Craig A Aspinwall
Professor, BIO5 Institute
Professor, Biomedical Engineering
Professor, Chemistry and Biochemistry-Sci
Primary Department
(520) 621-6338
Research Interest
Craig A. Aspinwall, PhD, is an Associate Professor of Chemistry and Biochemistry at the University of Arizona. Dr. Aspinwall’s research is focused on the development of novel technology that facilitates the investigation of the molecular underpinnings of disease states. His work encompasses a broad range of scientific disciplines and allows complex biochemical problems to be studied with an increasing level of molecular detail. Dr. Aspinwall has published over 40 original research papers and maintains active collaborations with several international investigators. His research has been funded by the National Institutes of Health, the National Science Foundation, the Arizona Biomedical Research Corporation, and other organizations. He is actively involved in mentoring and education of students and young scientists.

Publications

Jung, S., Aspinwall, C. A., & Kennedy, R. T. (1999). Detection of multiple patterns of oscillatory oxygen consumption in single mouse islets of Langerhans. Biochemical and Biophysical Research Communications, 259(2), 331-335.

PMID: 10362508;Abstract:

A novel oxygen microsensor was used to measure oxygen levels in single mouse islets as a function of glucose concentration. Oxygen consumption of individual islets was 5.99 ± 1.17, 9.21 ± 2.15, and 12.22 ± 2.16 pmol/min at 3, 10, and 20 mM glucose, respectively (mean ± SEM, n = 10). Consumption of oxygen was islet-size dependent as larger islets consumed more oxygen than smaller islets but smaller islets consumed more oxygen per unit volume than larger islets. Elevating glucose levels from 3 to 10 mM induced pronounced fast oscillations in oxygen level (period of 12.1 ± 1.7 s, n = 6) superimposed on top of large slow oscillations (period of 3.3 ± 0.6 min, n = 6). The fast oscillations could be completely abolished by treatment with the L-type Ca2+-channel blocker nifedipine (40 μM) with a lesser effect on slow oscillations. Slow oscillations were almost completely dependent upon extracellular Ca2+. The oxygen patterns closely mimic those that have previously been reported for intracellular Ca2+ levels and are suggestive of an important role for Ca2+ in amplifying metabolic oscillations.

Kennedy, R. T., Huang, L., & Aspinwall, C. A. (1996). Extracellular pH is required for rapid release of insulin from Zn - insulin precipitates in β-cell secretory vesicles during exocytosis. Journal of the American Chemical Society, 118(7), 1795-1796.
Aspinwall, C., Cheng, Z., D'Ambruoso, G. D., & Aspinwall, C. A. (2006). Stabilized porous phospholipid nanoshells. Langmuir : the ACS journal of surfaces and colloids, 22(23).

Chemically stabilized, porous phospholipid nanoshells (PPNs) were prepared via copolymerization of reactive monomers with unilamellar bis-Sorbyl phosphatidylcholine vesicles. The resulting PPN vesicular assemblies possess a highly porous membrane structure that allows passage of small molecules, which can react with encapsulated proteins and reporters. The unique combination of membrane stability and porosity will prove useful for preparing nanometer-sized sensor, container, and reactor platforms stable in harsh chemical and biological environments.

Bränström, R., Leibiger, I. B., Leibiger, B., Klement, G., Nilsson, J., Århem, P., Aspinwall, C. A., Corkey, B. E., Larsson, O., & Berggren, P. -. (2007). Single residue (K332A) substitution in Kir6.2 abolishes the stimulatory effect of long-chain acyl-CoA esters: Indications for a long-chain acyl-CoA ester binding motif. Diabetologia, 50(8), 1670-1677.

PMID: 17522836;Abstract:

Aims/hypothesis: The pancreatic beta cell ATP-sensitive potassium (K ATP) channel, composed of the pore-forming α subunit Kir6.2, a member of the inward rectifier K+channel family, and the regulatory β subunit sulfonylurea receptor 1 (SUR1), a member of the ATP-binding cassette superfamily, couples the metabolic state of the cell to electrical activity. Several endogenous compounds are known to modulate KATP channel activity, including ATP, ADP, phosphatidylinositol diphosphates and long-chain acyl coenzyme A (LC-CoA) esters. LC-CoA esters have been shown to interact with Kir6.2, but the mechanism and binding site(s) have yet to be identified. Materials and methods: Using multiple sequence alignment of known acyl-CoA ester interacting proteins, we were able to identify four conserved amino acid residues that could potentially serve as an acyl-CoA ester-binding motif. The motif was also recognised in the C-terminal region of Kir6.2 (R311-332) but not in SUR1. Results: Oocytes expressing Kir6.2ΔC26 K332A repeatedly generated K+currents in inside-out membrane patches that were sensitive to ATP, but were only weakly activated by 1 μmol/l palmitoyl-CoA ester. Compared with the control channel (Kir6.2ΔC26), Kir6.2ΔC26 K332A displayed unaltered ATP sensitivity but significantly decreased sensitivity to palmitoyl-CoA esters. Coexpression of Kir6.2ΔC26 K332A and SUR1 revealed slightly increased activation by palmitoyl-CoA ester but significantly decreased activation by the acyl-CoA esters compared with the wild-type KATP channel and Kir6.2ΔC26+SUR1. Computational modelling, using the crystal structure of KirBac1.1, suggested that K332 is located on the intracellular domain of Kir6.2 and is accessible to intracellular modulators such as LC-CoA esters. Conclusions/interpretation: These results verify that LC-CoA esters interact at the pore-forming subunit Kir6.2, and on the basis of these data we propose an acyl-CoA ester binding motif located in the C-terminal region. © 2007 Springer-Verlag.

Cheng, Z., Zaki, A. A., Jones, I. W., Hall, H. K., Aspinwall, C. A., & Tsourkas, A. (2014). Stabilized porous liposomes with encapsulated Gd-labeled dextran as a highly efficient MRI contrast agent. Chemical Communications, 50(19), 2502-2504.

Abstract:

A highly efficient contrast agent for magnetic resonance imaging was developed by encapsulating gadolinium within a stabilized porous liposome. The highly porous membrane leads to a high relaxivity of the encapsulated Gd. The stability of the liposome was improved by forming a polymer network within the bilayer membrane. © 2014 The Royal Society of Chemistry.