Office: 613-562-5800 ext. 8366
Work E-mail: firstname.lastname@example.org
Overview of Interests
NF-κB has critical roles in normal organogenesis, the immune system and cancer. Research in Dr. Pratt’s lab over the past several years has focused on the role that NF-κB plays in various forms of breast cancer. To study this, she utilizes both mouse models and mammary epithelial and tumor cell lines to dissect relevant signaling pathways. Breast cancer models include oncogenic transgenes (SV40Tg and erbB2) and carcinogen induction (dimethyl-benzanthracene). The effect of concomitant deletion/mutation of factors that impinge on the NF-κB pathway - including upstream kinases, inhibitory proteins and apoptotic regulatory factors, as well as NF-κB transgenic reporter mice - has facilitated the interrogation of the role of NF-κB in the development of breast cancers. Dr. Pratt also collaborates with pathologists to evaluate NF-κB pathway proteins as prognostic markers in pre-cancerous breast lesions in patients. Another interest includes novel small molecules that differentially interact with the estrogen receptors α and β and their potential for therapeutic applications.
Dr. Pratt currently coordinates and teaches the majority of the only comprehensive pharmacology course at the University to third and fourth year students from the Faculty of Science. She continues her longstanding teaching of the non-steroidal anti-inflammatory drugs to medical students. Dr. Pratt also developed the graduate course, “The Biology of Cancer” which she coordinates and teaches as well as “Signaling in Cancer Cells” and the graduate course, “Advanced Topics in Cancer”.
Scientific Breakthrough / Impact
Dr. Pratt’s early finding that estrogen regulates the anti-apoptotic protein Bcl-2 was instrumental in understanding the mechanism of endocrine-targeted therapies in hormone-responsive breast cancers. This paper has been cited more than 400 times and has also spurred studies in other areas, including neurobiology, where the role of estrogen in neuronal protection has now been widely investigated.
Most recently Dr. Pratt’s lab has discovered that the etiology of BRCA1 associated breast cancers derives from the propensity of BRCA1-deficient luminal progenitor cells to accumulate replication-associated DNA damage as a result of progesterone-induced proliferative signaling. The resulting induction of the DNA damage response activates NF-κB, which drives cells to continued proliferation independent of progesterone. This results in the accumulation of genetically unstable luminal progenitor cells. Patients with BRCA1 mutation typically develop hormone receptor negative breast cancers. Thus, for the first time, Dr. Pratt’s work explains the clinical phenomenon of reduced BRCA1 breast cancer risk after removal of the ovaries. From the chemoprevention perspective, her lab has also found that classes of NF-κB inhibitors can block this proliferation, both in vitro and in vivo, which may offer new hope for prevention to patient carriers of this mutation. Dr. Pratt is currently applying this general mechanism to other familial breast cancer genes, most of which encode proteins involved in DNA repair.
Dr. Pratt’s work has been supported by the Canadian Institute for Health Research, Canadian Cancer Society Research Institute, the Canadian Breast Cancer Foundation and the Cancer Research Society Inc. Her lab currently has grant support from the Canadian Breast Cancer Foundation and the Cancer Research Society.