Profiles
Amy H. Tang
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Courses Taught
Tumor Biology, Developmental Biology, Molecular Genetics and Innate Immunity
Biomedical Sciences Program Track: Molecular Integrative Biosciences (MIB)
Graduate Education
- PhD, The Pennsylvania State University
Postdoctoral Education
- Postdoctoral Training, University of California at Berkeley
Lab Location
Education and Research Building
Rooms 454 - 457
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.
Presentations and Scholarships
Publication List
Lab Page
Courses Taught
Tumor Biology, Developmental Biology, Molecular Genetics and Innate Immunity
Biomedical Sciences Program Track: Molecular Integrative Biosciences (MIB)
Graduate Education
- PhD, The Pennsylvania State University
Postdoctoral Education
- Postdoctoral Training, University of California at Berkeley
Lab Location
Education and Research Building
Rooms 454 - 457
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.
Presentations and Scholarships
Publication List
Lab Page