Jen-Tsan Ashley Chi, MD, PhD
Associate Professor
IGSP Center for Applied Genomics & Technology

Jen-Tsan Ashley Chi, MD PhD is an Assistant Professor in the Department of Molecular Genetics and Microbiology and IGSP's Center for Applied Genomics and Technology. He received his MD from National Taiwan University and his PhD from Stanford University. After his PhD, he was a post-doctoral fellow in Dr. Patrick Brown's lab in Stanford University focusing on using cDNA microarrays to elucidate the cellular differentiation as well as human pathogenesis. He joined the faculty at MGM and IGSP in 2004.

Research Interest
The use of high throughput parallel assays has brought tremendous progress to our understanding of different biological systems. But the impact of genomic tools has yet to be realized. My research interests are to use DNA microarrays and other genomic tools to understand the molecular architecture of our cells in the body and how they undergo physiological and pathological adaptation in human diseases.

Characterize the genetic and epigenetic mechanisms in setting up and maintaining positional memory and differentiation of endothelial and smooth muscle cells.
Different organs in our body are composed of different cell types, such as fibroblasts, endothelial cells, smooth muscles and epithelial cells. These cells play essential roles in the proper development and function of each organ system. Previously, these cells looked similar and were thought to play only supportive roles and to be easily interchangeable. With DNA microarrays, we have discovered unexpected levels of diversity present in the fibroblasts, endothelial and smooth muscle cells from different organs/sites of the human body exhibit. These differences in genetic programs persist with in vitro passage and shed important insights into the differentiation pathways and the location-specific disease involvement. For example, we have found that humans utilized the same pathways (Notch--Hey2/Gridlock) in setting up the arterial differentiation. We will further explore the underlying genetic and epigenetic mechanisms in setting up and maintaining such sophisticated pathways.

Define the molecular details of cellular responses to environmental stresses and their roles in human diseases with DNA microarrays.
Recently, the cellular responses to environmental stress in cell cultures have been shown to reflect the transcriptional programs triggered during physiological and pathological adaptations. The serum stimulation of vascular smooth muscle cells has also been related to their transition from contractile to synthetic phenotypes during the intimal formation of atherosclerosis. In my current studies, I have examined the genomic analysis of cellular responses of different environmental stresses such as hypoxia and serum stimulation. These responses reflect the transcriptional programs triggered during diverse disease processes such as acute ischemic insults, acute tubular necrosis and renal cell carcinoma and other solid tumors. For example, I have analyzed the genomic responses to hypoxia and used the "hypoxia signature' to provide the molecular gauge to monitor the intratumor hypoxia status from multiple onco-genomic data and explored the roles hypoxia plays in different human cancers. We will extend this approach to other stresses to explore the roles of different pathways in human cancers.

Characterize the circulating pathogenic factors in scleroderma and other systemic diseases with genomic approaches.
Scleroderma is a potentially fatal disorder that exhibits features of vascular abnormalities, autoimmunity and matrix deposition in different locations, leading to hardening of the skin and internal organs. The etiology of scleroderma is unknown, and there is no effective treatment. One important feature of scleroderma is the systemic involvement of the disease processes in many regions of the skin, as well as in many internal visceral organs. The nature of the systemic involvement is unknown. To test the hypothesis that circulating factors in the blood play important roles in the systemic involvement of scleroderma, I have developed a novel approach to expose normal cultured cells to the blood of scleroderma patients and assessing the impact with DNA microarrays. We have found that plasma from scleroderma patients is able to elicit a pathological response similar to that observed in patients. Therefore, plasma from scleroderma patients induces normal fibroblast to exhibit the phenotypes of scleroderma fibroblasts upon exposure for merely twelve hours. I propose to characterize and identify the soluble factors that contribute to the pathophysiology of scleroderma. I will also work to expand the approach to other diseases with systemic features, to understand the pathogenic roles of blood in patients with these diseases.

Hypoxia Photo