Publications

Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior

To understand the cellular basis of behavior, it is necessary to know the cell types that exist in the nervous system and their contributions to function. Spinal networks are essential for sensory processing and motor behavior and provide a powerful system for identifying the cellular correlates of behavior. Here, we used massively parallel single nucleus RNA sequencing (snRNA-seq) to create an atlas of the adult mouse lumbar spinal cord.

Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma: A Case Report Documenting the Potential for Very Late Tumor Recurrence.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma is a peculiar sinonasal tract tumor that demonstrates features of both a surface-derived and salivary gland carcinoma. Implicit in its name, this tumor has a consistent association with high-risk HPV, particularly type 33. It was first described in 2013 under the designation of HPV-related carcinoma with adenoid cystic carcinoma-like features.

Characterization of a Vesivirus Associated with an Outbreak of Acute Hemorrhagic Gastroenteritis in Domestic Dogs

Four out of eleven affected dogs died despite aggressive treatment during a 2015 focal outbreak of hemorrhagic gastroenteritis following a stay in a pet housing facility. Routine diagnostic investigations failed to identify a specific cause. Virus isolation from fresh necropsy tissues yielded a calicivirus with sequence homology to a vesivirus within the group colloquially known as the 2117 strains that were originally identified as contaminants in CHO cell bioreactors.

Immune or Genetic-Mediated Disruption of CASPR2 Causes Pain Hypersensitivity Due to Enhanced Primary Afferent Excitability.

Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury.

Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq

Mouse heart development arises from Mesp1 expressing cardiovascular progenitors (CPs) that are specified during gastrulation. The molecular processes that control early regional and lineage segregation of CPs have been unclear.

Human Fetal-Derived Enterospheres Provide Insights on Intestinal Development and a Novel Model to Study Necrotizing Enterocolitis (NEC)

Background & Aims

Untreated necrotizing enterocolitis (NEC) can lead to massive inflammation resulting in intestinal necrosis with a high mortality rate in preterm infants. Limited access to human samples and relevant experimental models have hampered progress in NEC pathogenesis. Earlier evidence has suggested that bacterial colonization of an immature and developing intestine can lead to an abnormally high inflammatory response to bacterial bioproducts. The aim of our study was to use human fetal organoids to gain insights into NEC pathogenesis.

Methods

A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors

Numerous clinical conditions can lead to organ fibrosis and functional failure. There is a great need for therapies that could effectively target pathophysiological pathways involved in fibrosis. GPR40 and GPR84 are G protein-coupled receptors with free fatty acid ligands and are associated with metabolic and inflammatory disorders.

BACE2 distribution in major brain cell types and identification of novel substrates

β-Site APP-cleaving enzyme 1 (BACE1) inhibition is considered one of the most promising therapeutic strategies for Alzheimer’s disease, but current BACE1 inhibitors also block BACE2. As the localization and function of BACE2 in the brain remain unknown, it is difficult to predict whether relevant side effects can be caused by off-target inhibition of BACE2 and whether it is important to generate BACE1-specific inhibitors. Here, we show that BACE2 is expressed in discrete subsets of neurons and glia throughout the adult mouse brain.

Dusp6 attenuates Ras/MAPK signaling to limit zebrafish heart regeneration.

Zebrafish regenerate cardiac tissue through proliferation of pre-existing cardiomyocytes and neovascularization. Secreted growth factors such as FGFs, IGF, PDGFs, and Neuregulin (Nrg) play essential roles in stimulating cardiomyocyte proliferation. These factors activate the Ras/MAPK pathway, which is finely controlled by the feedback attenuator Dual Specificity Phosphatase 6 (Dusp6), an ERK phosphatase. Here we show that suppressing Dusp6 function enhanced cardiac regeneration.

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