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Senior Scientist: London Regional Cancer Program, London Health Sciences Centre, London, Ontario
Assistant Professor: Department of Biochemistry, University of Western Ontario, London, Ontario
Cross Appointments: Department of Oncology, Department of Paediatrics
University Website: http://www.biochem.uwo.ca/fac/rozmahel/rozmahel.html
London Regional Cancer Program
Room A4-839, Cancer Research Laboratory Program
790 Commissioners Rd. E.
Canada N6A 4L6
Molecular genetic studies of cystic fibrosis and Alzheimer's disease
Dr. Zareen Amtul, Postdoctoral Fellow, Department of Oncology
Project: In vivo investigation of differential lipids on gamma-secretase activity
Email Dr. Zareen Amtul
Dr. Susan Newbigging, DVSc, Comparative Pathology
Project: Role of Gob-5 in differential lung disease
Email Dr. Susan Newbigging
Sonya Brijbassi, PhD Student, Department of Biochemistry
Project: Role of nicastrin on APP processing
Email Sonya Brijbassi
Fiona Young, MSc, Department of Biochemistry
Project: Role of Gob-5 in intestinal disease
Email Fiona Young
Mary Keet, Research Technician
Email Mary Keet
We have previously shown that genetic modifiers have a major influence on the intestinal and lung disease lesions in cystic fibrosis mouse models mice, and have mapped the loci harboring the major intestinal disease modifiers to mouse chromosomes 5 and 7. The human locus syntenic to mouse chromosome 7 has also been shown to have a prominent role in the presence or absence of early intestinal disease in CF patients. Strong candidate genes for these modifiers have now been identified and are currently being investigated for their potential role in the disease. In addition, we have identified several strong candidates for modifiers of lung disease in CF mice and are currently in the process of characterizing them and confirming them as the primary modulating factors. The identified genetic modifiers are also being evaluated for their therapeutic potential in mouse models of cystic fibrosis.
Our lab was also the first to identify genetic modifiers of the Notch signaling defect in mouse models deficient of the Alzheimer's disease-causing gene Presenilin 1. A major modifier of the Notch phenotype has been mapped to distal chromosome 1, a locus containing several genes related to, or interacting with, Presenilin 1 in facilitating Notch signaling. We have identified genetic variants in one of the genes (Nicastrin) that appear to correlate with severity of the Notch signaling defect, and thus modify the Presenilin 1 deficiency phenotype. A comprehensive genetic study in mouse models has also been instituted to identify primary genetic modifiers of the basic lesions in Alzheimer's Disease.
Our research focuses on the molecular biology and genetics of cystic fibrosis and Alzheimer's disease, specifically on the identification and characterization of genetic modifiers of these diseases in mouse models. This will provide further insight into the pathogenesis and pathophysiology of these devastating diseases, as well as undoubtedly uncover novel pathways for therapeutic interventions.