Publication

Rapid cell type identification by new genomic single-cell analysis methods has not been met with efficient experimental access to these cell types. To facilitate access to specific neural populations in mouse cortex, we collected chromatin accessibility data from individual cells and identified enhancers specific for cell subclasses and types. When cloned into recombinant adeno-associated viruses (AAVs) and delivered to the brain, these enhancers drive transgene expression in specific cortical cell subclasses.

The afferent synapses between inner hair cells (IHC) and spiral ganglion neurons are specialized to faithfully encode sound with sub-millisecond precision over prolonged periods of time. Here, we studied the role of Rab3 interacting molecule-binding proteins (RIM-BP) 1 and 2 – multidomain proteins of the active zone known to directly interact with RIMs, Bassoon and CaV1.3 – in IHC presynaptic function and hearing.

Acute kidney injury is highly prevalent and associated with high morbidity and mortality, and there are no approved drugs for its prevention and treatment. Vagus nerve stimulation (VNS) alleviates inflammatory diseases including kidney disease; however, neural circuits involved in VNS-induced tissue protection remain poorly understood. The vagus nerve, a heterogeneous group of neural fibers, innervates numerous organs. VNS broadly stimulates these fibers without specificity. We used optogenetics to selectively stimulate vagus efferent or afferent fibers.

Associative learning allows animals to adapt their behavior in response to environmental cues. For example, sensory cues associated with food availability can trigger overconsumption even in sated animals. However, the neural mechanisms mediating cue-driven non-homeostatic feeding are poorly understood. To study this, we recently developed a behavioral task in which contextual cues increase feeding even in sated mice. Here, we show that an insular cortex to central amygdala circuit is necessary for conditioned overconsumption, but not for homeostatic feeding.

Across species, expression of the basic helix-loop-helix transcription factor ATOH1 promotes differentiation of cochlear supporting cells to sensory hair cells required for hearing. In mammals, this process is limited to development, whereas nonmammalian vertebrates can also regenerate hair cells after injury. The mechanistic basis for this difference is not fully understood. Hypermethylated in cancer 1 (HIC1) is a transcriptional repressor known to inhibit Atoh1 in the cerebellum. We therefore investigated its potential role in cochlear hair cell differentiation.

Dermatofibrosarcoma protuberans (DFSP) is a spindle cell neoplasm of the skin and superficial soft tissue with a tendency for locally aggressive behavior; metastatic potential coincides with fibrosarcomatous transformation. The vast majority of DFSPs harbor the t(17;22) translocation resulting in a COL1A1-PDGFB fusion that drives autocrine growth stimulation via PDGFB overexpression. Here, we examined the utility of PDGFB RNA chromogenic in situ hybridization (CISH) for the diagnosis of DFSP.

High-risk human papillomavirus (hrHPVs), particularly HPV16 and HPV18, are the etiologic factors of ano-genital cancers and some head and neck squamous cell carcinomas. Viral E6 and E7 oncoproteins, controlled at both transcriptional and post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In this study, we investigated the implication of the DEAD-box helicase eIF4A3, an Exon Junction Complex factor, in the regulation of HPV16 gene expression. Our data revealed that the depletion of the factor eIF4A3 upregulated E7 oncoprotein levels.

Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described.

Combination antiretroviral therapy (ART) can suppress plasma HIV-RNA to < 50 copies/mL, decrease HIV transmission, reduce mortality, and improve quality of life for people living with HIV. ART cannot, however, eliminate HIV from an infected individual. The primary barrier to cure HIV infection is the multiple reservoir sites, including adipose tissue, bone marrow, central nervous system, liver, lungs, male and female reproductive system, secondary lymph nodes, and gut-associated lymphoid tissue, established 1 to 2 weeks after acquisition of HIV.