Ying-Hsiu Su

Ying-Hsiu Su

Associate Professor, Microbiology and Immunology
Drexel Institute for Biotechnology and Virology Research

Ph.D., 1992, University of South Alabama, Mobile, AL

3805 Old Easton Road
Doylestown, PA 18901
Tel: 215-489-4907
Fax: 215-489-4920
Email: Ying-Hsiu.Su@DrexelMed.edu

Research Staff: Li Zhu, Ph.D. (Postdoctoral fellow), Xiaohe (Lucy) Wang (Research assistant), Emily Oppenheim (student intern), Cherie Kleneiski (student intern)
Graduate Students: Selena Lin (BS/MS)

Keywords:

Herpes Simplex Virus Type 1, Viral Latency, DNA damage responses and DNA repair in neuronal cells, Cancer Detection, Molecular Diagnosis, Circulating DNA, Urine DNA

Research Interests

Research in my laboratory is focused on herpes simplex virus (HSV) latency, DNA damage responses/ DNA repair activities in neuronal cells, and detection of cancer DNA markers in urine.

HSV establishes latent infections in neurons of its natural human host. Reactivation of the viral genome from this latent state occurs sporadically. The mammalian cell genome is constantly exposed to endogenous metabolic by-products and environmental factors that can alter its chemical structure and influence its encoded message. It is often necessary that these lesions are removed to ensure complete and accurate DNA replication and even gene expression. Repair of damaged DNA in neuronal cells has been shown to be much more limited than in mitotically active cells and viral DNA in neuronal cells is also vulnerable to various endogenous toxins. However, there is little known about how the HSV genome is managed or repaired during latent infection.

Our recent finding suggests that DNA modifications or damages accumulated in latently infected HSV DNA and this might affect the reactivation frequency. A related fundamental question is if there are reactivation competent and incompetent pools of viral DNA in latently infected cells and if these two pools are the result, in part, of mutation accumulation. For practical reasons, and to limit animal use, the work begins in vitro the tissue culture model (NGF-differentiated PC12 cells) that we have developed, and is then validated in the mouse model. The over all goal of this project is to learn the Knowledge about how the HSV genome is managed or repaired during latent infection and the molecular mechanisms whereby HSV-1 and neuronal cells interact. The information learned from this study will provide clues regarding the fundamental viral and neurobiology of pathogenesis and thus aid antiviral drug discovery that can specifically target latent infections, which has not yet been possible.

Rat phaeochromocytoma (PC12) cells, in response to nerve growth factor (NGF), differentiate, extend long neurites, and acquire many biochemical properties characteristic of the peripheral nervous system. We have shown that NGF differentiated PC12 cells can support "long-term", quiescent infection of HSV-1 which resembles in vivo latency.

Several questions are being investigated using this in vitro HSV latency model. First, does the HSV-1 genome in quiescently infected NGF-differentiated PC12 (NGF-PC12) cells, accumulate damage as a function of time? Can we profile the genomes derived directly from quiescently infected cells for major physical modifications and single nucleotide mutations? Next, we investigate whether that the accumulation of modifications or damages in viral DNA is due to the high vulnerability of the HSV genome to DNA adducts or due to the poor repair of latent viral DNA in neuronal-like cells. With information and methods of mutant generation and detection learned from the in vitro studies, we will explore whether such mutations occur in vivo, using a mouse model. The results of these studies will test the hypothesis that HSV DNA accumulates lesions in latently infected cells and that this influences the natural biology of the virus. The foundation to determine if mutation and repair plays a role in the natural history of viral pathogenesis, in people, will be established.

The other exciting line of research is to explore the potential to use DNA in urine for cancer detection. This study is supported by the Early Detection Research Network (EDRN) of National Cancer Institute. DNA recovered from urine represents not only from cells of the urinary tract, but also from the apoptotic cells of the distal sites of body. Thus, DNA isolated from urine has the potential to be used to predict, diagnoses and forecast outcomes related to the malignant with genetic or epigenetic modification. Our current project is to study k-ras mutation in colorectal cancer and hyper-methylation of the promoter regions of tumor suppressor genes in hepatocellular carcinoma and colorectal cancer to explore urine DNA based technology for tumor screening and early detection.

Selected Research Publications

Wang, M., Block, T. M., Steel, L. B., Brenner, D. E., and Y-H. Su. Preferential Isolation of Fragmented DNA Enhances the Detection of Circulating Mutated k-ras DNA. Clinical Chemistry, 50(1): 211-213, 2004.
Su, Y-H., Wang, M., Brenner, D. E., Ng, A., Melkonyan, H., Umansky, S., Syngal, S., and T. M. Block. Human urine contains small, 150-250 nucleotide sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer*. Journal of Molecular Diagnostics, 6: 101-107, 2004.
Su, Y-H., Wang, M., Block, T. M., Landt, O., Botezatu, I., Serdyuk, O., Lichtenstein, A., Melkonyan, H., Tomei, L. D., and S. Umansky. Transrenal DNA as a diagnostic tool: important technical notes. Ann. N. Y. Acad. Sci. 1002: 81-89, 2004.
Ng, A., Aaimkitsumrit, B., Wang, M., Block, T. M., Clementi, E., Wu, T-T., Taylor, J., and Y-H. Su. Construction of a herpes simplex virus type I mutant with only 3-nucleotide change in the branchpoint region of the Latency Associate Transcript (LAT) and the stability of its 2-kb LAT intron. J. Virology, 78: 12097-12106, 2004.
Su, Y-H., Wang, M., Aiamkitsumrit, B., Brenner, D. E., and T. M. Block. Detection of K-ras mutation in urine of patients with colorectal cancer. Cancer Biomarkers 1: 177-182, 2005.
Su, Y-H., Aiamkitsumrit, B., Zhang, X., Fraser, N. W., and T. M. Block. The stability of herpes simplex virus type I (HSV-1) genomes in infected cells undergoing viral induced apoptosis. Journal of NeuroVirology, 12(5): 2006.
Su, Y-H., Zhang, X., Block, T. M., and N. W. Fraser. Evidence that the immediate early gene product ICP4 is necessary for HSV-1 DNA circularization in infected cells. Journal of Virology, 80(23): 11589-11597, 2006.
Sery, T. W., Su, Y-H., Eagle, R. Jr, Ueda, M., and N. Yamamoto. Experimental Autoimmune Uveitis simulating a clinical bacteremia. Ocular Immunology and Inflammation, 14: 277-283, 2006.
Aiamkitsumrit, B., Zhang, X., Fraser, N. W., Block, T. M., and Y-H. Su. HSV-1 ICP4 deletion mutant virus d120 infection failed to induce apoptosis in NGF-differentiated PC12 cells. Journal of NeuroVirology, 13: 305-324, 2007.
Su, Y-H., Wang, M., Brenner, D. E., Norton, P. A., and T. M. Block. Detection of mutated K-ras DNA in urine, plasma and serum from patients with colorectal carcinoma or adenomatous polyps. Ann. N. Y. Acad. Sci., in press, 2007.
Su, Y-H., Song, J., Wang, Z., Wang, X-H., Aiamkitsumrit, B., Wang, M., Brenner, D. E., and T. M. Block. Removal of high molecular weight DNA by carboxylated magnetic beads enhances the detection of mutated K-ras DNA in urine. Ann. N. Y. Acad. Sci., in press, 2007.