Zacharias Suntres, Ph.D.
Northern Ontario School of Medicine
Lakehead University Campus
955 Oliver Road
Thunder Bay ON P7B 5E1
Phone: (807) 766-7395
Fax: (807) 766-7362
Professor, Pharmacology and Toxicology, Division of Medical Sciences, Northern Ontario School of Medicine.
Adjunct Professor, Department of Chemistry, Lakehead University.
Adjunct Professor, Department of Biology, Lakehead University.
Adjunct Professor, Masters of Public Health Program, Lakehead University.
Adjunct Professor, Department of Chemistry and Biochemistry and Program in Biomolecular Sciences, Laurentian University.
Education and Training
BSC (Hon) – Department of Pharmacology and Toxicology, University of Western Ontario.
Ph.D - Department of Pharmacology and Toxicology, University of Western Ontario.
NSERC Post-Doctoral Fellow: Defence and Civil Institute of Environmental Medicine.
Defence Scientist-Defence and Civil Institute of Environmental Medicine.
Nanotechnology-Drug Delivery Systems.
Our research interests focus on the design, development, and characterization of nanoscale drug delivery devices, namely liposomes. We have been investigating the benefits of liposomes as drug delivery systems in several pathological disorders. Liposomes are multifunctional, targeted devices capable of bypassing biological barriers to deliver multiple therapeutic agents at high local concentrations, and with physiologically appropriate timing, directly to tissues of interest. Several studies have shown that the liposomal formulations overcome deficiencies of free drug treatment and improve clinical outcomes. So far, we have developed liposomal formulations containing antioxidants (N-acetylcysteine, alpha-tocopherol, and/or gamma-tocopherol, lipoic acid), anti-inflammatories (dexamethasone) and antimicrobials (polymyxin B) and these have been used successfully in the prophylaxis and treatment of organ and tissue injuries induced following exposure to infections (P. aeruginosa, E. coli), toxins (lipopolysaccharides, ricin), and herbicides/chemotherapeutic drugs (paraquat, phorbol myristate acetate, bleomycin).
Future research initiatives in our laboratory will focus on the use of liposomal technology for the delivery of chemotherapeutic agents. For example, paclitaxel is one of the most effective antineoplastic drugs used against a wide spectrum of cancers, especially ovarian, breast, colon, and small and nonsmall lung cancers. Because of poor aqueous solubility, paclitaxel is dissolved for clinical use in dehydrated ethanol and polyethoxylated castor oil (Cremophor EL) which is known to cause toxic effects such as life-threatening anaphylaxis. It is proposed that delivery of paclitaxel as a liposomal formulation will lower the systemic toxicity of the drug and would permit much more flexibility for treatment regimens such that smaller, more effective doses may be employed.
Biological Effects of Medicinal Herbs
We are members of an inter-disciplinary consortium that was formed to enhance the product quality, safety, and efficacy of Ontario ginseng products. In Asian medicine, ginseng has been used for over 2,000 years to replenish energy, build resistance, reduce susceptibility to illness and promote health and longevity. Our specific research deals with the investigation of the antimicrobial properties of selected ginseng extracts against sensitive and resistant clinical isolates of Pseudomonas aeruginosa in vitro and the assessment of the selected ginseng extracts against Pseudomonas aeruginosa-induced pulmonary infection.
In addition to ginseng, our research also focuses on assessing the antioxidant, antimicrobial, and chemotherapeutic properties of selected extracts from other herbs, including oregano and thyme.
Oxidant and antioxidant levels, DNA damage markers, and proteomic analysis of Antigen-Presenting Cells (APCs) in blood of cancer patients.
The development of cancer in humans is a multistep process. The complex series of cellular and molecular changes participating in cancer development are mediated by a diversity of endogenous and exogenous (eg. environmental agents, food constituents, etc.) stimuli that lead to DNA damage. One type of endogenous damage is that arising from intermediates of oxygen reduction – reactive oxygen species (ROS), which attack not only the bases but also the deoxyribosyl backbone of DNA. The human body, however, is equipped with various antioxidants (vitamin E, vitamin C, glutathione) that counteract the deleterious actions of reactive oxygen species and protect from cellular and molecular damage. Higher blood levels of certain antioxidants, such as lycopene, have been found to be associated with reduced risk of certain malignancies. Considerable laboratory evidence from chemical, cell culture, and animal studies indicates that antioxidants may slow or possibly prevent the development of cancer. However, information from recent clinical trials is less clear. There have been few systematic studies examining the associations between oxidant/antioxidant imbalances and endogenous levels of DNA damage in the blood of cancer patients. In the past two years we have been evaluating the relationship between antioxidant concentrations and biomarkers of oxidative damage in the blood of patients with breast, lung or colon cancer.
Also, we are assessing whether the proteomic profile of Antigen-Presenting cells (APC) is distinctive among the different cancers. The body's first line of defense against cancer and infections is the immune system, which innately or adaptively protects against pathogens and cancer. A subset of immune cells, dendritic cells (DC) and monocytes (Mo), are Antigen-Presenting cells (APCs). These specialized immune cells are in all tissues of the body, especially at mucosal barriers. Their task is to digest proteins called antigens from cancer cells or pathogens and present them to T cells. When APCs present cancer cell proteins to T cells, the T cells are primed to attack the cancer. By sequestering antigens, APCs act as bio-concentrators rendering them ideal cell populations to detect cancer specific protein and gene expression profiles. This altered gene expression is unique to the cancer to which the DCs are exposed. Thus, these unique changes in gene expression can be used to discriminate different cancers. In collaboration with the University of Harvard, the protein/peptide profiles in the APCs isolated from the cancer patients are being identified. This work should provide the foundation for the development of a means of accurate, rapid, and early detection of cancers.
Suntres, Z.E.: Role of Antioxidants in Paraquat Toxicity. Toxicology. 180: 65-77, 2002.
Alipour, M., Omri, A., Smith, MG, Suntres. Z. Liposomal N-Acetylcysteine protects against LPS-induced liver injuries in rats. J. of Endotoxin Res. 13:297-304, 2007.
Alipour, M., Omri, A., Halwani, M., Suntres. Z Liposomal Polymyxin B: Preparation, Characterization and Evaluation of its Activity towards Gram-negative Bacterial Strains. Intern. J. Pharmaceut. 355:293-298, 2008.
Mitsopoulos, P., Alipour M, Omri A, Smith MG, Suntres ZE. Effectiveness of liposomal-N-acetylcysteine against LPS-induced lung injuries in rodents. Int. J Pharm. 363:106-111, 2008.
Halwani M, Yebio B, Suntres ZE, Alipour M, Azghani AO, Omri A. Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa. Antimicrob Chemother. 62:1291-7, 2008.
Halwani, M., Hebert, S., Suntres, Z.E., Lafrenie, R.M., Azghani, A.O., Omri, A. Bismuth-thiol Incorporation Enhances Biological Activities of Liposomal Tobramycin against Bacterial Biofilm and Quorum Sensing Molecules Production by Pseudomonas aeruginosa. International Journal of Pharmaceutics, 373:141-146, 2009
Alipour, M., Suntres, Z.E., Omri, A. Importance of DNase and alginate lyase for enhancing free and liposome encapsulated aminoglycoside activity against Pseudomonas aeruginosa. J Antimicrob Chemother. 64:317-325, 2009.
Alipour M, Suntres ZE, Lafrenie RM, Omri A. Attenuation of Pseudomonas aeruginosa virulence factors and biofilms by co-encapsulation of bismuth-ethanedithiol with tobramycin in liposomes. J Antimicrob Chemother. 65:684-693, 2010.
Mitsopoulos, P. and Suntres, ZE. Cytotoxicity and gene array analysis of alveolar epithelial A549 cells exposed to paraquat. Chem Biol Interact. 188:427-436, 2010.