A5043898676- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- Immune cells in cancer
- Advanced Proteomics Techniques and Applications
- DNA Repair Mechanisms
- Biochemical and Molecular Research
- Cellular transport and secretion
- Pancreatic function and diabetes
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Chromatin Remodeling and Cancer
- Cancer Research and Treatments
- Diabetes and associated disorders
- ATP Synthase and ATPases Research
- Nicotinic Acetylcholine Receptors Study
- Autophagy in Disease and Therapy
- Neuroscience and Neuropharmacology Research
- Cancer Genomics and Diagnostics
Centre for Genomic Regulation
2019-2025
Universitat Pompeu Fabra
2023-2024
Institute of Science and Technology
2023
CeMM Research Center for Molecular Medicine
2014-2021
Austrian Academy of Sciences
2014-2021
Institute for Research in Biomedicine
2011-2012
Institute for Research in Biomedicine
2011
University of Florence
2008-2009
Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types a major aim regenerative medicine. One promising approach transdifferentiation developmentally related types, including glucagon-producing α cells. In genetic model, loss master regulatory transcription factor Arx sufficient to induce conversion functional β-like Here, we identify artemisinins as small molecules that functionally repress causing its...
While cellular metabolism impacts the DNA damage response, a systematic understanding of metabolic requirements that are crucial for repair has yet to be achieved. Here, we investigate enzymes and processes essential resolution damage. By integrating functional genomics with chromatin proteomics metabolomics, provide detailed description interplay between response. Further analysis identified Peroxiredoxin 1, PRDX1, contributes repair. During PRDX1 translocates nucleus where it reduces...
Abstract Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme of the folate-mediated one-carbon metabolism pathway. MTHFD2 has become highly attractive therapeutic target due to its consistent upregulation in cancer tissues and major contribution tumor progression, although it also performs vital functions proliferating healthy cells. Here, we review diversity canonical non-canonical this key metabolic under physiological conditions carcinogenesis. We provide an...
Abstract CSF-1, by binding to its high-affinity receptor CSF-1R, sustains the survival and proliferation of monocyte/macrophages, which are central cells innate immunity inflammation. The MAPK ERK5 (also known as big MAPK-1, BMK1, or MAPK7) is a 98-kDa molecule sharing high homology with ERK1/2. activated oxidative stress growth factor stimulation. This study was undertaken characterize involvement in macrophage signaling that elicited CSF-1. Exposure CSF-1 primary human macrophages murine...
Abstract Background TP53, the most frequently mutated gene in human cancers, orchestrates a complex transcriptional program crucial for cancer prevention. While certain TP53-dependent genes have been extensively studied, others, like recently identified RNF144B, remained poorly understood. This E3 ubiquitin ligase has shown potent tumor suppressor activity murine Eμ Myc -driven lymphoma, emphasizing its significance TP53 network. However, little is known about targets and role development,...
ABSTRACT Accumulation of lipids in the tumor microenvironment (TME) is a feature several solid tumors and increased palmitate (PA) availability fosters progression metastases. The intrinsic effects PA on cancer cells are well understood, but its role modulating CD8 + T (CTL) functional performances remains elusive. Here, we found that alters mitochondrial metabolism CTL prevents their effector functions an irreversible manner, resulting impaired antitumoral immunity. Mechanistically,...
Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into scaffold. Here, we investigate chemical and genetic dependencies caused by mutations in folate enzyme MTHFD1 discover a key role for Nudix hydrolase 5 (NUDT5) regulating synthesis. Through knockout development selective NUDT5 degrader, uncover an unprecedented scaffolding rather than enzymatic activity responsible this phenotype. We find that interacts with...
Subcellular compartmentalization of metabolic enzymes establishes a unique environment that elicits specific cellular functions. Indeed, the nuclear translocation certain is required for epigenetic regulation and gene expression control. Here, we show localization mitochondrial enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) ensures mitosis progression. Nuclear MTHFD2 interacts with proteins involved in centromere stability, including methyltransferases KMT5A DNMT3B. Loss induces...
Abstract Triple‐negative breast cancer (TNBC) often develops resistance to single‐agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro vivo . Mechanistically, interacts nucleus with short isoform (BRD4S), MED1, cell cycle transcriptional regulator B‐MyB. These interactions sustain formation MED1 nuclear foci control progression at gene...
Abstract Macromolecular protein complexes carry out most functions in the cell including essential required for survival. Unfortunately, we lack subunit composition all human complexes. To address this gap integrated >25,000 mass spectrometry experiments using a machine learning approach to identify > 15,000 We show our map of is highly accurate and more comprehensive than previous maps, placing ∼75% proteins into their physical contexts. globally characterize co-variation data...
Nuclear metabolism and DNA damage response are intertwined processes, but the precise molecular links remain elusive. Here, we explore this crosstalk using triple-negative breast cancer (TNBC) as a model, subtype often prone to accumulation. We show that de novo purine synthesis enzyme IMPDH2 is enriched on chromatin in TNBC compared other subtypes. localization dependent, repression leads On chromatin, interacts with modulates PARP1 activity by controlling nuclear availability of NAD
While it is recognised that protein functions are determined by their proteoform state, such as mutations and post-translational modifications, methods to determine differential abundance between conditions limited. Here, we present a novel workflow for classical immunoprecipitation coupled mass spectrometry (IP-MS) data focuses on identifying peptidoforms of the bait conditions, providing additional information about function.
Abstract Proteins are often referred to as the workhorses of cells, and their interactions necessary facilitate specific cellular functions. Despite recognition that protein-protein interactions, thus protein functions, determined by proteoform states, such mutations post-translational modifications (PTMs), methods for determining differential abundance proteoforms across conditions very limited. Classically, immunoprecipitation coupled with mass spectrometry (IP-MS) has been used understand...