Cancer immunotherapy is treatment that induces the immune system to attack tumor cells and is a promising therapy for a wide variety of malignancies. The Coller lab is working to develop a novel RNA-based reagent that will improve all T cell cancer immunotherapies by enhancing the proliferation capacity of tumor targeting immune cells. If successful, we will be able to partner with any corporate or academic entity developing T cell based cancer immunotherapies to improve the efficacy of their T cell therapy. In vitro transcribed (IVT) mRNA is emerging as a promising new drug class capable of delivering genetic information by transiently expressing proteins by structurally resembling natural mRNA. The advantage of mRNA (rather than integrating vectors carrying DNA) is that it poses no risk of genomic integration and will not transform the target cells to an immortalized or malignant state. Notably, our collaborators at Houston Methodist have recently shown that mRNA encoding the gene hTERT enhances the replicative capacity of human T cells, and increases the antitumor effects of CAR-T cells in an animal model of B-cell malignancy. These studies demonstrate that hTERT mRNA has great potential to improve the therapeutic benefits of CAR-T therapy. Our group is uniquely capable of developing mRNA-based therapeutics as we have developed new technology that can exquisitely control the expression of mRNA in vivo. Using our recent discovery, we are working with our collaborators at Houston Methodist to optimize therapeutic mRNAs for the use in cancer immunotherapy.
Radhakrishnan, A., Chen, Y.H., Martin, S., Alhusaini, A., Green, R., and Coller, J. (2016). The DEAD-box protein Dhh1p couples mRNA decay and translation by monitoring codon optimality. Cell, 167, 122-132.
Tat, T., Maroney, P., Chamnongpol, S., Coller, J., and Nilsen, T. (2016). Cotranslational microRNA mediated messenger RNA destabilization. eLife, 10.7554/eLife/12880.
Alhusaini, N., and Coller, J. (2016). The deadenylase components Not2p, Not3p, and Not5p promote mRNA decapping. RNA, 5:709-21
Zhang, L., Prosdocimo, D.A., Bai, X., Fu, C., Zhang, R., Campbell, F., Liao, X., Coller, J. and Jain, M. (2015). KLF15 establishes the landscape of diurnal expression in the heart, Cell Reports, 13:2368-2375.
Presnyak, V., Alhusaini, N., Chen, Y.H., Martin, S., Morris, N., Kline, N., Olson, S., Weinberg, D., Baker, K.E., Graveley, B.R., and Coller, J. (2015). Codon optimality is a major determinant of mRNA stability. Cell, 160: 1111-1124
Smith, J.E., Alvarez-Dominguez, J.R., Kline, N., Huynh, N., Geisler, S., Hu, W., Coller, J., and Baker, K.E. (2014). Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae. Cell Reports, 7:1858-1866.
Sweet, T.J., Kovalak, C., and Coller, J., (2012) The DEAD-box Protein Dhh1 Promotes Decapping by Slowing Ribosome Movement. PLoS Biology., 10(6):1-15.
Hu, W., and Coller, J., (2012) What comes first: translational repression or mRNA degradation? The deepening mystery of microRNA function. Cell Research, doi:10.1038/cr.2012.80.
Geisler, S., Lojek, L., Khalil, A., Baker, K.E., and Coller, J., (2012) A decapping pathway for long non-coding RNAs regulates inducible genes. Mol Cell, 45(3): 279-291. (Previewed by Wilkinson and colleagues)
Castellani, R. J., Gupta, Y., Sheng, B., Siedlak, S. L., Harris, P. L., Coller, J. M., Perry, G., Lee, H.-G., Tabaton, M., Smith, M. A., et al. (2011). A novel origin for granulovacuolar degeneration in aging and Alzheimer's disease: parallels to stress granules. Lab. Invest. 91, 1777–1786.
Blewett, N., Coller, J., and Goldstrohm A. (2011). A quantitative assay for measuring mRNA decapping by splinted ligation reverse transcription polymerase chain reaction: qSL-RT-PCR. RNA, 17:535-543
Geisler, S. and Coller, J. (2010). Alternate endings - A new story for mRNA decapping. Mol Cell, 40: 349-350
Hu, W., Petzold, C., Coller, J., and Baker, K.E. (2010). Nonsense-mediated mRNA decapping occurs on polyribosomes in Saccharomyces cerevisiae. Nat. Struct. Mol. Biol., 17: 244-247
Hu, W., Sweet, T., Chamnongpol, S., Baker, K., and Coller, J. (2009) Co-translational mRNA decay in Saccharomyces cerevisiae. Nature, 461: 225-229.
Sweet, T.J, Boyer, B., Hu, W., Baker, K.E., and Coller, J. (2007) Microtubule disruption stimulates P-body formation. RNA, 13: 493-502.
Barbee, S., Estes, P., Cziko, AM., Luedeman, R., Coller, J., Johnson, N., Howlett, I., MacDonald, P., Brand, A., Newbury, S., Levine, R., Wilhelm, J., Nakamura, A., Parker, R., and Ramaswami, R. (2006) Neuronal RNA granules and cytoplasmic processing bodies are similar in composition and function. Neuron, 21:997-1009
Coller J., and Parker R. (2005) General Translational Repression by Activators of mRNA Decapping. Cell 122:875-886.
Cheng Z., Coller J., Parker R., and Song H. (2005) Crystal structure of the DEAD box helicase, Dhh1p. RNA 11:1258-1270.
Baker K.E.*, Coller J.*, and Parker R. (2004) The yeast Apq12 protein affects nucleocytoplasmic mRNA transport. RNA 10:1352-1358.
*Authors contributed equally
Coller J., Tucker M., Sheth U., Valencia M., and Parker R. (2001) The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes. RNA 12:1717-1727.
Coller J. (2000) Control of mRNA metabolism via the poly (A) binding protein and development of the tethered function assay. Doctorate Thesis, University of Wisconsin.
Gray N., Coller J., Dickson K., and Wickens M. (2000) Multiple portions of poly (A) binding protein stimulate translation in vivo through a poly (A)-independent mechanism. EMBO J 19:4723-4733.
Coller J., Gray N., and Wickens M. (1998) mRNA stabilization by poly (A) binding protein is independent of a poly (A) tail and requires translation. Genes & Dev. 12:3226-3235.
REVIEWS AND CHAPTERS
Geisler, S. and Coller, J. (2013) RNA in unexpected places: long noncoding RNAs function in a variety of cellular contexts. Nature Reviews Molecular Cell Biology, doi:10.1038/nrm3679
Hu, W. and Coller, J.(2013) Method for measuring mRNA decay rates in Saccharomyces cerevisiae. Methods Enzymol. 530:137-55.
Khalil, A. and Coller, J. editors. (2013) The Molecular Biology of Non-coding RNA. Springer Science
Presnyak, V., and Coller, J. (2013). The DHH1/RCKp54 family of helicases: An ancient family of proteins that promote translational silencing. Biochimica et Biophysica Acta. 1829:817-823.
Geisler, S. and Coller, J. (2012) XRN1: A major 5' to 3' exoribonuclease in eukaryotic cells. The Enzymes, 31:1-20.
Coller J. (2008). Methods to determine mRNA half-life in Saccharomyces cerevisiae Methods Enzymol. 448:267-84.
Coller J. and Wickens, M. (2007). Tethered function assays: An adaptable approach to study RNA regulatory proteins Methods Enzymol. 429:299-321
Baker, K.E. and Coller J., (2006) Post-transcriptional control of gene expression: regulating mRNA translation. Genome Biology 7:332.
Coller J., and Parker R. (2004) Eukaryotic mRNA decapping. Annu. Rev. Biochem. 73:861-890.
Coller J., and Wickens M. (2002) Tethered function assays using 3’UTRs. Methods 26:142-150.