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.

Present Research

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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 Reports 2017).

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 Reports 2018, Cell Reports 2020).

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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 Reports 2016, J.Cell Biol 2017).

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 2019).

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Unpublished data

How Tumors Disturb Normal Stem Cell Function

Discover tumor-specific mechanisms that perturb normal stem cell function.

Past Contributions of the Miller Kaplan lab

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Past contributions of the Miller Kaplan labs include the identification of dermal stem cells and their function (Nature Cell Biology 2001, 2004, Journal of Neuroscience 2006, Cell Stem Cell 2009);

growth factors that regulate CNS stem cell biology, and neurodevelopmental disorder-associated genes and pathways that perturb stem cell function (Neuron 2002, 2005, 2007, 2016, 2017, Development 2007, Nature Neuroscience 2009, Developmental Cell 2010, Journal of Neuroscience 2005, 2013, 2014, Developmental Cell 2015);

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and how maternal infection and diabetes affect stem cell function in the fetus resulting in life-long cognitive dysfunction of progeny (Neuron 2014, Cell Reports 2016).

We have found that translational mechanisms are key determinants of how stem cells produce neurons at the precise time and place during development (Cell Stem Cell 2012, Neuron 2014, Journal of Neuroscience 2015, Neuron 2018);

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and identified drugs that prevent axon degeneration and mobilize endogenous stem cells in the CNS and skin, including metformin that is presently in a clinical trial at SickKids for the repair of acute brain damage in kids (Cell Stem Cell 2015, Stem Cell Reports 2016).

We have also determined how the Trk and p75 neurotrophin receptors regulate neural connectivity, pruning and degeneration (Neuron 2005, Nature Neuroscience 2008, 2010, Journal of Cell Biology 2017);

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and how the different p53 family members coordinate their activities to control neuronal survival, brain aging and embryonic and adult stem cell biology (Science 2000, Journal of Neuroscience 2002, 2004a, 2004b, 2009, 2013, Neuron 2005, 2008, Current Biology 2010, Cell Death and Differentiation 2014).

Historically, the Kaplan lab has examined how neuroblastoma arises and progresses (with Meredith Irwin, SickKids), and identified drugs that can be used to treat this often-deadly childhood cancer as well as glioblastoma (EMBO Molec Med 2010, Oncotarget 2016, Cancer Res 2011, 2017)

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