Publications

Objective The healthy alveolar epithelium is protected by a heparan sulfate rich, glycosaminoglycan layer called the epithelial glycocalyx. Our group found that the epithelial glycocalyx is shed in patients with acute respiratory distress syndrome (ARDS). In murine models of LPS- or bleomycin-induced acute lung injury, sheddases (membrane-bound enzymes that cleave extracellular potions of transmembrane proteins) are upregulated and associated with glycocalyx shedding and increased lung permeability. ARDS is commonly caused by viral infections including influenza A (IAV).

Neuropathic pain is a chronic disorder resulting from damage to the afferent nerve fibers or central pain pathways and is often a complication in pathological conditions such as diabetes, shingles, multiple sclerosis, and stroke. The opioid epidemic has elucidated the need for more efficacious treatments for neuropathic pain. In 2019 alone, nearly 1.6 million people were diagnosed with an opioid use disorder and 48,000 people died from a synthetic opioid overdose.

Here we administered Cre-dependent shRNA to knock-down _Scn8a_ (thus Nav1.6) in Cre-expressing glutamatergic neurons in preBötC and quantified mRNA per glutamatergic neuron. We used adult Vglut2Cre mice (10-14 weeks old) and injected 50 nL of AAVs carrying the shRNA. We used _in situ_ hybridization (RNAscope Fluorescent Assay) to label mRNA of _Scn8a_ and to identify transduced glutamatergic neurons in the preBötC for RNA quantification at 2 and 6 weeks after injection.

RNA expression data from all timepoints of perforation were merged and analyzed, revealing 8 distinct major populations of cells and revealing time-dependent transcriptional shifts in each layer of the TM. From both cross-sectional and whole-mount views, the TM shows a rapid, proliferative response to injury by 18 hours post-injury, predominantly in the KCs. 3 days after perforation, there are large transcriptional shifts in the immune, mesenchymal, and mucosal populations.

The polyamines putrescine, spermidine and spermine are organic polycations that regulate many cell functions including proliferation and differentiation. It is known that certain genes of the polyamine system are dysregulated after kidney ischemia reperfusion injury. Here we examined the hypothesis that different forms of acute and chronic kidney injury lead to similar changes in the expression patterns of the polyamine system. In different models of acute and chronic kidney injury expression of genes involved in polyamine homeostasis were analyzed by RT-qPCR and RNAScope.

In order to characterize these understudied receptors within the liver, we must first understand where they are localized and what activates them. Given the dearth of reliable antibodies, we began by examining expression using RNAscope, a powerful _in situ_ technique that specifically localizes mRNA sequences. GPR108, which has previously been linked to regulation of Toll-Like Receptor signaling, was found within hepatocytes.

Histone deacetylase 6 (HDAC6) is a Class IIb histone deacetylase, which is primarily localized to the cytoplasm and plays an important role in cell structure and dynamism, transcriptional repression, exocytosis and endocytocis. Preclinical evidence has suggested that HDAC6 inhibitors alleviate signs of chemotherapy-induced peripheral neuropathy (CIPN), such as mechanical allodynia. However, no group to our knowledge has investigated the mechanism of action of HDAC6 inhibitors in a severe nerve injury model, which has a different pathophysiology than milder models such as CIPN.

G protein-coupled receptors (GPCRs) are a diverse family of integral membrane proteins that have significant roles in numerous physiological systems. We previously reported that GPR116 (ADGRF5), an adhesion-class GPCR, is a critical regulator of vacuolar-type H+-ATPase (V-ATPase) surface expression in A-type intercalated cells (AICs) in mouse kidney cortical collecting ducts. The V-ATPase is a multi-subunit proton pump that localizes to the plasma membrane in specialized acid-secreting epithelial cells.

Exposure to low systemic oxygen (hypoxia, Hx) elevates blood pressure, heart rate and respiration via reflex sensory and central nervous system activation. We have shown transient receptor potential (TRP) vanilloid channels contribute to afferent-evoked activation of the brainstem nucleus tractus solitarii (nTS) following chronic Hx. Short sustained Hx exposure (10% O2, 24hr) in rats also enhances nTS activity, although the mechanisms are not completely understood.

The renin-angiotensin system (RAS) has been implicated in stress-related disorders, however the central mechanisms responsible for this remains unknown. The locus coeruleus (LC), a major noradrenergic nucleus of the brain, plays a critical role in modulating anxiety-like behaviors. The LC has also been previously shown to express angiotensinogen (AGT), the pre-cursor for angiotensin, as well as strong expression of angiotensin II receptors, but its role in stress-related disorders has not been examined.