Ricardo Capone, Dr., Ph.D.

Research Instructor

ricardo.f.capone@vanderbilt.edu
Faculty Appointments
Research Instructor in Biochemistry
Education
Ph.D., Biological Chemistry, Hebrew University of Jerusalem, Jerusalem, IsraelB.A., Biology and Molecular Genetics, State University of Milan, Milan, ItalyM.S., Biology and Molecular Genetics, State University of Milan, Milan, Italy
Research Description
I am a biological chemist with expertise in biophysics and cell biology, currently an Instructor of Biochemistry at Vanderbilt University. I earned my PhD from Hebrew University of Jerusalem and completed postdoctoral fellowships there and at the University of Michigan. Before Vanderbilt, I worked at the University of Chicago and UC San Diego. I joined the Vanderbilt faculty in 2017.

My research at Vanderbilt has focused on confocal microscopy and biophysical aspects of membrane proteins.

First, I studied the plasma membrane localization of C99, a fragment derived from the amyloid precursor protein (APP), using the giant plasma membrane vesicles (GPMVs) model. Unexpectedly, we found that C99 localizes to the liquid-disordered (Ld) phase. During this work, we developed improved methods for the production and automated imaging of GPMVs, which we subsequently used to screen for compounds that affect lipid or protein localization or properties in the GPMV model. This work was eventually patented.

In a second line of research, we investigated the use of amphipol polymers to deliver membrane proteins to the cell surface without the use of detergents. A potential application of this membrane protein delivery system is being explored in collaboration with researchers at Arizona State University (ASU). Other possible applications remain to be fully explored.

Since 2019, a purely basic science project—pursued as time permitted—has focused on the generation and study of a new type of nanoparticle (NP) composed of single-pass membrane proteins, nearly devoid of detergents or lipids. We call these particles DLPs, for Detergent-Limited Particles. DLPs made from C99 display unique biophysical and cellular properties as nanoparticles.

In the past 1–2 years, my work has focused on Peripheral Myelin Protein 22 (PMP22), which is implicated in the majority of Charcot-Marie-Tooth disease cases. PMP22 expression levels and surface trafficking are tightly regulated in cells and cell culture models. Rat Schwann cells expressing tunable levels of PMP22 form intracellular puncta of unclear significance. I am pleased to report that I have made progress in identifying some of the cellular markers involved and have begun to elucidate the complex degradation pathway of these PMP22 puncta.

Research Keywords
membrane protein, biophysics, cell biology, microscopy, nanoparticles, amphipol, GMPVs
Publications
Fricke N, Raghunathan K, Tiwari A, Stefanski KM, Balakrishnan M, Waterson AG, Capone R, Huang H, Sanders CR, Bauer JA, Kenworthy AK. High-Content Imaging Platform to Discover Chemical Modulators of Plasma Membrane Rafts. ACS Cent Sci [print-electronic]. 2022 Mar 3/23/2022; 8(3): 370-8. PMID: 35355811, PMCID: PMC8961798, DOI: 10.1021/acscentsci.1c01058, ISSN: 2374-7943.

Hutchison JM, Capone R, Luu DD, Shah KH, Hadziselimovic A, Van Horn WD, Sanders CR. Recombinant SARS-CoV-2 envelope protein traffics to the trans-Golgi network following amphipol-mediated delivery into human cells. J Biol Chem [print-electronic]. 2021 Aug; 297(2): 100940. PMID: 34237302, PMCID: PMC8256659, PII: S0021-9258(21)00740-7, DOI: 10.1016/j.jbc.2021.100940, ISSN: 1083-351X.

Hutchison JM, Capone R, Luu DD, Hadziselimovic A, Van Horn WD, Sanders CR. Delivery of recombinant SARS-CoV-2 envelope protein into human cells. BioRxiv. 2021 Feb 2/19/2021; PMID: 33619482, PMCID: PMC7899446, PII: 2021.02.18.431684, DOI: 10.1101/2021.02.18.431684, ISSN: 2692-8205.

Capone R, Tiwari A, Hadziselimovic A, Peskova Y, Hutchison JM, Sanders CR, Kenworthy AK. The C99 domain of the amyloid precursor protein resides in the disordered membrane phase. J Biol Chem [print-electronic]. 2021; 296: 100652. PMID: 33839158, PMCID: PMC8113881, PII: S0021-9258(21)00438-5, DOI: 10.1016/j.jbc.2021.100652, ISSN: 1083-351X.

De Maio A, Cauvi DM, Capone R, Bello I, Egberts WV, Arispe N, Boelens W. The small heat shock proteins, HSPB1 and HSPB5, interact differently with lipid membranes. Cell Stress Chaperones [print-electronic]. 2019 Sep; 24(5): 947-56. PMID: 31338686, PMCID: PMC6717221, PII: 10.1007/s12192-019-01021-y, DOI: 10.1007/s12192-019-01021-y, ISSN: 1466-1268.

Rivera I, Capone R, Cauvi DM, Arispe N, De Maio A. Modulation of Alzheimer's amyloid ß peptide oligomerization and toxicity by extracellular Hsp70. Cell Stress Chaperones [print-electronic]. 2017 Sep 9/27/2017; PMID: 28956268, PII: 10.1007/s12192-017-0839-0, DOI: 10.1007/s12192-017-0839-0, ISSN: 1466-1268.

Gillman AL, Lee J, Ramachandran S, Capone R, Gonzalez T, Wrasidlo W, Masliah E, Lal R. Small molecule NPT-440-1 inhibits ionic flux through Aß1-42 pores: Implications for Alzheimer's disease therapeutics. Nanomedicine [print-electronic]. 2016 Nov; 12(8): 2331-40. PMID: 27335341, PMCID: PMC5116404, PII: S1549-9634(16)30069-7, DOI: 10.1016/j.nano.2016.06.001, ISSN: 1549-9642.

Kagan BL, Jang H, Capone R, Teran Arce F, Ramachandran S, Lal R, Nussinov R. Antimicrobial properties of amyloid peptides. Mol. Pharm [print-electronic]. 2012 Apr 4/2/2012; 9(4): 708-17. PMID: 22081976, PMCID: PMC3297685, DOI: 10.1021/mp200419b, ISSN: 1543-8392.

Capone R, Jang H, Kotler SA, Connelly L, Teran Arce F, Ramachandran S, Kagan BL, Nussinov R, Lal R. All-d-Enantiomer of ß-Amyloid Peptide Forms Ion Channels in Lipid Bilayers. J Chem Theory Comput [print-electronic]. 2012 Mar 3/13/2012; 8(3): 1143-52. PMID: 22423218, PMCID: PMC3302213, DOI: 10.1021/ct200885r, ISSN: 1549-9626.

Allen MJ, Lacroix JJ, Ramachandran S, Capone R, Whitlock JL, Ghadge GD, Arnsdorf MF, Roos RP, Lal R. Mutant SOD1 forms ion channel: implications for ALS pathophysiology. Neurobiol. Dis [print-electronic]. 2012 Mar; 45(3): 831-8. PMID: 21930207, PMCID: PMC3384721, PII: S0969-9961(11)00297-X, DOI: 10.1016/j.nbd.2011.08.031, ISSN: 1095-953X.

Connelly L, Jang H, Arce FT, Capone R, Kotler SA, Ramachandran S, Kagan BL, Nussinov R, Lal R. Atomic force microscopy and MD simulations reveal pore-like structures of all-D-enantiomer of Alzheimer's ß-amyloid peptide: relevance to the ion channel mechanism of AD pathology. J Phys Chem B [print-electronic]. 2012 Feb 2/9/2012; 116(5): 1728-35. PMID: 22217000, PMCID: PMC4342054, DOI: 10.1021/jp2108126, ISSN: 1520-5207.

Capone R, Jang H, Kotler SA, Kagan BL, Nussinov R, Lal R. Probing structural features of Alzheimer's amyloid-ß pores in bilayers using site-specific amino acid substitutions. Biochemistry [print-electronic]. 2012 Jan 1/24/2012; 51(3): 776-85. PMID: 22242635, PMCID: PMC3265145, DOI: 10.1021/bi2017427, ISSN: 1520-4995.

Jang H, Arce FT, Mustata M, Ramachandran S, Capone R, Nussinov R, Lal R. Antimicrobial protegrin-1 forms amyloid-like fibrils with rapid kinetics suggesting a functional link. Biophys. J. 2011 Apr 4/6/2011; 100(7): 1775-83. PMID: 21463591, PMCID: PMC3072611, PII: S0006-3495(11)00242-6, DOI: 10.1016/j.bpj.2011.01.072, ISSN: 1542-0086.

Jang H, Arce FT, Ramachandran S, Capone R, Lal R, Nussinov R. ß-Barrel topology of Alzheimer's ß-amyloid ion channels. J. Mol. Biol [print-electronic]. 2010 Dec 12/17/2010; 404(5): 917-34. PMID: 20970427, PII: S0022-2836(10)01133-2, DOI: 10.1016/j.jmb.2010.10.025, ISSN: 1089-8638.

Jang H, Teran Arce F, Ramachandran S, Capone R, Lal R, Nussinov R. Structural convergence among diverse, toxic beta-sheet ion channels. J Phys Chem B. 2010 Jul 7/29/2010; 114(29): 9445-51. PMID: 20608696, PMCID: PMC2908347, DOI: 10.1021/jp104073k, ISSN: 1520-5207.

Godovikova V, Wang HT, Goetting-Minesky MP, Ning Y, Capone RF, Slater CK, Fenno JC. Treponema denticola PrcB is required for expression and activity of the PrcA-PrtP (dentilisin) complex. J. Bacteriol [print-electronic]. 2010 Jul; 192(13): 3337-44. PMID: 20435733, PMCID: PMC2897659, PII: JB.00274-10, DOI: 10.1128/JB.00274-10, ISSN: 1098-5530.

Capone R, Mustata M, Jang H, Arce FT, Nussinov R, Lal R. Antimicrobial protegrin-1 forms ion channels: molecular dynamic simulation, atomic force microscopy, and electrical conductance studies. Biophys. J. 2010 Jun 6/2/2010; 98(11): 2644-52. PMID: 20513409, PMCID: PMC2877344, PII: S0006-3495(10)00275-4, DOI: 10.1016/j.bpj.2010.02.024, ISSN: 1542-0086.

Jang H, Arce FT, Ramachandran S, Capone R, Azimova R, Kagan BL, Nussinov R, Lal R. Truncated beta-amyloid peptide channels provide an alternative mechanism for Alzheimer's Disease and Down syndrome. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Apr 4/6/2010; 107(14): 6538-43. PMID: 20308552, PMCID: PMC2851998, PII: 0914251107, DOI: 10.1073/pnas.0914251107, ISSN: 1091-6490.

Jang H, Arce FT, Capone R, Ramachandran S, Lal R, Nussinov R. Misfolded amyloid ion channels present mobile beta-sheet subunits in contrast to conventional ion channels. Biophys. J. 2009 Dec 12/2/2009; 97(11): 3029-37. PMID: 19948133, PMCID: PMC2784570, PII: S0006-3495(09)01460-X, DOI: 10.1016/j.bpj.2009.09.014, ISSN: 1542-0086.

Macrae MX, Blake S, Jiang X, Capone R, Estes DJ, Mayer M, Yang J. A semi-synthetic ion channel platform for detection of phosphatase and protease activity. ACS Nano. 2009 Nov 11/24/2009; 3(11): 3567-80. PMID: 19860382, PMCID: PMC2805247, DOI: 10.1021/nn901231h, ISSN: 1936-086X.

Mustata M, Capone R, Jang H, Arce FT, Ramachandran S, Lal R, Nussinov R. K3 fragment of amyloidogenic beta(2)-microglobulin forms ion channels: implication for dialysis related amyloidosis. J. Am. Chem. Soc. 2009 Oct 10/21/2009; 131(41): 14938-45. PMID: 19824733, PMCID: PMC2782653, DOI: 10.1021/ja9049299, ISSN: 1520-5126.

Capone R, Quiroz FG, Prangkio P, Saluja I, Sauer AM, Bautista MR, Turner RS, Yang J, Mayer M. Amyloid-beta-induced ion flux in artificial lipid bilayers and neuronal cells: resolving a controversy. Neurotox Res [print-electronic]. 2009 Jul; 16(1): 1-13. PMID: 19526294, PMCID: PMC2864106, DOI: 10.1007/s12640-009-9033-1, ISSN: 1476-3524.

Horger KS, Estes DJ, Capone R, Mayer M. Films of agarose enable rapid formation of giant liposomes in solutions of physiologic ionic strength. J. Am. Chem. Soc. 2009 Feb 2/11/2009; 131(5): 1810-9. PMID: 19154115, PMCID: PMC2757642, PII: 10.1021/ja805625u, DOI: 10.1021/ja805625u, ISSN: 1520-5126.

Blake S, Capone R, Mayer M, Yang J. Chemically reactive derivatives of gramicidin A for developing ion channel-based nanoprobes. Bioconjug. Chem [print-electronic]. 2008 Aug; 19(8): 1614-24. PMID: 18630940, DOI: 10.1021/bc800180z, ISSN: 1520-4812.

Capone R, Wang HT, Ning Y, Sweier DG, Lopatin DE, Fenno JC. Human serum antibodies recognize Treponema denticola Msp and PrtP protease complex proteins. Oral Microbiol. Immunol. 2008 Apr; 23(2): 165-9. PMID: 18279185, PII: OMI404, DOI: 10.1111/j.1399-302X.2007.00404.x, ISSN: 0902-0055.

Capone R, Blake S, Restrepo MR, Yang J, Mayer M. Designing nanosensors based on charged derivatives of gramicidin A. J Am Chem Soc [print-electronic]. 2007 Aug 8/8/2007; 129(31): 9737-45. PMID: 17625848, DOI: 10.1021/ja0711819, ISSN: 0002-7863.

Capone RF, Ning Y, Pakulis N, Alhazzazi T, Fenno JC. Characterization of Treponema denticola pyrF encoding orotidine-5'-monophosphate decarboxylase. FEMS Microbiol. Lett [print-electronic]. 2007 Mar; 268(2): 261-7. PMID: 17187656, PII: FML589, DOI: 10.1111/j.1574-6968.2006.00589.x, ISSN: 0378-1097.

Askari N, Diskin R, Avitzour M, Capone R, Livnah O, Engelberg D. Hyperactive variants of p38alpha induce, whereas hyperactive variants of p38gamma suppress, activating protein 1-mediated transcription. J. Biol. Chem [print-electronic]. 2007 Jan 1/5/2007; 282(1): 91-9. PMID: 17088247, PII: M608012200, DOI: 10.1074/jbc.M608012200, ISSN: 0021-9258.

Diskin R, Askari N, Capone R, Engelberg D, Livnah O. Active mutants of the human p38alpha mitogen-activated protein kinase. J. Biol. Chem [print-electronic]. 2004 Nov 11/5/2004; 279(45): 47040-9. PMID: 15284239, PII: M404595200, DOI: 10.1074/jbc.M404595200, ISSN: 0021-9258.

Capone R, Tiwari BS, Levine A. Rapid transmission of oxidative and nitrosative stress signals from roots to shoots in Arabidopsis. Plant Physiol. Biochem. 2004 May; 42(5): 425-8. PMID: 15191746, PII: S0981-9428(04)00042-7, DOI: 10.1016/j.plaphy.2004.03.005, ISSN: 0981-9428.

Bell M, Capone R, Pashtan I, Levitzki A, Engelberg D. Isolation of hyperactive mutants of the MAPK p38/Hog1 that are independent of MAPK kinase activation. J. Biol. Chem [print-electronic]. 2001 Jul 7/6/2001; 276(27): 25351-8. PMID: 11309396, PII: M101818200, DOI: 10.1074/jbc.M101818200, ISSN: 0021-9258.

Pozzi C, Faccioli P, Terzi V, Stanca AM, Cerioli S, Castiglioni P, Fink R, Capone R, Müller KJ, Bossinger G, Rohde W, Salamini F. Genetics of mutations affecting the development of a barley floral bract. Genetics. 2000 Mar; 154(3): 1335-46. PMID: 10757774, PMCID: PMC1460976, ISSN: 0016-6731.

Kleinberger-Doron N, Shelah N, Capone R, Gazit A, Levitzki A. Inhibition of Cdk2 activation by selected tyrphostins causes cell cycle arrest at late G1 and S phase. Exp. Cell Res. 1998 Jun 6/15/1998; 241(2): 340-51. PMID: 9637776, PII: S0014-4827(98)94061-7, DOI: 10.1006/excr.1998.4061, ISSN: 0014-4827.

Foiani M, Nadjar-Boger E, Capone R, Sagee S, Hashimshoni T, Kassir Y. A meiosis-specific protein kinase, Ime2, is required for the correct timing of DNA replication and for spore formation in yeast meiosis. Mol. Gen. Genet. 1996 Dec 12/13/1996; 253(3): 278-88. PMID: 9003314, ISSN: 0026-8925.