Current Research Interests:
Evolution of the cerebral cortex is thought to underlie our species' most remarkable cognitive, perceptive, and motor capabilities, the execution of which depends on the precise establishment of axonal connectivity during development. Miswiring of cortical circuitry can lead to disorders, including autism and schizophrenia, that affect the most distinctly human cognitive functions.
Research in the Kwan laboratory is aimed at the molecular and cellular mechanisms that underlie normal neural circuit assembly in the cerebral cortex and their dysregulation in human neurodevelopmental disorders, in particular autism spectrum disorder, fragile X syndrome, and schizophrenia. Our work examines both fundamental and pathogenic mechanisms that can lead to in vivo consequences on neural circuit development and function. Our two overarching goals are: 1) to understand the mechanisms by which neural progenitor cells give rise to diverse repertoires of cortical neuronal subtypes; and 2) to understand the mechanisms that ultimately wire cortical neurons into functional neural circuits. We use an integrative approach at the interface of mouse genetics, functional genomics, molecular biology, and circuit neurobiology. As the pace of genetic discoveries in brain disorders accelerates, we are ideally positioned to generate mechanistic knowledge into normal cortical development and neurodevelopmental disorders.
For further information, please visit www.kwanlab.org.
Awards and Honors:
2016 Fay/Frank Seed Grant Program, Brain Research Foundation
2015 Basil O’Connor Award, March of Dimes Foundation
2014 SFARI Explore Award, Simons Foundation Autism Research Initiative
2012 Pathway to Independence Award, National Institutes of Health
2012 Biological Sciences Scholar, University of Michigan
2012 Neuroscience Scholar, University of Michigan
2012 Finalist, Lap-Chee Tsui Award, Canadian Institutes of Health Research
2008 Krieg Cortical Kudos Scholar Award, Cajal Club
2005 Doctoral Research Award, Canadian Institutes of Health Research
2004 Postgraduate Scholarship, Natural Sciences & Engineering Research Council
1999 Biochem Pharmaceutical Inc. Award, University of Waterloo
2008 Ph.D., Neuroscience, Yale University
2002 B.Sc., Biochemistry, University of Waterloo
Shi L, Qalieh A, Mandy MMS, Keil JM, Kwan KY (2019).
Robust elimination of genome-damaged cells safeguards against brain somatic aneuploidy following Casc5 deletion.
Nat Commun, 10: 2588.
Keil JM, Qalieh A, Kwan KY (2018).
Brain transcriptome databases: a user's guide.
J Neurosci, 38: 2399.
Shim S, Kwan KY, Li M, Lefebvre V, Sestan N (2012).
Cis-regulatory control of corticospinal system development and evolution.
Nature, 486: 74-79.
Kwan KY, Lam MMS, Johnson MB, Dube U, Shim S, et al. (2012).
Species-dependent post-transcriptional regulation of NOS1 by FMRP in the developing cerebral cortex.
Cell, 149: 899-911.
Kwan KY, Sestan N, Anton ES (2012).
Transcriptional co-regulation of neuronal migration and laminar identity in the neocortex.
*Barak T, *Kwan KY, Louvi A, Demirbilek V, Sayg S, et al. (2011).
Recessive LAMC3 mutations cause malformations of occipital cortical development.
Nature Genetics, 43: 590-594. [*equal contributors]
*Kwan KY, *Lam MMS, Krsnik Z, Imamura Kawasawa Y, Lefebvre V, Sestan N (2008).
SOX5 postmitotically regulates migration, postmigratory differentiation, and projections of subplate and deep-layer neocortical neurons.
Proc Natl Acad Sci U S A, 105: 16021-16026. [*equal contributors]
*Abelson JF, *Kwan KY, *O'Roak BJ, Baek DY, Stillman AA, et al. (2005).
Sequence variants in SLITRK1 are associated with Tourette's syndrome.
Science, 310: 317-320.[*equal contributors]