SICKKIDS & UBC
Our Research Focus
The Miller/Kaplan lab studies how stem cells build, maintain and regenerate the mammalian nervous system and digits. Many mammalian tissues, including the brain, contain resident stem cells that build these tissues developmentally and maintain and/or repair them in adulthood. The biology of these tissue stem cells is determined by the interplay between cues they encounter in their environment and intrinsic cellular mechanisms. These findings imply that understanding how the environment regulates tissue stem cell behavior would provide new insights into normal and pathological development and aging. They also suggest that if we could activate tissue stem cells pharmacologically, then this might promote tissue repair and regeneration.
We have a keen interest in identifying how growth factors, signalling pathways and epigenetic factors regulate stem cell function during development, and how aberrations in the expression and/or the activity of these factors and pathways perturb development and result in neurodevelopmental disorders.
CURRENT RESEARCH
How Stem Cells Communicate with their Environment
Transcriptomic, proteomic, and single cell transcriptomic analysis to generate a map of how the different cell types in the CNS and PNS communicate to control development and repair (Neuron 2016, Cell Rep 2017, eNeuro 2020).
How Stem Cells are Generated and Maintained
Identify the mechanisms used by stem cells to generate neurons and oligodendrocytes (Dev Cell 2015, Neuron 2017, 2018, Stem Cell Rep 2018, Cell Rep 2020 - Jeong, Cell Rep 2020 - Tomita, Cell Rep 2020 - Borrett).
Discovering Drugs that Mobilize Endogenous Stem Cells
Discover drugs to delay axon degeneration and to promote neurogenesis and oligodendrogenesis for endogenous repair of the injured and aging brain (Cell Stem Cell 2012, Stem Cell Rep 2016, J Cell Biol 2017, Nature Med 2020).
How Stem Cells Repair Injured Digits
Determine how stem cells in the mammalian digit facilitate and coordinate digit tip regeneration (Cell Stem Cell 2016, 2019, Dev Cell 2020).
How Tumors Disturb Normal Stem Cell Function
Discover tumor-specific mechanisms that perturb normal stem cell function.
PAST CONTRIBUTIONS
Identification of Dermal Stem Cells and their Function
(Nat Cell Bio 2001, 2004, J Neurosci 2006, Cell Stem Cell 2009);
Growth Factors that Regulate CNS Stem Cell Biology
including neurodevelopmental disorder-associated genes and pathways that perturb stem cell function (Neuron 2002, 2005, 2007, 2016, 2017, Development 2007, Nat Neurosci 2009, Dev Cell 2010, J Neurosci 2005, 2013, 2014, Dev Cell 2015);
Maternal Infection and Diabetes Effects on Stem Cell Function in the Fetus
and the life-long cognitive dysfunction of progeny (Neuron 2014, Cell Rep 2016);
Translational Mechanisms of Stem Cells
as the key determinants of neuron production at the precise time and place during development (Cell Stem Cell 2012, Neuron 2014, J Neurosci 2015, Neuron 2018);
Identification of Drugs that Prevent Axon Degeneration and Mobilize Endogenous Stem Cells
both in the CNS and skin, including metformin which is presently in a clinical trial at SickKids for the repair of acute brain damage in kids (Cell Stem Cell 2015, Stem Cell Rep 2016).
