Publications

Severe debilitating pain is the most common complication and reason for hospitalization for individuals with sickle cell disease (SCD), a genetic blood disorder that affects 100,000 people in the US and over 3 million worldwide. Despite this, the biological basis of chronic SCD pain is not fully understood. Using transgenic SCD mice and fecal material transplant paradigms, we determined that gastrointestinal tract contents drive persistent SCD pain. Mechanical allodynia was temporarily alleviated in SCD mice following fecal transplant from wildtype animals.

We developed an animal model of activity-induced muscle pain that combines muscle fatigue with a non-painful, low-dose muscle insult. We previously showed that pharmacological blockade of acid-sensing ion channel 3 (ASIC3) in muscle prevents the activity-induced muscle pain, however, genetic deletion of ASIC3 in primary afferents innervating muscle has no effect on pain. We hypothesized that genetic deletion of ASIC3 on macrophages would prevent activity-induced muscle pain. ASIC3fl/fl mice were crossed with Cx3cr1-Cre mice to generate macrophage/monocyte-specific deletion of ASIC3.

Transmembrane Cav2.2 (N-type) voltage-gated calcium channels are genetically and pharmacologically validated pain targets. Clinical block of Cav2.2 (e.g., with Prialt) or indirect modulation (e.g., with gabapentinoids) mitigates chronic pain but is constrained by side effects. The cytosolic auxiliary subunit collapsin response mediator protein 2 (CRMP2) targets Cav2.2 to the sensory neuron membrane and regulates their function. A CRMP2-derived peptide (CBD3) uncouples the Cav2.2-CRMP2 interaction to inhibit calcium influx, transmitter release and pain.

Facial grimaces are now commonly used to quantify spontaneous pain in mice and other mammalian species, but scoring remains subjective and relies on humans with very different levels of proficiency. Here, we developed a Mouse Grimace Scale (MGS) for black-coated (C57BL/6) mice consisting of four facial action units (orbitals, nose, ears, whiskers). We used this scale to generate ground truth data from over 70,000 images of black mice in different settings.

Targeting specific opioid receptor types in distinct sensory neurons could lead to safer and more effective treatments against pain. However, the extent to which different DRG neurons that express opioid receptors (MOR, DOR, KOR) innervate distinct organs, and what sensory information is encoded by these neurons, represent long-standing questions in the field. To fill this knowledge gap, we utilized novel knock-in mouse lines in which the DNA recombinases Cre and/or Flp are expressed in opioid receptor-positive DRG neurons.

Although anesthesia is commonly used in the fields of medicine and scientific research, the neural mechanisms and circuits through which it produces analgesia is still unclear. Utilizing c-fos labeling of neuronal activity, this project aimed to investigate the brain regions of C57BL/6 mice, which become activated subsequent to isoflurane anesthesia. RNAscope in situ hybridization was used to examine c-fos mRNA activation in the brain. Confocal microscopy was utilized to locate and characterize brain regions displaying c-Fos activation.

SR-17018 was identified as a highly G protein-biased mu opioid peptide (MOP) receptor agonist and lacked MOP agonist-associated adverse effects in mice. The aim of this study was to determine the functional profile of spinal and systemic administration of SR-17018 in non-human primates. In vivo effects of SR-17018 were compared with those of MOP agonists in different intrinsic efficacies, DAMGO, morphine, heroin, and buprenorphine, in behavioral assays established in rhesus monkeys (Macaca mutatta).

There are a number of G-protein-coupled receptors (GPCRs) that are considered "orphan receptors" because the information on their known ligands is incomplete. Yet, these receptors are important targets to characterize, as the discovery of their ligands may lead to potential new therapies. GPR75 was recently deorphanized because at least two ligands appear to bind to it, the chemokine CCL5 and the eicosanoid 20-Hydroxyeicosatetraenoic acid. Recent reports suggest that GPR75 may play a role in regulating insulin secretion and obesity.

The p53 isoform Δ133p53β is known to be associated with cancers driven by inflammation. Many of the features associated with the development of inflammation in rheumatoid arthritis (RA) parallel those evident in cancer progression. However, the role of this isoform in RA has not yet been explored. The aim of this study was to determine whether Δ133p53β is driving aggressive disease in RA.Using RA patient synovia, we carried out RT-qPCR and RNAScope-ISH to determine both protein and mRNA levels of Δ133p53 and p53.

Chronic HBV infection evolves through different phases. Interactions between viral replication and the host immune response in the liver underlie the pathogenesis of this disease.