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SRI Profiles

David W. Andrews

Senior scientist

Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room M7 621
Toronto, ON
M4N 3M5

 

Phone: 416-480-6100, ext. 5120

Education:

  • 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:

Research Foci:

  • Cancer research
  • Molecular membrane biology
  • High-content screening
  • Automated image analysis
  • Apoptosis

Research Summary:

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.

Selected Publications:

See current publications list at PubMed.

  1. Niu X, Brahmbhatt H, Mergenthaler P, Zhang Z, Sang J, Daude M, Ehlert FGR, Diederich WE, Wong E, Zhu W, Pogmore J, Nandy JP, Satyanarayana M, Jimmidi RK, Arya P, Leber B, Lin J, Culmsee C, Yi J, Andrews DW. A small-molecule inhibitor of Bax and Bak oligomerization prevents genotoxic cell death and promotes neuroprotection. Cell Chem Biol. 2017 Apr 20;24(4):493–506.
  2. Oppermann S, Ylanko J, Shi Y, Hariharan S, Oakes CC, Brauer PM, Zúñiga-Pflücker JC, Leber B, Spaner DE, Andrews DW. High-content screening identifies kinase inhibitors that overcome venetoclax resistance in activated CLL cells. Blood. 2016 Aug 18;128(7):934–47.
  3. Andrews DW. Pores of no return. Mol Cell. 2014 Nov 20;56(4):465–6.
  4. Kale J, Liu Q, Leber B, Andrews DW. Shedding light on apoptosis at subcellular membranes. Cell. 2012 Dec;151(6):1179–1184.
  5. 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.

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