A5007412481- Gene Regulatory Network Analysis
- Single-cell and spatial transcriptomics
- Fungal and yeast genetics research
- Microfluidic and Capillary Electrophoresis Applications
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
- Viral Infectious Diseases and Gene Expression in Insects
- Microtubule and mitosis dynamics
- Pancreatic function and diabetes
- Microbial Metabolic Engineering and Bioproduction
- Yeasts and Rust Fungi Studies
- Neuroblastoma Research and Treatments
- Cancer Cells and Metastasis
- Plant Molecular Biology Research
- Microfluidic and Bio-sensing Technologies
- Transgenic Plants and Applications
- Autophagy in Disease and Therapy
- Immune cells in cancer
- Lung Cancer Research Studies
- Nonlinear Dynamics and Pattern Formation
- Calcium signaling and nucleotide metabolism
- Molecular Communication and Nanonetworks
Telethon Institute Of Genetics And Medicine
2018-2025
University of Naples Federico II
2018-2025
Dana-Farber Cancer Institute
2019-2024
InBio: Experimental and Computational Methods for Modeling Cellular Processes
2023
Harvard University
2022
Université Paris Cité
2022
Institut Pasteur
2022
Broad Institute
2013-2022
Institut national de recherche en informatique et en automatique
2022
Abstract Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated fresh tumors, single-nucleus (snRNA-Seq) needed profile frozen or hard-to-dissociate tumors. Each requires customization different tissue and types, posing a barrier adoption. Here, we have developed systematic toolbox for profiling clinical samples using scRNA-Seq snRNA-Seq, respectively. We analyzed 216,490 nuclei 40 across 23 specimens spanning...
Immune checkpoint blockade (ICB) results in durable disease control a subset of patients with advanced renal cell carcinoma (RCC), but mechanisms driving resistance are poorly understood. We characterize the single-cell transcriptomes cancer and immune cells from metastatic RCC before or after ICB exposure. In responders, subsets cytotoxic T express higher levels co-inhibitory receptors effector molecules. Macrophages treated biopsies shift toward pro-inflammatory states response to an...
SUMMARY Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage with complex inter- and intra-tumoral heterogeneity. To chart this complexity, we generated comprehensive cell atlas of 55 neuroblastoma patient tumors, collected two institutions, spanning range clinical, genetic, histologic features. Our combines single-cell/nucleus RNA-seq (sc/scRNA-seq), bulk RNA-seq, whole exome sequencing, DNA methylation profiling, spatial transcriptomics, proteomic...
Divergence in gene regulation can play a major role evolution. Here, we used phylogenetic framework to measure mRNA profiles 15 yeast species from the phylum Ascomycota and reconstruct evolution of their modular regulatory programs along time course growth on glucose over 300 million years. We found that modules have diverged proportionally distance, with prominent changes accompanying lifestyle ploidy, especially carbon metabolism. Paralogs significantly contributed divergence, typically...
Gene networks and signaling pathways display complex topologies and, as a result, nonlinear behaviors. Accumulating evidence shows that both static (concentration) dynamical (rate-of-change) features of transcription factors, ligands environmental stimuli control downstream processes ultimately cellular functions. Currently, however, methods to generate with the desired probe cell response are still lacking. Here, combining tools from Control Engineering Synthetic Biology (cybergenetics), we...
Transcription Factor EB (TFEB) controls lysosomal biogenesis and autophagy in response to nutritional status other stress factors. Although its regulation by nuclear translocation is known involve a complex network of well-studied regulatory processes, the precise contribution each these mechanisms unclear. Using microfluidics technology real-time imaging coupled with mathematical modelling, we explored dynamic TFEB under different conditions. We found that upon nutrient deprivation happens...
Abstract Optimizing the production of recombinant proteins is a problem major industrial and pharmaceutical importance. Secretion protein by host cell considerably simplifies downstream purification processes. However, for many proteins, this also limiting step. Current solutions involve extensive engineering chassis to facilitate trafficking limit degradation triggered excessive secretion-associated stress. Here, we propose instead regulation-based strategy in which induction dynamically...
Extracting quantitative measurements from time-lapse images is necessary in external feedback control applications, where segmentation results are used to inform algorithms. We describe ChipSeg, a computational tool that segments bacterial and mammalian cells cultured microfluidic devices imaged by microscopy, which can be also the context of control. The method based on thresholding uses same core functions for both cell types. It allows us segment individual high density devices, quantify...
Controlling cell fate has great potential for regenerative medicine, drug discovery, and basic research. Although transcription factors are able to promote reprogramming transdifferentiation, methods based on their upregulation often show low efficiency. Small molecules that can facilitate conversion between types ameliorate this problem working through safe, rapid, reversible mechanisms. Here, we present DECCODE, an unbiased computational method identification of such transcriptional data....
Abstract The cell cycle is the process by which eukaryotic cells replicate. Yeast asynchronously with each in population budding at a different time. Although there are several experimental approaches to synchronise cells, these usually work only short-term. Here, we build cyber-genetic system achieve long-term synchronisation of population, interfacing genetically modified yeast computer means microfluidics dynamically change medium, and microscope estimate phases individual cells....
Abstract Single cell genomics is essential to chart the complex tumor ecosystem. While single RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated fresh tissues, nucleus (snRNA-Seq) needed profile frozen or hard-to-dissociate tumors. Each strategy requires modifications fit unique characteristics of different tissue and types, posing a barrier adoption. Here, we developed systematic toolbox for profiling clinical samples using scRNA-Seq snRNA-Seq, respectively. We tested eight types...
Reliable quantification of cellular treatment effects in many bioassays depends on the accuracy cell colony counting. However, counting processes tend to be tedious, slow, and error-prone. Thus, pursuing an effective technique is ongoing, varies from manual approaches partly automated fully techniques. Most techniques were developed using deep learning (DL). A significant problem applying DL this task lack sizeable collections annotated plate images. For reason, here we propose application...
Cells are defined by their unique ability to self-replicate through cell division. This periodic process is known as the cell-cycle and it happens with a period in each cell. The budding yeast divides asymmetrically mother generating multiple daughter cells. Within population same but asynchronously. Here, we investigate problem of synchronising across cells microfluidics-based feedback control platform. We propose theoretical experimental approach for considering strain that can be forced...
The periodic process of cell replication by division, known as cell-cycle, is a natural phenomenon occurring asynchronously in any population. Here, we consider the problem synchronising cell-cycles across population yeast cells grown microfluidics device. Cells were engineered to reset their cell-cycle response low methionine levels. Automated syringes enable changing levels (control input) However, control input resets only those that are specific phase (G1 phase), while others continue...
The transcription factor EB (TFEB) is a key component of the transcriptional regulation lysosomal biogenesis and autophagy in response to starvation. Autophagy self-degradative process activated by cells survive during nutrient deficiency. In normal conditions, TFEB sequestered cytoplasm through phosphorylation. Following starvation, dephosphorylated translocates into nucleus binding DNA promoting activation its target genes. Here, we developed quantitative dynamical model elucidate...
Abstract Controlling cell fate has great potential for regenerative medicine, drug discovery, and basic research. Although numerous transcription factors have been discovered that are able to promote reprogramming trans-differentiation, methods based on their up-regulation tend show low efficiency. The identification of small molecules can facilitate conversion between types ameliorate this problem working through safe, rapid, reversible mechanisms. Here we present DECCODE, an unbiased...
ABSTRACT Extracting quantitative measurements from time-lapse images is necessary in external feedback control applications, where segmentation results are used to inform algorithms. While such image applications have been previously reported, there the literature a lack of open-source and documented code for community. We describe ChipSeg, computational tool segment bacterial mammalian cells cultured microfluidic devices imaged by microscopy. The method based on thresholding uses same core...
Abstract The production of recombinant proteins is a problem major industrial and pharmaceutical importance. Secretion the protein by host cell considerably simplifies downstream purification processes. However, it also limiting step for many hard-to-secrete proteins. Current solutions involve extensive chassis engineering to favor trafficking limit degradation triggered excessive secretion-associated stress. Here, we propose instead regulation-based strategy in which induction dynamically...
ABSTRACT Neuroendocrine tumors (NETs) are rare cancers that may arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP) NET growth remain incompletely elucidated; however, heterogeneous clinical behavior of GEP-NETs suggests both cellular lineage dynamics tumor microenvironment influence pathophysiology. Here, we investigated single-cell transcriptomes immune cells from patients with NETs. Malignant GEP-NET expressed genes regulons...
The Transcription Factor EB (TFEB) plays a pivotal role in the transcriptional regulation of lysosomal biogenesis and autophagy response to starvation. TFEB activity is regulated by kinase mTOR. In nutrient-rich conditions, mTOR phosphorylates sequestering it cytoplasm. During starvation, inhibited unphosphorylated translocates into nucleus, where regulates expression its target genes. We performed an experiment monitoring real-time nuclear localization individual cells growing microfluidics...