David Andrews

Dr. Andrews has served as President of the Canadian Federation of Biological Societies and of the Canadian Society of Biochemistry, Molecular and Cellular Biology and contributed to their advocacy activities for 11 years. As part of the Partnership Group for Science and Engineering he was an invited speaker at the Canadian Parliament and has been a speaker in many public forums including Science in the City and the Canadian Cancer Society. He is a contributing member of the Faculty of 1000 (www.facultyof1000.com) and is on the editorial board of BMC Cell Biology.

Dr. Andrews is active in the private sector where he was a founding partner in MBI Fermentas and a member of the Scientific Advisory Board of Isogenica Ltd., Cambridge, England. He holds two patents licensed to industry and has two additional patents submitted. Recent private sector research projects include research for PerkinElmer, Spectral Applied Research, Abbott and Genentech.

Manipulating Programmed Cell Death to Kill Cancer

Ironically mitochondria both provide cells with the energy required to live and also serve as a platform that organizes programmed cell death or apoptosis (Kale et al., 2012). The complex signals that regulate the fate of the cell are integrated at the mitochondria and endoplasmic reticulum, and rely on the irreversible step of mitochondrial outer membrane permeabilization (MOMP) and/or an undefined signal from the endoplasmic reticulum that leads to loss of transmembrane potential at mitochondria. Apoptosis is normally used to get rid of unwanted cells during development, damaged cells in adults and prevents premalignant cells from progressing on to cancer. The same system governs selective kill of cancer cells by conventional chemotherapy agents. When the system fails or is inhibited, cancer frequently develops and cells become profoundly drug resistant. As a process MOMP is hard to study because it is largely mechanical and occurs in membranes.

Understanding Bcl-2 family proteins and how they function

The Bcl-2 family of proteins plays a major role in both sensing different types of cellular stress and regulating MOMP. To accomplish these tasks, different members of the Bcl-2 family are located in multiple parts of the cell and function both as cytoplasmic and membrane proteins that adopt distinct conformations that dictate their function. The Bcl-2 proteins modulate apoptosis through a series of intricate protein-protein and protein-membrane interactions that exist in equilibrium. We use and develop new fluorescence techniques to study the regulation of apoptosis in vitro and in cells. Fluorescence based assays uniquely permit quantitative analyses in real-time of the interaction mechanisms that govern the biology of complex systems. By attaching fluorescent dyes to purified recombinant proteins we were able to reveal the ordering of the discrete steps in the activation of Bax by cBid in vitro.Fluorescence techniques can also be used to extend the results to live cells by expressing Bcl-2 family proteins fused with fluorescent proteins and measuring protein-protein interactions and binding dynamics by FRET. We have used these techniques to identify novel small molecule inhibitors of Bcl-XL as well as Bax and Bak. These tool compounds are being used for a variety of studies including to validate new chemotherapy targets, to extend the life of stem cells, prevent damage during stroke etc.

Personalizing medicine by evaluating cellular responses to genetic changes and drugs

Unlike apoptosis for many cellular processes we don’t know which proteins or genes are critically important and we don’t have detailed molecular assays that we can use to measure cellular responses the way we do for apoptosis. For that reason we are developing new methods instruments and fluorescent dyes that can be used for both genetic and chemical screens in live cells. Our main goal is determining how cells respond to drugs, particularly anti-cancer agents. However, we are applying these techniques to study a variety of cellular responses and to develop new approaches to personalized medicine. Using new dyes and image analysis techniques similar to those used for automated facial recognition from pictures we extract a large amount of data from fluorescence micrographs of cells. We use this data to measure the biological effects of new candidate drugs on cell physiology or by knocking down the expression of genes we can validate new drug targets. We are currently using these techniques to examine cells from patients to optimize cancer treatment for individual patients.

Appointments, Cross Affiliations, Memberships

Director, Biological Sciences, Sunnybrook Research Institute
Senior Scientist, Sunnybrook Research Institute
Professor, Dept of Medical Biophysics, University of Toronto
Visiting Professor, Charite, Berlin, Germany
Editorial Board, BMC Cell Biology
Editorial Board, Molecular & Cellular Oncology
Editorial Board, Cell Death and Differentiation
European Research Institute for Integrated Cellular Pathology (ERI-ICP) International Member
Scientific Advisory Board, MCFOCAL
Scientific Consultant, Prosetta Anti-Viral
Scientific Advisory Board, Vasomune
Tier 1 Canada Research Chair

Courses Taught

BCH 20122H The Use of High Content Screening in Biomolecular Medicine
BCH374Y1 Research Project in Biochemistry
BCH445H Organelles and Cell Function