Photo of Dr. Ryan Limbocker

Dr. Ryan Limbocker

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 is a passionate academic mentor. In particular, he helps cadets consider, plan, and execute applications for technical, national, and international scholarships and prepare for medical school. 

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), DEVCOM Army Research Labs grants (2020, 2021, 2022), DEVCOM Chemical Biological Center Seedling grant (2022), and 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 neurodegenerative disorders ranging from Alzheimer’s and Parkinson’s diseases to Chronic Traumatic Encephalopathy. 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 Publications

Limbocker, 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. 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.

Kreiser, 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.

Joshi, 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.

Limbocker, 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.

Perni, M., van der Goot, A., Limbocker, R. (co-first author), 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.

Heller, 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.

Aprile, 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. 

Limbocker, 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.

Limbocker, 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-b oligomers.” International Journal of Molecular Sciences. 2020, 21, 4542.

Kreiser, 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.

Ikenoue, 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.

Eslinger, 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.

Nguyen, 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.

Limbocker, 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.

Perni, 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. 

Perni, M., Flagmeier, P., Limbocker, R. (co-first author), 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.

Kaplan, 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.

Perni, 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.

Habchi, 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.

Kaplan, 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. 

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.

*Corresponding author

Abstracts & Peer-Reviewed Conference Proceedings

Limbocker, R., Kreiser, R.P., Sasser, L.R., Wright, A.K., Rinauro, D.J., Vendruscolo, M. "Modulators of the plasma membrane protect cells from diverse toxic agents, ranging from protein misfolded oligomers to pore forming agents." Biophysical Journal. 2022, 121, 3, 350a.

McKenzie, T.L., Kreiser, R.P., Rinauro, D.J., Vendruscolo, M., Limbocker, R. "Small molecule and antibody mediated inhibition of the aggregation of a tau fragment implicit in Alzheimer’s disease." Biophysical Journal. 2022, 121, 3, 189a.

Kreiser, R.P., Wright, A.K., Sasser, L.R., McKenzie, T.L., Nguyen, L.T. Limbocker, R. "Key membrane lipids can alter the resiliency of neuronal cells to protein misfolded oligomers." Biophysical Journal. 2022, 121, 3, 79a.

Sasser, L.R., Wright, A.K., Kreiser, R.P., Nguyen, L.T., Limbocker, R. "Attenuating the toxicity of protein misfolded oligomers using aminosterols." Biophysical Journal. 2022, 121, 3, 352a.

Wright, A.K., Kreiser, R.P., Sasser, L.R., Nguyen, L.T., Limbocker, R. "Protecting the cell membrane against pore-forming agents via a brain-permeable aminosterol." Biophysical Journal. 2022, 121, 3, 189a.

Limbocker, R., Wright, A.K., Kreiser, R.P., Mannini, B., Vendruscolo, M. “Therapeutics against protein misfolded oligomers in neurodegenerative diseases.” Biophysical Journal. 2021, 120, 3, 286a.

Kreiser, R.P., Wright, A.K., Nguyen, L.T., Hollows, J.E., Limbocker, R. “Cell membrane properties can mediate the toxicity of protein misfolded oligomers and folded toxins.” Biophysical Journal. 2021, 120, 3, 308a.

Wright, A.K., Kreiser, R.P., Nguyen, L.T., Hollows, J.E., Limbocker, R. “Development of molecular countermeasures to modulate the populations and toxicity of Aβ42 oligomers.” Biophysical Journal. 2021, 120, 3, 202a.

Joshi, P., Perni, M., Limbocker, R., Mannini, B., Casford, S., Chia, S., Labbadia, J., Dobson, C.M., Vendruscolo, M. "Endogenous metabolites rescue a C. elegans model of Alzheimer's disease by triggering a heat shock response." FEBS Open Bio. 2019, 9, 225.

Aprile, F.A., Sormanni, P., Perni, M., Arosio, P., Limbocker, R., Chhangur, S., Mannini, B., Linse, S., Knowles, T.P.J., Dobson, C.M., Vendruscolo, M. “Targeting amyloid formation using rationally designed antibodies.” Alzheimer’s & Dementia. May 2018, 14, 7, P611. (Oral)

Limbocker, R., Mannini, B., Chia, S., Ruggeri, F.S., Perni, M., Cascella, R., Xu, C.K., Habchi, J., Kumita, J.R., Chiti, F., Knowles, T.P.J., Vendruscolo, M., Dobson, C.M. “Modulating amyloid-beta aggregation to reduce the toxicity of its oligomeric aggregates.” Biophysical Journal. 2018, 114, 3, P430a. (Poster)

Chia, S., Habchi, J., 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 amyloid-beta42 aggregation in Alzheimer’s disease.” Biophysical Journal. 2018, 114, 3, 225a. (Poster)

Limbocker, R., Mannini, B., Perni, M., Chia, S., Heller, G.T., Ruggeri, F.S., Habchi, J., Meisl, G., Challa, P.K., Zasloff, M., Knowles, T.P.J., Vendruscolo, M., Dobson, C.M. “Attenuating the toxicity of amyloid-beta aggregation with specific species.” Biophysical Journal. 2017, 112, 3, 494a. (Oral and poster)