulted from the long term exposure to these stresses. We have identified modified of the stress responses which modulate the cellular survival under stresses. We have performed these analyses in 1) human cancers and 2) the erythrocyte microRNAs of sickle cell disease. We have identified the cellular response to hypoxia, lactic acidosis and glucose deprivation as well as the deprivation of all amino acids. We have found that these stresses induce distinct sets of gene expression response and provide selection pressures to select the somatic mutations which can confer the survival advantages under these stresses. In addition, we have identified abundant microRNAs in the anuclear mature erythrocytes. The genetic analysis of the erythrocyte microRNAs in the context of anemia disorders led to mechanistic understanding of the pathophysiological events underlying the severity of anemia. In addition, we have found a subset of erythrocyte microRNAs may regulate the gene expression of malaria parasites and contribute to the malaria resistance in sickle erythrocytes.

Publications: 
Functional interaction between responses to lactic acidosis and hypoxia regulates genomic transcriptional outputs.
Tang X, Lucas JE, Chen JL, LaMonte G, Wu J, Wang MC, Koumenis C, Chi JT.
Cancer Res. 2012. 72:491-502.

Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia.
Kung HN, Marks JR, Chi JT.
PLoS Genet. 2011. 7:e1002229.

Analysis of tumor environmental response and oncogenic pathway activation identifies distinct basal and luminal features in HER2-related breast tumor subtypes.
Gatza ML, Kung HN, Blackwell KL, Dewhirst MW, Marks JR, Chi JT.
Breast Cancer Res. 2011. 13:R62.

Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA.
Chen JL, Merl D, Peterson CW, Wu J, Liu PY, Yin H, Muoio DM, Ayer DE, West M, Chi JT.
PLoS Genet. 2010. 6:e1001093.

microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease.
Sangokoya C, Telen MJ, Chi JT.
Blood. 2010. 116:4338-48.