Maria obtained her PhD degree at McGill University in Experimental Medicine.
She completed post-doctoral research at the Samuel Lunenfeld Research Institute in the lab of Prof. Tony Pawson.
Our research program focuses on molecular networks implicated in cancer and diabetes.
We are investigating signaling pathways contributing to tumor initiation, cancer stem cell maintenance and metastatic dissemination of breast cancers.
We are also exploring mechanisms governing insulin resistance and pancreatic β-cell replication important for the design of regenerative therapies for type 1 and type 2 diabetes.
Among women, breast cancer is the most common cancer worldwide and is the leading cause of cancer mortality.
Of the more than 5 million women currently living with a diagnosis of breast cancer, recurrence represents the most common cause of death from this disease.
Basal, or basal-like breast cancer accounts for approximately 15-20% of all breast cancers.
Basal breast cancer is frequently associated by conventional immunohistochemical techniques as "triple negative" because it lacks staining for estrogen receptor (ER), progesterone receptor (PR), and HER2. Triple-negative breast cancers (TNBC) often express markers that are characteristic of the myepithelium of the normal mammary gland, such as epidermal growth factor receptor (EGFR), p63, CK14, 5/6 and 17.
Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties and show reduced intercellular adhesion and increased cell motility.
Accumulating evidence suggests an important role for EMT during malignant transformation, providing cancer cells with self-renewal capability, which is crucial for metastatic colonization at secondary sites.
Recent evidence has suggested that human mammary stem cells (MaSCs) are the cells of origin of basal-like and claudin-low tumors.
Studies of neoplastic tissues has provided evidence of self-renewing, stem-like cells within tumors, which have been called cancer stem cells (CSCs). CSCs constitute a small minority of neoplastic cells within a tumor and are defined operationally by their ability to seed new tumors. For this reason, they have also been termed 'tumor-initiating cells' (TICs).
It has been proposed that residual disease present after chemotherapy treatment is enriched for cells with stem-like features. However, isolation and better characterization of these CSCs still requires further investigation.
Our lab has identified novel signaling intermediates that are enriched in human mammary stem cells (MaSC) and whose expression correlates with highly aggressive claudin-low human breast tumors and cell lines.
We seek to understand how these cellular components contribute to stem cell-associated biological processes, EMT features, immune system responses and metastatic dissemination.
Elucidating the mechanisms that govern pancreatic β-cell mass is important for the design of regenerative therapy for both type 1 and type 2 diabetes, which are characterized by insufficient β-cell mass.
There is now evidence in rodents demonstrating that the dominant mechanism of β-cell mass expansion is through β-cell replication, however, the signals and proteins that mediate this important adaptive response are not fully defined.
Our laboratory has recently uncovered novel transcriptional networks that control nutrient metabolism, oxidative and ER stress signaling and immunomodulatory responses in β-cells.
We are now using a number of transgenic and knock-out animal models to help us understand the contribution of these networks in forestalling the development of β-cell destruction in response to inflammatory cytokines and high-fat feeding.
We have expertise in the areas of islet biology, signal transduction, gene regulation, chromatin remodeling and use of proteomic technologies.
Podchecko, A., Northcott, P., Bikopoulos, G., Lee, A., Swaroop B., Kushner, JA., Farhang Fallah, J., Rozakis-Adcock, M. (2007) Identification of a WD-40 repeat containing isoform of PHIP as a novel regulator of pancreatic beta cell growth and survival. Mol Cell Biol 27, 6484-96.
Bikopoulos, G., da Silva Pimenta, A., Lee, SC., Lakey, JR., Der, SD., Chan, CB. Ceddia, RB., Wheeler, MB, Rozakis Adcock, M. (2008) Ex vivo transcriptional profiling of human pancreatic islets following chronic exposure to monounsaturated fatty acids. J of Endocrinology 196, 455-464.
Lai, E, Bikopoulos, G., Wheeler, M., Rozakis-Adcock, M, Allen Volchuk, A. (2008) Differential activation of ER stress and apoptosis in response to chronically elevated free fatty acids in pancreatic β-cells. Am J Physiol Endocrinol Metab 294, 540-50.
Sun, J., Khalid, S., Rozakis-Adcock, M., Fantus, F, Tianru Jin (2009) P-21 activated protein kinase-1 functions as a Linker between Insulin and Wnt Signaling Pathways in the Intestine. Oncogene 28, 3132-44.
Király, MA., Campbell, J., Park, E., Bates, HE., Yue, JTY., Rao, V., Matthews, SG., Bikopoulos, G., Rozakis-Adcock, M., Giacca, A., Vranic. M., and Riddell, MC. (2010) Exercise maintains euglycemia in association with decreased activation of cJUN NH2-terminal kinase and serine phosphorylation of IRS1 in the liver of ZDF rats. Am J Physiol Endocrinol Metab 298, 671-82.
Copeland E., Balgobin S., Lee, CM. and Rozakis Adcock, M. (2011) hTid-1 defines a novel regulator of c-Met receptor signaling in renal cell carcinomas. Oncogene 30, 2252–2263.
Lee, A., Hakuno, F., Northcott, P., Pessin J.E., and Rozakis-Adcock, M. (2012) Cardiomyopathy-associated Z-disc protein binds IRS1 and regulates insulin signalling in skeletal muscle cells (PLoS ONE)