Mark Dell'Acqua, PhD
Professor and Vice Chairman
Director, NeuroTechnology Center
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
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 Name | Last Name | Middle Initial | Degree | Position |
| Kevin | Crosby | C. | PhD | Instructor |
| Philip | Dittmer | J. | PhD | Instructor |
| Ronald | Freund | K. | PhD | Instructor |
| Katlin | Hahm | BS | Graduate Student | |
| Tyler | Martinez | BS | Graduate Student | |
| Jennifer | Sanderson | L. | PhD | Instructor |
Former Trainees
| First Name | Last Name | Middle Initial | Degree | Position |
| Jessica | Gorski | A. | PhD | Postdoctoral Fellow |
| Eric | Horne | A. | PhD | Graduate Student |
| Alex | Huffman | MS | Graduate Student | |
| Johnathan | Murphy | G. | BS | Graduate Student |
| Jill | Neiman | M. | BS | Graduate Student |
| Matthew | Pink | D. | BS | Graduate Student |
| Alicia | Purkey | BS | Graduate Student | |
| Holly | Robertson | R. | PhD | Graduate Student |
| Karen | Smith | E. | PhD | Graduate Student |
| Angela | Wild | PhD | Postdoctoral Fellow | |
| Kevin | Woolfrey | M. | PhD | Postdoctoral Fellow |
View Dr. Dell'Acqua's Publications on PubMed
Selected Recent Publications
- Wild, A.R., Dell’Acqua, M.L. (2018) Potential for Therapeutic Targeting of AKAP Signaling Complexes in Nervous System Disorders. Pharmacology and Therapeutics 185: 99-121. (PMC5899024)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Rajgor D, Purkey AM, Sanderson JL, Welle TM, Garcia JD, Dell’Acqua ML, Smith KR (2020) Local miRNA-Dependent Translational Control of GABAAR Synthesis during Inhibitory Long-Term Potentiation. Cell Reports 31: 107785-107802 (PMC7486624)
- Purkey, A.M. and Dell'Acqua M.L. (2020) Phosphorylation-dependent Regulation of Ca2+-permeable AMPA Receptors during Hippocampal Synaptic Plasticity. Front Syn Neurosci 12:8. (PMC7119613)
- Sanderson JL, Freund RF, Gorski JA, Dell’Acqua ML (2021) β-Amyloid disruption of LTP/LTD balance is mediated by AKAP150-anchored PKA and Calcineurin regulation of Ca2+-permeable AMPA receptors. Cell Reports 37: 10976. (PMC8530450)
- Actor-Engel HS, Schwartz SL, Crosby KC., Sinnen BL, Prikhodko O, Ramsey HJ, Bourne JN, Winborn C, Lucas S, Smith KR, Dell'Acqua ML, Kennedy MJ (2021) Precision mapping of amyloid beta binding reveals perisynaptic localization and spatially restricted plasticity deficits. eNeuro, 8 (6) ENEURO.0416-21.2021 (PMC8687484)
- Chen X, Crosby KC, Feng A, Purkey AM, Aronova MA, Winters CA, Crocker V, Leapman RD, Reese TS, Dell’Acqua ML (2022) Palmitoylation of A-kinase anchoring protein 79/150 modulates its nanoscale organization, trafficking, and mobility in postsynaptic spines. Front Syn Neurosci 14:1004154 (PMC- In process)
Postdoctoral Position (Dabertrand Lab)
A postdoctoral position is available in the Dabertrand lab in collaboration with the Dell’Acqua lab at the University
of Colorado, Anschutz Medical Campus near Denver. Research will focus on understanding the contribution of vascular dysfunction to synaptic plasticity deficits and cognitive impairment. Specifically, how much restoration of neurovascular coupling
in Alzheimer’s disease and other related dementias (AD/ADRD) mitigates the deterioration of hippocampal long-term potentiation, and its behavioral consequences in genetic mouse models. The approach will use a newly discovered treatment to promote
cerebral blood flow in conjunction with extracellular field Excitatory Postsynaptic Potential (fEPSP) recording, pressure myography, ex vivo confocal imaging, and in vivo two-photon laser-scanning microscopy. We are looking for a highly motivated,
creative scientist to fill this position. The project is NIH-funded for up to five years. Start date is negotiable but ideally would be no later than early 2023.
The desired candidate will have experience in neuroscience, pharmacology,
physiology, and/or the vascular field. Prior experience in electrophysiology and/or fluorescence imaging is a plus but not required. Solid publication record is desired, with strong written and verbal communication skills in English. Annual salary
depends on level of experience. Minimum duration of two years, with potential for extension beyond this point contingent on performance.
The research of the Dabertrand and Dell’Acqua labs thrives in a collaborative and interdisciplinary
scientific environment within a strong neuroscience research community. Denver is an active, growing metropolitan area with a highly educated and physically active population. The environs are breathtaking with over 300 days per year of sunshine,
and world-class skiing, hiking, and mountain biking in the Rocky Mountains are easily accessible.
Please send curriculum vitae, a cover letter describing research interests, experience, and goals (<2 pages), and contact information for
two references to:
Mark Dell’Acqua (Mark.Dellacqua@CUAnschutz.edu ) or
Fabrice Dabertrand ( Fabrice.Dabertrand@CUAnschutz.edu )
Postdoctoral Position (Dell'Acqua Lab)
A postdoctoral position is available in the Dell’Acqua lab in the Department of Pharmacology at the University of Colorado, Anschutz Medical Campus (CU-Anschutz) near Denver. Research will focus on understanding the role of palmitoylation of the
scaffold protein AKAP79/150 in regulating neuronal postsynaptic kinase and phosphatase signaling complexes that are required for hippocampal long-term potentiation (LTP) and depression (LTD) synaptic plasticity, with relevance to mechanisms of synaptic
and ion channel dysfunction in Alzheimer’s disease and autism spectrum disorders. Training will include biochemical methods to measure palmitoylation, sophisticated live-cell and super-resolution fluorescence imaging approaches to study protein
localization and Ca2+ and cAMP signaling dynamics, and electrophysiological approaches to measure synaptic strength. We are looking for a highly motivated, creative scientist to fill this position. The project is NIH-funded for up to five years. Start
date is negotiable but ideally would be no later than early to mid-2023.
The desired candidate will have experience in neuroscience, pharmacology, cell biology, and/or biochemistry. Prior experience in electrophysiology and/or fluorescence
imaging is a plus but not required. Solid publication record is desired, with good written and verbal communication skills in English. Annual salary depends on level of experience. Minimum duration of two years, with potential for extension beyond
this point contingent on performance.
The research of the Dell’Acqua lab thrives in a collaborative and interdisciplinary scientific environment at CU-Anschutz. Denver is an active, growing metropolitan area with a highly educated
and physically active population. The environs are breathtaking with over 300 days per year of sunshine, and world-class skiing, hiking, and mountain biking in the Rocky Mountains are easily accessible.
Please send curriculum vitae, a cover
letter describing research interests, experience, and goals (<2 pages), and contact information for two references to:
Mark Dell’Acqua (Mark.Dellacqua@CUAnschutz.edu)
To inquire about other available positions please e-mail Mark Dell'Acqua.