Publications

Over three decades of evidence indicate that dopamine (DA) D3 receptors (D3R) are involved in the control of drug-seeking behavior and may play an important role in the pathophysiology of substance use disorders (SUD). The expectation that a selective D3R antagonist/partial agonist would be efficacious for the treatment of SUD is based on the following key observations.

In this protocol, we describe the use of ChipCytometry to combine RNA in situ hybridization and antibody staining for multiplexed tissue imaging of human formalin-fixed and paraffin-embedded tissue samples. The advantages of ChipCytometry are long-term storage for re-interrogation and advanced image quality by high dynamic range imaging of staining and background. A titrated pretreatment of tissue samples bypasses challenges because of the retrieval of antigens on coverslips and achieves an optimal staining quality at the minimal expense of tissue integrity.

Stem and progenitor cells residing in the intestinal crypts drive the majority of colorectal cancers (CRCs), yet vascular contribution to this niche remains largely unexplored. VEGFA is a key driver of physiological and tumor angiogenesis. Accordingly, current anti-angiogenic cancer therapies target the VEGFA pathway. Here we report that in CRC expansion of the stem/progenitor pool in intestinal crypts requires VEGFA-independent growth and remodeling of blood vessels.

The mammalian suprachiasmatic nucleus (SCN) functions as a master circadian pacemaker. In order to examine mechanisms by which it keeps time, entrains to periodic environmental signals (zeitgebers), and regulates subordinate oscillators elsewhere in the brain and in the periphery, a variety of molecular methods have been applied.

In situ hybridization has been a robust method for detection of mRNA expression in whole-mount samples or tissue sections for more than 50 years. Recent technical advances for in situ hybridization have incorporated oligo-based probes that attain greater tissue penetration and signal amplification steps with restricted localization for visualization of specific mRNAs within single cells. One such method is third-generation in situ hybridization chain reaction (V3HCR).

Intestinal cells marked by Lgr5 function as tissue-resident stem cells that sustain the homeostatic replenishment of the epithelium. By incorporating a diphtheria toxin receptor (DTR) cassette linked to the Lgr5 coding region, native Lgr5-expressing cells are susceptible to ablation upon DT administration in vivo. A similar strategy can be used for Lgr5-expressing cells within organoids established from DTR models. Together, these in vivo and in vitro approaches will facilitate dissection of the roles of Lgr5-expressing cells residing in different tissue compartments.

Cell-specific RNA sequencing has revolutionized the study of cell biology. Here, we present a protocol to assess cell-specific translatomes of genetically targeted cell types. We focus on astrocytes and describe RNA purification using RiboTag tools. Unlike single-cell RNA sequencing, this approach allows high sequencing depth to detect low expression genes, and the exploration of RNAs translated in subcellular compartments. Furthermore, it avoids underestimation of transcripts from cells susceptible to cell isolation procedures. The protocol can be applied to a variety of cell types.

Senecavirus A (SVA) has been demonstrated to be a causative agent for vesicular disease in swine. It is clinically indistinguishable from other agents that cause vesicular disease such as foot-and-mouth disease virus (FMDV), which is a reportable foreign animal disease (FAD). Thus, an investigation is initiated to rule out FMDV every time a vesicle is observed. Senecavirus A has now been reported across the Americas and Asia, and it appears the ecology of this virus has changed from sporadic infections to an endemic disease in some areas.

Studies indicate a very low rate of SARS-CoV-2 detection in the placenta or occasionally a low rate of vertical transmission in COVID-19 pregnancy. SARS-CoV-2 Delta variant has become a dominant strain over the world and possesses higher infectivity due to mutations in its spike receptor-binding motif.To determine whether SARS-CoV-2 Delta variant has increased potential for placenta infection and vertical transmission, we analyzed SARS-CoV-2 infection in the placenta, umbilical cord, and fetal membrane from a case that unvaccinated mother and her neonate were COVID-19 positive.

As mucosal barriers in fish are the main sites where pathogens are encountered, mucosal immunity is crucial to avoid infection in the aquatic environment. In teleost fish, immunoglobulins are present in gut, gill and skin mucus, although not in the same amounts as in higher vertebrates. In mammals, the poly-Ig receptor (pIgR) is synthesized in epithelial cells and mediates the active transport of poly-immunoglobulins (pIgs) across the epithelium.