Katharine Smith, PhD

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University of Colorado Anschutz Medical Campus

Katharine Smith, PhD

Associate Professor

Contact Information:

University of Colorado Denver
Department of Pharmacology
Mail Stop 8303, RC1-North
12800 East 19th Ave
Aurora CO 80045

Phone: (303) 724-0267

Fax: (303) 724-3663

E-mail: katharine.r.smith@cuanschutz.edu

Office: RC1-North, P18-6117

curriculum vitae

Affiliated Programs

Smith Lab Website

Plasticity of excitatory and inhibitory synapses during pathology

A major focus of our lab is to understand how the coordinated plasticity of excitatory and inhibitory synapses is altered during different pathologies. In many brain disorders there is thought to be an imbalance between excitation and inhibition in key brain regions (eg. autism, schizophrenia, down syndrome). Therefore understanding how excitatory and inhibitory synapses function together to maintain the correct excitability of neurons and their circuits is essential to understand how these disorders develop. To study this we interrogate the plasticity of both excitatory and inhibitory synapses, and the function of a number of disease-associated proteins that are involved in synaptic function.We use a range of methods including advanced imaging, electrophysiology and biochemistry. In particular we have a focus on using advanced live-confocal, glutamate uncaging, FRAP, FRET and super-resolution imaging techniques.

The nanoscale composition of synapses

Another key area of research in the lab is to characterize the nanoscale changes that occur at synapses during plasticity and pathology. My previous work has shown the nanoscale structure of synapses and the distribution of synapse-associated proteins is important for our understanding of synaptic function (Smith et al. 2014, Neuron). We utilize a range of super-resolution imaging techniques to further this goal (STED, STORM and SIM), combined with the development of novel computational methods to analyze data from super-resolution imaging modalities. Further, our lab is lucky to have its own super-resolution Structured Illumination Microscope (SIM) to fully explore the nanoscale structure of synapses and their associated proteins.

Example of super-resolution microscope images

Sara E. Gookin, Matthew R. Taylor, Samantha L. Schwartz, Matthew J. Kennedy, Mark L. Dell’Acqua, Kevin C. Crosby and Katharine R. Smith (2022). Complementary Use of Super-Resolution Imaging Modalities to Study the Nanoscale Architecture of Inhibitory Synapses, Frontiers in Synaptic Neuroscience [Frontiers]

Joshua D Garcia, Sara E Gookin, Kevin C Crosby, Samantha L Schwartz, Erika Tiemeier, Matthew J Kennedy, Mark L Dell'Acqua, Paco S Herson, Nidia Quillinan, Katharine R Smith (2021). Stepwise disassembly of GABAergic synapses during pathogenic excitotoxicity, Cell Reports, PMID: 34936876.

Actor-Engel HS, Schwartz SL, Crosby KC, Sinnen BL, Prikhodko O, Ramsay HJ, Bourne JN, Winborn CS, Lucas A, Smith KR, Dell'Acqua ML, Kennedy MJ (2021). Precision Mapping of Amyloid-β Binding Reveals Perisynaptic Localization and Spatially Restricted Plasticity Deficits, eNeuro, PMID: 34789478 .

Dipen Rajgor, Theresa M Welle, Katharine R Smith (2021). The Coordination of Local Translation, Membranous Organelle Trafficking, and Synaptic Plasticity in Neurons, Frontiers in Cell and Developmental Biology, PMID: 34336865 .

Towers CG, Wodetzki DK, Thorburn J, Smith KR, Caino MC, Thorburn A. Mitochondrial-derived vesicles compensate for loss of LC3-mediated mitophagy, Developmental Cell, PMID: 34171288 .

Dipen Rajgor, Alicia M. Purkey, Jennifer L. Sanderson, Theresa M. Welle, Joshua D. Garcia, Mark L. Dell’Acqua, Katharine R. Smith (2020). Local miRNA-Dependent Translational Control of GABAAR Synthesis during Inhibitory Long-Term Potentiation, Cell Reports, PMID: 32579917 .

E Mae Guthman, Joshua D Garcia, Ming Ma, Philip Chu, Serapio M Baca, Katharine R Smith, Diego Restrepo, Molly M Huntsman (2020). Cell-type-specific control of basolateral amygdala neuronal circuits via entorhinal cortex-driven feedforward inhibition, eLife, PMID: 31916940 .

Kevin C. Crosby, Sara E. Gookin, Joshua D. Garcia, Katlin M. Hahm, Mark L. Dell’Acqua, and Katharine R. Smith (2019). Nanoscale Subsynaptic Domains Underlie the Organization of the Inhibitory Synapse, Cell Reports, PMID: 30893601.

Won Chan Oh and Katharine R. Smith (2018). Activity-dependent development of GABAergic synapses, Brain Research, PMID: 30439352.

Smith KR, Penzes P (2018). Ankyrins: Roles in synaptic biology and pathology, Molecular and Cellular Neuroscience, PMID: 29730177.

Katharine R. Smith, Dipen Rajgor and Jonathan G. Hanley (2017). Differential regulation of the Rac1 GTPase activating protein (GAP) BCR during oxygen/glucose deprivation in hippocampal and cortical neurons, Journal of Biological Chemistry, PMID: 29046349.

Hiester BG, Bourke AM, Sinnen BL, Cook SG, Gibson ES, Smith KR, Kennedy MJ (2017). L-Type Voltage-Gated Ca2+ Channels Regulate Synaptic-Activity-Triggered Recycling Endosome Fusion in Neuronal Dendrites, Cell reports, PMID: 29166605.

Katharine R. Smith, Kelly A. Jones, Katherine J. Kopeikina, Alain C. Burette, Bryan A. Copits, Sehyoun Yoon, Marc Forrest, Jessica M. Fawcett-Patel, Jonathan G. Hanley, Richard J. Weinberg,Geoffrey T. Swanson and Peter Penzes (2017). Cadherin-10 maintains excitatory/inhibitory ratio through interactions with synaptic proteins, Journal of Neuroscience, PMID: 29030434.

Katharine R. Smith, Katherine J. Kopeikina, Jessica Fawcett-Patel, Katherine Leaderbrand, Ruoqi Gao, Britta Schürmann, Kristoffer Myczek, Jelena Radulovic, Geoffrey T. Swanson and Peter Penzes (2014). Psychiatric risk factor ANK3/Ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses, Neuron, PMID: 25374361.

Katharine R. Smith, Elizabeth C. Davenport, Jing Wei, Xiangning Li, Manavendra Pathania, Victoria Vaccaro, Zhen Yan and Josef T. Kittler (2014). GIT1 and βPIX are essential for GABAA receptor synaptic stability and inhibitory neurotransmission, Cell Reports, PMID: 25284783.

Katharine R. Smith, James Muir, Yijian Rao, Marietta Browarski, Marielle Gruenig, David F. Sheehan, Volker Haucke, Josef T Kittler (2012), Stabilisation of GABAA receptors at endocytic zones is mediated by an AP2 binding motif within the GABAA receptor β3 subunit, Journal of Neuroscience, PMID: 22396422.

James Muir, I Lorena Arancibia-Carcamo*, Andrew F MacAskill*, Katharine R. Smith*, Lewis Griffin, Josef T Kittler (2010), NMDA receptors regulate GABAA receptor lateral mobility and clustering at inhibitory synapses through serine 327 on the γ2 subunit, PNAS, PMID: 20823221. *equal contribution to the work.

Katharine R. Smith and Josef T Kittler (2010), The cell biology of synaptic inhibition in health and disease, Current Opinion in Neurobiology, PMID: 20650630.

Principle Investigator
	Katharine Smith, PhD Associate Professor katharine.r.smith@cuanschutz.edu Education: Ph.D.- University College London, MSci- Imperial College London Hometown: London, UK
Graduate Students
	Sarah Wolfe June 2021 - Present Neuroscience Graduate Student SARAH.2.WOLFE@CUANSCHUTZ.EDU Education: Bachelor of Science in Cell and Molecular Biology from Towson University Hometown: Joppa, MD
	Amber Stewart June 2022 - Present Pharmacology Graduate Student AMBER.STEWART@CUANSCHUTZ.EDU Education: Bachelor of Science in Honors Chemistry from Towson University Hometown: Glen Burnie, MD
	Theresa Welle June 2019 - Present Neuroscience Graduate Student THERESA.WELLE@CUANSCHUTZ.EDU Education: Bachelor of Science in Molecular and Cellular Biology & Chemistry – University of Illinois at Urbana–Champaign Hometown: Urbana, IL
Professional Research Assistant
	Sara Gookin May 2017 - Present Professional Research Assistant SARA.GOOKIN@CUANSCHUTZ.EDU Education: Bachelor of Science in Biomedical Engineering - Michigan Technological University Hometown: Byron, MI
Research Associate
	Kevin Crosby, PhD 2017 - Present Research Associate KEVIN.CROSBY@CUANSCHUTZ.EDU Education: Ph.D. Virginia Tech, 2008; Postdoc, University of Amsterdam 2009-2013 Hometown: New York City, NY
Alumni
	Dipen Rajgor, PhD March 2018 - November 2020 DIPEN.RAJGOR@CUANSCHUTZ.EDU Education: Ph.D.- King’s College London Home town: London, UK
	Joshua Garcia May 2017 - May 2023 Pharmacology Graduate Student American Heart Association Predoctoral Fellow JOSHUA.D.GARCIA@CUANSCHUTZ.EDU Education: Bachelor of Science in Biology - University of New Mexico Hometown: Mora, NM

We are currently seeking highly motivated individuals for postdoctoral positions. Those with experience in one or more of the following areas are especially encouraged to apply: electrophysiology, cell biology, live cell imaging, optogenetics, and super-resolution imaging. A number of projects incorporate a broad range of techniques, concepts and new tools, offering outstanding training potential. To apply for a postdoc position in the lab, please email Dr. Smith directly.

Graduate students should arrange rotations through their respective graduate programs. Dr. Smith is currently a member of the University of Colorado Pharmacology, Neuroscience and BSP programs.

Pharmacology (SOM)

CU Anschutz

Research I North

12800 East 19th Avenue

6126

Aurora, CO 80045

303-724-3560

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