A5029449854- Circadian rhythm and melatonin
- Immune cells in cancer
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Dietary Effects on Health
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Cell death mechanisms and regulation
- Cancer Genomics and Diagnostics
- Tryptophan and brain disorders
- Receptor Mechanisms and Signaling
- RNA regulation and disease
- Birth, Development, and Health
- NF-κB Signaling Pathways
- Genetics, Aging, and Longevity in Model Organisms
- Physiological and biochemical adaptations
- Health, Environment, Cognitive Aging
- Light effects on plants
- Photoreceptor and optogenetics research
- DNA Repair Mechanisms
- Inflammatory Bowel Disease
AC Camargo Hospital
2021-2025
Universidade de São Paulo
2015-2022
Weizmann Institute of Science
2019-2021
American Committee for the Weizmann Institute of Science
2021
To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored relevance T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for generation local antitumour immunity.We characterised functional states spatial organisation PDAC-infiltrating cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling microdissected TLSs, as well in vitro assays. In addition,...
Lung cancer patients face a dismal prognosis mainly due to the low efficacy of current available treatments. Cisplatin is first-line chemotherapy treatment for those patients, however, resistance this drug common and yet not fully understood phenomenon. Aiming shed new light into puzzle, we used established normal malignant lung cell lines displaying different sensitivity towards cisplatin treatment. We observed negative correlation between viability DNA damage induction upon Interestingly,...
Melanoma is the most lethal type of skin cancer, with increasing incidence and mortality rates worldwide. Multiple studies have demonstrated a link between cancer development/progression circadian disruption; however, complex role tumor-autonomous molecular clocks remains poorly understood. With that in mind, we investigated pathophysiological relevance clock genes expression metastatic melanoma.We analyzed gene expression, somatic mutation, clinical data from 340 melanomas The Cancer Genome...
Abstract Tissue architecture and cell–extracellular matrix (cell–ECM) interaction determine the organ specificity; however, influences of these factors on anticancer drugs preclinical studies are highly neglected. For considering such aspects, three-dimensional (3D) cell culture models relevant tools for accurate analysis cellular responses to chemotherapy. Here we compared MCF-7 breast cancer cells cisplatin in traditional two-dimensional (2D) 3D-reconstituted basement membrane (3D-rBM)...
Stressful experiences can promote harmful effects on physiology and fitness. However, stress-mediated hormonal immune changes are complex may be highly dependent body condition. Here, we investigated captivity-associated stress effects, over 7, 30, 60, 90 days plasma corticosterone (CORT) testosterone (T) levels, index, innate immunity (bacterial killing ability phagocytosis of peritoneal cells) in toads (Rhinella icterica). Toads captivity exhibited elevated CORT decreased T immunity,...
The biological clock has received increasing interest due to its key role in regulating body homeostasis a time-dependent manner. Cancer development and progression been linked disrupted molecular clock; however, melanoma, the of is largely unknown. We investigated effects tumor on micro- (TME) macro-environments (TMaE) non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 cells 2 weeks later animals euthanized every 6 h during 24 h. presence localized...
Abstract Environmental pollution in the form of particulate matter <2.5 μm (PM 2.5 ) is a major risk factor for diseases such as lung cancer, chronic respiratory infections, and cardiovascular diseases. Our goal was to show that PM eliciting proinflammatory response activates immune‐pineal axis, reducing pineal synthesis increasing extrapineal melatonin. Herein, we report exposure rats polluted air 6 hours reduced nocturnal plasma melatonin levels increased levels. Melatonin lipid...
Abstract The search for new therapeutical targets cutaneous melanoma and other cancers is an ongoing task. We expanded this knowledge by evaluating whether opsins, light- thermo-sensing proteins, could display tumor-modulatory effects on cancer. Using different experimental approaches, we show that cell proliferation slower in the absence of Opn4 , compared to WT due impaired cycle progression reduced melanocyte inducing transcription factor ( Mitf ) expression. In vivo tumor KO cells...
Abstract Chimeric antigen receptor (CAR) T cell therapy is increasingly being adopted as a clinical modality for patients with relapsed/refractory hematological malignancies. Despite the efficacy of CAR-T therapy, considerable fraction still relapses during first months following infusion. The limited efficiency thought to relate epigenetic mechanisms involved in suppression and dysfunction. Here, screening multiple inhibitors revealed that targeting PRC2 consistently induced development...
Cutaneous melanocytes and melanoma cells express several opsins, of which melanopsin (OPN4) detects temperature UVA radiation. To evaluate the interaction between OPN4 radiation, normal malignant Opn4WT Opn4KO were exposed to three daily low doses (total 13.2 kJ/m2) radiation led a reduction proliferation in both cell lines; however, only this effect was associated with increased death by apoptosis. Daily stimuli induced persistent pigment darkening (PPD) lines. Upon Opn4 knockout, all...
Gliomas, the most common primary brain tumors in adults, are classified into four malignancy grades according to morphological features. Recent studies have shown that melatonin treatment induces cytotoxicity glioma-initiating cells and reduces invasion migration of glioma cell lines, inhibiting nuclear factor κB (NFκB) oncopathway. Given C6 rat produce melatonin, we investigated correlation between capacity gliomas synthesize/metabolize their overall malignancy. We first characterized...
Abstract Melatonin production by pineal glands is modulated several immune signals. The nuclear translocation of factor kappa‐B (NFκB) homodimers, lacking transactivation domains, once induced lipopolysaccharide (LPS) or tumor necrosis (TNF), inhibits the expression Aanat gene and synthesis noradrenaline (NA)‐induced melatonin. Interferon gamma (IFN‐γ), on other hand, increases melatonin synthesis. Furthermore, this cytokine activates signal transducer as well activator transcription 1...
Abstract Daily oscillation of the immune system follows central biological clock outputs control such as melatonin produced by pineal gland. Despite literature showing that is also synthesized macrophages and T lymphocytes, no information available regarding temporal profile melatonergic cells organs in steady-state. Here, expression enzymes arylalkylamine-N-acetyltransferase (AA-NAT), its phosphorylated form (P-AA-NAT) acetylserotonin-O-methyltransferase (ASMT) were evaluated phagocytes...
The pandemic dissemination of the SARS-CoV-2 led, on one hand, to a worldwide effort develop mechanistic-based therapeutics and vaccines, other searching for determining spreaders mechanisms transmission. Melatonin, multitask molecule, orchestrates defense responses by allowing proper mounting, duration, magnitude innate immune responses. Melatonin is synthesized demand immune-competent cells constitutively resident macrophages such as alveolar macrophages. Here we investigated whether...
Abstract Lower-grade gliomas (LGGs), which are uniformly fatal in young adults, classified as grades II-III tumors according to their histological features. The NFκB transcription factor, a crucial player cancer initiation and progression, is inactivated the cytoplasm by inhibitory proteins (IκBs) that have been shown exert tumor-suppressor activity. Therefore, using Cancer Genome Atlas copy number alteration RNA-Seq data from 398 patients, we evaluated association between expression dosage...
The imbalance between Th17 and regulatory T cells in inflammatory bowel diseases (IBD) promotes intestinal epithelial cell damage. In this scenario, helper lineage commitment is accompanied by dynamic changes to the chromatin that facilitate or repress gene expression.Here, we characterized landscape heterogeneity of peripheral CD4 cellsfrom IBD patients using house ATAC-Seq single RNA-Seq libraries.We show accessibility profiles from inflamed biopsies relate genes associated with a network...
Abstract Cultured cell lines are the workhorse of cancer research, but it is unclear to what extent they recapitulate cellular heterogeneity observed among malignant cells in tumors, given absence a native tumor microenvironment. Here, we used multiplexed single RNA-seq profile ~200 lines. We uncovered expression programs that recurrently heterogeneous within many and largely independent genetic diversity. These associated with diverse biological processes, including cycle, senescence,...
Melanoma skin cancer is extremely aggressive with increasing incidence and mortality. Among the emerging therapeutic targets in treatment of cancer, family transient receptor potential channels (TRPs) has been reported as a possible pharmacological target. Specifically, ankyrin subfamily, representing TRPA1 channels, can act pro-inflammatory hub. These have already implicated control intracellular metabolism several cell models, but little known about their role immune cells, how it could...