Regulation of protein synthesis in cancer:
In eukaryotic cells, the process of gene expression is tightly regulated at various levels including transcriptional, translational and post translational steps. Translational control is a critical component of gene expression process that maintains cellular homeostasis during physiological and pathophysiological stress conditions. Moreover, the regulation of gene expression at the translation level allows cells to rapidly reprogram proteome output in response to stress stimuli. Deregulation of protein translation has been implicated in various physiological disorders including cancer, alzheimer disease (AD), diabetes, stroke, X- linked Dyskeratosis Congenita (X-DC), etc. Specifically, and directly relevent to my research interests, extensive evidence exists suggesting that deregulation of protein translation directs tumourigenesis by affecting both the global control of protein translation as well as the translation of specific subsets of transcripts. Significantly, key pro- and anti- apoptotic proteins that play crucial roles in deciding the fate of cell are, to a large extent, translationally regulated. Accordingly, our research interest is in investigating the cellular, biochemical, molecular and structural aspects of the regulation of protein translation and to determine how these processes impact on tumourigenesis.
RNA synthetic biology for environmental applications:
With a continuous decrease in the supply of fossil fuel and substantial environmental concerns governments, industries and scientific community are looking for greener, sustainable and renewable source of hydrocarbon fuels. Our research aims towards contributing to solve the crisis in ‘energy and environment’ sector by developing commercially viable and environment friendly technologies for the production of microbial biofuels. Significant amount of effort has been directed towards metabolic engineering of microorganisms for the production of biofuels. Although these proof-of-concept studies are informative, they face a common problem of generating limited yields of biofuels. One contributing factor to this problem is the non-portability of the metabolic engineering tools. Accordingly, we are interested in developing novel and versatile RNA synthetic biology tools which can be used for sustainable microbial production of biofuels and can also be leveraged for several other biotechnological processes for production of value added goods. Ultimately, utilizing the RNA synthetic biology tools, we want to create metabolic network/s for the production of microbial hydrocarbon fuels.
- Li, W., Atkinson, G. C., Thakor, N. S., Allas, Ü., Lu, C. C., Chan, K. Y., Tenson, T., Schulten, K., Wilson, K. S., Hauryliuk, V., and Frank, J., Mechanism of tetracycline resistance by ribosomal protection protein Tet(O). Nature Communications, 2013, 4: 1477. (Impact Factor: 10.742)
- Faye, M. D., Graber, T. E., Liu, P., Thakor, N., Baird, S. D., Durie, D., and Holcik, M., Nucleotide composition of cellular IRES defines dependence on NF45 and predicts a post-transcriptional mitotic regulation. Molecular and Cellular Biology, 2013: 33, 307-318. (IF: 5.036)
- Thakor, N., and Holcik, M., IRES-mediated translation of cellular messenger RNA operates in eIF2α- independent manner during stress. Nucleic Acids Research,2012: 40, 541-542. (IF: 8.808)
- Liwak, U., Thakor, N., Jordan, L.E., Roy, R., Lewis, S.M., Pardo, O., Seckl, M., and Holcik, M., S6 Kinase 2 activity enhances IRES-dependent translation via phosphorylation and degradation of the tumour suppressor PDCD4. Molecular and Cellular Biology, 2012: 32, 1818-1829. (IF: 5.036)
- Li, W., Thakor, N., Xu, E. Y., Huang, Y., Chen, C., Yu, R., Holcik, M., and Kong, A.N., An internal ribosomal entry site mediates redox-sensitive translation of Nrf2. Nucleic Acids Research, 2010: 38, 778-788. (IF: 8.808)
Invited Book Chapter:
Former Lab Members
- Harshil Patel (Undergraduate)
- Chris Cote (Undergraduate)
- Rochelle Caruso (Undergraduate)
- Michelle Kwan (Undergraduate)