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Robert A. Screaton, PhD
Associate Professor of Biochemistry
Canada Research Chair In Apoptotic Signaling
Biographical Sketch
Robert Screaton received his undergraduate and graduate training
at McGill University in Montreal, Canada (1998), and pursued post-doctoral studies
at the Burnham Institute (1999-2002) and the Salk Institute (2002-2005) in San Diego,
California. Dr Screaton joined the Children's Hospital of Eastern Ontario Research
Institute and the University of Ottawa in July 2005 where he is now Scientist and
Assistant Professor. Dr Screaton is also the co-director of the CHEO-RI robotic cell
based screening facility. He is the recipient of awards such as the Canada
Research Chair In Apoptotic Signaling, Tier II (2006-2011, renewed 2011-2016) and Ontario
Early Researcher Award (2006-2011). He has also recently received the CHEO Research
Institute's Outstanding New Investigator Award (2009) and the University of Ottawa
Faculty of Medicine's Young Professor Award (2009).
Click here for PubMed listing
Research Interests
Islet Biology
Current work in the lab is
directed towards understanding how insulin-producing β cells respond to
glucose and cAMP signals and to understand the signaling machinery that regulates
β cell proliferation and regeneration. In this regard, we focus on the role
of LKB1-AMPK signaling pathway and the CREB coactivator CRTC2. To identify novel gene
products and signal transduction mechanisms that are involved in β cell
biology, we employ biochemical, cell biological, proteomic and functional genomic
approaches, and generate animal models to test the role of these genes in islet
function and glucose metabolism in vivo.
Kinomics
Protein phosphorylation regulates
virtually all cellular events. Protein kinases and their target proteins control
central cell behaviours as proliferation, cell growth, differentiation, innate
immunity, cell survival and death, and are of central importance both to basic
research and to disease treatment. Identifying kinase substrate pairs, critical
nodes in signal transduction pathways, represents a major challenge for
understanding how information transfer takes place within a cell. We have developed
a kinase screening platform to permit identification of kinase substrate pairs, and
used this to elucidate novel pathways involved in glucose sensing. We have also
applied the approach to a wide range of biological processes, including
mitochondrial dynamics, phagocytosis axon guidance, and stem cell determination.
Cell Based Screening
We employ a
state-of-the art robotic cell based screening facility to perform functional genetic
screens in mammalian cells to identify novel genes involved in cell function and
survival. We are currently performing large scale imaging screens using siRNA
technology to identify novel genes that govern the initiation stages of the
mitochondrial cell death program, with a view to identifying novel targets for
therapeutic intervention for diseases in which inappropriate cell death is a root
cause.
Mitochondrial Dynamics
The mitochondrial
network is exquisitely sensitive to extracellular signals. Mitochondria becomes
hyperfused in response to stress and fragment during cell death. Mitochondrial
morphology is largely governed by opposing fission and fusion processes controlled by
GTPase molecular switches. However, in mammalian systems, only a few players are
known to affect the delicate balance between fragmentation and elongation of the
mitochondrial network. Altered mitochondrial dynamics is seen in various disease
models ranging from multiple neurodegenerative diseases to diabetes. We are currently
using high throughput, high-content screens to identify novel regulators of
mitochondrial dynamics, and also evaluating the potential for modulating the network
for cancer therapy.
Mitochondrial Integrity
Recent data indicates
that mitochondria possess several independent pathways for quality control and
integrity, including mitophagy, or autophagic recycling of damaged mitochondria.
Parkin, an E3 ubiquitin ligase and a Parkinson's disease gene, appears to function as
a sensor of mitochondrial integrity. We are using a high-throughput, robotic imaging
screen to look upstream in this pathway to identify novel genes that control Parkin
activity, which may affect its recruitment (i.e. damage sensing or its
retention of mitochondria).
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