Use of genomic tools to enhance understanding of human diseases and disease-related biological questions.
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.