Mark Dell'Acqua, PhD

Professor and Vice Chairman

Director, NeuroTechnology Center


 
Mark Dell'Acqua

Contact Information: 

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

Phone: (303) 724-3616
Fax: (303) 724-3663
E-mail: mark.dellacqua@cuanschutz.edu
Office: RC1-North, P18-6100

curriculum vitae​

Over the last decade it has become apparent that cellular signal transduction from receptors through second messengers to downstream kinases and phosphatases is regulated both spatially and temporally within cells through the assembly of multi-protein complexes. Central to the organization of these signaling complexes are multivalent scaffold proteins that recruit receptors, effectors, protein kinases and phosphatases, and target substrates at specific subcellular locations to promote very specific and efficient signal transduction events in different specialized cell types.

 

My laboratory’s specific research in the area of neuropharmacology focuses on understanding how cAMP and calcium second messenger signaling pathways are organized at the postsynaptic specializations of excitatory neuronal synapses. In particular, we are interested in A-kinase anchoring protein (AKAP) scaffold complexes that anchor the cAMP-dependent protein kinase PKA and the calcium-calmodulin stimulated protein phosphatase 2B-calcineurin near postsynaptic AMPA and NMDA-type ionotropic glutamate receptors and L-type voltage-gated calcium channels. We are studying the roles of these locally anchored kinase/phosphatase signal transduction complexes in regulation of glutamate receptor and L-channel activity, trafficking, and signaling to the transcription factors in the nucleus to control synaptic structure and function. 

 

We are exploring these fundamental mechanisms of ion channel and transcription factor regulation during long-term potentiation (LTP) and depression (LTD) hippocampal synaptic plasticity that underlie normal spatial and declarative learning and memory. In addition, we are interested in understanding how these forms of plasticity are altered in neurodevelopmental, mental health, and neurological disorders such as Down syndrome, Alzheimer’s, epilepsy, schizophrenia, autism, PTSD, and traumatic brain injury that are all associated with impaired cognitive function. We are exploring the mechanisms of synaptic regulation in a variety of systems including cultured primary neurons, acute brain slices, and knock-out and knock-in mice that delete postsynaptic AKAP anchoring sites for PKA and calcineurin. 

 

We are using a variety of experimental approaches to analyze AKAP-regulated signal transduction in these in vitro and in vivo systems including neurobehavioral testing, neuropharmacology, structural biology and biochemistry, electrophysiology, and fluorescence microscopy. In particular, we employ a number of cutting-edge confocal, FRAP, FRET, and super-resolution fluorescence imaging methods to visualize signal transduction at neuronal synapses. See our recent publications in Neuron, Nat. Struc. Mol. Biol. and J. Neurosci. and  Cell Reports for more information on these experimental methods and our latest research findings.

Current Lab Members

First NameLast NameMiddle InitialDegreePosition
 KevinCrosby C. PhD Postdoctoral Fellow 
 PhilipDittmer J. PhD Postdoctoral Fellow 
RonaldFreundK.PhDInstructor
KatlinHahm BSGraduate Student
TylerMartinez BSGraduate Student
OlgaPrikhodko PhDPostdoctoral Fellow
JenniferSandersonL.PhDInstructor
KevinWoolfreyM.PhDPostdoctoral Fellow

 

Former Trainees

First NameLast NameMiddle InitialDegreePosition
JessicaGorskiA.PhDPostdoctoral Fellow
 EricHorne A. PhD Graduate Student 
 JohnathanMurphy G. BSGraduate Student
 JillNeimanM. BSGraduate Student
MatthewPink D.  BS

 

Graduate Student 
AliciaPurkey BSGraduate Student
HollyRobertsonR.PhDGraduate Student
KarenSmithE.PhDGraduate Student
AngelaWild PhDPostdoctoral Fellow

 

View Dr. Dell'Acqua's Publications on PubMed

Selected Recent Publications
  1. Sinnen, B.L, Bowen, A.B, Forte, J.S., Hiester, B.G., Crosby, K.C., Gibson, E.S., Dell’Acqua, M.L., Kennedy, M.J. (2017) Optogenetic control of synaptic composition and function Neuron 93: 646-660.  (PMC5300939)
  2. Dittmer, P.J., Wild, A.R., Dell’Acqua, M.L., Sather, W.A., (2017) STIM1 Ca2+ sensor control of L-type Ca2+-channel-dependent dendritic spine structural plasticity and nuclear signaling. Cell Reports 19: 321-334. (PMC5451256) 
  3. Woolfrey, K.M., O’Leary, H., Goodell, D.J., Robertson, H.R., Horne, E.A., Coutrap, S.J., Dell’Acqua, M.L., Bayer, K.U. (2018) CaMKII regulates the de-palmitoylation and synaptic removal of the scaffold protein AKAP79/150 to mediate structural LTD. J. Biol. Chem. 293:  1551–1567  (PMC5798287).
  4. Sanderson, J.L., Scott, J,D., Dell’Acqua, M.L. (2018) Control of homeostatic synaptic plasticity by AKAP-anchored kinase and phosphatase regulation of Ca2+-permeable AMPA receptors J. Neurosci. 14: 2863-2876. (PMC5852664)
  5. Purkey, A.M., Woolfrey, K.M., Crosby,  K.C., Stich, D.G., Chick, W.S., Aoto, J., Dell’Acqua, M.L. (2018) AKAP150 palmitoylation regulates synaptic incorporation of Ca2+-permeable AMPA receptors to control LTP. Cell Reports 25: 974-987. (PMC6263960)
  6. Gibson, E.S., Woolfrey, K.M., Li, H., Hogan, P.G., Nemenoff, R.A., Heasley, L.E., Dell’Acqua, M.L. (2019) Subcellular Localization and Activity of the Mitogen-activated Protein Kinase Kinase 7 (MKK7) γ Isoform are Regulated through Binding to the Phosphatase Calcineurin.  Mol Pharm 95: 20-32. (PMC6277928)
  7. Wild, A.R., Sinnen, B.L., Dittmer, P.J., Kennedy, M.J., Sather, W.A., Dell’Acqua, M.L. (2019) Synapse-to-nucleus communication through NFAT is mediated by L-type Ca2+ channel Ca2+ spike propagation to the soma.  Cell Reports 26:3537-3550. (PMC6521872)
  8. Crosby, K.C., Gookin, S.E., Garcia, J.D., Hahm, K.M., Dell’Acqua, M.L., Smith, K.R. (2019) Nanoscale subsynaptic domains underlie the organization of the inhibitory synapse.  Cell Reports 26: 3284–3297 (PMC6529211)
  9. Dittmer, PJ, Dell’Acqua, ML, Sather, WA (2019) Synaptic crosstalk conferred by a zone of differentially-regulated Ca2+ signaling in the dendritic shaft adjoining a potentiated spine.  PNAS 116:13611-13620 (PMC6613087) 
  10. Murphy, JG, Crosby, KC, Dittmer, PJ, Sather, WA, Dell’Acqua, ML (2019) AKAP79/150 recruits the transcription factor NFAT to regulate signaling to the nucleus by neuronal L-type Ca2+ channels.  Mol Biol Cell  30:1743-1756 (PMC6727748)
To inquire about available positions please e-mail Mark Dell'Acqua.