A5087565406- Cancer-related Molecular Pathways
- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- Colorectal Cancer Treatments and Studies
- Heat shock proteins research
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Blood Coagulation and Thrombosis Mechanisms
- Carcinogens and Genotoxicity Assessment
- Connexins and lens biology
- Immune cells in cancer
- Genetic factors in colorectal cancer
- Genomics and Chromatin Dynamics
- Effects and risks of endocrine disrupting chemicals
- Chronic Lymphocytic Leukemia Research
- Toxic Organic Pollutants Impact
- Prostate Cancer Treatment and Research
- Phagocytosis and Immune Regulation
- CRISPR and Genetic Engineering
- Hormonal and reproductive studies
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
Università della Svizzera italiana
2024
Institute of Oncology Research
2023-2024
Weizmann Institute of Science
2021-2022
University of Sussex
2021
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, which refractory to all currently available treatments and bears dismal prognosis. About 70% of PDAC cases harbor mutations in the TP53 tumor suppressor gene. Many those are missense mutations, resulting abundant production mutant p53 (mutp53) protein cancer cells. Analysis human patient data from The Cancer Genome Atlas (TCGA) revealed negative association between presence mutp53 infiltration CD8+ T cells into tumor....
The TP53 gene is mutated in approximately 60% of all colorectal cancer (CRC) cases. Over 20% TP53-mutated CRC tumors carry missense mutations at position R175 or R273. Here we report that harboring R273 are more prone to progress metastatic disease, with decreased survival, than those mutations. We identify a distinct transcriptional signature orchestrated by p53R273H, implicating activation oncogenic signaling pathways and predicting worse outcome. These features shared also the hotspot...
Abstract The MRN complex (MRX in Saccharomyces cerevisiae , made of Mre11, Rad50 and Nbs1/Xrs2) initiates double-stranded DNA break repair activates the Tel1/ATM kinase damage response. Telomeres counter both outcomes at chromosome ends, partly by keeping MRN-ATM check. We show that MRX is disabled telomeric protein Rif2 through an N-terminal motif (MIN, M RN/X- hibitory motif). MIN executes suppression Tel1, end-resection non-homologous end joining binding region. Our data suggest promotes...
Missense mutations in the p53 tumor suppressor abound human cancer. Common (“hotspot”) endow mutant (mutp53) proteins with oncogenic gain of function (GOF), including enhanced cell migration and invasiveness, favoring cancer progression. GOF is usually attributed to transcriptional effects mutp53. To elucidate transcription-independent mutp53, we characterized protein interactome p53R273H cells derived from pancreatic ductal adenocarcinoma (PDAC), where most frequent mutant. We now report...
Abstract The MRN complex (MRX in Saccharomyces cerevisiae ) initiates the repair of DNA double-stranded breaks (DSBs) and activates Tel1/ATM kinase, which orchestrates damage response (DDR). Telomeres prevent DDR activation at chromosome ends, partly by keeping MRN-ATM check. We show that multiple activities MRX are disabled telomeric protein Rif2 through action a short motif (MIN, M RN/X- hibitory motif) N-terminal end protein. MIN executes suppression Tel1, non-homologous joining (NHEJ)...
Abstract Colorectal cancer (CRC) is the third most common worldwide. The TP53 gene mutated in approximately 60% of all CRC cases. Sporadic characterized by high prevalence hotspot missense mutations. In particular, over 20 percent -mutated tumors carry either p53 R175H structural mutant or R273H DNA contact mutant. Importantly, clinical data analysis suggests that harboring R273 mutations are more prone to progress metastatic disease than those with R175 mutations, association decreased...