A5046067488- Protein Structure and Dynamics
- Retinoids in leukemia and cellular processes
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Machine Learning in Bioinformatics
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- Advanced Proteomics Techniques and Applications
- Acute Myeloid Leukemia Research
- Neuroblastoma Research and Treatments
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Aortic Disease and Treatment Approaches
- Genetic Associations and Epidemiology
- Cellular transport and secretion
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Mass Spectrometry Techniques and Applications
- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- Enzyme Structure and Function
- Lung Cancer Treatments and Mutations
- Connective tissue disorders research
- Ovarian cancer diagnosis and treatment
- Celiac Disease Research and Management
Politecnico di Milano
2014-2024
Centro Cardiologico Monzino
2023-2024
Bioengineering Technology and Systems (Italy)
2019
Lund University
2008
Leonardo (United Kingdom)
2006
University of Milan
2003
Previous genome-wide scans of positive natural selection in humans have identified a number non-neutrally evolving genes that play important roles skin pigmentation, metabolism, or immune function. Recent studies also shown pattern local adaptation can be detected by identifying correlations between patterns allele frequencies and environmental variables. Despite these observations, the degree to which is primarily driven environments, role pathogens other ecological factors as selective...
The genetic bases of many complex phenotypes are still largely unknown, mostly due to the polygenic nature traits and small effect each associated mutation. An alternative approach classic association studies determining such is an evolutionary framework. As sites targeted by natural selection likely harbor important functionalities for carrier, identification signatures in genome has potential unveil mechanisms underpinning human phenotypes. Popular methods detecting signals rely on...
Synaptosomal-associated protein of 25 kDa (SNAP-25) is a that participates in the regulation synaptic vesicle exocytosis through formation soluble NSF attachment receptor complex and modulates voltage-gated calcium channels activity. The Snap25 gene has been associated with schizophrenia, attention deficit hyperactivity disorder, bipolar lower levels SNAP-25 have described patients schizophrenia. We used heterozygous (SNAP-25+/−) mice to investigate at which extent reduction affects neuronal...
Synaptosomal-associated protein of 25 kDa (SNAP-25) is involved in different neuropsychiatric disorders, including schizophrenia and attention-deficit/hyperactivity disorder. Consistently, SNAP-25 polymorphisms humans are associated with hyperactivity and/or low cognitive scores. We analysed five gene (rs363050, rs363039, rs363043, rs3746544 rs1051312) 46 autistic children trying to correlate them Childhood Autism Rating Scale electroencephalogram (EEG) abnormalities. The functional effects...
Forty-two cell lines recapitulating mammary carcinoma heterogeneity were profiled for all-trans retinoic acid (ATRA) sensitivity. Luminal and ER(+) (estrogen-receptor-positive) are generally sensitive to ATRA, while refractoriness/low sensitivity is associated with a Basal phenotype HER2 positivity. Indeed, only 2 (MDA-MB157 HCC-1599) highly the retinoid. Sensitivity of HCC-1599 cells confirmed in xenotransplanted mice. Short-term tissue-slice cultures surgical samples validate cell-line...
Elucidating the molecular basis of tumor metastasis is pivotal for eradicating cancer-related mortality. Triple-negative breast cancer (TNBC) encompasses a class aggressive tumors characterized by high rates recurrence and metastasis, as well poor overall survival. Here, we find that promyelocytic leukemia protein PML exerts prometastatic function in TNBC can be targeted arsenic trioxide. We found that, patients, constitutive HIF1A activity induces expression PML, along with number target...
Alternative splicing in the brain is dynamic and instrumental to adaptive changes response stimuli. Lysine-specific demethylase 1 (LSD1/KDM1A) a ubiquitously expressed histone H3Lys4 that acts as transcriptional co-repressor complex with its molecular partners CoREST HDAC1/2. In mammalian brain, alternative of LSD1 mini-exon E8a gives rise neuroLSD1, neurospecific isoform that, upon phosphorylation, dominant-negative causing disassembly de-repression target genes. Here we show LSD1/neuroLSD1...
Thoracic aortic aneurysm is a life-threatening condition due to either genetic syndromes (e.g., Marfan syndrome) or cardiovascular risk factors hypertension, aging and smoking), which favour the onset of sporadic thoracic aneurysms. Activation transforming growth factor-β pathway dysregulation mechanotransduction signals in vascular smooth muscle cells play key role development both syndromic forms aneurysm. The precise molecular mechanisms underlying progression are still unresolved...
Label-free LC-MS analysis allows determining the differential expression level of proteins in multiple samples, without use stable isotopes. This technique is based on direct comparison runs, obtained by continuous detection MS mode. Only differentially expressed peptides are selected for further fragmentation, thus avoiding bias toward abundant typical data-dependent tandem MS. The computational framework includes detection, alignment, normalization and matching peaks across sets, several...
Previous genome-wide scans of positive natural selection in humans have identified a number non-neutrally evolving genes that play important roles skin pigmentation, metabolism, or immune function.Recent studies also shown pattern local adaptation can be detected by identifying correlations between patterns allele frequencies and environmental variables.Despite these observations, the degree to which is primarily driven environments, role pathogens other ecological factors as selective...
Common variants in the UMOD gene encoding uromodulin, associated with risk of hypertension and CKD general population, increase expression urinary excretion causing salt-sensitive renal lesions. To determine effect selective pressure on variant frequency, we investigated allelic frequency lead rs4293393 156 human populations, eight ancient genomes, primate genomes. The T allele rs4293393, risk, has high most modern populations was one detected In contrast, identified only derived, C...
Abstract Acute promyelocytic leukemia ( APL ) is epitomized by the chromosomal translocation t(15;17) and resulting oncogenic fusion protein PML ‐ RAR α. Although acting primarily as a transcriptional repressor, α can also exert functions of co‐activation. Here, we find that stimulates transcription driven HIF factors, which are critical regulators adaptive responses to hypoxia stem cell maintenance. Consistently, ‐related gene signatures upregulated in leukemic promyelocytes from patients...
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a focal form of characterized by seizures occurring during non-REM sleep. We have developed and the first mouse model for ADNFLE type III carrying V287L mutation β2 subunit neuronal nicotinic receptor. Mice expressing mutant receptors show spontaneous epileptic phenotype electroencephalography with very frequent interictal spikes seizures. Expression driven neuronal-specific tetracycline-controlled promoter, which allows planned...
All-trans retinoic acid (ATRA), a recognized differentiating agent, has significant potential in the personalized/stratified treatment of breast cancer. The present study reports on molecular mechanisms underlying anti-tumor activity ATRA work is based transcriptomic experiments performed ATRA-treated cancer cell-lines, short-term tissue cultures patient-derived mammary-tumors and xenograft model. upregulates gene networks involved interferon-responses, immune-modulation antigen-presentation...
We present a new method for rejecting noise from HPLC–MS data sets. The algorithm reveals peptides at low concentrations by minimizing both the chemical and random noise. goal is reached through systematic approach to characterize remove background. are represented as two-dimensional maps, in order optimally exploit complementary dimensions of separation offered LC−MS technique. virtual chromatograms, reconstructed spectrographic data, have proved be more suitable than raw mass spectra. By...
In chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival, and expansion. However, nature of cells molecular pathways involved remain largely unknown. Here, we demonstrate that leukemic B lymphocytes induce activation retinoid acid synthesis signaling microenvironment. Inhibition RA-signaling causes deregulation genes associated with adhesion, tissue organization chemokine secretion...
High-grade serous epithelial ovarian cancer (HGS-EOC) is a systemic disease, with marked intra and interpatient tumor heterogeneity. The issue of spatial temporal heterogeneity has long been overlooked, hampering the possibility to identify those genomic alterations that persist, before after therapy, in genome all cells across different anatomical districts. This knowledge first step clarify molecular determinants characterize biology HGS-EOC their route toward malignancy. In our study,...