Numerous studies have documented the potent pro- and anti-tumorigenic functions of microRNAs and other noncoding RNAs. Yet the vast noncoding landscape of the human genome in cancer remains largely uncharted. My research aims to elucidate the role of noncoding RNAs in gene - environment interaction and to define the precise noncoding molecular events that are responsible for cancer initiation, cancer progression, and cancer susceptibility. I employ molecular cell biology, mouse models, and human specimens to understand the underlying mechanisms of noncoding RNAs in cancer and to discover novel compounds targeting noncoding RNAs for cancer therapeutics and prevention.
In other words ...
Over the past twenty years, scientists have learned that many genes do not produce proteins. These noncoding genes produce ribonucleic acids that function without being translated into protein. Recent advancement has found that there are more noncoding genes than protein-coding genes in the human genome. Numerous studies have documented that changes in these noncoding genes cause cancer. My laboratory studies the function of these noncoding genes in mice and human cells. We hope our studies will add more information about cancer causing genes and environmental toxicants, which will help us to find new ways in the fight against cancer.
1. Ma X, Conklin DJ, Li F, Dai Z, Hua X, Li Y, Xu-Monette ZY, Young, KH, Xiong W, Wysoczynski, Sithu SD, Srivastava A, Bhatnagar A, Li, Y. (2015) The Oncogenic MicroRNA miR-21 Promotes Regulated Necrosis in Mice. Nature Communications, 6:7151.
2. Deng Q, Becker L, Ma X, Zhong X, Young K, Ramos K, Li Y. (2014) The dichotomy of p53 regulation by noncoding RNAs. J Mol Cell Biol 6(3):198-205.
3. Li, Y., Gordon, M.W., Xu-Monette, Z.Y., Visco, C., Tzankov, A., Zou, D., Qiu, L., Montes-Moreno, S., Dybkaer, K., Orazi, A., Zu, Y., Bhagat, G., Richards, K.L., Hsi, E.D., Choi, W.W., van Krieken, J.H., Huang, Q., Ai, W., Ponzoni, M., Ferreri, A.J., Winter, J.N., Go, R.S., Piris, M.A., Moller, M.B., Wu, L., Wang, M., Ramos, K.S., Medeiros, L.J. and Young, K.H. (2013) Single nucleotide variation in the TP53 3' untranslated region in diffuse large B-cell lymphoma treated with rituximab-CHOP: a report from the International DLBCL Rituximab-CHOP Consortium Program. Blood. 121(22):4529-40.
4. Takwi A., Li, Y., Buscaglia L.E.B., Zhang J. Choudhury S., Park A.K., Liu, M., Young K.H., Park WY. Martin R.C.G., Li, Y (2012) A Statin-regulated MicroRNA Represses Human c-Myc Expression and Function, EMBO Mol Med, 4(9):896-909.
5. Ma, X., Kumar, M., Choudhury, S.N., Buscaglia, L.E.B., Barker J.R., Kanakamedala, K., Liu, M., Li, Y. (2011) Loss of the miR-21 Allele Elevates the Expression of its Target Genes and Reduces Tumorigenesis. Proc Natl Acad Sci U S A, 108(25):10144-9.
6. Lu, Z., Li, Y., Takwi, A., Li, B., Zhang, J., Conklin, D. J., Young, K. H., Martin, R., Li, Y. (2011) miR-301a as a NF-kB Activator in Pancreatic Cancer Cells, EMBO J, 30(1):57-67.
The use of chimeric antigen receptors (CAR) to enhance the ability of the immune system's T cells to target and kill cancer cells has advanced the treatment of patients with B-cell malignancies. However, CAR T-cell therapy for solid tumors has lagged, due to the complex microenvironment of solid tumors that includes suppressive cells, T-cell-intrinsic negative regulatory mechanisms and overexpression of inhibitory molecules.