Mice harboring the human R138X loss-of-function mutation have increased insulin secretory capacity.

encodes a zinc transporter that is primarily expressed in the pancreatic islets of Langerhans. In β-cells it transports zinc into insulin-containing secretory granules. Loss-of-function (LOF) mutations in protect against type 2 diabetes in humans.

Inflammatory mediators reduce surface PrP on human BMVEC resulting in decreased barrier integrity.

The cellular prion protein (PrP) is a surface adhesion molecule expressed at junctions of various cell types including brain microvascular endothelial cells (BMVEC) that are important components of the blood-brain barrier (BBB). PrP is involved in several physiological processes including regulation of epithelial cell barrier function and monocyte migration across BMVEC. BBB dysfunction and disruption are significant events in central nervous system (CNS) inflammatory processes including HIV neuropathogenesis.

The Role of Shed PrP in the Neuropathogenesis of HIV Infection.

HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrP) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrP (sPrP) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment.

Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions.

Brain injury induces a peripheral acute cytokine response that directs the transmigration of leukocytes into the brain. Because this brain-to-peripheral immune communication affects patient recovery, understanding its regulation is important. Using a mouse model of inflammatory brain injury, we set out to find a soluble mediator for this phenomenon.

Protease resistant protein cellular isoform (PrP(c)) as a biomarker: clues into the pathogenesis of HAND.

HIV infection and HIV neurocognitive impairment are major global health problems. The prevalence of HIV associated neurocognitive disorders (HAND) is increasing as people with HIV are living longer due to the success of antiretroviral therapies. Our laboratory identified the soluble form of (sPrP(c)), the cellular non-pathogenic isoform of the prion protein, as a biomarker of HAND.