Associate Professor, Department of Microbiology and Molecular Cell Biology

Lewis Hall, #3148
Office: (757) 446-5664
Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Education

• B.S., Fudan University
• Ph.D., The Pennsylvania State University
• Postdoctoral Training, University of California at Berkeley

Academic Positions

Lab People and Photos

The 2010 AACR-PanCAN Innovative Grant Recipient: Dr. Amy Tang with Dr. Tyler Jacks, 2010 President of the AACR's, of the Massachusetts Institute of Technology (MIT), and Julie Fleshman, JD, MBA, President and CEO of the Pancreatic Cancer Action Network. ©2010 AACR/Todd Buchanan.

From left: Dr. Minglei Bian from Peking University (Postdoctoral Fellow); Dr. Yang Liao from Fudan University (Postdoctoral Fellow), Mr. Oscar Gonzales from Wake Forest School of Medicine (Technician); Ms. Zena Urban from Boston University School of Medicine (PhD Graduate Student), Dr. Amy H. Tang from Eastern Virginia Medical School (The Principal Investigator); Ms. Kristin Sica from Eastern Virginia Medical School (summer M1 medical student), Dr. Vassilena Zheleva from Dartmouth Medical School (a PGY3 Resident in General Surgery); Dr. Yajun Cao from Fudan University (Postdoctoral Fellow).(Summer of 2011)

From left, Mr. John Crook from UC Davis; Mr. Matthew Ambler from Yale University (summer student); Dr. Yang Liao from Fudan University; Dr. Yajun Cao from Fudan University and Dr. Amy H. Tang, Principal Investigator. (Summer of 2010)

Postdoctoral Fellows

• ·Dr. Yang Liao (May 28, 2008 – present)

• ·Dr. Yajun Cao (April 12, 2010 – present)

• Dr. Minglei Bian (September 1, 2010 – present)

• Dr. YingYing Liu (August 1, 2010 – present)

  Clinical Fellows

• Dr. Vassilena Zheleva (July 1, 2011 – present)

Graduate Students

• Miss. Zena Urban (August 1, 2011 – present)

Technicians

·

• Mr. Oscar A. Gonzales (July 5, 2011 – present)

• ·Mr. John A. Crooks (August 2, 2011 – May, 13, 2011)

Summer Students

·

• Miss. Kristin Sica

• Mr. Matthew Ambler

Research Interests

Project I: Regulated Proteolysis in K-RAS-Mediated Tumorigenesis and Metastasis in human cancers

Dr. Tang's laboratory studies the RAS signal transduction pathway using multiple model organisms/systems including Drosophila, transgenic mice, human cancer cell lines and human cancer tissue specimens. As oncogenic RAS promotes the genesis of many human cancers, how best to contravene activated RAS signaling has been an intense area of investigation in the field of cancer biology for the past 30 years. Seven-In-Absentia (SINA), an E3 ubiquitin ligase, is an essential downstream component of the Drosophila RAS signal transduction pathway. The human homologue of SINA, SIAH, is a member of this evolutionarily highly conserved family of RING finger E3 ubiquitin ligases; however, the roles and regulation of SIAH-dependent proteolysis are not well understood in the context of RAS signal transduction in mammalian systems.

Dr. Tang's lab has accumulated evidence demonstrating the importance of proper SIAH function in mammalian K-RAS signaling. We show that by inhibiting the enzymatic activity of SIAH, and thus SIAH-mediated proteolysis, RAS-mediated neoplastic transformation and tumorigenesis can be effectively blocked in human cancer cells [Can Res 67(24):1798-810, 2007; JNCI 100(22):1606-29, 2008]. Furthermore, SIAH-deficient cells have reduced MAPK signaling, suggesting that SIAH might be involved in aberrant K-RAS signaling through a regulatory feedback loop mechanism. Thus, these studies provide an initial glimpse into the significance of the SIAH E3 ubiquitin ligase-regulated proteolysis in the K-RAS pathway during tumor initiation, progression and oncogenesis in human pancreatic cancer, lung cancer, invasive and metastatic breast cancer and hormonal-refractory prostate cancer.

Advancing understanding of the role of SIAH E3 ligases in K-RAS signaling and, more importantly, the potential to target SIAH as a novel new anti-K-RAS and anti-cancer target in the treatment of the most aggressive and the deadliest forms of human cancers represent exciting steps forward in the fields of K-RAS signaling, cancer biology and cancer therapy. Ultimately, we hope such SIAH-based anti-cancer therapies will lead to novel and efficacious treatments for human cancer patients, especially the ones with metastatic diseases.

Project II:   Innate Immunity and Cellular Defense

To understand how a host cell differentiates a pathogenic microbe from a nonpathogenic microorganism is a fundamental question in biology. Drosophila has an innate immune system that is similar to humans but is devoid of the complication of the adaptive immune system. We use the Drosophila as the model organism to study the molecular mechanism of how innate immunity is activated upon pathogen recognition. We found that the structural integrity of the sentinel receptors/innate sensors is modulated during infection and inflammation. We hypothesize that proteases release that is common during pathogen-host antagonism may provide an important cue for the host to distinguish a pathogenic versus a nonpathogenic microorganism. We are using transgenic fly models to demonstrate that protease release after pattern recognition provides a "tissue damage" signal that could alert host cells to the onset of endogenous tissue damage and exogenous pathogen invasion.

Project III:   Genetic Screens for Anti-Cancer Drug Resistance 

The development drug/chemical resistance is a recurring problem. There is an important need for us to understand the mechanisms by which drug/chemical resistance is acquired in multicellular organisms and cancers. We will carry out genetic screens in Drosophila for resistance to several key anticancer drugs that are prone to develop resistance. This effort, coupled with genomic and microarray analyses, should help to identify the alterations of key signaling pathways that could forecast and predict drug resistance development.

Research Grants Awarded

Ongoing Research Support

AACR 2010 Pancreatic Cancer Action Network- American Association for Cancer Research (AACR) Innovative Grant "SIAH is a novel and effective anti-K-RAS drug target in pancreatic cancer"
(AACR-PanCan #169458)
Principal Investigator: Amy H. Tang, Ph.D.
2010 - 03/01/2010-02/29/2012

DOD Department of Defense "Targeting SIAH E3 Ligase Downstream of the HER2/Neu/RAS Signaling Pathway to Block Highly Invasive Human Breast Cancer Tumorigenesis and Metastasis" (DOD-Idea Award-BC095305)
Principal Investigator: Amy H. Tang, Ph.D.
09/30/2010 - 09/29/2013

NIGMS "Regulated Proteolysis in the RAS Signal Transduction"
(R01 GM 069922)
Principal Investigator: Amy H. Tang, Ph.D.
05/01/2004 - 04/30/2011

NIH supplement "Regulated Proteolysis in the RAS Signal Transduction" (R01 GM 069922Z-05S1)
Principal Investigator: Amy H. Tang, Ph.D.
09/30/2009 - 04/30/2011

NCI R01 "SIAH2-Dependent Proteolysis in Cell Migration, Tumor Growth and Cancer Metastasis"
(R01 CA140550)
Principal Investigator: Amy H. Tang, Ph.D.
07/01/2010 - 06/30/2015

Publications

• Podratz, J. L., Staff, N. P., Froemel, D., Wallner, A., Wabnig, F., Bieber, A. J., Tang, A. H. and A. J. Windebnk. (2011) Drosophila melanogaster: A new model to study Cisplatin-induced neurotoxicity Neurobiology of Diseases 43, 330-337. http://www.sciencedirect.com/science/article/pii/S0969996111001173

• Behling KC, A. H. Tang, Freydin B, Chervoneva I, Kadakia S, Schwartz GF, Rui H, Witkiewicz AK. (2010) Increased SIAH expression predicts DCIS progression to invasive carcinoma. Breast Cancer Research and Treatment, November 19 issue, pp1254-1258. http://www.springerlink.com/content/02471q382n033354/fulltext.html

• Ahmed, A. U., Schmidt, R. L., Park, C. H., Reed, N. R., Hesse, S. E. Thomas, C. F., Molina, J. R., Deschamps, C., Aubry, M. C. and A. H. Tang. (2008) Effect of Disrupting Seven In Absentia Homolog 2 Function on Lung Cancer Cell Growth Journal National Cancer Institute 100, 1606-1629. http://jnci.oxfordjournals.org/cgi/content/full/100/22/1606.

• Schmidt, R. L., Park, C. H. Ahmed, A. U., Gundelach, J.H., Reed, N. R., Cheng, S., Knudsen, B. E. and A. H. Tang. (2007) Inhibition of RAS-Mediated Tumorigenesis by Targeting the downstream E3 Ubiquitin Ligase, SIAH. Cancer Research, 67, 11798-11810. http://cancerres.aacrjournals.org/cgi/content/full/67/24/11798

• Schmidt, R. L., Trejo, T. R., Plummer, T. B. Platt, J. L. and A. H. Tang. (2008) The Infection-Induced Proteolysis of PGRP-LC Controls the IMD Activation and Melanization Cascades in Drosophila. FASEB J. 22, 918-929. http://www.fasebj.org/cgi/content/full/22/3/918

• Schmidt, R. L., Rinaldo, F. M., Hesse, S. E., Hamada, M., Ortiz, Z., Beleford, D. T., Page-McCaw, A., Platt, J. L. and A. H. Tang. (2009). Protease-Dependent Activation of the Drosophila IMD Pathway in Response to Gram-Negative Bacterial Infection. Innate Immunity 1, 1-15.

• Tang, A. H., G. J. Brunn, M. Cascalho and J. L. Platt. (2007) Endogenous pathway to SIRS, sepsis and related conditions. Journal of Leukocyte Biology 82, 282-285. http://www.jleukbio.org/cgi/content/full/82/2/282

• Tang, A. H. and J. L. Platt. (2007) Accommodation of grafts: implications for health and disease. Human Immunology 68, 645-651. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703470/

• Reed, N. R., Schmidt, R. L., Smyrk, T. C., Qin, R. Chari, S. T., Sarr, M. G., Grande, J. P., Petersen, G. M and A. H. Tang. Predicting Pancreatic Cancer Patient Survival by Combining Clinical and Biomarkers and Tissue Microarrays (Manuscript in revision).

• G. B. Johnson^, G. J. Brunn, A. H. Tang, J. L. Platt (2003). Evolutionary Clues to the Functions of the Toll-like Family as Surveillance Receptors. Trends in Immunology 24, 19-24. http://www.cell.com/trends/immunology/abstract/S1471-4906(02)00014-5

• Tang, A. H., T. P. Neufeld, G. M. Rubin and H. -Arno J. Müller (2001). Transcriptional Regulation of Cytoskeletal Functions and Segmentation by a Novel Maternal Pair-Rule Gene, lilliputian. Development 128, 801-813. http://dev.biologists.org/content/128/5/801.full.pdf+html

• T. P. Neufeld, A. H. Tang and G. M. Rubin (1998). A genetic screen to identify components of the sina signaling pathway in Drosophila eye development. Genetics 148, 277-286. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459784/

•  Tang, A. H., T. P. Neufeld, E. Kwan and G. M. Rubin (1997). PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal cell fates, by a SINA-dependent mechanism. Cell 90, 459-467. http://www.cell.com/abstract/S0092-8674(00)80506-1

• G. M. Rubin, H. C. Chang, F. Karim, T. Laverty, N. R. Michaud, D. K. Morrison, I. Rebay, A. H. Tang, M. Therrien and D. A. Wassarman (1997). Signal transduction downstream of RAS in Drosophila. Cold Spring Habor Symp. on Quant. Biol. Volume LXII. 347-352. http://symposium.cshlp.org/content/62/347

• Tang, A. H. and C.-P. D. Tu. (1995). Pentobarbital-induced changes in Drosophila glutathione S-transferase D21 mRNA stability: gstD21 mRNA stability. J Biol. Chem. 270, 13819-13825. http://www.jbc.org/cgi/content/full/270/23/13819

• Tang, A. H. and C.-P. D. Tu. (1994) Biochemical characterization of Drosophila glutathione S-transferase D1 and D21: Drosophila DDT dehydrochlorinase J. Biol. Chem. 269, 27876-27884. http://www.jbc.org/cgi/reprint/269/45/27876

• Z.-H. Zhang, H.-Z. Liu, H. Tang and Y.-D. You (1988) The Effect of hemoglobin on the fluidity of human erythrocyte membrane. Acta Biophysics Sinica 4, 129-133.

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