Publication

Human papillomaviruses (HPVs) contribute to approximately 5% of all human cancers. Species-specific barriers limit the ability to study HPV pathogenesis in animal models. Murine papillomavirus (MmuPV1) provides a powerful tool to study the roles of papillomavirus genes in pathogenesis arising from a natural infection. We previously identified Protein Tyrosine Phosphatase Non-Receptor Type 14 (PTPN14), a tumor suppressor targeted by HPV E7 proteins, as a putative cellular target of MmuPV1 E7. Here, we confirmed the MmuPV1 E7-PTPN14 interaction.

Hv1 is the only voltage-gated proton-selective channel in mammalian cells. It contains a conserved voltage-sensor domain, shared by a large class of voltage-gated ion channels, but lacks a pore domain. Its primary role is to extrude protons from the cytoplasm upon pH reduction and membrane depolarization. The best-known function of Hv1 is the regulation of cytosolic pH and the nicotinamide adenine dinucleotide phosphate oxidase-dependent production of reactive oxygen species. Accumulating evidence indicates that Hv1 is expressed in nervous systems, in addition to immune cells and others.

Nociceptive input to the spinal cord is transmitted by primary afferent neurons in the dorsal root ganglia (DRG). A subset of DRG neurons has the ability to attenuate nociceptive transmission through expression of the µ-opioid receptor. The relationship between algesic and analgesic properties of individual DRG neurons has not yet been evaluated in the human. By using a combination of six different 4-Plex in-situ hybridization experiments, we were able to identify three different main nociceptive populations.

Complex regional pain syndrome (CRPS) is a debilitating chronic pain disorder that with no effective treatments. Several microRNA (miRNA) are commonly dysregulated in CRPS patient and tibia fracture model of CRPS (TFM) mice, including miR-25 which is associated with positive treatment outcomes in patients. Interestingly, these miRNAs are predicted to target several genes critical to resident memory T cell (Trm) function. We hypothesize that miRNA dysregulation contributes to the pathology of CRPS through regulation of skin Trm development and maintenance.

Oncostatin M (OSM) is one of the least studied cytokines in the interleukin-6 family especially considering that its expression correlates with hallmarks of chronic itch, rheumatoid arthritis, irritable bowel syndrome, and more recently neuropathic pain. This gap in knowledge is attributed to numerous species differences in the protein structure of OSM, and its receptor usage both of which affect physiological function. Here we uncover some of these discrepancies across mouse, rat, and human models, further underpinning the importance of studying OSM in human context.

Sudden, unpredictable, severe acute pain episodes are the most common sickle cell disease (SCD) complication. Some SCD patients experience frequent pain episodes while others experience rare episodes. Knowledge of the biology driving this variability is limited. Using gene transcription analyses, we previously showed an elevated inflammatory response is associated with increased SCD pain episode frequency. We sought to replicate these findings in a larger SCD cohort and identify hub genes closely associated with increased pain frequency.

Investigation of spontaneous- so-called‘resting-state'-activity of the central nervous system with functional magnetic resonance imaging (fMRI) holds great clinical potential to identify possible prognostic and diagnostic biomarkers for pain disorders and provides novel insights into the functional architecture of the central nervous system.

Controlling primary afferent nociceptive input is a known route to analgesia. This path is exemplified by agonists of the mu opioid receptors that are expressed in nociceptive DRG neurons and can be activated by intrathecal or systemic opioid agonists. For other peripheral analgesic targets, the hypothesis is that similar neuronal expression would validate their development as analgesic agents.

Previous studies have demonstrated effects of racialized minority status on thermal pain sensitivity, sensibility, and tolerance. However, there is limited evidence demonstrating effects of minority status on painful punctate mechanical stimuli and self-report pain. We analyzed the effects of racialized minority status on heat pain sensitivity, sensibility to painful heat and punctate mechanical stimuli, and Pain Sensitivity Questionnaire (PSQ) scores. Our secondary purpose was to test face validity of the PSQ in a US population.

GPR37 is an orphan GPCR and expressed in different brain regions. However, its biological function in pain regulation remains poorly understood. Recently, we identified Neuroprotectin D1 (NPD1) as a novel ligand of GPR37. NPD1 is a specialized pro-resolving mediator (SPM) and bio-synthesized from fish oil DHA (docosahexaenoic acid) . Here we reported a protective role of GRP37/NPD1 signaling in traumatic brain injury (TBI)-induced neuropathic pain. Mild TBI was induced by closed-head impact and the neuropathic pain was assessed by periorbital and cutaneous mechanical allodynia.