Katharine Smith, PhD

Assistant Professor


 
Kate Smith

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
Office: RC1-North, P18-6117


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.


 

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AnkG8_overlay2.jpgInhib synapses.png


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.

 

 SIMsynapses.png

SIM figure.png


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, Kath​erine 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 

Kate Smith

Katharine Smith, PhD

Assistant Professor

katharine.r.smith@cuanschutz.edu​​

Education: Ph.D.- University College London, MSci- Imperial College London

Hometown: London, UK​

 

Postdoctoral Fellow 

Dipen_IMG_1709

Dipen Rajgor, PhD

March 2018 - Present 

DIPEN.RAJGOR@CUANSCHUTZ.EDU

Education: Ph.D.- King’s College London

Home town: London, UK

Graduate Students 

Joshua_Garcia

Joshua Garcia

May 2017 - Present

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

TheresaWelle

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

Sara Gookin

May 2017 - Present

Pharmacology Graduate Student

SARA.GOOKIN@CUANSCHUTZ.EDU

Education: Bachelor of Science in Biomedical Engineering - Michigan Technological University

Hometown: Byron, MI

 

​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 PharmacologyNeuroscience​ and BSP programs.​