Scientist profiles A-F
Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room M7 621
Administrative Assistant: Melisha Abeysena
Phone: 416-480-6100, ext. 85482
- B.Sc., 1979, biochemistry, University of Ottawa, Canada
- PhD, 1985, medical biophysics, University of Toronto, Canada
- Postdoctoral fellowship, 1988, cell physiology, University of California, San Francisco, U.S.
Appointments and Affiliations:
- Senior scientist, Biological Sciences (director), Odette Cancer Research Program, Sunnybrook Research Institute
- Professor, department of biochemistry, University of Toronto
- Cancer research
- Molecular membrane biology
- High-content screening
- Automated image analysis
Our research areas include cancer chemotherapy, the molecular mechanisms by which Bcl-2 family proteins regulate apoptosis, the assembly of proteins into the cellular membranes, high-content screening, the development of new fluorescence microscopes and automated image analysis techniques.
We are studying the mechanisms by which the Bcl-2 family of proteins regulate selective programmed cell death (apoptosis) of cancer cells. We are particularly interested in determining how cells respond to chemotherapy drugs. The Bcl-2 family proteins that we study include those that initiate cell execution (Bax and Bak), as well as those that inhibit (Bcl-2, Bcl-XL, Mcl-1) or promote (Bim, Bid, Bad) the process. Our recent data indicate an unexpected role for binding to membranes in regulating how Bcl-2 family proteins interact with each other. We believe that by studying protein to protein interactions where they take place-in the membranes of live cells-we will be able to identify more effective therapies.
Examining protein to protein interaction is one of the most challenging areas of cell biology. To extend our analyses to live cells and to include measurements of the effects of drugs and drug candidates we have developed new approaches, instruments and software. With industrial partners we are developing new automated microscopes that provide both time and chromatic spectral data that we use to measure protein to protein interactions and to perform drug mechanism studies. These instruments generate data sets containing millions of images. In order to analyse these images we have written new machine learning software for image analysis and cell classification. Our current imaging techniques include automated fluorescence microscopy, fluorescence lifetime imaging, fluorescence correlation spectroscopy, single molecule imaging and hyperspectral imaging. Our imaging research recently culminated in the establishment of a new $9-million image-based screening facility at Sunnybrook Research Institute.
- Brahmbhatt H, Oppermann S, Osterlund EJ, Leber B, Andrews DW. Molecular pathways: leveraging the BCL-2 interactome to kill cancer cells—mitochondrial outer membrane permeabilization and beyond. Clin Cancer Res. 2015 Jun 15;21(12):2671–6.
- Osterlund EJ, Liu Q, Andrews DW. The use of FLIM-FRET for the detection of mitochondria-associated protein interactions. Methods Mol Biol. 2015;1264:395–419.
- Andrews DW. Pores of no return. Mol Cell. 2014 Nov 20;56(4):465–6.
- Kale J, Liu Q, Leber B, Andrews DW. Shedding light on apoptosis at subcellular membranes. Cell. 2012 Dec;151(6):1179–1184.
- Aranovich A, Liu Q, Collins TJ, Geng F, Dixit S, Leber B, Andrews DW. Differences in the mechanisms of proapoptotic BH3 proteins binding to Bcl-XL and Bcl-2 quantified in live MCF-7 cells. Mol Cell. 2012 Mar;45(6):754–763.
Related News and Stories:
- Canada Research Chair awarded to head biologist: Dr. David Andrews now a Tier 1 chairholder (Feb. 9, 2016)
- National agency recognizes scientific excellence at Sunnybrook Research Institute: Scientists score high with multimillion-dollar funding investment (Oct. 13, 2015)
- Field of view: Research day proclaims promise of image-guided medicine (Jan. 15, 2014)
- An incubator of medical innovation, The Globe and Mail (July 10, 2013)
- On target? The promise and challenges of molecular therapies (2012 SRI Magazine)
- Tool kit: the Opera: SRI's head of Biological Sciences teams with industry to build high-content screening system (June 15, 2013)
- Seeing things: Federal award will allow biologist to study effects of ‘knocked-out' genes on cells (Jan. 15, 2013)
- At the edge: Federal government awards leaders in innovation (Nov. 27, 2012)
- In death, life: Suicide by cell: The drama and the promise (2011 SRI Magazine)
- Sugar for the brain: Charité scientists decipher mechanism to prevent programmed cell death of nerve cells, Charité Press (Jan. 1, 2012)