Ph.D., Washington State University
- Canada Research Chair Tier II in Molecular Genetics of Human Disease
In response to extracellular stimuli, cells modulate intracellular signal transduction pathways, leading to altered transcriptional programs and ultimately a cellular response, such as survival, proliferation, and cell death. This process is crucial for normal development and maintenance; when it goes awry, it can cause a wide range of diseases from developmental disorders to cancer.
We are particularly interested in one of such quintessential signal transduction-transcription axis, the RAS/MAPK-capicua axis. In this pathway, the RAS/MAPK signal cascade modulates the transcriptional activity of capicua to control gene expression. Dysfunctions in this axis, either the upstream RAS/MAPK pathway or the downstream effector capicua, can cause a spectrum of developmental disorders and various cancers, depending on the cell types affected and the degree of dysfunction. Using multiple mouse genetic models, in vitro systems, and an integrated genomic, transcriptomic, and proteomic approach, our lab addresses how the RAS/MAPK-capicua axis generate cell type-specific output, and the impact on cellular and whole-organism physiology when this axis is perturbed. Answers to these questions will not only help us understand the molecular underpinnings of disease pathogenesis, but also provide therapeutic entry point with broad applicability to developmental disorders and cancer.
Q Tan, LM Brunetti, MWC Rousseaux, H-C Lu, Y-W Wan, JP Revelli, Z Liu, MA Goodell, HY Zoghbi. (2018) Loss of Capicua alters early T cell development and predisposes mice to T cell lymphoblastic leukemia/lymphoma. Proc Natl Acad Sci U S A. In press.
MWC Rousseaux, T Tschumperlin, H-C Lu, EP Lackey, VV Bondar, Y-W Wan, Q Tan, CJ Adamski, J Friedrich, K Twaroski, W Chen, J Tolar, C Henzler, A Sharma, A Bajić, T Lin, L Duvick, RV Sillitoe, HY Zoghbi, HT Orr. (2018) Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1. Neuron. Accepted.
H-C Lu*, Q Tan*, MWC Rousseaux, J-Y Kim, Y-W Wan, S-Y Yeh, JM Patel, X Liu, Y Lee, JD Fryer, J Han, M Chahrour, RH Finnell, Y Lei, EZ Zurita-Jimenez, P Ahimaz, K Anyane-Yeboa, D Lehalle, N Jean-Marcais, A-L Mosca-Boidron, J Thevenon, MA Cousin, DE Bro, BC Lanpher, EW Klee, N Alexander, MN Bainbridge, HT Orr, Z Liu, CP Schaaf, HY Zoghbi. (2017) Disruption of the ATXN1-CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans. Nature Genetics 49 527-536. (*co-first author)
Q Tan, H Krishna Yalamanchili, J Park, A De Maio, H-C Lu, Y-W Wan, JJ White, VV Bondar, LS Sayegh, X Liu, Y Gao, RV Sillitoe, HT Orr, Z Liu, HY Zoghbi. (2016) Extensive cryptic splicing upon loss of RBM17 and TDP43 in neurodegeneration models. Human Molecular Genetics 25, 5083-5093. Selected for journal issue cover.
J Park, I Al-Ramahi, Q Tan, N Mollema, JR Diaz-Garcia, T Gallego-Flores, H-C Lu, S Lagalwar, L Duvick, H Kang, Y Lee, P Jafar-Nejad, LS Sayegh, R Richman, X Liu, Y Gao, CA Shaw, JSC Arthur., HT Orr, TF Westbrook, J Botas, HY Zoghbi. (2013) RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature 498, 325-331.
L Zhang, Q Tan, R Lee, A Trethewy, Y Lee, M Tegeder. (2010) Altered xylem-phloem transfer of amino acids affects metabolism and leads to increased seed yield and oil content in Arabidopsis. The Plant Cell 22: 3603-3620.
Q Tan, L Zhang, J Grant, P Cooper, M Tegeder. (2010) Increased phloem transport of S-methylmethionine positively affects sulfur and nitrogen metabolism and seed development in pea plants. Plant Physiology 154:1886-1896.
Q Tan, AK Grennan, H Pelissier, D Rentsch, M Tegeder. (2008) Characterization and expression of French bean amino acid transporter PvAAP1. Plant Science 174: 348-356.
M Tegeder, Q Tan, AK Grennan, JW Patrick. (2008) Amino acid transporter expression and localisation studies in pea (Pisum sativum). Functional Plant Biology 34: 1019-1028.
Z Liao, Q Tan, Y Chai, K Zuo, M Chen, Y Gong, P Wang, Y Pi, F Tan, X Sun, K Tang. (2004) Cloning and characterization of the gene encoding HMG-CoA reductase from Taxus media and its functional identification in yeast. Functional Plant Biology 31: 73-81.