Publication

Inhibitors of fibroblast growth factor receptor (FGFR) signaling have been investigated in various human cancer diseases. Recently, the first compounds received FDA approval in biomarker-selected patient populations. Different approaches and technologies have been applied in clinical trials, ranging from protein (immunohistochemistry) to mRNA expression (e.g., RNA in situ hybridization) and to detection of various DNA alterations (e.g., copy number variations, mutations, gene fusions).

Cannabinoid receptor 1 (CB1R) has been one of the major targets in medication development for treating substance use disorders (SUDs). Early studies indicated that rimonabant, a selective CB1R antagonist with an inverse agonist profile, was highly promising as a therapeutic for SUDs. However, its adverse side effects, such as depression and suicidality, led to its withdrawal from clinical trials worldwide in 2008.

Tissue availability remains an important limitation of single-cell genomic technologies for investigating cellular heterogeneity in human health and disease. Bronchoalveolar lavage (BAL) represents a minimally invasive approach to assess an individual's lung cellular environment for diagnosis and research. However, the lack of high-quality healthy lung reference data is a major obstacle to using single-cell approaches to study a plethora of lung diseases. Here, we performed single-cell RNA-sequencing (scRNA-seq) on over 40,000 cells isolated from BAL of four healthy volunteers.

Microglia, the innate immune cells of the central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply of genes, receptors and released cytokines, chemokines and neurotrophic factors. Moreover, microglia functions are closely linked to the constant communication with other cell types, among them neurons. Depending on the signaling pathway and type of stimuli involved, the outcome of microglia operation can be neuroprotective or neurodegenerative.

It is hard to overestimate the influence of the endocannabinoid signaling (ECS) system on central nervous system (CNS) function. In the 40 years since cannabinoids were found to trigger specific cell signaling cascades, studies of the ECS system continue to cause amazement, surprise, and confusion! CB1 cannabinoid receptors are expressed widely in the CNS and regulate cell-cell communication via effects on the release of both neurotransmitters and gliotransmitters.

The most abundant circulating CD3- population in patients with cHL was a newly identified monocyte subset with increased expression of multiple immunosuppressive and tumorigenic cytokines and chemokines, PD-L1 and SIRPa. This newly identified monocytic population was virtually absent from the blood of healthy donors. RNAscope analysis of the intact tumor microenvironment localized these tumor-infiltrating monocytes/macrophages to the immediate proximity of HRS cells.

Ductal carcinoma in situ (DCIS) is the most common type of in situ premalignant breast cancers. What drives DCIS to invasive breast cancer is unclear. Basal-like invasive breast cancers are aggressive. We have previously shown that NRAS is highly expressed selectively in basal-like subtypes of invasive breast cancers and can promote their growth and progression.

Pancreatic insulin was discovered a century ago, and this discovery led to the first lifesaving treatment for diabetes. While still controversial, nearly one hundred published reports suggest that insulin is also produced in the brain, with most focusing on hypothalamic or cortical insulin-producing cells.However, specific function for insulin produced within the brain remains poorly understood.

RGS2 is a GTPase activating protein that modulates GPCR-Gα signaling and mice lacking RGS2 globally exhibit metabolic alterations. While RGS2 is known to be broadly expressed throughout the body including the brain, the relative contribution of brain RGS2 to metabolic homeostasis remains unknown.