Dr. Yuan’s group has two major missions, namely, 1) reveal the impact of epigenetic changes on normal and disease development enabled by our novel single-cell tools; and 2) develop low-cost point-of-care tools for disease detection and monitoring. Our research has been funded by NSF, US Army and various NGO.

Develop single cell tools for tracking cellular epigenetic changes

DNA is the essential building block of all life forms. Genetic information is usually stably inherited during cell proliferation and are almost identical across the body. A lung and a bone cell of the same person share the same genetic content. These cells, however, assume different functionality responding to various developmental signals and extracellular matrix by reprogramming the epigenetic modifications that decorate the DNA, such as DNA methylation and histone post-translational modification (also known as epigenetic modifications). It is thus of vital importance to understand how cells change their epigenetic content during normal and disease development. Our group is dedicated to develop enabling single cell tools to track epigenetic changes under physiological relevant conditions. We have successfully made several in situ sensors to track epigenetic changes in live cells and are working towards establishing the next-generation probes to monitor live cell epigenetic changes.

Identify and reverse epigenetic memory arising from environmental chemical exposure

Exposure to environmental chemical, such as lead (Pb) and pesticides, is inevitable in modern life. Chronic exposure to low dose of Pb, for example, has an established connection with increased disease risk in later life with low-dose exposure at developmental stage having the most detrimental effect. Low-dose exposure is associated with decreased intelligence quotient, learning ability and various autism spectra of diseases in adulthood and increased risk of Alzheimer’s and Parkinson’s disease at a later life stage. There are no preventative procedure or treatments available for exposed population. Findings from our group and others have provided overwhelming evidence suggesting that epigenetic modifications are likely to be the molecular origin that lead to systematic injury arising from environmental exposure. Our research goal is thus to identify epigenetic changes that persist after chronic exposure to low-dose environmental chemicals. Once identified, we will screen a large number of epigenetic molecular drugs and validate the feasibility of reversing environmental-exposure induced epigenetic changes in cells and animal models for restoring normal epigenetic state and reverse and/or delay the on-set of exposure-related diseases.

Reveal the molecular origin conferring drug resistance in tumors

Two of the remaining challenges in cancer therapy are: 1) the same treatments do not always work for all patients. An efficient approach to identify non-responding patients prior to treatment can significantly alleviate the physical and mental stress that patients have to go through; and 2) during or after treatments, patients may develop drug-resistance and consequently result in high death rate in relapsed patients. Genetic and epigenetic mutations are believed to both contribute significantly to the acquisition and development of drug resistance. While extensive genetic screening is enabled by next-generation tools, identifying epigenetic mechanism and pathways that contribute to drug resistance have been challenging given that cells are intrinsically heterogeneous in epigenetic background. Our research group is uniquely equipped to separate tumor cells into distinctive subpopulations with distinctive epigenetic background. We will thus assess the response of individual cells to drug treatments and associate them with the predefined epigenetic backgrounds. Along with our biological and clinical collaborators, we are working towards elucidating the epigenetic contribution to drug resistance.

Develop point-of-care devices for early-stage disease detection and chronic disease management

The development in modern medicinal science has enabled treatments of various diseases, which are once un-treatable. The efficacy and cost of treatments, however, are closely affiliated with the progression of diseases. Early detection of many diseases (e.g., cancer and infectious disease) has significant health and economic benefits if performed in a minimally invasive way. Our group aims to develop no-invasive detection devices for biomarkers in circulating body fluid, such as sweat and saliva, using colorimetric approaches harnessing the power of modern smart phone technologies. The integrated device is expected to be less than $ 1 in cost and thus feasible for point-of-care applications in low-resource settings.

"DNA methylation regulated nucleosome dynamics," I. Jimenez-Useche, J. Ke, Y. Tian, D. Shim, S. C. Howell, X. Qiu, and C. Yuan, Biophysical Journal, in press (2014)

"Lipase-catalyzed Process for Biodiesel Production: Protein Engineering and Lipase Production," H. T. Hwang, Q. Feng, C. Yuan, X. Zhao, D. Ramkrishna, D. Liu, and A. Varma, Biotechnology and Bioengineering, 111, 639-653 (2014)

“One-pot Approach for Examining the DNA Methylation Patterns Using an Engineered Methyl-probe,” S. K. Kim, C. Matthew, and C. Yuan, Biosensors and Bioelectronics, 58, 333-337 (2014)

"Unmethylated and Methylated CpG Dinucleotides Distinctively Regulate the Physical Properties of DNA," I. Jimenez-useche, D. Shim, J. Yu, and C. Yuan, Biopolymers, 101, 517-524 (2014)

“Solution Scattering and FRET Studies on Nucleosomes Reveal DNA Unwrapping Effects of H3 and H4 Tails,” K. Andresen, I. Jimenez-Useche, S. Howell, C. Yuan, and X. Qiu, PLoS ONE, 8(11), e78587 (2013)

"Elucidating Internucleosome Interactions and the Roles of Histone Tails," S. C. Howell, K. Andreson, I. Jimenez, C. Yuan, and X. Qiu,Biophysical J., 2013, 105:194-199

"Histone H3 and H4 Tail Clipping Affects the Nucleosome Dynamics," N. Nurse, I. Jimenez-Useche, I. T. Smith, and C. Yuan, Biophysical J., 2013:104:1-8

"The Effect of DNA CpG Methylation on the Dynamic Conformation of a Nucleosome," I. Jimenez-Useche, and C. Yuan, Biophysical J., 2012, 103:1-11