Dr. John Th’ng Career Scientist, Regional Cancer Care   Dr. Th’ng is the lead research scientist with RCC. He is also an Associate Professor of Biochemistry with the Northern Ontario School of Medicine, and Adjunct Assistant Professor with Lakehead University’s Chemistry and Biology departments.   He has a Ph.D. in Biochemistry from the University of Western Ontario.

Dr. Th’ng’s main research interests include:

Histone modifications in controlling cellular functions.

The genes that control cellular functions in human cells are encoded in DNA that has now been completely sequenced. Epigenetics exerts a second level of control that regulates the expression pattern these genes, thereby allowing every cell in the body to have differential functions while containing the same genes. Mutations in the basic DNA sequence and alterations in epigenetic patterns in the chromosomes contribute to development of many diseases such as cancer, and may play significant roles in dictating severities and outcomes. There is increasing interest in other applications of epigenetics, such as in forensics identification. His research is focused on the roles played by histone phosphorylation and acetylation in the epigenetic regulation of gene expression and function as cells progress through the division cycle, and when cells undergo differentiation or senescence.

Development of chemoresistance in primary cancer cells.

Primary cancer cells isolated from the ascites and pleural fluids of patients with metastatic cancers show similar resistance to the anticancer agents used during chemotherapy treatments. These cancer cells are used to study their gradual development of resistance to chemotherapy, and to identify the genes that are responsible for conferring chemoresistance. The pattern of genetic changes could eventually be used to predict the response to specific treatments, and may lead to designing future treatments. In addition to the understanding of resistance to chemotherapy, the cancer cells are also used for studying novel agents under development, including plant extracts and gene therapy.

Click here for list of select publications and presentations.

Dr. Ingeborg Zehbe Career Scientist, Regional Cancer Care   Dr. Zehbe joined the RCC team in 2005 and is an Adjunct Professor with the Department of Biology at Lakehead University.   She completed her B.A. in Anthropology and Archaeology at the University of Uppsala, Sweden, where she also obtained her Ph.D. and D.Sc. in Molecular Pathology. Prior to coming to Thunder Bay, Dr. Zehbe worked as a research scientist for the Department of Medical Microbiology, at the Johannes Gutenberg University in Mainz, Germany, and as a research scientist and post-doctoral fellow at the German Cancer Research Centre in Heidelberg, Germany.

Dr. Zehbe’s research interests include:

Virus-related cancer with focus on human papillomavirus:

Infectious agents such as bacteria or viruses have been identified as carcinogens. About 20% of all malignancies are caused by tumour viruses. Our research deals with virus-related cancer using high-risk human papillomavirus (HPV) and skin or mucosa as a model. Our previous epidemiological, functional and structural studies strongly suggest diverse properties among intratype variants of the E6 oncoprotein. The rational of our research is to substantiate this evidence by systematically testing the biological activity and immunogenicity of naturally occurring E6 variants. We focus on virus-host interactions for conducting a systematic study involving all steps of carcinogenesis from the beginning of viral infection to malignant transformation. This approach can also be used for viral life cycle studies and will be complemented by an in vivo mouse model as well as ex vivo evidence using human biospsy specimens and blood for immune profiling.

Significance of our research:

The impact of natural HPV variants has not been adequately addressed in functional or immunological studies. Our program is thus novel and we have created a niche in HPV research. This will substantially advance the knowledge in virus research, tumour biology and tumour immunology. Differences in function, structure and stability amongst E6 strains could explain differential host susceptibility to viral persistence and cancer. The obtained results will be essential for the development and commercialization of individual treatment regimens.

1. Interaction of HPV16 E6 variants with the host cell machinery.
   Collaboration with: Dr. Neelam Khaper, Northern School of Medicine, Thunder Bay, Canada, Dr. Carita Lanner, Northern School of Medicine, Sudbury, Canada, Dr Paul Lambert, University of Wisconsin, USA, Dr. David Law, Biology Department, Lakehead University, Thunder Bay, Canada, Drs Ian and Lynne Hampson, University of Manchester, UK, Dr. Levana Sherman, University of Tel Aviv, Israel, Dr. Momar Ndao, Unviversity of Montreal, Canada, Dr. Alioune Ngom, University of Windsor, Canada, Dr. Massimo Tommasino, International Agency for Research on Cancer, Lyon, France and Dr. Gilles Trave, University of Strasbourg, France.

   
   

2. A novel interferon and perturbation of its signaling pathways in HPV-related cervical disease.
   Collaboration with: Dr. Nick Escott, Pathology Department, Thunder Bay Regional Health Sciences Centre, Thunder Bay, Canada and Dr. Marina Ulanova, Northern School of Medicine, Thunder Bay, Canada.

   
   

3. A mouse model to elucidate the immunogenicity of naturally occurring human papillomavirus 16 E6 variants.
   Joint project with: Dr. George Carayanniotis, Memorial University of Newfoundloand, St. John’s, Canada.

   
   

4. Ex vivo evidence of human leukocyte antigen polymorphism linked to viral epitope variants: differential recognition by human T cells.
   Collaboration with Dr. George Carayanniotis, Memorial University of Newfoundland, St. John’s, Canada and Dr. Andreas Kaufmann, Charité Campus Benjamin Franklin, Berlin, Germany.

   
   

5. Integrin receptors as potential targets for therapy of cervical cancer.
   Joint project with Dr. Marina Ulanova, Northern School of Medicine, Thunder Bay, Canada.

Members of the Research Team:

Correne DeCarlo (Master’s Student), Jeff Werner (Master’s Student), Jenna Piechota (Honour’s Student) and Christina Richard (Research Technician).

Click here for list of select publications.

Dr. Mary Lynn Tassotto Post-Doctoral Research Fellow, Regional Cancer Care   Dr. Tassotto completed her B.Sc. Honours Biology at Pennsylvania State University and her Ph.D. in Molecular and Cellular Biology at Oregon State University.

Her research interests include:

Role of BRCA1 and BRCA2 mutations in breast cancer.

Individuals carrying mutations in the BRCA genes have a greater risk of developing breast and ovarian cancers, and patients with familial cancer are routinely tested for mutations in these genes. Biochemical studies have shown that these genes are involved in DNA repair, cell cycle regulation, and transcriptional regulation. Ovarian tumours with BRCA mutations grow faster and respond better to chemotherapy; however, clinical observations suggest that breast cancers with BRCA mutations have similar outcomes as those that develop sporadically. In a collaborative project with the Northwestern Ontario Regional Genetics Program, Dr. Tassotto is examining lymphocytes from individuals with BRCA1 and BRCA2 mutations for their growth and sensitivity to chemotherapeutic agents. These studies will determine if cells with BRCA mutations have higher growth rates and if they are more sensitive to chemotherapeutic agents.

New evidence suggests that epigenetic changes resulting in reduced or absent expression of BRCA1 is also an important contributing factor in sporadic breast cancer. The BRCA1 gene encodes a nuclear protein that has recently been implicated in the protection of cells from oxidative stress. In collaboration with researchers at the Northern Ontario School of Medicine and the Radiation Oncology Program at Regional Cancer Care, Dr. Tassotto will investigate the correlation between BRCA1 protein and mRNA expression levels with the cellular response to oxidative stress induced by ionizing radiation using human lymphocytes from individuals with both sporadic breast cancer and BRCA1-associated familial breast cancer. These studies are of great clinical significance for BRCA mutation carriers as well as for those individuals with sporadic breast cancer, as the results may impact the selection of their treatment regimen and the management of their disease.

Assessing radiation-induced DNA damage and repair:

Ionizing radiation has long been used to eradicate cancerous tissues, but it is also a well-known etiological agent that acts in the induction of breast cancer and other cancers. Dr. Tassotto is using Single Cell Gel Electrophoresis (Comet Assay) and other sensitive detection methods to measure levels of DNA damage in cancer cell lines and in primary cell cultures after exposure to ionizing radiation. In a collaborative project with the Medical Physics Program, she is looking at the level of DNA damage in cells outside the treatment field during radiation therapy. This research will give insight into the radiation damage suffered by healthy tissue during treatment, which is especially important to consider in patients with germline mutations in a tumour suppressor gene or a DNA repair gene (for example, in the BRCA genes), as these individuals may be more susceptible to radiation-induced mutations in healthy cells that may lead to secondary carcinogenesis.

Click here for list of select publications and presentations.