Education

Postdoctoral Training
Baylor College of Medicine, Pharmacology/ Cancer Research, Houston, TX
Postdoctoral Training
Immunology, National Jewish Medical and Research Center, Denver, CO
Postdoctoral Training
Carcinogenesis, Harvard University and Massachusetts Institute of Technology, Boston, MA,
Post Internship
Pediatrics, General Hospital Ratnapura, Ratnapura, Sri Lanka
Internship
Medicine and OB GYN, Base Hospital Matale, Matale, Sri Lanka
Ph.D.
Cancer Research and Tumor Immunology, Memorial University of Newfoundland, St. John’s, NF, Canada
M.Sc.
Pharmacology, University of Toronto, Toronto, Canada
M.D.
Medicine, Vitebsk Medical Institute, Vitebsk, Belarus

Areas of Interest

Research Interests

Oncosis; Natural Products

Videos
Normal Cardiomyocytes I
Normal Cardiomyocytes II
Oncosis in Cardiomyocytes
(1) Signaling pathways of oncosis

It is now known that there are at least two basic patterns of cell injury progressing to death: cell injury with swelling and karryolysis, known as oncosis, and cell injury with shrinkage and karryorhexis, known as apoptosis.

Recent studies have explored the relationship of myocardial ischemic injury to the major modes of cell death, and it appears that myocardial ischemic and reperfusion injury of cardiomyocytes involves the pathways of apoptosis and oncosis.

Studies pertaining to the relationship between cell injury and death during ischemia indicate that apoptotic and oncotic mechanisms can proceed together leading to a hybrid form of myocardial ischemic cell death with oncotic mechanisms and morphology dominating the end stage of irreversible injury.

We have developed a cell model system, closely resembling this hybrid form of myocardial ischemic cell death, to unravel the molecular mechanisms of oncosis, in comparison to apoptosis in murine ventricular cardiomyocytes. Dose-response studies have consistently shown that cardiomyocytes, when exposed to sanguinarine (a benzophenanthridine alkaloid biosynthesized from phenylalanine in plants of the papaveraceae family) at lower concentrations displayed the classic morphology of apoptosis in over 75% of cells and at higher concentrations displayed the characteristic morphology of oncosis in over 90% of cells.

Tumor cell killing by anticancer agents are also known to involve the major modes of cell death. Our findings indicate several tumor cell lines including leukemia (K562), lymphoma (CEM-VLB and CEM-T4), prostate (DU145 and LNCap), breast (MDA-MB-435 and MCF-7), cervical and neuroblastoma undergo this classic pattern of bimodal cell death, when exposed to sanguinarine.

Using our cell model system, coupled with a combination of DNA microarray and multiblot protein detection technics for high throughput screening and siRNA inhibition and forced expression technics for more targeted analysis of candidate genes, we are studying the kinetics of the molecular expression profile of oncosis.

This study has the potential to reveal novel oncosis-related molecules that will serve as drug targets and biomarkers facilitating the design of more effective diagnostic and treatment strategies.

(2) Non-toxic substances and biological response modifying agents for the prevention and treatment of disease

Natural products have greatly influenced the development of antitumor agents. Of the nearly 121 prescription drugs in use today for cancer treatment, 90 are derived from plants. Between 1981 and 2002, 48 out of 65 drugs approved for cancer treatment were natural products, based on natural products, or mimicked natural products in one form or another.

Our laboratory is investigating the molecular signaling mechanisms and immunomodulatory properties of natural compounds and herbal extracts including sanguinarine, salinomycin, curcumin and metformin.

The rediscovery of natural compounds in the light of modern molecular medicine is conducted with a view to identifying the most promising agents for the prevention and treatment of disease and elucidating critical drug targets and biomarkers.