Dr. Ryan Limbocker Director, Center for Molecular Science Assistant Professor ryan.limbocker@westpoint.edu Biography Ryan Limbocker is an Assistant Professor of Chemistry in the Department of Chemistry and Life Science. Dr. Limbocker graduated with a B.S. in Chemistry from the University of Kansas with Highest Distinction, University Honors, and Departmental Honors. He attended graduate school at the University of Cambridge in the Centre for Misfolding Diseases and conducted a postdoctoral fellowship at Columbia University. Alongside teaching and researching Alzheimer’s disease, Parkinson’s disease, traumatic brain injuries, biological threat agents, and chemical threat agents, Dr. Limbocker serves as the Director for the Center for Molecular Science, is an OR for the Army Women’s Tennis team, and is the CLS Scholarships Representative. He enjoys helping all cadets consider, plan, and execute applications for technical, national, and international scholarships and prepare for medical school. Limbocker lab cadets have earned the Goldwater Scholarship (Ryan Kreiser, 2021; Aidan Wright, 2022; Justus Gabriel, 2023), NSF Graduate Research Fellowship (Ryan Kreiser, 2022), Stamps Scholarship (Ryan Kreiser, 2020; Aidan Wright, 2020; Tristan McKenzie, 2021; Sophie Cohen, 2021; Justus Gabriel, 2022; Michael Nguyen, 2023; Supria Shroff, 2023; Johnathan Pinc, 2023), matriculation to Medical School (Alex Albright, Brown, 2020; Aidan Wright, Dartmouth, 2023; Liam Sasser, Cornell, 2023; Abigail Graham, Columbia, 2023; Caleb Buettner, Johns Hopkins, 2024; Sophie Cohen, Medical College of Wisconsin, 2024; Justus Gabriel, Yale, 2024; Tristan McKenzie, Uniformed Services University, 2024; Martin Park, Oregon Health Sciences University, 2024), and matriculation to graduate school (Ryan Kreiser, Purdue, 2022; Thomas Tan, Purdue, 2024).Dr. Limbocker is the recipient of the following: Goldwater Scholarship (2014), NSF Graduate Research Fellowship (2015), St. John’s College Cambridge Benefactors’ Scholarship (2015-2018), Gates Cambridge Scholarship (2015-2018), Department of the Army Civilian Service Achievement Medal for teaching (2020), USMA Faculty Development Research Fund grant (2020), Defense Threat Reduction Agency SARI grants (2020, 2021, 2022, 2023), DEVCOM Army Research Labs grants (2020, 2021, 2022, 2023), Dean’s Award for Scholarship Excellence (2022). Ongoing Research Projects The Limbocker research group focuses on understanding the etiology of protein misfolding diseases with emphasis on the pathological consequences of protein aggregation. By integrating in vitro biophysical methods with cellular models of toxicity, we aim to understand and target the principles that drive toxicity in Alzheimer's and similar neurodegenerative disorders. Our team also actively investigates the efficacy of medical countermeasures to protect Soldiers from traumatic brain injuries, biological threat agents, and chemical threat agents. Publications & Presentations Peer-Reviewed PublicationsBigi, A., Limbocker, R., Cecchi, C. Editorial: Promising therapeutic strategies for Alzheimer's disease: A focus on amyloid-β targeting. Frontiers in Neuroscience. 2024, 18:1415641, 1-2, DOI: 10.3389/fnins.2024.1415641Chia, S., Cataldi, R.L., Ruggeri, F.S., Limbocker, R., Condado-Morales, I., Pisani, K., Possenti, A., Linse, S., Knowles, T.P.J., Habchi, J., Mannini, B., Vendruscolo, M. A relationship between structure and neurotoxic effect of Aβ oligomers stabilized by metal ions. ACS Chemical Neuroscience. 2024, 15, 6, 1125-1134, DOI: 10.1021/acschemneuro.3c00718Rinauro, D.J., Chiti, F., Vendruscolo, M., Limbocker, R.* Misfolded protein oligomers: Mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases. Molecular Neurodegeneration. 2024, 19, 20, 1-32, DOI: 10.1186/s13024-023-00651-2Limbocker, R., Cremades, N., Cascella, R., Tessier, P., Vendruscolo, M., Chiti, F. Pairs of toxic and nontoxic misfolded protein oligomers elucidate the structural determinants of toxicity in protein misfolding diseases. Accounts of Chemical Research. 2023, 56, 12, 1395-1405, DOI: 10.1021/acs.accounts.3c00045. Featured on the journal cover.Gabriel, J.M.†, Tan, T.†, Rinauro, D.J., Hsu, C.M.†, Buettner, C.J.†, Gilmer, M.†, Kaur, A.†, McKenzie, T.L.†, Park, M.†, Cohen, S.†, Errico, S., Chiti, F., Vendruscolo, M., Limbocker, R.* EGCG inactivates a pore-forming toxin by promoting its oligomerization and decreasing its solvent-exposed hydrophobicity. Chemico-Biological Interactions. 2023, 371, 110307, 1-10, DOI: 10.1016/j.cbi.2022.110307Joshi, P., Chia, S., Yang, X., Perni, M., Gabriel, J.M.†, Gilmer, M.†, Limbocker, R., Habchi, J., Vendruscolo, M. Vitamin A and E metabolites comodulate amyloid-β aggregation. ACS Chemical Neuroscience. 2023, 14, 4, 657-666, DOI: 10.1021/acschemneuro.2c00523Errico, S., Lucchesi, G., Odino, D., Osman, E.Y., Casecella, R., Neri, L., Bemporad, F., Cecchi, C., Barbut, D., Relini, A., Canale, C., Caminati, C., Limbocker, R., Vendruscolo, M., Zasloff, M., Chiti, F. A global fitting analytical approach to attribute quantitatively the protective biological effect of aminosterols to their chemical moieties and physicochemical perturbations of biological membranes. Journal of Medicinal Chemistry. 2023, 66, 14, 9519-9536, DOI: 10.1021/acs.jmedchem.3c00182Limbocker, R., Errico, S., Knowles, T.P.J., Vendruscolo, M., Barbut, D., Chiti, F., Zasloff, M. Squalamine and trodusquemine, two natural products for neurodegenerative diseases: From physical chemistry to the clinic. Natural Product Reports. 2022, 39, 742-753, DOI: 10.1039/D1NP00042J. Featured on the journal cover.Kreiser, R.P.†, Wright, A.K.†, Sasser, L.R.†, Rinauro, D.J., Gabriel, J.M.†, Hsu, C.M.†, Hurtado, J.A.†, McKenzie, T.†, Albright, J.A., Richardson, L., Jaffett, V.A., Riegner, D.E., LeForte, K., Nguyen, L.T., Hollows, J.E., Vendruscolo, M., Limbocker, R.* A brain permeable aminosterol regulates cell membranes to mitigate the toxicity of diverse pore-forming agents. ACS Chemical Neuroscience. 2022, 13, 8, 1219-1231, DOI: 10.1021/acschemneuro.1c00840Kreiser, R.P.†, Wright, A.K.†, McKenzie, T.L.†, Albright, J.A.†, Mowles, E.D., Hollows, J.E., Limbocker, S., Eslinger, M., Limbocker, R.*, Nguyen, L.T. Utilization of standardized college entrance metrics to predict and promote undergraduate student success in chemistry. Journal of Chemical Education. 2022, 99, 4, 1725-1733, DOI: 10.1021/acs.jchemed.1c00719Joshi, P., Perni, M., Limbocker, R., Mannini, B., Casford, S., Chia, S., Habchi, J., Labbadia, J., Dobson, C.M., Vendruscolo, M. Two human metabolites rescue a C. elegans model of Alzheimer's disease via a cytosolic unfolded protein response. Communications Biology. 2021, 4, 843, 1-14, DOI: 10.1038/s42003-021-02218-7Limbocker, R.*, Staats, R., Chia, S., Ruggeri, F.S., Mannini, B., Xu, C.K., Perni, M., Cascella, R., Bigi, A., Sasser, L.R.†, Block, N.R.†, Wright, A.K.†, Kreiser, R.P.†, Custy, E.T.†, Meisl, G., Errico, S., Habchi, J., Flagmeier, P., Kartanas, T., Hollows, J.E., Nguyen, L.T., LeForte, K., Barbut, D., Kumita, J.R., Cecchi, C., Zasloff, M., Knowles, T.P.J., Dobson, C.M., Chiti, F., Vendruscolo, M. Squalamine and its derivatives modulate the aggregation of amyloid-β and α-synuclein and suppress the toxicity of their oligomers. Frontiers in Neuroscience. 2021, 15, 680026, 1-17, DOI: 10.3389/fnins.2021.680026Perni, M.‡, van der Goot, A.‡, Limbocker, R.‡, van Ham, T., Aprile, F.A., Xu, C.K., Flagmeier, P., Thijssen, K., Sormanni, P., Fusco, G., Chen, S.W., Challa, P.K., Kirekegaard, J.B., Laine, R.F., Ma, K.Y., Muller, M.B.D., Sinnige, T., Kumita, J.R., Cohem, S.I.A., Seinstra, R., Kaminski, G.S., Kaminski, C.F., Barbut, D., De Simone, A., Knowles, T.P.J., Zasloff, M., Nollen, E.A.A., Vendruscolo, M., Dobson, C.M. Comparative studies in the A30P and A53T α-synuclein C. elegans strains to investigate the molecular origins of Parkinson's disease. Frontiers in Cellular and Developmental Biology. 2021, 9, 552549, 1-10, DOI: 10.3389/fcell.2021.552549Heller, G.T., Aprile, F.A., Michaels, T.C.T., Limbocker, R., Perni, M., Ruggeri, F.S., Mannini, B., Lohr, T., Bonomi, M., De Simone, A., Felli, I., Pierattelli, R., Knowles, T.P.J., Dobson, C.M. Vendruscolo, M. Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer’s disease. Science Advances. 2020, 6, 45, eaab5924, 1-15, DOI: 10.1126/sciadv.abb5924Aprile, F.A., Sormanni, P., Podpolny, M., Chhangur, C., Needham, L.-M., Ruggeri, F.S., Perni, M., Limbocker, R., Heller, G.T., Sneideris, T., Scheidt, T., Mannini, B., Habchi, J. Lee, S.F., Salinas, P.C., Knowles, T.P.K., Dobson, C.M., Vendruscolo, M. Rational design of a conformation-specific antibody for the quantification of Aβ oligomers. Proceedings of the National Academy of Sciences U.S.A. 2020, 117, 13509-13518, DOI: 10.1073/pnas.191946411Limbocker, R.‡, Mannini, B.‡, Ruggeri, F.S., Cascella, R., Xu, C.K., Perni, M., Chia, S., Chen, S., Habchi, J., Bigi, A., Kreiser, R.P.†, Wright, A.K.†, Albright, J.A.†, Kartanas, T., Kumita, J.R., Cremades, N., Zasloff, M., Cecchi, C., Knowles, T.P.J., Chiti, F., Vendruscolo, M., Dobson, C.M. Trodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism. Communications Biology. 2020, 3, 435, 1-10, DOI: 10.1038/s42003-020-01140-8Limbocker, R.*, Mannini, B., Cataldi, R., Chhangur, S., Wright, A.K.†, Kreiser, R.P.†, Albright, J.A.†, Chia, S., Habchi, J., Sormanni, P., Kumita, J.R., Ruggeri, F.S., Dobson, C.M., Chiti, F., Aprile, F.A., Vendruscolo, M. Rationally designed antibodies as research tools to study the structure–toxicity relationship of amyloid-β oligomers. International Journal of Molecular Sciences. 2020, 21, 4542, 1-19, DOI: 10.3390/ijms21124542Kreiser, R.P.†, Wright, A.K.†, Block, N.R.†, Hollows, J.E., Nguyen, L.T., LeForte, K., Mannini, B., Vendruscolo, M., Limbocker, R.* Therapeutic strategies to reduce the toxicity of misfolded protein oligomers. International Journal of Molecular Sciences. 2020, 21, 8651, 1-33, DOI: 10.3390/ijms21228651Ikenoue, T., Aprile, F.A., Sormanni, P., Ruggeri, F.S., Perni, M., Heller, G.T., Haas, C., Middel, C., Limbocker, R., Mannini, B., Michaels, T.C.T., Knowles, T.P.J., Dobson, C.M., Vendruscolo, M. A rationally designed bicyclic peptide remodels Aβ42 aggregation in vitro and reduces its toxicity in a worm model of Alzheimer’s disease. Scientific Reports. 2020, 10, 15280, 1-15, DOI: 10.1038/s41598-020-69626-3Eslinger, M., Washington, M., Pekny, C., Nepa, N., Wickiser, J., Limbocker, R., Shanks, D. Non-Pharmaceutical Interventions and Military Hygiene at the United States Military Academy between 1890 and 1910. Military Medicine. 2020, usaa226, 1-6, DOI: 10.1093/milmed/usaa226Nguyen, C.K., DeNeve, D.R., Nguyen, L.T., Limbocker, R. Impact of COVID-19 on general chemistry education at the United States Military Academy. Journal of Chemical Education. 2020, 9, 2922-2927, DOI: 10.1021/acs.jchemed.0c00771Limbocker, R., Chia, S., Ruggeri, F.S., Perni, M., Cascella, R., Heller, G.T., Meisl, G., Mannini, B., Habchi, J., Michaels, T.C.T., Challa, P.K., Ahn, M., Casford, S.T., Fernando, N., Xu, C.K., Kloss, N.D., Cohen, S.I.A., Kumita, J.R., Cecchi, C., Zasloff, M., Linse, S., Knowles, T.P.J., Chiti, F., Vendruscolo, M., Dobson, C.M. Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes. Nature Communications. 2019, 10, 225, 1-13, DOI: 10.1038/s41467-018-07699-5Perni, M., Challa, P.K., Kirkegaard, J.B., Limbocker, R., Koopman, M., Hardenberg, M.C., Sormanni, P., Muller, T., Saar, K.T., Roode, L.W.Y., Habchi, J., Vecchi, G., Fernando, N., Casford, C., Nollen, E.A.A., Vendruscolo, M., Dobson, C.M., Knowles, T.P.J. Massively parallel C. elegans tracking provides multi-dimensional fingerprints for phenotypic discovery. Journal of Neuroscience Methods. 2018, 306, 57-69, DOI: 10.1016/j.jneumeth.2018.02.005Perni, M.‡, Flagmeier, P.‡, Limbocker, R.‡, Cascella, R., Aprile, F.A., Galvagnion, C., Heller, G.T., Meisl, G., Chen, S.W., Kumita, J.R., Challa, P.K., Kirkegaard, J.B., Cohen, S.I.A., Mannini, B., Barbut, D., Nollen, E.A.A., Cecchi, C., Cremades, N., Knowles, T.P.J., Chiti, F., Zasloff, M., Vendruscolo, M., Dobson, C.M. Multistep inhibition of a-synuclein aggregation and toxicity in vitro and in vivo by trodusquemine. ACS Chemical Biology. 2018, 13, 2308-2319, DOI: 10.1021/acschembio.8b00466Kaplan, S.V., Limbocker, R.†, Levant, B., Johnson, M.A. Regional differences in dopamine release in the R6/2 mouse Caudate Putamen. Electroanalysis. 2018, 30, 1066–1072, DOI: 10.1002/elan.201700827Perni, M., Galvagnion, C., Maltsev, A., Meisl, G., Muller, M.B.D., Challa, P.K., Kirkegaard, J.B., Flagmeier, P., Cohen, S.I.A., Cascella, R., Chen, S.W., Limbocker, R., Sormanni, P., Heller, G.T., Aprile, F.A., Cremades, N., Cecchi, C., Chiti, F., Nollen, E.A.A., Knowles, T.P.J., Vendruscolo, M., Bax, A., Zasloff, M., Dobson, C.M. A natural product inhibits the initiation of a-synuclein aggregation and suppresses its toxicity. Proceedings of the National Academy of Sciences U.S.A. 2017, 114, E1009–E1017, DOI: 10.1073/pnas.161058611Habchi, J., Chia, S., Limbocker, R., Mannini, B., Ahn, M., Perni, M., Hansson, O., Arosio, P., Kumita, J.R., Challa, P.K., Cohen, S.I.A., Linse, S., Dobson, C.M., Knowles, T.P.J., Vendruscolo, M. Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer’s disease. Proceedings of the National Academy of Sciences U.S.A. 2017, 114, E200–E208, DOI: 10.1073/pnas.1615613114Kaplan, S.V., Limbocker, R.†, Gehringer, R.C., Divis, J.L., Osterhaus, G.L., Newby, M.D., Sofis, M.J., Jarmolowicz, D.P., Newman, B.D., Matthews, T.A., Johnson, M.A. Impaired brain dopamine and serotonin release and uptake in Wistar rats following treatment with Carboplatin. ACS Chemical Neuroscience. 2016, 7, 689-699, DOI: 10.1021/acschemneuro.5b00029 Sun, M., Kaplan, S.V., Gehringer, R.C., Limbocker, R.†, Johnson, M.A. Localized drug application and sub-second voltammetric dopamine release measurements in a brain slice perfusion device. Analytical Chemistry. 2014, 86, 4151–4156, DOI: 10.1021/ac5008927Sun, M., Kaplan, S.V., Gehringer, R.C., Limbocker, R.†, Johnson, M.A. Localized drug application and sub-second voltammetric dopamine release measurements in a brain slice perfusion device. Analytical Chemistry. 2014, 86, 4151–4156, DOI: 10.1021/ac5008927 *Corresponding author, ‡Co-First Author, †Undergraduate Student