Biochemistry and Molecular Biology
Honorary Senior Lecturer Centre for Experimental Medicine School of Medicine, Dentistry, and Biomedical Sciences Queen's University Belfast Northern Ireland, United Kingdom
Education and Training
I received a B.A. in Biology from Northwestern University and the Ph.D. in Biochemistry from the University of Illinois at Urbana-Champaign with Thomas Baldwin on the primary structure of bacterial luciferase. I did postdoctoral training with Joseph Lakowicz at the University of Maryland, Baltimore (UMB), on the effects of high pressure on biomolecules, then was awarded a National Research Council Associateship at the U.S. Naval Research Laboratory in Washington, DC. I continued work on fluorescence-based fiber optic sensors at NRL as Supervisory Research Chemist, and received a U.S. Navy Special Act Award for Operation Desert Storm.
Since I joined the faculty here at Maryland, much of our work has focused on developing and applying fluorescence-based biosensors to address questions in biology, human health, and oceanography. These biosensors use a biological molecule (usually an enzyme) to recognize and bind the analyte in aqueous media; they mostly transduce the presence or level of the analyte as a change in fluorescence or other luminescence. We have been particularly interested in quantitatively measuring and imaging zinc, copper, and other metal ions that are required nutrients in humans and other organisms, as well as important pollutants. Working together with Carol A. Fierke (now of Brandeis University) and David W. Christianson of the University of Pennsylvania, we demonstrated that using an enzyme, human apocarbonic anhydrase II, as a recognition element conferred extreme (and controllable) sensitivity and selectivity as well as unmatched response speed on the biosensors. This enables us to measure and image zinc and copper ions in real time in matrices as complex as cell cytoplasm, growth media, and, in collaboration with James Moffett (now of the University of Southern California), sea water. By use of fiber optics we have demonstrated real time measurements remotely at depth in the ocean or in the living brain.
Our other recent focus has been on the unexpected discovery of hydroxyapatite (a hard, very stable form of calcium phosphate found in bones and teeth) in the sub-retinal pigment epithelial layer of the retina in the eye in older persons. The hydroxyapatite is in the form of microscopic spherules, and our work with Imre Lengyel of Queens University Belfast, UK, showed these spherules are likely involved in the development of deposits in the retina that lead to age-related macular degeneration (AMD), the most common cause of blindness in the elderly in the developed world. We devised fluorescence methods for imaging the spherules that may prove useful in following the course of the disease, and perhaps predicting its onset in time to initiate treatment.
We have been grateful for support from the NIH, NSF, Office of Naval Research, National Oceanic and Atmospheric Administration/CICEET, Maryland Innovation Initiative, and Bright Focus Foundation. I would also like to thank my many undergraduate and graduate students, postdoctoral fellows, collaborators and faculty colleagues with whom it has been a pleasure to work.
fluorescence, biosensor, fluorescence lifetime, fluorescence anisotropy, fluorescence polarization, FRET, zinc, copper, hydroxyapatite, retina, sub-RPE deposits, drusen, fiber optics, sensors, fluorescence lifetime imaging microscopy, age-related macular degeneration
Recent Publications of Interest
M.G. Pilgrim, S. Marouf, S. Fearn, L. Csincsik, E. Kortvely, J.C. Knowles, G. Malek, R. B. Thompson, and I. Lengyel, “Characterisation of calcium phosphate spherical particles in the sub-retinal pigment epithelium-basal lamina space in aged human eyes,” Ophthalmology Science, 1, 100053 (2021). https://doi.org/10.1016/j.xops.2021.100053 .
Henryk Szmacinski, Kavita Hegde, Hui-Hui Zeng, Katayoun Eslami, Adam C. Puche, Imre Lengyel, Richard B. Thompson, "Imaging hydroxyapatite in sub-retinal pigment epithelial deposits by fluorescence lifetime imaging microscopy with tetracycline staining," J. Biomed. Opt. 25(4), 047001 (2020), doi: 10.1117/1.JBO.25.4.047001. PMID 32319262 PMCID: PMC7171513
Connor N. Brown, Brian D. Green, Richard B. Thompson, Anneke I. den Hollander, Imre Lengyel, and on behalf of the EYE-RISK consortium, “Metabolomics and Age-Related Macular Degeneration,” Metabolites 9, 1 (2019) ; doi:10.3390/metabo9010004 PMID: 30591665 PMCID:PMC6358913
Joanna M.P. Melia*, Ruxian Lin, Ramnik J. Xavier, Richard B. Thompson, Dax Fu, Fengyi Wan, Cynthia L. Sears, Mark Donowitz, “Induction of the metal transporter ZIP8 by interferon gamma in intestinal epithelial cells: Potential role of metal dyshomeostasis in Crohn's disease” Biochem. Biophys. Res. Commun. 515, 325-331 (2019) https://doi.org/10.1016/j.bbrc.2019.05.137 PMID 30591665
Po-Jung Pao, Eszter Emri, Safiya Bishar Abdirahman, Talha Soorma, Hui-Hui Zeng, Stefanie M. Hauck, Richard B. Thompson, Imre Lengyel, “The effects of zinc supplementation on primary human retinal pigment epithelium,” J. Trace Elements Medicine Biology, 49, 184-191 (2018), doi: 10.1016/j.jtemb.2018.02.028. Epub 2018 Mar 1. PMID: 29523386
H. Szmacinski, K. Hegde, H. H. Zeng, K. Eslami, J. R. Lakowicz, I. Lengyel, and R. B. Thompson, “Towards early detection of age-related macular degeneration using tetracyclines and FLIM,” Proc. SPIE Conf. on Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVI, Vol. 10484 (T. Vo-Dinh and W. Grundfest, Eds.), pp. 1048409-1-7 (2018).
R.B. Thompson, V. Reffatto, J.G. Bundy, E. Kortvely, J.M. Flinn, A. Lanzirotti, E. A. Jones, D.S. McPhail, S. Fearn, K. Boldt, M. Ueffing, S.G.S Ratu, L. Pauleikhoff, A.C. Bird, and I. Lengyel, “Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye, Proc. Natl. Acad. Sciences USA 112 (5) 1575-1570 (2015); doi/10.1073/pnas.1413347112. PMID: 25605911 PMCID: PMC4321314
B. J. McCranor, H. Szmacinski, H-H. Zeng, A.K. Stoddard, T.K. Hurst, C. A. Fierke, J.R. Lakowicz, and R. B. Thompson, "Fluorescence Lifetime Imaging of Physiological Free Cu(II) Levels in Live Cells with a Cu(II)-Selective Carbonic Anhydrase-Based Biosensor," Metallomics 6, 1034-1042 (2014); DOI: 10.1039/c3mt00305a; NIHMS 585083
Hui Hui Zeng, Evgenia G. Matveeva, Andrea K. Stoddard, Carol A. Fierke, and Richard B. Thompson, "Long wavelength fluorescence ratiometric zinc biosensor," Journal of Fluorescence 23(3) 375-9(2013) DOI: 10.1007/s10895-013-1161-6. NIHMS 438849
B. J. McCranor, R. A. Bozym, M. Vitolo, C. A. Fierke, L. Bambrick, B. Polster, G. Fiskum, and R. B. Thompson, "Quantitative imaging of mitochondrial and cytosolic free zinc levels in an in vitro model of ischemia/reperfusion" Journal of Bioenergetics and Biomembranes44(2) 253 - 263 (2012). DOI: 10.1007/s10863-012-9427-2 PMID 22430627NIHMS382081
D. Wang, T. K. Hurst, R. B. Thompson, and C. A. Fierke “Genetically Encoded Ratiometric Biosensors to Measure Intracellular Exchangeable Zinc in Escherichia coli”J. Biomed. Opt. 16(8) 087011/1-11 (2011) [DOI: 10.1117/1.3613926. PMID: 21895338 PMCID: PMC3166341
R. B. Thompson and C. A. Fierke, Eds. Enzymes as Sensors: Methods in Enzymology Vol. 589 New York, Academic Press 530 pp. (2017) ISBN: 9780128054062
R. B. Thompson and C. A. Fierke, “Measuring and Imaging Metal Ions with Fluorescence-Based Biosensors: Speciation, Selectivity, Kinetics, and Other Issues” in Enzymes as Sensors: Methods in Enzymology Vol. 589 (pp. 281-297) (R. B. Thompson and C. A. Fierke, eds.) New York, Academic Press (2017) ISBN:9780128054062.
R.B. Thompson and H.-H. Zeng, "Fluorescent indicators for ionic copper in biology," in Annual Reviews in Fluorescence 2015 (C. D. Geddes, ed.) New York: Springer, pp. 147-169 (2015); doi: 10.1007/978-3-319-24609_6.
W. Maret, J. A. Caruso, C. H. Contag, D. P. Giedroc, P. L. Hagedoorn, A. Matusch, E. P. Skaar, and R. B. Thompson, “Methods and technologies for studying metals in biological systems,” in Strungmann Forum Report: Trace Metals and Infectious Diseases(pp. 341-402) (J. O. Nriagu and E. P. Skaar, eds.) Cambridge, MA: MIT Press (2015), ISBN 978-0-262-02919-3
R.B. Thompson, H.H. Zeng, H. Szmacinski, and I. Lengyel, "Imaging of hydroxyapatite in retinal deposits by fluorescence lifetime imaging," US patent 11,253,614 B2 (2022)
R. B. Thompson and I. Lengyel, “Method for visualizing drusen in the eye,” U.S. Patent 9,801,955 B2 (Appl no. 14/424,904)Oct 31, 2017.
R.B. Thompson, E.G. Matveeva, C. A. Fierke, L. Bourne, G. Franke, “Bioluminescent metal Ion Assay,” U. S. Patent No. 9,193,990 B2 (Appl. No. 14/218,085) Nov 24, 2015.
R. B. Thompson, “Analyte sensor devices and holders, and methods and systems utilizing the same,” U.S. Patent No.8,038,947 B2 (Appl. No, 12/099,952) Oct. 18, 2011.
R. B. Thompson, V. Feliccia, B. P. Maliwal, M. W. Patchan, Z. Ge, D. W. Christianson, and D. Elbaum, “Determination of metal ions in solution by fluorescence anisotropy,” U. S. Patent No.7,842,491 B2 (Nov 30 2010).