Neutrophils are the most abundant leukocytes in circulation and the first responders to infectious and sterile inflammation, including skin exposure to ultraviolet (UV) light. We demonstrate that neutrophils not only migrate to the UV light–exposed skin but also disseminate systemically. In the kidney, neutrophils mediate inflammatory and injury responses triggered by skin exposure to UV. They had a proinflammatory phenotype:…
Read More
Processing within the anterior cingulate cortex (ACC) is crucial for the patterning of appropriate behavior, and ACC dysfunction following chronic drug use is thought to play a major role in drug addiction. However, cortical pyramidal projection neurons can be subdivided into two major types (intratelencephalic (IT) and pyramidal tract (PT)), with distinct inputs and projection targets, molecular and receptor profiles,…
Read More
Skin epithelium can accumulate a high burden of oncogenic mutations without morphological or functional consequences. To investigate the mechanism of oncogenic tolerance, we induced HrasG12V in single murine epidermal cells and followed them long-term. We observed that HrasG12V promotes an early and transient clonal expansion driven by increased progenitor renewal that is replaced with an increase in progenitor differentiation leading to reduced…
Read More

Clocks, Cancer, and Chronochemotherapy

The core of the mammalian circadian clock mechanism is a time-delayed transcription-translation feedback loop (TTFL), which influences the transcription and expression of a large fraction of the transcriptome. Through this mechanism, the mammalian circadian clock modulates many physiological functions, including the timing of cell division and rates of metabolism in specific tissues. Circadian clock dysfunction is associated with several human…
Read More
Single-cell RNA-sequencing (scRNA-seq) has become an essential tool for characterizing gene expression in eukaryotes but current methods are incompatible with bacteria. Here, we introduce microSPLiT, a high-throughput scRNA-seq method for gram-negative and gram-positive bacteria that can resolve heterogeneous transcriptional states. We applied microSPLiT to >25,000 Bacillus subtilis cells sampled at different growth stages, creating an atlas of changes in metabolism and lifestyle.…
Read More
Engineering chimeric antigen receptors (CAR) or T cell receptors (TCR) helps create disease-specific T cells for targeted therapy, but the cost and rigor associated with manufacturing engineered T cells ex vivo can be prohibitive, so programing T cells in vivo may be a viable alternative. Here we report an injectable nanocarrier that delivers in vitro-transcribed (IVT) CAR or TCR mRNA…
Read More
The large intestine, with its array of crypts lining the epithelium and diverse luminal contents, regulates homeostasis throughout the body. In vitro crypts formed from primary human intestinal epithelial stem cells on a 3D shaped hydrogel scaffold replicate the functional and architectural features of in vivo crypts. Collagen scaffolding assembly methods are provided, along with the microfabrication and soft lithography…
Read More

Characterizing Viral Infection by Electron Microscopy

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, causing coronavirus disease 2019 (COVID-19), has presented many challenges and spurred intense investigations into the pathogenesis of this disease. In addition to respiratory disease, many patients with SARS-CoV-2 infection are experiencing systemic illnesses, including kidney failure, heart failure, liver injury, neurologic dysfunction, and skin manifestations (eg, COVID toe). The etiology and…
Read More
The SARS-CoV-2 virus is causing a global pandemic and cases continue to rise. Most infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that could contribute to immunity. We performed a longitudinal assessment of individuals recovered from mild COVID-19 to determine if they develop and sustain multifaceted SARS-CoV-2-specific immunological…
Read More
While the effect of bacterial molecules on the host immune system is well studied, how host factors affect the expression of bacterial molecules is less appreciated. Here we uncover the impact of inflammasome activation and type 1 interferon on the expression of bacterial flagellin. Flagellin induces NLRC4 inflammasome-mediated pyroptosis causing clearance of Salmonella. We show that inflammasome activation also produces lysophospholipids…
Read More