Publications

A major social challenge of modern societies is to prevent and treat neurodegenerative diseases suffered by the constantly increasing elderly population. We are investigating the changes in gene expression in single neurons in response to nerve terminal dysfunction in the brain of genetically modified mice. Machine Learning approaches imported from other disciplines are key for the bioinformatic analysis of data sets comprising thousands of cells expressing thousands of genes each.

Background: Novel therapies are needed upon progression to first-line CDK4/6 inhibitor (CDKi) plus endocrine therapy in advanced HR+ breast cancer. One frequent alteration driving resistance to CDKi plus hormones is FGFR1/2 amplification/overexpression. We have demonstrated that a combined assay of RNAScope and FISH, detecting RNA overexpression and genomic amplification of FGFR1/2, captures more FGFR-aberrant cases than either test alone.

Introduction: Inverted papillomas (IPs) are rare, benign, sinonasal tumors with the ability to undergo malignant transformation. While rare, they are the most common type of papilloma within the sinonasal cavity and represent up to 5% of primary nasal cavity tumors. There have been many studies attempting to define a causal link between HPV and malignant transformation of IPs with mixed results. Additionally, these tumors have a high recurrence rate, and their malignant transformation potential has spurred significant investigation into their etiology, disease course, and treatment.

Background Pain is the most common cause of disability in IBD. What causes inter-individual variability in chronic pain after successful treatment of inflammation remains elusive. We have shown that activation of TRPV1+ colonic nociceptors is essential for the establishment of persistent pain in DSS colitis. Nociceptor development coincides with microbial colonization, while early life dysbiosis can lead to visceral hypersensitivity in adulthood. Whether the microbiota dictates nociceptor development and pain susceptibility remains unknown.

Studies show that postmenopausal women with breast cancer treated with long-term use of tamoxifen are at an increased risk for uterine cancer, but why this occurs has been somewhat of a mystery.

AimsPharmacological activation of the antioxidative transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) improves outcomes in experimental models of intracerebral haemorrhage (ICH). However, the Nrf2 pathway has not been previously studied in humans after ICH. Our study aims to address this gap.MethodsWe selected cases with fatal ICH from a prospective community-based inception cohort study and age-matched and sex-matched controls who died suddenly of non-neurological disease.

The use of body-focused repetitive behaviors (BFRBs) is conceptualized as a means for emotion regulation upon stress exposure. However, it is unclear about the neurological mechanism on how repetitive behaviors affect emotion regulation to cope with stress. Here, we identify that excitatory somatostatin-positive neurons in the medial paralemniscal nucleus (MPLSST neurons) control self-grooming and encode reward. MPLSST neuronal activity is responsible for self-grooming initiation and maintenance.

The serotonin (5HT) system mediates pathophysiology of stress responses and influences adult hippocampal neurogenesis from radial neural stem cells (rNSCs) in a sex-dependent manner. However, the mechanisms underlying sex differences in serotonergic regulation and stress vulnerability of rNSCs remain elusive. Here we report sex-dependent expression of 5HT1ARs in rNSCs of adult mouse hippocampus, with higher levels of 5HT1AR expression in rNSCs of females. Functionally, selective deletion of 5HT1ARs decreases rNSC production through decreased symmetric self-renewal in females.

Crosstalk between metabolic and signaling events that induce tumor metastasis remains elusive. Here, we determined how oncogenic sphingosine 1-phosphate (S1P) metabolism activates intracellular C3-complement molecules to enhance migration/metastasis. We demonstrate that increased S1P metabolism activates C3-complement processing through S1P receptor 1 (S1PR1). S1P/S1PR1-activated intracellular C3b-α′2 was associated with PPIL1 through glutamic acid 156 (E156) and aspartic acid 111 (D111) residues, resulting in NLRP3/inflammasome induction.

Cancer cells have an imbalance in oxidation-reduction (redox) homeostasis. Understanding the precise mechanisms and the impact of the altered redox microenvironment on the immunologic reaction to tumors is limited.We isolated exosomes from ovarian cancer cells through ultracentrifuge and characterized by Western-blots and Nanoparticle Tracking Analysis. 2D, 3D-coculture tumor model, and 3D live cell imaging were used to study the interactions between tumor cells, macrophages and CD3 T cells in vitro.