The development and progression of complex diseases and even rare diseases are caused by complex interactions between genetic and environmental (including dietary and lifestyle) factors. We aim to delineate the genetic and environmental factors and their interactions contributing to increased risk and progression of genetic diseases. Understanding the pathogenesis and the interplay between gene and environment interactions of complex disease are important steps for personalized medicine and for developing optimal approaches for preventing or delaying the onset of such disorders.
Studying gene-environment interactions of genetic diseases using family- and population-based designs remains extremely challenging. We tackle the challenge starting from characterization of disease-causing genes and pathogenic pathways of rare diseases, followed by stratification of environmental modifiers of the pathogenesis pathways and their effects on disease progression.
We currently focus on connective tissue disorders, as many common age-related diseases are highly associated with connective tissue deterioration. These diseases include cardiovascular diseases, type II diabetes, bone and cartilage degeneration, and cancers. Furthermore, both genetic and environmental factors play important roles in disease progression.
Lin YW, Kao HJ, Chen WT, Kao CF, Wu JY, Chen YT, Lee YC (2023) Cell-based screen identifies porphyrins as FGFR3 activity inhibitors with therapeutic potential for achondroplasia and cancer. JCI Insight 8 (22). doi:10.1172/jci.insight.171257
Jiang CL, Tsao CY, Lee YC (2022) Vitamin C attenuates predisposition to high-fat diet-induced metabolic dysregulation in GLUT10-deficient mouse model. Genes Nutr 17 (1):10. doi:10.1186/s12263-022-00713-y
Wagner BM, Robinson JW, Lin YW, Lee, Y.C., Kaci N, Legeai-Mallet L, Potter LR, 2021, “Prevention of guanylyl cyclase-B dephosphorylation rescues achondroplastic dwarfism.”, JCI insight, 6(9), e147832.
Jen, W.P., Chen, H.M., Lin, Y.S., Chern, Y. and Lee, Y.C.* (2020) Twist1 Plays an Anti-apoptotic Role in Mutant Huntingtin Expression Striatal Progenitor Cells. Mol Neurobiol, 57, 1688-1703.
Syu, Y.W., Lai, H.W., Jiang, C.L., Tsai, H.Y., Lin, C.C. and Lee, Y.C.* (2018) GLUT10 maintains the integrity of major arteries through regulation of redox homeostasis and mitochondrial function. Hum Mol Genet, 27, 307-321.
Lee, Y.C.,* Song, I.W., Pai, Y.J., Chen, S.D. and Chen, Y.T.* (2017) Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia. Sci Rep, 7, 43220.
Ko, T.M., Kuo, H.C., Chang, J.S., Chen, S.P., Liu, Y.M., Chen, H.W., Tsai, F.J., Lee, Y.C., Chen, C.H., Wu, J.Y.* Chen, Y.T.* (2015) CXCL10/IP-10 is a biomarker and mediator for Kawasaki disease. Circ Res, 116, 876-883.
Chen, C.H., Lee, C.S., Lee, M.T., Ouyang, W.C., Chen, C.C., Chong, M.Y., Wu, J.Y., Tan, H.K., Lee, Y.C., et al., Chen YT*, Cheng AT* (2014) Variant GADL1 and response to lithium therapy in bipolar I disorder. N Engl J Med, 370, 119-128.