Priya Weerasinghe, MD, MSc, PhD
- Assistant Professor, Department of Pathology and Laboratory Medicine
(713) 500 - 5385
- Vitebsk Medical Institute, Vitebsk, Belarus, Medicine
- University of Toronto, Toronto, Canada, Pharmacology
- Memorial University of Newfoundland, St. John’s, NF, Canada, Cancer Research and Tumor Immunology
- Postdoctoral Training
- Baylor College of Medicine, Pharmacology/ Cancer Research, Houston, TX, USA
- Postdoctoral Training
- National Jewish Medical and Research Center, Denver, CO, USA, Immunology
- Postdoctoral Training
- Harvard University and Massachusetts Institute of Technology, Boston, MA, USA, Carcinogenesis
- Post Internship
- General Hospital Ratnapura, Ratnapura, Sri Lanka, Pediatrics
- Base Hospital Matale, Matale, Sri Lanka, Medicine and OB GYN
Areas of Interests
Oncosis; Natural Products
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.
- Weerasinghe, P., Hallock, S., Brown, R., Loose, D.S., and Buja, L.M., (2013). A Model for Cardiomyocyte Cell Death: Insights into Mechanisms of Oncosis. Exp. Mol. Pathol., 94: 289-300.
- Weerasinghe, P. and Buja, L.M. (2012). Oncosis: An important nonapoptotic mode of cell death. Exp. Mol. Pathol. 93: 302-308.
- Chi H., Luo A. Z., Weerasinghe P. and Brown R.E. (2010) Sorafenib downregulates ERK/Akt and STAT3 survival pathways and induces apoptosis in a human neuroblastoma cell line. Int. J. Clin Exp. Pathol, 3(4): 408-415.
- Guan, Y., Ramasamy-Reddy, K., Zhu, Q., Li, Y., Lee, K., Weerasinghe, P., Prchal, J., Semenza, G.L. and Jing, N. (2009). G-rich Oligonucleotides Inhibit HIF-1alpha and HIF-2alpha and Block Tumor Growth. Mol Ther., 18(1):188-97.
- Buja, L.M and Weerasinghe, p. (2009). Unresolved issues in myocardial reperfusion injury. Cardiovasc Pathol. 19(1):29-35.
- Weerasinghe, P., Li, Y., Guan, Y., Zhang, R., Tweardy, D.J. and Jing, N. (2008). T40214/PEI complex: A potent therapeutics for prostate cancer that targets STAT3 Signaling. Prostate, 68(13):1430-42.
- Priya Weerasinghe, Gabriela E. Garcia, Ping Yuan, Lili Feng, Li Mao and Naijie Jing (2007). STAT3 is a critical therapeutic target for non-small cell lung cancer (NSCLC) and GQ-ODN, as a STAT3 inhibitor, represents a promising treatment in NSCLC. Int. J. Oncol., 31(1):129-36.
- Aggarwal, B.B., Ichikawa, H., Garodia, P., Weerasinghe, P., Sethi, G., Bhatt, I.D., Pandey, M.K., Shishodia, S., Nair, M.G. (2006). From traditional Ayurvedic medicine to modern medicine: identification of therapeutic targets for suppression of inflammation and cancer. Expert Opin. Ther. Targets, 10(1): 87-118.
- Hallock, S., Tang, S.C., Buja, L.M., Trump, B.F., Liepins, A. and Weerasinghe, P. (2007). Aurintricarboxylic Acid Inhibits Protein Synthesis Independent, Sanguinarine-Induced Apoptosis and Oncosis. Toxicol. Pathol., 35(2):300-9.
- Weerasinghe, P., Hallock, S., Tang, S.C., Trump, B. and Liepins A. (2006). Sanguinarine overcomes P-glycoprotein-mediated multidrug-resistance via induction of apoptosis and oncosis in CEM-VLB 1000 cells. Exp Toxicol. Pathol. 58: 21-30.
- Ding, Z., Tang, S.C., Weerasinghe, P., Yang, X., Pater, A. and Liepins, A. (2002). The alkaloid sanguinarine is effective against multidrug resistance in human cervical cells via bimodal cell death. Biochem. Pharmacol., 63(8):1415-1421.
2014-pres Lecturer, Pathology, University of Texas Houston (UTH) Medical School.
2012-pres Facilitator, Problem Based Learning (PBL), UTH Medical School.
2008-2013 Lecturer, Medical Immunology, UTH Medical School.
2008-2009 Lecturer, Histology, UTH Dental School.
2013-2014 Dean’s Teaching Excellence Award, UTH Medical School.
2013-2014 Curriculum Development Committee, UTH Medical School.
2012-2014 Mentor for the Paul E. Strandjord Young Investigator Award from the Academy of Clinical Physicians and Scientists (ACLPS).
2010-2011 Teaching Excellence in Medical Immunology, Department of Pathology, UTH Medical School.
2010-2011 Chair, Committee for the Status of Women (CSW), University of Texas Health Sciences Center (UTHSC) at Houston.