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

Smith, K. E., Kelly, A. C., Min, C. G., Weber, C. S., McCarthy, F. M., Steyn, L. V., Badarinarayana, V., Stanton, J. B., Kitzmann, J. P., Strop, P., Gruessner, A. C., Lynch, R. M., Limesand, S. W., & Papas, K. K. (2017). Acute Ischemia Induced by High-Density Culture Increases Cytokine Expression and Diminishes the Function and Viability of Highly Purified Human Islets of Langerhans. Transplantation, 101(11), 2705-2712.
BIO5 Collaborators
Sean W Limesand, Ronald M Lynch

Encapsulation devices have the potential to enable cell-based insulin replacement therapies (such as human islet or stem cell-derived β cell transplantation) without immunosuppression. However, reasonably sized encapsulation devices promote ischemia due to high β cell densities creating prohibitively large diffusional distances for nutrients. It is hypothesized that even acute ischemic exposure will compromise the therapeutic potential of cell-based insulin replacement. In this study, the acute effects of high-density ischemia were investigated in human islets to develop a detailed profile of early ischemia induced changes and targets for intervention.

Steyn, L. V., Ananthakrishnan, K., Anderson, M. J., Patek, R., Kelly, A., Vagner, J., Lynch, R. M., & Limesand, S. W. (2015). A Synthetic Heterobivalent Ligand Composed of Glucagon-Like Peptide 1 and Yohimbine Specifically Targets β Cells Within the Pancreas. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.
BIO5 Collaborators
Sean W Limesand, Ronald M Lynch

β Cell specificity for a heterobivalent ligand composed of glucagon-like peptide-1 (GLP-1) linked to yohimbine (GLP-1/Yhb) was evaluated to determine its utility as a noninvasive imaging agent.

Brabez, N., Nguyen, K. L., Saunders, K., Lacy, R., Xu, L., Gillies, R. J., Lynch, R. M., Chassaing, G., Lavielle, S., & Hruby, V. J. (2013). Synthesis and evaluation of cholecystokinin trimers: a multivalent approach to pancreatic cancer detection and treatment. Bioorganic & medicinal chemistry letters, 23(8), 2422-5.

In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface. Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling the potential for early detection. There is a lack of tools for early detection of pancreatic cancer, one of the deadliest forms of cancer, but CCK2-R overexpression on pancreatic cancer cells makes CCK based multimers potential markers for these cells. In this Letter, we describe the synthesis and evaluation of CCK trimers targeting overexpressed CCK2-R.

Wojtkowiak, J. W., Cornnell, H. C., Matsumoto, S., Saito, K., Takakusagi, Y., Dutta, P., Kim, M., Zhang, X., Leos, R., Bailey, K. M., Martinez, G., Lloyd, M. C., Weber, C., Mitchell, J. B., Lynch, R. M., Baker, A. F., Gatenby, R. A., Rejniak, K. A., Hart, C., , Krishna, M. C., et al. (2015). Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302. Cancer & metabolism, 3(1), 2.

Hypoxic niches in solid tumors harbor therapy-resistant cells. Hypoxia-activated prodrugs (HAPs) have been designed to overcome this resistance and, to date, have begun to show clinical efficacy. However, clinical HAPs activity could be improved. In this study, we sought to identify non-pharmacological methods to acutely exacerbate tumor hypoxia to increase TH-302 activity in pancreatic ductal adenocarcinoma (PDAC) tumor models.

Carmines, P., & Lynch, R. M. (2010). Changes in APS sectional programming for EB2011. Expanded programming and meeting-within-a-meeting structure. The Physiologist, 53(5), 137, 140.