Ulli Bayer, PhD


Ulli Bayer


Contact Information: 

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

Phone: (303) 724-3610
Fax: (303) 724-3663
E-mail: ulli.bayer@cuanschutz.edu​
Office: RC1-North, P18-6106

curriculum vitae​​

Our field is molecular and cellular neuroscience. Specifically, we are interested in the molecular and cellular mechanisms underlying learning, memory and cognition. These higher brain functions are thought to require “synaptic plasticity”, i.e. changes in the strength of the synapses that form the connections between neurons. We are studying the mechanisms by which such changes at individual synapses are initiated and maintained. The main forms of plasticity that we are studying are long-term potentiation (LTP) and long-term depression (LTD) of excitatory synapses in the hippocampus, a brain region required for declarative learning and memory. We are also interested in how changes at one synapse are communicated to other nearby synapses. For instance, how do excitatory LTD-stimuli also cause long-term potentiation of inhibitory synapses (iLTP) on the dendrites of the same neuron?

Additionally, we apply our fundamental neuroscience findings to a better understanding of neurological disorders. This specifically includes conditions with aberrant synaptic plasticity, such as Alzheimer’s disease, Down syndrome, schizophrenia, and addiction. However, our recent advances also included neuroprotection after acute injuries such as stroke or global cerebral ischemia (Deng et al., 2017, Cell Rep; Buonarati et al., 2020, Cell Rep). We are particularly excited about the fact that studying the plasticity impairments in our disease-related projects also lead us to a better understanding of the fundamental mechanisms of how plasticity normally works.

Our techniques include sophisticated biochemistry; live-imaging of molecular interactions/movements in heterologous cells and neurons; whole-cell and field electrophysiology; and behavioral studies on mutant mice. The molecules in the focus of our interest are the NMDA-type glutamate receptor (NMDAR) and the Ca2+/calmodulin-dependent protein kinase II (CaMKII; for which we have published the 12meric holoenzyme structure; Myers et al. 2017, Nature Comm). The NMDAR is a Ca2+-conducting channel that is activated by glutamate, the major excitatory neurotransmitter in the mammalian brain; CaMKII is a robust sensor and frequency detector of the NMDAR Ca2+ influx and is unique as its activity can become Ca2+-independent (“autonomous”) after autophosphorylation at T286, a process regarded as molecular memory. The NMDAR and CaMKII have been recognized as central mediators of LTP for over 30 years, but our more recent findings demonstrated that CaMKII and its autonomous activity are also required for NMDAR-dependent LTD (Coultrap et al., 2014, Cell Rep). But how can CaMKII mediate both of these two opposing forms of synaptic plasticity? We are continuing to unravel the mechanisms that enable the intricate underlying signal computation by the CaMKII holoenzyme (Coultrap et al. 2014, Cell Rep; Goodell et al., 2017, Cell Rep;  Cook et al., 2021 Science Adv). Intriguingly, CaMKII can also mediate the communication of plasticity at excitatory synapses to inhibitory synapses (Cook et al., 2021 Science Adv), further controlling the excitation/inhibition balance and adding another layer of cellular computation.

3 translocation.png

Regulation of synaptic strength by CaMKII involves the physical movement of the kinase to and from excitatory and inhibitory synapses. Stimulation-induced CaMKII translocation to excitatory synapses is largely dependent on a regulated direct binding of CaMKII to the NMDAR subunit GluN2B, a binding interaction we have intensively studies over the last 20 years (Bayer et al., 2001, Nature; Goodell et al., 2017, Cell Rep). We still want to address several important questions and apparent conundrums regarding the GluN2B interaction and translocation to excitatory synapses. For instance, how is input-specificity achieved? I.e. how is translocation to non-stimulated synapses prevented? Additionally, almost nothing is known to date about the mechanisms controlling translocation to inhibitory synapses. Excitingly, we now have a method that allows us to live-monitor the movement of endogenous CaMKII in neurons after different stimulation protocols (using intrabodies specific to CaMKII; published as cover article in Cook et al. 2019, Cell Rep). In contrast to over-expression of GFP-labelled CaMKII, expressing these intrabodies does not interfere with any type of stimulation-induced CaMKII movement that we have tested so far (by comparing the different live imaging methods to immunostaining).

Current Lab Members​

Bayer Lab



Ulli Bayer

U​lli Bayer​​


PhD Heinrich-Pette-Institute
PostDoc Stanford University

olivia buonarati

O​livia Buonarati​​


BS Seattle University
PhD University of California Davis

Fellowship: NIH F32 AG066536


Nicole Brown

Graduate Student (Pharmacology)

BS University of Colorado, Boulder
Fellowship: NIH T32 GM007635



sarah cook

Sarah Cook

Graduate Student (Pharmacology)

BS University of Texas at Austin
Fellowship: NIH F31 AG062160


steve coultrap

Steve Coultrap

Senior Research Associate
BS University of Texas at San Antonio
PhD Texas Tech University Health Science Center

PostDoc University of Colorado

janna mize

Janna Mize-Berge

Professional Research Assistant

BS University of Houston


Nikki Rumian

Graduate Student (Neuroscience)

BA University of Colorado Boulder

Fellowship: NIH F31 AG069458


jonathan tullis

Jonathan Tullis

Graduate Student (Pharmacology)

BS University of Santa Clara

Fellowship: NIH T32 GM007635


Previous Trainees

Hillary Allen, MS

Subsequent positions:
North-Face sponsored ultra trail runner

Kelsey Barcomb, PhD

Fellowship: NIH F31 NS083298
Subsequent positions:
PostDoc at Brown University, Providence, RI​

Rebekah Borup, PhD

(formerly Rebekah Vest)
Fellowship:  NIH F31 NS061584
Subsequent positions:
PostDoc at USC, Los Angeles, Dept. of Biology;
Adjunct Professor, Dept. of Biology, Mt San Antonio College, CA.

Isabelle Buard, PhD

Fellowship: Thorkildsen Fellowhip
Subsequent positions:
Research Instructor (faculty rank), UC Denver, Dept. of Neurology

Ron Freund, PhD

Subsequent positions:
Instructor (faculty rank), UC Denver, Dept. of Pharmacology

Dayton Goodell, PhD

Fellowship: NIH F31 NS092265
Subsequent positions:
PostDoc at University of Utah

Nicolas Haynes, BS

Subsequent positions:
graduate student, UC Boulder

Eric Horne, PhD

Subsequent positions:
PostDoc, U. Washington, Seattle, Dept. of Pharmacology;
Lead Scientist/Program Manager, Stella Therapeutics, Seattle;
Medical Science Liason, Lundbeck

Jacqueline Kulbe, BS

Subsequent positions:
MD/PhD student, University of Kentucky, Lexington

Heather O’Leary, PhD

Subsequent positions:
PostDoc, UC Denver, Dept. of Pediatrics

Vincent Zaegel, PhD

Subsequent positions:
Senior Professional Research Assistant, University of Colorado

Selected Review Article (of 9): (*: as corresponding author)


*  Bayer, K. U. and Schulman, H. (2019) CaM kinase: Still inspiring at 40. Neuron, 103: 280-394

            Free download here




Selected Research Articles(of >60):  (*: as corresponding author, even if not listed last)


* Cook, S. G., Buonarati, O. R., Coultrap, S. J., and Bayer, K. U. (2021) CaMKII holoenzyme mechanisms that govern the LTP versus LTD decision. Science Advances. 7: eabe2300 https://advances.sciencemag.org/content/7/16/eabe2300


* Buonarati, O. R., Cook, S. G., Goodell, D. J., Chalmers, N. E., Rumian, N. L. Tullis., J. E., Restrepo, S, Coultrap, S. J., Quillinan, N., Herson, P. S., and Bayer, K. U. (2020) CaMKII versus DAPK1 binding to GluN2B in ischemic neuronal cell death after resuscitation from cardiac arrest. Cell Reports. 30: 1-8.


* Cook, S. G., Goodell, D. J., Restrepo, S., Arnold, D. B., and Bayer, K. U. (2019) Simultaneous live-imaging of three endogenous proteins reveals that β amyloid blocks the LTP-induced synaptic accumulation of CaMKII. Cell Reports. 27: 658-665. (cover article) https://doi.org/10.1016/j.celrep.2019.03.041


* Woolfrey, K., O’Leary, H., Goodell, D. J., Robertson, H., Horne, E., Coultrap, S. J., Dell’Acqua, M. L., and Bayer, K. U. (2018) CaMKII regulates the de-palmitoylation and synaptic removal of AKAP79/150 to mediate structural LTD. J. Biol. Chem. 293:1551-1567. (editor’s pick and cover article)


* Goodell, D. J., Zaegel, V., Coultrap, S. J., and Bayer, K. U. (2017) DAPK1 mediates LTD by making the CaMKII/GluN2B binding LTP-specific. Cell Reports 19:2231-2243.


* Myers, J., Zaegel, V., Coultrap, S. J., Miller, A., Bayer, K. U., and Reichow, S. L. (2017) The CaMKII holoenzyme structure in activation-competent conformations. Nature Commun. 8:15742. https://www.nature.com/articles/ncomms15742


* Deng, G., Orfila, J. E., Dietz, R. M., Moreno-Garcia, M., Coultrap, S. J., Quilinan, N., Traystman, R. J., Bayer, K. U., and Herson, P. S. (2017) Autonomous CaMKII activity as a drug target for histological and functional neuroprotection after resuscitation from cardiac arrest. Cell Reports 18:1109-1117.


* Barcomb, K., Hell, J. W. Benke, T. A., and Bayer, K. U. (2016) The CaMKII/GluN2B protein interaction maintains synaptic strength. J. Biol. Chem. 291:16082-16089.


* Coultrap, S. J., Freund, R., O’Leary, H., Sanderson, J., Roche, K., Dell’Acqua, M.L., and Bayer, K. U. (2014) Autonomous CaMKII mediates both LTP and LTD using a mechanism for differential substrate site selection. Cell Reports 6:431-437.


* Coultrap, S. J., and Bayer, K. U. (2014) Nitric oxide induces Ca2+-independent activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII). J. Biol. Chem. 289:19458-19465.


* Barcomb, K., Buard, I., Coultrap, S. J., Kulbe, J. R., O’Leary, H., Benke, T.A., and Bayer, K. U. (2014) Autonomous CaMKII requires further stimulation by Ca2+/calmodulin for enhancing synaptic strength. FASEB J. 28:3810-3819.


* Buard, I., Freund, R., Lee, Y.-S., Coultrap, S. J., Dell’Acqua, M. L., Silva, A. J., and Bayer, K. U. (2010) CaMKII "autonomy" is required for initiating but not for maintaining neuronal long-term information storage. J. Neurosci. 30:8214-8220.


* Vest, R. S., O’Leary, H., Coultrap, S. J., Kindy, M. and Bayer, K. U. (2010) Effective post-insult neuroprotection by a novel CaMKII inhibitor. J. Biol. Chem. 285:20675-20682.


* Bayer, K. U., LeBel, E., McDonald, G.L., O’Leary, H., Schulman, H. and DeKoninck, P. (2006) Transition from reversible to persistent binding of CaMKII to postsynaptic sites and NR2B. J. Neurosci.. 26:1164-1174.


* Bayer, K. U., De Koninck, P. and Schulman, H. (2002) Alternative splicing modulates the frequency-dependent response of CaMKII to Ca2+-oscillations. EMBO J., 21:3590-3597.


* Bayer, K.-U., De Koninck, P., Leonard, A.S., Hell, J.W. and Schulman, H. (2001) Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature, 411:801-805.


   Bayer, K.-U., Harbers, K. and Schulman, H. (1998) aKAP is an anchoring protein for a novel CaM kinase II isoform in skeletal muscle. EMBO J., 17:5598-5605.




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, 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 contact Dr. Bayer directly.
Graduate students should arrange rotations through their respective graduate programs. Dr. Bayer is currently a member of the University of Colorado MSTPBSPPharmacologyNeuroscience, and Molecular Biology programs. Out of 20 previous three-months rotations, 9 resulted in authorships on publications from the lab, 2 of them as co-first authors (in J. Biol. Chem., Mol. Biol. Cell, PLoS One, and Brain Res.)

Current funding:


NIH R01 AG067713 (PI: Bayer; 25% effort)             $2,447,725      08/01/2020 – 07/31/2025    

“CaMKII nitrosylation in the age-related decline of synaptic plasticity” will investigate the mechanism and roles of CaMKII misregulation related to the cognitive decline during aging.


NIH R01 NS118786  (MPIs: Bayer/Herson; 12.5%)     $1,943,750      01/15/2021 – 11/30/2025

“CaMKII in global cerebral ischemia: mechanisms and therapeutic intervention” will explore underlying disease mechanism and the possibility for extended therapeutic time windows.


NIH R01 NS110383 (Bayer/Dell’Acqua/Kennedy)      $2,815,825      09/30/2018 – 06/30/2023    

 “Postsynaptic kinase/phosphatase networks in amyloid beta-induced synaptic dysfunction” will investigate the signaling mechanisms underlying synaptic pathology related to Alzheimer’s.


NIH R01 NS081248  (Bayer)                                  $2,989,567      07/01/2013 – 03/31/2022    

“CaMKII autophosphorylation in opposing directions of synaptic plasticity” will investigate the functions of newly discovered mechanisms of CaMKII substrate site selection in promotion of LTD versus LTP. This grant has been competitively renewed and is now in its 2nd funding period.




NIH F31 AG069458 (to Nicole Rumian)                      $   71,156                    03/05/21-02/28/23

       “CaMKII hypo-nitrosylation in age-related decline of synaptic plasticity and cognition”


NIH F32 AG066536 (to Olivia Buonarati)                $ 195,930        05/01/20-04/30/23

       “APP signaling impairs CaMKII-dependent synaptic plasticity after ischemic brain injury”


NIH F31 AG062160  (to Sarah Cook)                       $   69,594        05/01/2019-04/30/2021

“Suppression of CaMKII synaptic targeting and beta-amyloid pathology”