Thu Annelise Nguyen
PhD, Texas A&M University
MBA, Kansas State University
Associate Professor, Toxicology
K-244 Mosier Hall
The intercellular signaling system mediated by intercellular communication is crucial in maintaining the synchronized responses of cells to stimuli, tissue homeostasis, growth control and development. In normal tissues, gap junctions (GJs), one type of intercellular communications, are membrane channels that allow a direct exchange of small molecules between the cytoplasm of contacting cells. GJs are made of hexamers of gap junction proteins, called connexins. There are many protein kinases identified that phosphorylate different connexins. Our lab focuses on specific isoforms of Protein Kinase C (PKC) that are regulated connexins during cancer formation. We know that tumor cells have reduced or altered gap junctional intercellular communication (GJIC) capacity. Increasing cell-cell communication in tumor cells enhances drug sensitivity. Hence, increasing gap junction activity or enhancing GJIC in tumor cells provides the means to enhance anti-neoplastic therapies. Thus, we have designed synthetic small molecules that specifically activate GJIC activity and inhibit cancer cell growth.
Breast cancer is the major life-threatening malignancy among women in United States. Breast tumor is dependent on estrogen and estrogen receptor and responsive to estrogen ablation therapy; however, there is a high rate of treatment failure. Estrogen-independent cells aggressively emerge after one to five years. Worldwide, a 40-70% of patients ultimately develop metastatic disease. This may due to treatment failure, poor prognosis, morbidity and mortality. In our lab, we have assembled an in vitro integrated cellular model of breast cancer pattern to mimic the progression from an estrogen-dependent to an estrogen-independent stage and evaluate the processes of cell survival, invasion and metastasis. This integrated cellular system plays a significant role in promoting invasion and metastasis from a physiological toward pathological conditions. The mimicking metastatic development can provide insight into the mechanism of invasion and metastasis and facilitate the findings of new approaches for its control and/or eradication.
My primary teaching role is to further develop graduate student training in molecular toxicology. In addition, I assist in teaching Veterinary Toxicology (DMP 801 – 3 credit hour) and Environmental Toxicology (DMP 806 – 2 credit hour).
Julie Bernzweig, Brian Heiniger, Keshar Prasain, Jianyu Lu, Duy H. Hua and Thu A. Nguyen. (2011) Anti-breast Cancer Agents, Quinolines, Targeting Gap Junction. Medicinal Chemistry, in press.
Brian Heiniger, Gunjan Gakhar, Keshar Prasain, Duy H. Hua and Thu A. Nguyen. (2010) Second Generation of Substituted Quinolines as Anti-Cancer Drugs for Breast Cancer. Anticancer Research 30(10): 3927-3932.
Debarshi Banerjee, Gunjan Gakhar, Dan Madgwick, Amy Hurt, Dolores Takemoto and Thu Annelise Nguyen. (2010) Connexin46, a gap junction protein that protects breast cancer tumors from hypoxia. International Journal of Cancer 127(4): 839-848.
E. M. Perchellet, K. R. Crow, Gunjan Gakhar, A. Shi, D. H. Hua, T.A. Nguyen, and J.P Perchellet. (2010) Bioactivity and Molecular Targets of Novel Substituted Quinolines in Murine and Human Tumor Cell Lines in Vitro. International Journal of Oncology 36:673-688.
Gunjan Gakhar, Duy H. Hua, and Thu Annelise Nguyen. (2010) Combinational treatment of PQ1 and tamoxifen induces increased apoptosis in T47D breast cancer cells. Anti-Cancer Drugs 21: 77-88.
Gunjan Gakhar, Mary Wight-Carter, Gordon Andrews, Sally Olson, Thu Annelise Nguyen. (2009) Hydronephrosis and Urine Retention in Estrogen Implanted Athymic Nude Mice. Veterniary Pathology 46(3): 505-508
Gunjan Gakhar, Diana Schrempp, and Thu Annelise Nguyen. (2009) Regulation of gap junctional intercellular communication by TCDD in HMEC and MCF-7 breast cancer cells. Toxicology and Applied Pharmacology 235(2):171-181.
Gunjan Gakhar, Takahiro Ohira, Aibin Shi, Duy H. Hua and Thu Annelise Nguyen. (2008) Antitumor Effect of Substituted Quinolines via Gap Junctional Intercellular Communication in Breast Cancer Cells. Drug Development Research 69 : 526–534.
Aibin Shi, Thu A. Nguyen, Srinivas K. Battina, Sandeep Rana, Dolores J. Takemoto, Peter K. Chiang, and Duy H. Hua. (2008) Synthesis and anti-breast cancer activities of substituted quinolines. Bioorg Med Chem Lett. 18(11):3364-8.
Sabah JR, Schultz BD, Brown ZW, Nguyen AT, Reddan J, Takemoto LJ. (2007) Transcytotic passage of albumin through lens epithelial cells. Invest Ophthalmol Vis Sci. 48(3):1237-1244.
T. A. Nguyen, L.J. Takemoto, and D.J. Takemoto. Inhibition of gap junction activity through the release of the C1B domain of PKCg from 14-3-3: Identification of PKCg binding sites. (2004) J. Biol. Chem. 279(50):52714-25.
T. A. Nguyen, D. Boyle, L.M. Wagner, T. Shinohara, and D.J. Takemoto. LEDGF Activation of PKC g and Gap Junction Disassembly in Lens Epithelial Cells. (2003) Experimental Eye Research 76, 565-572.
C. Qin, T. Nguyen, J. Stewart, I. Samudio, R. Burghardt, and S. Safe. Estrogen Up-Regulation of p53 Gene Expression in MCF-7 Breast Cancer Cells Is Mediated by Calmodulin Kinase IV-Dependent Activation of a Nuclear Factor kappaB/CCAAT-Binding Transcription Factor-1 Complex. (2002) Mol Endocrinol. 16, 1793-1809.
Matthew Stoner, Fan Wang, Mark Wormke, Thu Nguyen, Ismael Samudio, Carrie Vyhlidal, Dieter Marme, Gunter Finkenzeller, and Stephen Safe. Inhibition of Vascular Endothelial Growth Factor Expression in HEC1A Endometrial Cancer Cells through Interactions of Estrogen Receptor a and Sp3 Proteins. (2000) J. Biol. Chem. 275, 22769-22779.
Brad Saville, Mark Wormke, Fan Wang, Thu Nguyen, Eva Enmark, George Kuiper, Jan-Ake Gustafsson, and Stephen Safe. Ligand-, Cell-, and Estrogen Receptor Subtype (a/b)-dependent Activation at GC-rich (Sp1) Promoter Elements. (2000) J. Biol. Chem. 275, 5379-5387.
Thu Nguyen, Debie Hoivik, Jeong-Eun, and Stephen Safe. Interactions of Nuclear Receptor Coativator/Corepressor Proteins with the Aryl Hydrocarbon Receptor Complex. (1999) Archives of Biochemistry and Biophysics. 367, 250-257.