null Suhad Ali, PhD
differentiation • cancer stem cells/tumor initiating cells • RNA editing • genomic stability • centrosome biology • apical/basal polarity • epigenetics (cell fate determination) • biologics • gene therapy • precision oncology
Advanced metastatic breast cancer is a major clinical challenge. Loss of cellular differentiation and increased plasticity and stemness are major drivers of tumour relapse, metastasis, heterogeneity, and therapeutic failure. Identifying the drivers of tumour cellular differentiation is therefore vital to the discovery of new biomarkers and development of targeted and safe anti-cancer therapies. These differentiation therapies (DTs) promise to be particularly effective in poorly differentiated and metastatic cancer types such as the therapeutically challenging metastatic breast cancer subtypes. My research program collectively advances and builds on this concept. We have provided molecular and preclinical evidence establishing the lactation hormone prolactin as a differentiation therapeutic modality in breast cancer. Moving forward, we are further characterizing and detailing this novel anti-tumorigenic role of prolactin-driven differentiation and cellular reprograming limiting breast tumorigenesis. The overarching objectives are to develop specific “first-in-class” prolactin-based differentiation therapeutics and novel prognostic biomarkers in breast cancer.
Hachim, IY, Shams, A, Lebrun, JJ, Ali, S*. (2016). A Favorable Role of Prolactin in Human Breast Cancer Reveals Novel Pathway Based Gene Signatures Indicative of Tumor Differentiation and Favorable Patient Outcome.Human Pathology. 53: 142-52.
Lopez, V., Hachim, Y. I., Hachim, Y. M., Lebrun, J-J., Ali, S.*. (2016). Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy. Sci Rep. 6: 30934.
Binothman, N., Hachim, IY., Lebrun, JJ., and Ali, S*. (2017). CPSF6 is a novel clinically relevant breast cancer vulnerability target. EBioMedicine (Lancet Publication). 21: 65-78.
Shams, A, Binothman, N, Boudreault, J, Wang, N, Shams, F, Hamam, D, Tian, J, Moamer, A, Dai, A, Lebrun, JJ and Ali, S*. (2021). Prolactin receptor-driven combined luminal and epithelial differentiation in breast cancer restricts plasticity, stemness, tumorigenesis and metastasis. Oncogenesis. 10(1): 010.
Dai M, Yan G, Wang N, Daliah G, Edick AM, Poulet S, Boudreault J, Ali S, Burgos SA, Lebrun JJ. (2021). Invivo genome-wide CRISPR screen reveals breast cancer vulnerabilities andsynergistic mTOR/Hippo targeted combination therapy.Nat Commun. 2021 May 24;12(1):3055. 12(1): 3055.