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Breast and prostate cancer • DNA methylation • proteases and growth factors • bone metastasis • cancer progression • epigentic biomarkers • cancer therapeutics
My research focuses on determining the blood-based “DNA methylation signature” of patients with breast cancer, prostate cancer or osteoporosis, for introduction into clinical practice. We are evaluating a novel therapeutic and preventive approach to breast cancer metastasis based on blocking DNA demethylation processes using xenograft and transgenic models. Collectively, the results from these studies will provide a molecular mechanistic basis for both prevention and treatment of breast cancer that will be translated into human clinical trials. Our group is developing novel diagnostic and therapeutic strategies to block uPA production and its interaction with cell surface uPAR to block tumour growth and metastasis. Using our well-established models of breast and prostate cancer, we are examining the efficacy of various therapeutic strategies to block tumour progression. Additionally, determination of the methylation of uPA and PAI-1 is being developed as a reliable diagnostic and prognostic marker in cancer.
Cheishvili D, Parashar S, Mahmood N, Arakelian A, Kremer R, Goltzman D, Szyf M, Rabbani SA. Identification of an Epigenetic Signature of Osteoporosis in Blood DNA of Postmenopausal Women. J Bone Miner Res. 2018 Nov;33(11):1980-1989. doi: 10.1002/jbmr.3527. Epub 2018 Jul 20. PMID: 29924424.
Parashar S, Cheishvili D, Mahmood N, Arakelian A, Tanvir I, Khan HA, Kremer R, Mihalcioiu C, Szyf M, Rabbani SA. DNA methylation signatures of breast cancer in peripheral T-cells. BMC Cancer. 2018 May 18;18(1):574. doi: 10.1186/s12885-018-4482-7. PMID: 29776342.
Mahmood N, Cheishvili D, Arakelian A, Tanvir I, Khan HA, Pépin AS, Szyf M, Rabbani SA. Methyl donor S-adenosylmethionine (SAM) supplementation attenuates breast cancer growth, invasion, and metastasis in vivo; therapeutic and chemopreventive applications. Oncotarget. 2017 Dec 26;9(4):5169-5183. doi: 10.18632/oncotarget.23704. eCollection 2018 Jan 12. PMID: 29435170.
Parashar S, Cheishvili D, Arakelian A, Hussain Z, Tanvir I, Khan HA, Szyf M, Rabbani SA. S-adenosylmethionine blocks osteosarcoma cells proliferation and invasion in vitro and tumor metastasis in vivo: therapeutic and diagnostic clinical applications. Cancer Med. 2015 May;4(5):732-44. doi: 10.1002/cam4.386. Epub 2015 Jan 26. PMID: 25619880.
Shukeir N, Stefanska B, Parashar S, Chik F, Arakelian A, Szyf M, Rabbani SA. Pharmacological methyl group donors block skeletal metastasis in vitro and in vivo. Br J Pharmacol. 2015 Jun;172(11):2769-81. doi: 10.1111/bph.13102. Epub 2015 Mar 27. PMID: 25631332.