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Profiles

Eric Villalón Landeros, PhD

Title/s:  <p>Assistant Professor</p> <p>Molecular Pharmacology and Neuroscience</p>

Office #:  Bldg 115 Room 418

Email: evillalon@luc.edu

External Webpage:

Assistant Professor

Molecular Pharmacology and Neuroscience

Research Interests

Optimal development and function of the Peripheral Nervous System (PNS) requires balanced intracellular protein synthesis and proteasome-dependent protein degradation. Indeed, inhibiting proteasome function in vivo using global proteasome inhibitors, such as those used for cancer treatments, results in development of painful peripheral neuropathy that manifests in severe neuropathic pain, numbness, tingling, and itch sensation. Despite extensive studies, the precise nature and function of proteasomes in PNS biology is not well understood. In 2024 we discovered a unique 20S proteasome that localizes to the membrane of a subpopulation of somatosensory neurons in the PNS. This is the Neuronal Membrane Proteasome (NMP). We found that this NMP modulates the function of sensory neurons, through non-cell autonomous signaling mechanisms, important for sensation of pain and itch.

The focus of the Villalón Landeros Laboratory is to use biochemical, behavioral, cell & molecular, physiological, and proteomic approaches in combination with mouse models and pharmacology to understand and delineate the NMP-dependent mechanisms that modulate PNS somatosensory neuron function in health and disease. Our current focus is:

  • To identify and study the NMP derived signaling peptides and target receptors in PNS somatosensory neurons.
  • To investigate the mechanisms of cell specific expression of spatially subdivided NMPs and their role in modulating neuronal activity.
  • To investigate the regulation and function of NMP-dependent pain and itch sensation in health and disease.

These are initial steps towards our long-term goal of understanding the biology of the NMP in the PNS. Our findings of the NMP-dependent sensory neuron modulation pathways are crucial to better understand the mechanisms that control pain and itch sensation in health and disease. We hope to leverage our findings to develop novel treatment approaches for neuropathic pain and itch conditions.

Selected Publications

  • Villalón-Landeros E, Kho SC, Brennan A, Church T, Turker F, Delannoy M, Caterina MJ, Margolis SS. The Nociceptive Activity of Peripheral Sensory Neurons is Modulated by the Neuronal Membrane Proteasome. Cell Reports. 2024, April 12. Doi: 10.1016/j.celrep.2024.114058
  • Arpke R, Moritz T, Hahn K, Villalón E, Lorson C, Cornelison DDW. Normal muscle fiber type distribution is recapitulated in aged ephrin-A3-/- mice that previously lacked most slow myofibers. American Journal of Physiology. Jan 2023.
  • Comley LH, Kline RA, Thomson AK, Woschitz V, Villalón Landeros E, Osman EY, Lorson CL, Murray LM. Motor Unit Recovery Following Smn Restoration in Mouse Models of Spinal Muscular Atrophy. Hum Mol Genet. 2022, Sep 10;31(18):3107-3119. doi: 10.1093/hmg/ddac097. PMID: 35551393
  • Dumas SA, Villalón E, Bergman EM, Wilson KJ, Marugan JJ, Lorson CL, Burnett BG. A Combinatorial Approach Increases SMN Level in SMA Model Mice. Hum Mol Genet. 2022 Aug 25;31(17):2989-3000. doi: 10.1093/hmg/ddac068. PMID: 35419606
  • Smith CE, Lorson MA, Ricardez Hernandez SM, Al Rawi Z, Mao J, Marquez J, Villalón E, Keilholz AN, Smith CL, Garro-Kacher MO, Morcos T, Davis DJ, Bryda EC, Nichols NL, Lorson CL. The Ighmbp2D564N Mouse Model is the First SMARD1 Model to Demonstrate Respiratory Defects. Hum Mol Genet. 2022 Apr 22;31(8):1293-1307. doi: 10.1093/hmg/ddab317. PMID: 34726235
  • Shababi M* Smith CE*, Ricardez-Hernandez S, Marquez J, Al Rawi ZY, Villalón E, Farris DK, Kacher M, Lorson CL. Defining the Optimal Dose and Therapeutic Window in the FVB Model of SMARD1 (FVB-nmd). Molecular Therapy Methods and Clinical Development. 2021. Dec 10;23:23-32. org/10.1016/j.omtm.2021.07.008. PMID: 34553000
  • McCormack NM, Villalón E, Viollet C, Dalgard CL, Lorson CL, Burnett BG. Survival Motor Neuron Deficiency Slows Myoblast Fusion Through Reduced Myomaker and Myomerger Expression. J Cachexia Sarcopenia Muscle. 2021. Aug. doi: 10.1002/jcsm.12740.
  • Kaifer KA, Villalón E, Smith CE, Simon ME, Marquez J, Hopkins AE, Morcos TI, Lorson CL. AAV9-DOK7 gene therapy reduces disease severity in Smn2b/- SMA model mice. Biochem Biophys Res Commun. 2020. Sep. doi: 10.1016/j.bbrc.2020.07.031.
  • Toedebusch CM, Garcia VB, Snyder JC, Jones MR, Schulz DJ, Johnson GC, Villalón E, Coates JR, Garcia ML. Lumbar Spinal Cord Microglia Exhibited Increased Activation in Aging Dogs Compared with Young Adult Dogs. Geroscience. 2020. Feb. doi: 10.1007/s11357-019-00133-8. PMID: 31828496
  • Shababi M, Smith CE, Kacher M, Alrawi Z, Villalón E, Davis D, Bryda EC, Lorson CL. Development of a Novel Severe Mouse Model of Spinal Muscular Atrophy with Respiratory Distress Type-1: FVB-nmd. Biochem Biophys Res Commun. 2019. doi: 10.1016/j.bbrc.2019.10.032.
  • Villalón E, Kline RA, Smith CE, Lorson ZC, Osman EY, O’Day S, Murray LM, Lorson CL. AAV9-Stathmin1 Gene Delivery Improves Disease Phenotype in an Intermediate Mouse Model of Spinal Muscular Atrophy. Hum Mol Genet. 2019 Nov 15; doi: 10.1093/hmg/ddz188. PMID: 31363739
  • Villalón E, Lee NN, Marques J, Lorson CL. Muscle Fiber-Type Selective Propensity to Pathology in the nmd Mouse Model of SMARD1. Biochem Biophys Res Commun. 2019. Aug 13; 516(1):313-319. doi: 10.1016/j.bbrc.2019.06.117. PMID: 31256932.
  • Kaifer KA, Villalón E, O'Brien BS, Sison SL, Smith CE, Simon M, Marquez J, O’Day S, Hopkins AE, Neff R, Rindt H, Ebert AD, Lorson CL. AAV9-Mediated Delivery of miR-23a Reduces Disease Severity in Smn2B/- SMA Model Mice. Hum Mol Genet. 2019 Oct 1; org/10.1093/hmg/ddz142. PMID: 31211843.
  • Osman EY, Bolding MR, Villalón E, Kaifer KA, Lorson ZC, Tisdale S, Hao Y, Conant GC, Pires JC, Pellizzoni L, Lorson CL. Functional Characterization of SMN Evolution in Mouse Model of SMA. Sci. Rep. 2019 Jul 1; 9(1):9472; doi: 10.1038/s41598-019-45822-8. PMID: 31263170
  • Shababi M, Villalón E, Kaifer KA, DeMarco V, Lorson CL. A Direct Comparison of IV and ICV Delivery Methods for Gene Replacement Therapy in a Mouse Model of SMARD1. Mol Ther Methods Clin Dev. 2018 Aug 17; 10:348-360. doi: 10.1016/j.omtm.2018.08.005. PMID: 30202772.
  • Villalón E, Barry DM, Byers N, Frizzi K, Jones MR, Landayan DS, Dale JM, Downer NL, Calcutt NA, Garcia ML. Internode Length is Reduced During Myelination and Remyelination by Neurofilament Medium Phosphorylation in Motor Axons. Exp Neurol. 2018 Aug; 306:158-168. doi: 10.1016/j.expneurol.2018.05.009. Epub 2018 May 14. PMID: 29772247.
  • Toedebusch CM, Snyder JC, Jones MR, Garcia VB, Johnson GC, Villalón E, Coates JR, Garcia ML. Arginase-1 Expressing Microglia in Close Proximity to Motor Neurons were Increased Early in Disease Progression in Canine Degenerative Myelopathy, a Model of Amyotrophic Lateral Sclerosis. Mol Cell Neurosci. 2018 Apr; 88:148-157. doi: 10.1016/j.mcn.2018.01.009. Epub 2018 Feb 20. PMID: 29408267.
  • Villalón E, Shababi M, Kline R, Lorson ZC, Florea KM, Lorson CL. Selective Vulnerability in Neuronal Populations in nmd/SMARD1 Mice. Hum Mol Genet. 2018 Feb 15; 27(4):679-690. doi: 10.1093/hmg/ddx434. PMID: 29272405.
  • Sison SL, Patitucci TN, Seminary ER, Villalón E, Lorson CL, Ebert AD. Astrocyte-produced miR-146a as a Mediator of Motor Neuron Loss in Spinal Muscular Atrophy. Hum Mol Genet. 2017 Sep 1; 26(17):3409-3420. doi: 10.1093/hmg/ddx230. PMID: 28637335.
  • Jones MR, Villalón E, Northcutt AJ, Calcutt NA, Garcia ML. Differential Effects of Myostatin Deficiency on Motor and Sensory Axons. Muscle Nerve. 2017 Dec; 56(6):E100-E107. doi: 10.1002/mus.25570. Epub 2017 Apr 11. PMID: 28073155.
  • Kaifer KA, Villalón E, Osman EY, Glascock JJ, Arnold LL, Cornelison DD, Lorson CL. Plastin-3 Extends Survival and Reduces Severity in Mouse Models of Spinal Muscular Atrophy. JCI Insight. 2017 Mar 9; 2(5):e89970. doi: 10.1172/jci.insight.89970. PMID: 28289706.
  • Villalón E, Jones MR, Sibigtroth C, Zino SJ, Dale JM, Landayan DS, Shen H, Cornelison DD, Garcia ML. Muscle Spindle Alterations Precede Onset of Sensorimotor Deficits in Charcot-Marie-Tooth type 2E. Genes Brain Behav. 2017 Feb; 16(2):260-270. doi: 10.1111/gbb.12341. PMID: 27643807.
  • Shababi M, Feng Z, Villalón E, Sibigtroth CM, Osman EY, Miller MR, Williams-Simon PA, Lombardi A, Sass TH, Atkinson AK, Garcia ML, Ko CP, Lorson CL. Rescue of a Mouse Model of Spinal Muscular Atrophy with Respiratory Distress Type 1 by AAV9-IGHMBP2 Is Dose Dependent. Mol Ther. 2016 May 5; 24(5):855-66. doi: 10.1038/mt.2016.33. PMID: 26860981.
  • Villalón E, Dale JM, Jones M, Shen H, Garcia ML. Exacerbation of Charcot-Marie-Tooth type 2E Neuropathy Following Traumatic Nerve Injury. Brain Res. 2015 Nov 19; 1627:143-53. doi: 10.1016/j.brainres.2015.09.024. PMID: 26423936.
  • Dale JM, Villalon E, Shannon SG, Barry DM, Markey RM, Garcia VB, Garcia ML. Expressing hNF-LE397K Results in Abnormal Gaiting in a Transgenic Model of CMT2E. Genes Brain Behav. 2012 Apr; 11(3):360-5. doi: 10.1111/j.1601-183X.2012.00771.x. PubMed PMID: 22288874.
  • Jones MR, Villalón E, Garcia ML. Genetic Manipulation of Neurofilament Protein Phosphorylation. Methods Enzymol. 2016; 568:461-76. doi: 10.1016/bs.mie.2015.07.027. Epub 2015 Oct 24. PMID: 26795480.
  • Villalón E, Schulz DJ, Waters ST. Real-time PCR quantification of Gene Expression in Embryonic Mouse Tissue. Methods Mol Biol. 2014; 1092:81-94. doi: 10.1007/978-1-60327-292-6_6. Epub 2013 Oct 17; PMID: 24318815.