Profiles

Kelly Langert, PhD

Research Interests

Research in the Langert laboratory lies at the intersection of pharmacology, neuroscience, and bioengineering, and embodies their long-term goal of advancing treatment options for inflammatory neuropathies. Specific areas of interests can be broken down into three primary research areas:

Advancing targeted drug delivery to the inflamed peripheral nerve. To accomplish this, the laboratory is utilizing biodegradable polymeric nanoparticles that can deliver different therapeutic compounds. Through chemical modifications of the particle surface or physical methods of extrusion, the nanoparticles can be coated with leukocyte plasma membranes or other targeting moieties, facilitating targeted delivery to the inflamed vascular wall.

Identifying novel therapeutic targets at the blood-nerve barrier and the leukocyte-endothelial interface. We have demonstrated that inhibition of monomeric GTPase signaling at the blood-nerve barrier attenuates endothelial release of chemotactic cytokines and subsequent leukocyte recruitment. Monomeric GTPases cycle between GDP-bound inactive and GTP-bound active states with the assistance of a host of other GAP and GEF proteins. Current studies are exploring the therapeutic potential of different targets within the GTPase signaling cascade, including specific GAPs and GEFs, as aberrant GTPase signaling has been implicated in several inflammatory disorders.

• Elucidating the physiological and pathophysiological roles of monomeric GTPases in endothelial cells. Earlier work from the Langert laboratory revealed a previously unknown role of Cdc42 and RalA GTPases in promoting the intracellular trafficking and release of the chemokine CCL2. This is surprising, but not without reason, as Rab GTPases are involved in vesicle trafficking and docking at the synapse. Ongoing research is further investigating this phenomenon in the context of leukocyte recruitment and autoimmune disease to advance our understanding of this neglected area of research.

Selected Publications

• Feipeng Yang, Maleen Cabe, Hope A. Nowak and Langert K.A. (2022) Chitosan/poly(lactic-co-glycolic)acid Nanoparticle Formulations with Finely-Tuned Size Distributions for Enhanced Mucoadhesion MDPI Pharmaceutics 2022, 14, 95
• Feipeng Yang, Maleen Cabe, Sean D. Ogle, Veronica Sanchez and Langert K.A. (2021) Optimization of critical parameters for coating of polymeric nanoparticles with plasma membrane vesicles by sonication Scientific Reports, 23996.
• Langert K.A. and Brey E.M. (2018) Strategies for targeted delivery to the peripheral nerve Frontiers in Neuroscience, 12: 887. PMID 30542262.
• Somo S.I., Langert K., Yang C.Y., Vaicik M.K., Ibarra V., Appel A.A., Akar B., Cheng M.H., and Brey E.M. (2018) Synthesis and evaluation of dual crosslinked alginate microbeads Acta Biomaterialia, 65: 53-65. PMID 29101016.
• Langert K.A, Goshu B. and Stubbs Jr. E.B. (2017).  Locally administered lovastatin-encapsulating nanoparticles protect against experimental autoimmune neuritis  Journal of Neurochemistry, 140:  334-346. PMID 27861905.
• Pervan C.L., Lautz J.D., Blitzer A.L., Langert K.A., and Stubbs Jr. E.B. (2015) Rho GTPase signaling promotes constitutive expression and release of TGF-β2 by human trabecular meshwork cells  Experimental Eye Research, 146, 95-102. PMID: 26743044.
• Calik M.W., Shankarappa, S.A., Langert K.A., Stubbs Jr. E.B. (2015). Forced-Exercise Preconditioning Attenuates Experimental Autoimmune Neuritis by Altering Th1 Lymphocyte Composition and Egress ASN Neuro, 7(4)e00104. PMID: 26186926.
• Langert K.A, Pervan C.L. and Stubbs Jr. E.B. (2014).  Novel Role for Cdc42 and RalA GTPases in TNF-α mediated secretion of CCL2  Small GTPases, 5, pii:e29260. PMID: 24911990.
• Langert K.A, Von Zee C.L. and Stubbs Jr. E.B. (2013).  Cdc42 GTPases facilitate TNF-α mediated secretion of CCL2 from peripheral nerve microvascular endothelial cells  Journal of the Peripheral Nervous System,18(3), 199-208. PMID: 24028188.
• Langert K.A, Von Zee C.L. and Stubbs Jr. E.B. (2013).  Tumor Necrosis Factor-α enhances CCL2 and ICAM-1 expression in peripheral nerve microvascular endoneurial endothelial cells  ASN Neuro, 5:e00104. PMCID: PMC3565377.