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Mark M. W. Chong
Helen and Martin Kimmel Fellow
Ph.D. University of Melbourne 2004
Mark.Chong@med.nyu.edu

In the traditional paradigm of “gene expression”, a protein-coding gene is first transcribed into RNA, and this RNA (frequently after splicing) is then translated into a protein. With a few notable exceptions where the RNA itself is the end product, such as rRNA or tRNAs, most transcribed RNA was thought to lead to a protein product. However, it is now clear that in the order of 80% of the genome, including in humans, is transcribed at some point despite the fact that protein-coding genes (including introns) only account for 2% of the genome. My interest is to understand how non-coding RNAs contribute to the regulation of T cell development. MicroRNAs constitute one well-defined class of non-coding RNAs. These ~22 nucleotide RNAs translationally repress protein-coding mRNAs through base-pairing in the 3’UTR of target mRNAs. We have recently found that microRNAs have critical functions in T cells. In particular, they are indispensable for maintaining the function of Foxp3+ regulatory T cells (JEM, 2008).

Additionally, I’m interested in the regulation of the Cd4 gene, and its impact on T cell development. We have found that CD4 expression in T helper cells is epigenetically imprinted following lineage commitment in the thymus.

Publications

Chong, M.M.W., Rasmussen, J.P., Rudensky, A.Y. & Littman, D.R. (2008) The RNaseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease, J. Exp. Med., 205:2005-17.

Zhou, L., Lopes, J.E., Chong, M.M.W., Ivanov, I.I., Min, R., Victora, G.D., Shen, Y., Du, J., Rubtsov, Y.P., Rudensky, A.Y., Ziegler S.F. & Littman, D.R. (2008), TGF-b-induced Foxp3 inhibits Th17 cell differentiation by antagonizing RORgt function, Nature, 453: 236-40.

Croom, H.A., Izon, D.J. Chong, M.M., Curtis, D.J., Roberts, A.W., Kay, T.W.H., Hilton, D.J., Alexander, W.S. & Starr, R. (2008), Perturbed thymopoiesis in vitro in the absence of Suppressor of Cytokine Signalling 1 and 3, Mol. Immunol. 45:2888-96

McKenzie, M.D., Dudek, N.L., Mariana, L., Chong, M.M.W., Trapani, J.A., Kay, T.W.H. & Thomas, H.E. (2006), Perforin and Fas induced by IFNg and TNFa mediate b cell death by OT-I CTL, Int. Immunol., 18: 837-846.

Browne, E.P., Li, J., Chong, M. & Littman, D.R. (2005), Virus-host interactions: new insights from the small RNA world, Genome Biol., 6:238.

Jamieson, E., Chong, M.M.W., Steinberg, G.R., Jovanovska, V., Fam, B.C., Bullen, D.V.R., Chen, Y., Kemp, B.E., Proietto, J., Kay, T.W.H. & Andrikopoulos, S. (2005), Socs1 deficiency enhances hepatic insulin signaling, J. Biol. Chem., 280:31516-31521.

Chong, M.M.W., Metcalf, D., Jamieson, E., Alexander, W.S. & Kay, T.W.H. (2005), Suppressor of Cytokine Signaling-1 in T cells and Macrophages is Critical for Preventing Lethal Inflammation, Blood, 106:1668-1675.

Chen, Y., Chong, M.M.W., Darwiche, R., Thomas, H.E. & Kay, T.W.H. (2004), Severe Pancreatitis with Exocrine Destruction and Islet Neogenesis in Mice with Suppressor of Cytokine Signaling-1 Deficiency, Am. J. Pathol., 165:913-921.

Chong, M.M.W., Chen, Y., Darwiche, R., Dudek, N.L., Irawaty, W., Santamaria, P., Allison, J., Kay, T.W.H. & Thomas, H.E. (2004), Suppressor of Cytokine Signaling-1 Overexpression Protects Pancreatic b cells from CD8+ T cell-Mediated Autoimmune Destruction, J. Immunol., 172: 5714-5721.

Cornish, A.L., Chong, M.M., Davey, G., Darwiche, R., Nicola, N.A., Hilton, D.J., Kay, T.W.H., Starr, R. & Alexander, W.S. (2003), SOCS-1 regulates signaling in response to IL-2 and other gc-dependent cytokines in peripheral T cells, J. Biol. Chem., 278:22755-22761.

Darwiche, R., Chong, M.M.W., Thomas, H.E. & Kay, T.W.H. (2003), Expression of FAS on b cells in Accelerated, but not Spontaneous Diabetes in Nonobese Diabetic Mice, J. Immunol., 170:6292-6297.

Chong, M.M.W., Cornish, A.L., Darwiche, R., Stanley, E.G., Purton, J.E., Godfrey, D.I., Hilton, D.J., Starr, R., Alexander, W.S. & Kay, T.W.H. (2003), Suppressor of Cytokine Signaling-1 is a Critical Regulator of Interleukin-7-Dependent CD8+ T cell Differentiation, Immunity, 18:475-487.

Kay, T.W.H., Darwiche, R. Irawaty, W., Chong, M.M.W., Pennington, H.L. & Thomas, H.E. (2003), The role of cytokines as effectors of tissue destruction in autoimmunity, Adv. Exp. Med. Biol., 520:73-86.

Chong, M.M.W., Thomas, H.E., & Kay, T.W.H. (2002), Suppressor of cytokine signaling -1 regulates the sensitivity of pancreatic b cells to tumor necrosis factor, J. Biol. Chem, 277: 27945-27952.

Chong, M.M.W., Thomas, H.E., & Kay, T.W.H. (2001), g-Interferon signaling in pancreatic b cells is persistent but can be terminated by overexpression of suppressor of cytokine signaling-1, Diabetes, 50: 2744-2752.