Bharati Bapat

Dr. Bharati Bapat is Professor in the Department of Laboratory Medicine and Pathobiology at the University of Toronto, Staff Scientist at the Department of Laboratory Medicine and Pathology, University Health Network and the Lunenfeld-Tanenbaum Research Institute. Dr. Bapat has authored over 120 peer-reviewed publications. Her research program is focused on translational genomics and epigenomics, specifically the discovery of cancer biomarkers, and to understand their role in cancer development.  Dr. Bapat is leading national and international collaborative prostate cancer research projects aimed at making discoveries at a faster pace to help patients and their families. Dr. Bapat envisions the application of these discoveries into clinical practice by utilizing such diagnostic, prognostic and predictive cancer biomarkers to improve patient care. 

Dr. Bapat’s laboratory is located at suite L6-304b, 6th floor, 60 Murray Street, Toronto, Ontario, Canada M5T 3L9. The Bapat lab group is made up of 9-10 members including mostly graduate students and also post-doctoral fellows and research technologist. Graduate students are registered with the Department of Laboratory Medicine, School of Graduate Studies (SGS) and /or with the Institute of Medical Sciences, University of Toronto.

The overarching focus of our ongoing research projects is to understand epigenetic mechanisms underlying events leading to the transition from normal to cancer state. Lab members use a diverse array of state-of-the-art and high throughput genome-wide interrogation strategies to gain a better understanding of these changes and also explore their significance by analyzing cancer cell-derived models and different patient populations. The goal is to translate these discoveries into developing biomarkers for early and accurate diagnosis, predicting the course of tumor development and response to different therapies.

The lab is well funded from national and international granting agencies, and has excellent space, equipment and access to other relevant facilities. Lab members have opportunities to interact with multi-disciplinary team of co-investigators and collaborators from different countries. In addition, lab members participate in weekly research meetings and have opportunities to present their research project findings at national and international scientific meetings.

Research Synopsis

Dr. Bapat's research program is focused on translational genomics - specifically discovery and functional characterization of cancer biomarkers and their applications to clinical setting. A major area of current research is investigation of epigenetic markers of genitor-urinary and gastro-intestinal neoplasms using genome-wide interrogation strategies.

Dr. Bapat's research program is focused on understanding the role of genetic and epigenetic factors (biomarkers) associated with risk and progression of common malignancies such as prostate, bladder and colon cancer. Using an integrated, multidisciplinary approach, we have discovered novel epigenetic biomarkers of prostate cancer, and provided insight into their potential utility as diagnostic and / or prognostic markers. We have identified genetic and epigenetic risk factors that contribute to increased susceptibility to distinct subtypes of colon cancer, using molecular pathology and genetic epidemiologic strategies. The ultimate goal of my research is to translate our findings into clinical practice by working with physician researchers and clinicians, to develop a personalized medicine approach utilizing such prognostic and predictive cancer biomarkers.

Discovery and validation of prognostic and predictive biomarkers of prostate cancer

A major current focus of research investigation is on the epigenetic mechanisms of differential methylation and their contribution to distinct pathways of prostate cancer development. Using genome-wide high throughput profiling strategies, we have discovered novel epigenetic biomarkers. We have identified distinct methylation signatures associated with different course of tumour progression and outcome in prostate cancer. Further characterization of these candidate genes is currently in progress, using statistical and bioinformatic approaches; and these biomarkers are validated by high-throughput, quantitative, gene-specific differential methylation detection assays. Related studies address functional significance of selected candidate genes and their epigenetic regulation in normal and disease state.

Emerging initiatives are focused on the investigation of unique genetic and novel epigenetic profiles (e.g. 5-hydroxymethylation marks) that will provide potential targets for therapeutic intervention, using genome-wide profiling and high-throughput technologies as well as pathway-based approaches.

Molecular Pathways of Bladder Carcinogenesis

A recently initiated project is aimed at discovery and characterization of biomarkers associated with distinct pathways of bladder cancer development.

Molecular genetic and epidemiologic approaches to cancer risk stratification

Dr. Bapat's research team has investigated genetic modifiers of cancer susceptibility. We have evaluated functional polymorphisms (SNPs) in DNA mismatch repair genes and metabolic pathway genes associated with colorectal cancer susceptibility, and analysis of the specific contributions of gene-gene and gene-environment interactions involved in the etiology of cancer among colorectal cancer patients identified through population-based cancer registries. Using molecular genetic, epidemiologic approaches, we recently showed that certain SNPs in the MLH1 gene region serve as a risk modifier allele for developing a distinct subtype of colorectal cancer. We have examined the link between a group of modifier genes involved in DNA repair and carcinogen metabolism pathways, and diet, and their impact on the progression of colon cancer. A current initiative is focused on combining these findings with genome-wide lymphocyte methylation profiling data to investigate dynamic interplay between genetic and epigenetic mechanisms.   

Recent Publications

Selected list of publications

Kamdar, S., Ho, L.T., Kron, K.J., van der Kwast, T., Zlotta, A.R., Fleshner, N.E., Bapat, B. Dynamic interplay between locus-specific DNA methylation and hydroxymethylation regulates distinct biological pathways in prostate carcinogenesis. Clinical Epigenetics 8:32, 2016.  (SRA)

Savio, A., Daftary, D., Dicks, E., Buchanan, D.D., Parfrey, P.S., Young, J.P., Weisenberger, D., Green, R.C., Gallinger, S., McLaughlin, J.R., Knight, J.A., Bapat, B. Promoter methylation of ITF2, but not APC, is associated with microsatellite instability in two populations of colorectal cancer patients. BMC Cancer 16:113, 2016.  (SRA)

Weisenberger, D.J., Levine, A.J., Long, T.I., Buchanan, D.D., Walters, R., Clendenning, M., Rosty, C., Joshi, A.D., Stern, M.C., LeMarchand,L., Lindor, N.M., Daftary, D., Gallinger, S., Selander, T., Bapat, B., Newcomb, P.A., Campbell, P.T., Casey, G., Ahnen, D.J., Baron, J.A., Haile, R.W., Hopper, J.L., Young, J.P., Laird, P.W., Siegmund, K.D. for the Colon Cancer Family Registry. Association of the Colorectal CpG Island Methylator Phenotype with molecular features, risk factors and family history. Cancer Epidemiology Biomarkers Prevention 24(3):512-519, 2015. (Coll)

van Rhijn, B.W.G., Musquera, M., Liu, L., Vis, A.N., Zuiverloon, T.C.M., van Leenders, G.J.L.H., Kirkels, W.J., Zwarthoff, E.C., Boevé, E.R., Jöbsis, A.C., Bapat, B., Jewett, M.A.S., Zlotta, A.R., van der Kwast, T.H. Molecular and clinical support for a four-tiered grading system for bladder cancer based on the WHO 1973 and 2004 classifications. Modern Pathology 28(5):695-705, 2015.  (Coll)

White-Al Habeeb, N.M., Ho, L.T., Olkhov-Mitsel, E.,Kron, K., Pethe, V., Lehman, M., Jovanovic, L., Fleshner, N., van der Kwast, T., Nelson, C.C., Bapat, B. Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer. Oncotarget 5(17):7858-7869, 2014.  (SRA)

Olkhov-Mitsel, E., Zdravic, D., Kron, K., van der Kwast, T., Fleshner, N., Bapat, B. Novel multiplex MethyLight protocol for detection of DNA methylation in patient tissues and bodily fluids. Scientific Reports 4:4432, 2014.  (SRA)

Kron, K., Trudel, D., Pethe, V., Briollais L., Fleshner, N., van der Kwast, T., Bapat, B. Altered DNA methylation landscapes of polycomb-repressed loci are associated with prostate cancer progression and ERG oncogene expression in prostate cancer. Clinical Cancer Research:19(13): 3450-3461, 2013 (SRA)  

Skeldon, SC., Semotiuk, K., Aronson, M., Holter, S., Gallinger, S., Pollett, A., Kuk, C., van Rhijn, B., Bostrom, P., Cohen, Z., Fleshner, NE., Jewett, MA., Hanna, S., Shariat, SF., van der Kwast, TH., Evans, A., Cato, J., Bapat, B., Zlotta, AR. Patients with Lynch syndrome mismatch repair gene mutations are at higher risk for not only upper tract urothelial cancer but also bladder cancer. Eur Urol: 63(2): 379-385, 2013 (Coll)

Savio, AJ, Lemire, M., Mrkonjic M., Gallinger, S., Zanke, BW., Hudson, TJ., Bapat, B. MLH1 region polymorphisms show a significant association with CpG island shore methylation in a large cohort of healthy individuals. PLoS One: 7(12): e51531, 2012  (SRA)

Kron, K., Liu, L., Trudel, D., Pethe, V., Trachtenberg, J, Fleshner, N., Bapat, B., van der Kwast, T. Correlation of ERG expression and DNA methylation biomarkers with adverse clinicopathological features of prostate cancer. Clinical Cancer Research: 18(10): 2896-2904, 2012 (SRA)

Rawson, J., Sun. Z., Dicks. E., Daftray. D., Parfrey. P., Green. R., Gallinger. S., McLaughlin. J., Wang. P., Knight. J., Bapat B. Vitamin D intake is negatively associated with promoter methylation of the Wnt antagonist gene DKK1 in a large group of colorectal cancer patients. Nutrition and Cancer: 64(7): 919-928, 2012 (SRA)

Savio, AJ, Lemire, M., Mrkonjic M., Gallinger, S., Zanke, BW., Hudson, TJ., Bapat, B. MLH1 region polymorphisms show a significant association with CpG island shore methylation in a large cohort of healthy individuals. PLoS One: 7(12): e51531, 2012  (SRA)

Olkhov-Mitsel, E., van der Kwast, T., Kron, K., Ozcelik, H., Briollais, L., Massaey, C., Recker, F., Kwiatkowski, M., Fleshner, N., Diamandis, EP., Zlotta, AR., Bapat, B. Quantitative DNA methylation analysis of genes coding for kallikrein-related peptidases 6 and 10 as biomarkers for prostate cancer. Epigenetics:  7(9):1037-1045, 2012 (SRA)

Perera, S., Mrkonjic, M., Rawson, JB., Bapat, B. Functional effects of the MLH1-93G>A polymorphism on MLH1/EPM2AIP1 promoter activity. Oncol Rep: 25(3): 809-815, 2011 (SRA)

Liu, L., Kron, K.J., Pethe, V.V., Demetrashvili, N., Nesbitt, M.E., Trachtenberg, J., Ozcelik, H., Fleshner, N.E., Briollais, L., van der Kwast, T.H., Bapat, B. Association of tissue promoter methylation levels of APC, TGFβ2, HOXD3, and RASSF1A with prostate cancer progression. Int J Cancer: 129(10): 2454-2462, 2011 (SRA)