Ronald M Lynch

Ronald M Lynch

Professor, Physiology
Associate Professor, Pharmacology
Professor, Biomedical Engineering
Professor, Physiological Sciences - GIDP
Director, Aribi Institute
Associate Director, Shared Resources
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-2472

Work Summary

Precise diagnosis and treatment of disease requires an ability to target agents to specific tissues and cell types within those tissues. We are developing agents that exhibit cell type specificity for these purposes.

Research Interest

Ron Lynch received a B.S. from the University of Miami (1978) with a dual major in Chemistry (Physical) and Biology, and a Ph.D. degree from the University of Cincinnati (1984) in Physiology and Biophysics. Dr. Lynch began training in optical imaging and MR spectroscopy of cardiac metabolism while at the NIH/NHLBI under the direction of Dr. Robert Balaban from 1984-1987. In 1987, Dr. Lynch moved to a staff position in the Biomedical Imaging Group with appointment in the Physiology Department at the University of Massachusetts Medical Center where he was involved in the development of approaches for 3-dimensional imaging including deconvolution and confocal microscopy. Dr. Lynch joined the faculty of the University of Arizona in 1990 with dual appointment in the Departments of Physiology and Pharmacology, and is currently a full professor, and director of the Arizona Research Institute for Biomedical Imaging. In 2000, Dr. Lynch was a visiting scientist at the Laboratory of Functional and Molecular Imaging and the Magnetic Resonance Imaging Center with Dr. Alan Koretsky at the NIH/NINDS. Dr. Lynch is a member of the Biophysical Society, the American Physiological Society and American Diabetes Association, and regularly serves on grant review panels for the JDRF, NIH/NIDDK, and NSF. Research in the Lynch lab focuses on second messenger signaling in vascular smooth muscle cells and nutrient sensing cells (e.g., Pancreatic Beta-cells) with emphasis on alterations in signaling that occur during development of Diabetes. We are developing methods to modify and analyze beta cell mass in order to evaluate the initiation of the pre-diabetic state, and efficacy of its treatment. Analyses of subcellular protein distributions, second messenger signaling, and ligand binding is performed in our lab using state of the art microscopy and analysis approaches which is our second area of expertise. Over the past 3 decades, our lab has been involved in the development of unique microscopic imaging and spectroscopy approaches to study cell and tissue function, as well as screening assays for cell signaling and ligand binding. Keywords: Diabetes, Cancer, Optical Imaging, Targeted Contrast Agents, Metabolism, Biomedical Imaging, Drug Development

Publications

McKay, B. S., Lynch, R. M., & Stamer, W. D. (2017). Comment on "Identification of Novel G Protein-Coupled Receptor 143 Ligands as Pharmacologic Tools for Investigating X-Linked Ocular Albinism". Investigative ophthalmology & visual science, 58(11), 4733-4734.
Dehigaspitiya, D. C., Anglin, B. L., Smith, K. R., Weber, C. S., Lynch, R. M., & Mash, E. A. (2015). Linear scaffolds for multivalent targeting of melanocortin receptors. Organic & biomolecular chemistry, 13(47), 11507-17.

Molecules bearing one, two, three, or four copies of the tetrapeptide His-dPhe-Arg-Trp were attached to scaffolds based on ethylene glycol, glycerol, and d-mannitol by means of the copper-assisted azide-alkyne cyclization. The abilities of these compounds to block binding of a probe at the melanocortin 4 receptor were evaluated using a competitive binding assay. All of the multivalent molecules studied exhibited 30- to 40-fold higher apparent affinites when compared to a monovalent control. These results are consistent with divalent binding to receptor dimers. No evidence for tri- or tetravalent binding was obtained. Differences in the interligand spacing required for divalent binding, as opposed to tri- or tetravalent binding, may be responsible for these results.

Brabez, N., Saunders, K., Nguyen, K. L., Jayasundera, T. B., Weber, C., Lynch, R. M., Chassaing, G., Lavielle, S., & Hruby, V. J. (2013). Multivalent Interactions: Synthesis and Evaluation of Melanotropin Multimers - Tools for Melanoma Targeting. ACS medicinal chemistry letters, 4(1), 98-102.

In order to develop agents for early detection and selective treatment of melanomas, high affinity and high specificity molecular tools are required. Enhanced specificity may be obtained by simultaneously binding to multiple cell surface targets via the use of multimeric analogs of naturally occurring ligands. Trimers targeting overexpressed melanocortin receptors have been found to be potential candidates for this purpose. In the present letter, we describe the synthesis and study of multimers based on a dendrimer-like scaffold. The binding affinity and activity results revealed that dendrimers promote multivalent interactions via statistical and/or cooperative effects on binding. Moreover, viability studies showed no significant toxicity at micromolar concentrations, which will allow these molecular complexes to be used in vivo. Finally, imaging studies showed effective internalization for all the molecules confirming their potential as delivery agents.

Marmorstein, A. D., Kinnick, T. R., Stanton, J. B., Johnson, A. A., Lynch, R. M., & Marmorstein, L. Y. (2015). Bestrophin-1 influences transepithelial electrical properties and Ca2+ signaling in human retinal pigment epithelium. Molecular vision, 21, 347-59.

Mutations in BEST1, encoding Bestrophin-1 (Best1), cause Best vitelliform macular dystrophy (BVMD) and other inherited retinal degenerative diseases. Best1 is an integral membrane protein localized to the basolateral plasma membrane of the retinal pigment epithelium (RPE). Data from numerous in vitro and in vivo models have demonstrated that Best1 regulates intracellular Ca2+ levels. Although it is known from in vitro and crystal structure data that Best1 is also a calcium-activated anion channel, evidence for Best1 functioning as a channel in human RPE is lacking. To assess Best1-associated channel activity in the RPE, we examined the transepithelial electrical properties of fetal human RPE (fhRPE) cells, which express endogenous Best1.