A5056944771- Axon Guidance and Neuronal Signaling
- Pain Mechanisms and Treatments
- Ion channel regulation and function
- Angiogenesis and VEGF in Cancer
- Neuroscience and Neuropharmacology Research
- Vagus Nerve Stimulation Research
- Pain Management and Placebo Effect
- Cancer, Stress, Anesthesia, and Immune Response
- Anesthesia and Neurotoxicity Research
- Hippo pathway signaling and YAP/TAZ
- Lymphatic System and Diseases
- Hereditary Neurological Disorders
- Microbial metabolism and enzyme function
- Endoplasmic Reticulum Stress and Disease
- 14-3-3 protein interactions
- Neuropeptides and Animal Physiology
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neural Engineering
University of Arizona
2019-2023
Zhejiang Chinese Medical University
2021
Duke University
2020
Abstract Global spread of severe acute respiratory syndrome coronavirus 2 continues unabated. Binding 2's spike protein to host angiotensin-converting enzyme triggers viral entry, but other proteins may participate, including the neuropilin-1 receptor (NRP-1). Because both and vascular endothelial growth factor-A (VEGF-A)—a pronociceptive angiogenic factor, bind NRP-1, we tested whether could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuron firing was blocked by NRP-1 inhibitor...
Small molecules directly targeting the voltage-gated sodium channel (VGSC) Na
The sodium channel Nav1.7 is a master regulator of nociceptive input into the central nervous system. Mutations in this can result painful conditions and produce insensitivity to pain. Despite being recognized as "poster child" for signaling human pain, targeting has not yet produced clinical drug. Recent work illuminated interactome, offering insights regulation these channels identifying potentially new druggable targets. Among regulators cytosolic collapsin response mediator protein 2...
Abstract Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that binds numerous ligands including vascular endothelial growth factor A (VEGFA). Binding of this ligand to NRP-1 and the co-receptor, tyrosine kinase receptor VEGFR2, elicits nociceptor sensitization resulting in pain through enhancement activity voltage-gated sodium calcium channels. We previously reported blocking interaction between VEGFA with Spike protein SARS-CoV-2 attenuates VEGFA-induced dorsal root ganglion (DRG)...
Pharmacological enhancement of endoplasmic reticulum (ER) proteostasis is an attractive strategy to mitigate pathology linked etiologically-diverse protein misfolding diseases. However, despite this promise, few compounds have been identified that enhance ER through defined mechanisms action. We previously the phenylhydrazone-based compound AA263 as a promotes adaptive remodeling including activation ATF6 signaling arm unfolded response (UPR). target(s) and potential for further development...
TAF1/MRSX33 intellectual disability syndrome is an X-linked disorder caused by loss-of-function mutations in the TAF1 gene. How these cause dysmorphology, hypotonia, and motor defects unknown. Mouse models which have embryonically targeted failed, possibly due to being essential for viability, preferentially expressed early brain development, intolerant of mutation. Novel animal are valuable tools understanding neuronal pathology. Here, we report development characterization a novel model ID...
Abstract Vascular endothelial growth factor A (VEGF-A) is a pronociceptive that causes neuronal sensitization and pain. We reported blocking the interaction between membrane receptor neuropilin 1 (NRP1) VEGF-A–blocked VEGF-A–mediated sensory neuron hyperexcitability reduced mechanical hypersensitivity in rodent chronic neuropathic pain model. These findings identified NRP1-VEGF-A signaling axis for therapeutic targeting of In an in-silico screening approximately 480 K small molecules binding...
T-type calcium channels, in the central nervous system, are involved pathogenesis of many neurodegenerative diseases, including TAF1 intellectual disability syndrome (TAF1 ID syndrome). Here, we evaluated efficacy a novel Ca
Abstract Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding SARS-CoV-2’s Spike protein to host angiotensin converting enzyme triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both and vascular endothelial growth factor-A (VEGF-A) – a pro-nociceptive angiogenic factor, bind NRP-1, we tested if could block VEGF-A/NRP-1 signaling. VEGF-A–triggered sensory neuronal firing was blocked by...
Abstract Mechanistic studies principally focusing on primary afferent nociceptive neurons uncovered the upregulation of collapsin response mediator protein 2 (CRMP2)—a dual trafficking regulator N-type voltage-gated calcium (Ca v 2.2) as well Na 1.7 sodium channels—as a potential determinant neuropathic pain. Whether CRMP2 contributes to aberrant excitatory synaptic transmission underlying pain processing after peripheral nerve injury is unknown. Here, we interrogated CRMP2's role in and...
Abstract Despite identification of several small molecules directly targeting the voltage-gated sodium channel NaV1.7, none has been clinically successful. We reported that preventing addition a ubiquitin-like modifier (SUMO) on NaV1.7-interacting cytosolic collapsin response mediator protein 2 (CRMP2) blocked NaV1.7 functions and was antinociceptive in rodents. Here, we discovered 15 amino acid CRMP2 regulatory sequence (CRS) unique to is essential for this coupling. preferentially bound...
Abstract The sodium channel NaV1.7 is a master regulator of nociceptive neuronal firing. Mutations in this can result painful conditions as well produce insensitivity to pain. Despite being recognized “poster child” for signaling and human pain, targeting has not yet produced clinical drug. Recent work illuminated the interactome, offering insights into regulation these channels identifying potentially new druggable targets. Amongst regulators cytosolic collapsin response mediator protein 2...