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Te-Hua T. Chu

ASSOCIATE PROFESSOR  Pharmacology and Systems Therapeutics

Overview

Gender Female
E-mail tearina.chu@mssm.edu

Dr. Chu is Director of the Microarray Shared Resource Facility.

Research

It is widely believed that in a given cell at a unique time, thousands of genes and their products (i.e., RNA and proteins) function in a complicated though orchestrated way. The consequences of genome-initiated events are passed on to tissues, organisms, systems and thus the network of molecular, cellular biology and biochemistry support the processes of life. However, imbalanced or abnormal operation in such networks leads to various human diseases. Traditional methods in molecular biology generally work on the basis of a "single gene in one experiment", which means that the throughput is very limited and the "whole picture" of gene function and networking are hard to obtain. With the development of microarray technology and the decoding of the human genome, such obstacle has been eliminated as the microarray permits high throughput and screening of "tens of thousands of genes in one experiment". Such layout paves a new way of examining parallel biological functions/regulations among thousands of genes in areas of fundamental/clinical research, gene discovery, drug discovery and diagnostic tools. My lab aims to have involvement in diverse research projects, contributing our unique expertise in helping to shape microarray experiments to various disease efforts in general, with particular research interests in the following areas:

1) Genome-wide gene expression analysis on single cells
Many microarray studies have worked on a block of tissues where assayed RNA was obtained from mixed populations of cell types. However, in many cases, changes of gene expression are constrained to a particular cell type, therefore such contamination or sample heterogeneity masks small changes and reduces the sensitivity of the microarray assay. Thus, it is essential to perform gene expression analysis in single cells when necessary. We used Laser-Capture microdissection (LCM) technique to isolate neurons in the parvocelluar subdivision of mediodorsal nucleus of thalamus in postmortem tissue. Nanograms of pure RNA were obtained and profiled on whole-genome microarrays. Positive confirmation of selected genes by quantitative PCR demonstrates the validity of genome profiling on single cells.

2) Region-specific analyses of neuronal transcriptomes in psychiatric diseases
More than 1 percent of the population suffers psychiatric illnesses, e.g. schizophrenia, bipolar mood disorder and major depression in the US. However, the cause of these diseases and their underlying molecular mechanisms are poorly understood. In contrast to neurodegenerative disorders in which pathology may be localized to a particular brain region and cell type, neuropsychiatric disorders are generally believed to involve multiple cellular and regional pathological changes at the molecular level, which makes microarray a great tool to simultaneously examine the transcriptome changes in these diseases. While various cell types in various cor tical brain regions have been demonstrated to be involved in psychiatric disorders, our lab focus has been on neurons of thalamic subregions, which are of particular interests due to the unique anatomical clusters of neurons in subdivisions or nuclei, which form specific neuronal circuitry to various regions in the cortex, as well as its involvement in brain development. Our goal is to investigate gene expression alterations in functional presentation in different thalamic regions in order to better understand the molecular mechanisms involved in psychiatric disorders.

Publications

Mzhavia N, Yu S, Ikeda S, Chu TT, Goldberg I, Dansky HM. Neuronatin: a new inflammation gene expressed on the aortic endothelium of diabetic mice. Diabetes 2008 Oct; 57(10): 2774-2783.


Tam LS, Shang Q, Li EK, Tomlinson B, Chu TT, Leung YY, Kwok LW, Wong KC, Li TK, Yu T, Zhu TY, Kun EW, Yip GW, Yu CM. Subclinical carotid atherosclerosis in patients with psoriatic arthritis. Arthritis Rheum 2008 Sep; 59(9): 1322-1331.


Tam LS, Tomlinson B, Chu TT, Li M, Leung YY, Kwok LW, Li TK, Yu T, Zhu YE, Wong KC, Kun EW, Li EK. Cardiovascular risk profile of patients with psoriatic arthritis compared to controls--the role of inflammation. Rheumatology (Oxford) 2008 May; 47(5): 718-723.


Uttamsingh S, Bao X, Nguyen KT, Bhanot M, Gong J, Chan JL, Liu F, Chu TT, Wang LH. Synergistic effect between EGF and TGF-beta1 in inducing oncogenic properties of intestinal epithelial cells. Oncogene 2008 Apr 17; 27(18): 2626-2634.


Kim H, Chu TT, Kim DY, Kim DR, Nguyen CM, Choi J, Lee JR, Hahn MJ, Kim KK. The crystal structure of guamerin in complex with chymotrypsin and the development of an elastase-specific inhibitor. J Mol Biol 2008 Feb 8; 376(1): 184-192.


Chu TT, Fink MY, Mong JA, John G, Auger AP, Ge Y, Sealfon SC. Effective use of microarrays in neuroendocrine research.. J Neuroendocrinol 2007 Mar; 19(3): 145-161.


Hotchkiss H, Chu TT, Hancock WW, Schroppel B, Kretzler M, Schmid H, Liu Y, Dikman S, Akalin E. Differential expression of profibrotic and growth factors in chronic allograft nephropathy. Transplantation 2006 Feb 15; 81(3): 342-9.


Ou Y, Adler V, Chu T, Platica O, Michl J, Pestka S, Izotova L, Boutjdir M, Pincus MR. Two dual specificity kinases are preferentially induced by wild-type rather than by oncogenic RAS-P21 in Xenopus oocytes. Front Biosci 2006 Sep 1; 11: 2420-7.


Shreffler WG, Beyer K, Chu TH, Burks AW, Sampson HA. Microarray immunoassay: association of clinical history, in vitro IgE function, and heterogeneity of allergenic peanut epitopes. J Allergy Clin Immunol 2004 Apr; 113(4): 776-82.


Gherardi D, D'Agati V, Chu TH, Barnett A, Gianella-Borradori A, Gelman IH, Nelson PJ. Reversal of collapsing glomerulopathy in mice with the cyclin-dependent kinase inhibitor CYC202. J Am Soc Nephrol 2004 May; 15(5): 1212-22.


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