Luca Lignitto, PhD
Group Leader
Career summary
Throughout my career, I have been interested in the molecular mechanisms underlying the degradation of proteins controlled by the Ubiquitin-Proteasome System (UPS). For the last 14 years, I specialized in the study of E3 ubiquitin ligases, identifying their proteolytic substrates and defining the pathophysiological relevance of their degradation. For my investigations I acquired extensive expertise in a wide range of experimental methods of molecular biology, biochemistry, proteomics, genomics, and mouse models. During my PhD training in the lab of Dr. Antonio Feliciello at the University of Naples “Federico II” in Italy, I dissected the molecular machinery mediating the cross-regulation between the cyclic AMP signaling pathway and the UPS (Lignitto et al., Nature Cell Biol., 2011). As a postdoc, first, in my graduate student lab, and afterwards at New York University (NYU) in the USA, I focused my studies on the UPS-regulated signaling networks underpinning oncogenesis (Lignitto et al., Nature Commun., 2013) (Lignitto et al., Cell, 2019). In particular, during my postdoc in the lab of Dr. Michele Pagano at NYU, I uncovered the existence of a molecular network that links mutations of the oxidative stress pathway to alterations of the heme signaling and UPS-mediated protein degradation, which ultimately promotes oncogenesis. Currently, I am a Group Leader at the Marseille Cancer Research Centre (CRCM) and at the Centre national de la recherche scientifique (CNRS) in Marseille. My laboratory focuses on understanding how heme signaling and oxidative stress regulate cellular physiology and cancer pathogenesis. Our long-term goal is to identify new therapeutic approaches for cancer patients harboring alterations of the heme-oxidative stress pathway.
Luca Lignitto, PhD
Group Leader
Career summary
Throughout my career, I have been interested in the molecular mechanisms underlying the degradation of proteins controlled by the Ubiquitin-Proteasome System (UPS). For the last 14 years, I specialized in the study of E3 ubiquitin ligases, identifying their proteolytic substrates and defining the pathophysiological relevance of their degradation. For my investigations I acquired extensive expertise in a wide range of experimental methods of molecular biology, biochemistry, proteomics, genomics, and mouse models. During my PhD training in the lab of Dr. Antonio Feliciello at the University of Naples “Federico II” in Italy, I dissected the molecular machinery mediating the cross-regulation between the cyclic AMP signaling pathway and the UPS (Lignitto et al., Nature Cell Biol., 2011). As a postdoc, first, in my graduate student lab, and afterwards at New York University (NYU) in the USA, I focused my studies on the UPS-regulated signaling networks underpinning oncogenesis (Lignitto et al., Nature Commun., 2013) (Lignitto et al., Cell, 2019). In particular, during my postdoc in the lab of Dr. Michele Pagano at NYU, I uncovered the existence of a molecular network that links mutations of the oxidative stress pathway to alterations of the heme signaling and UPS-mediated protein degradation, which ultimately promotes oncogenesis. Currently, I am a Group Leader at the Marseille Cancer Research Centre (CRCM) and at the Centre national de la recherche scientifique (CNRS) in Marseille. My laboratory focuses on understanding how heme signaling and oxidative stress regulate cellular physiology and cancer pathogenesis. Our long-term goal is to identify new therapeutic approaches for cancer patients harboring alterations of the heme-oxidative stress pathway.
Luca Lignitto, PhD
Group Leader
Career summary
Throughout my career, I have been interested in the molecular mechanisms underlying the degradation of proteins controlled by the Ubiquitin-Proteasome System (UPS). For the last 14 years, I specialized in the study of E3 ubiquitin ligases, identifying their proteolytic substrates and defining the pathophysiological relevance of their degradation. For my investigations I acquired extensive expertise in a wide range of experimental methods of molecular biology, biochemistry, proteomics, genomics, and mouse models. During my PhD training in the lab of Dr. Antonio Feliciello at the University of Naples “Federico II” in Italy, I dissected the molecular machinery mediating the cross-regulation between the cyclic AMP signaling pathway and the UPS (Lignitto et al., Nature Cell Biol., 2011). As a postdoc, first, in my graduate student lab, and afterwards at New York University (NYU) in the USA, I focused my studies on the UPS-regulated signaling networks underpinning oncogenesis (Lignitto et al., Nature Commun., 2013) (Lignitto et al., Cell, 2019). In particular, during my postdoc in the lab of Dr. Michele Pagano at NYU, I uncovered the existence of a molecular network that links mutations of the oxidative stress pathway to alterations of the heme signaling and UPS-mediated protein degradation, which ultimately promotes oncogenesis. Currently, I am a Group Leader at the Marseille Cancer Research Centre (CRCM) and at the Centre national de la recherche scientifique (CNRS) in Marseille. My laboratory focuses on understanding how heme signaling and oxidative stress regulate cellular physiology and cancer pathogenesis. Our long-term goal is to identify new therapeutic approaches for cancer patients harboring alterations of the heme-oxidative stress pathway.
Luca Lignitto, PhD
Group Leader
Career summary
Throughout my career, I have been interested in the molecular mechanisms underlying the degradation of proteins controlled by the Ubiquitin-Proteasome System (UPS). For the last 14 years, I specialized in the study of E3 ubiquitin ligases, identifying their proteolytic substrates and defining the pathophysiological relevance of their degradation. For my investigations I acquired extensive expertise in a wide range of experimental methods of molecular biology, biochemistry, proteomics, genomics, and mouse models. During my PhD training in the lab of Dr. Antonio Feliciello at the University of Naples “Federico II” in Italy, I dissected the molecular machinery mediating the cross-regulation between the cyclic AMP signaling pathway and the UPS (Lignitto et al., Nature Cell Biol., 2011). As a postdoc, first, in my graduate student lab, and afterwards at New York University (NYU) in the USA, I focused my studies on the UPS-regulated signaling networks underpinning oncogenesis (Lignitto et al., Nature Commun., 2013) (Lignitto et al., Cell, 2019). In particular, during my postdoc in the lab of Dr. Michele Pagano at NYU, I uncovered the existence of a molecular network that links mutations of the oxidative stress pathway to alterations of the heme signaling and UPS-mediated protein degradation, which ultimately promotes oncogenesis. Currently, I am a Group Leader at the Marseille Cancer Research Centre (CRCM) and at the Centre national de la recherche scientifique (CNRS) in Marseille. My laboratory focuses on understanding how heme signaling and oxidative stress regulate cellular physiology and cancer pathogenesis. Our long-term goal is to identify new therapeutic approaches for cancer patients harboring alterations of the heme-oxidative stress pathway.
Luca Lignitto, PhD
Group Leader
Career summary
Throughout my career, I have been interested in the molecular mechanisms underlying the degradation of proteins controlled by the Ubiquitin-Proteasome System (UPS). For the last 14 years, I specialized in the study of E3 ubiquitin ligases, identifying their proteolytic substrates and defining the pathophysiological relevance of their degradation. For my investigations I acquired extensive expertise in a wide range of experimental methods of molecular biology, biochemistry, proteomics, genomics, and mouse models. During my PhD training in the lab of Dr. Antonio Feliciello at the University of Naples “Federico II” in Italy, I dissected the molecular machinery mediating the cross-regulation between the cyclic AMP signaling pathway and the UPS (Lignitto et al., Nature Cell Biol., 2011). As a postdoc, first, in my graduate student lab, and afterwards at New York University (NYU) in the USA, I focused my studies on the UPS-regulated signaling networks underpinning oncogenesis (Lignitto et al., Nature Commun., 2013) (Lignitto et al., Cell, 2019). In particular, during my postdoc in the lab of Dr. Michele Pagano at NYU, I uncovered the existence of a molecular network that links mutations of the oxidative stress pathway to alterations of the heme signaling and UPS-mediated protein degradation, which ultimately promotes oncogenesis. Currently, I am a Group Leader at the Marseille Cancer Research Centre (CRCM) and at the Centre national de la recherche scientifique (CNRS) in Marseille. My laboratory focuses on understanding how heme signaling and oxidative stress regulate cellular physiology and cancer pathogenesis. Our long-term goal is to identify new therapeutic approaches for cancer patients harboring alterations of the heme-oxidative stress pathway.
Important questions matter
“If I had an hour to solve a problem I'd spend 55 minutes thinking about the problem and five minutes thinking about solutions”… Albert Einstein
What we like to do:
The overarching goal of our laboratory is to discover how the signaling system controlled by the heme molecule regulates the life of the cells and intact organisms. We aim to explore its relationship with oxidative stress, and to dissect the role of this molecular axis in the mechanisms driving cancer formation and evolution.
While heme has been known for decades as an indispensable prosthetic group which allowed the development of aerobic life, more recent discoveries have demonstrated that heme exists also as an exchangeable molecule, capable of transmitting “messages” by dynamically and reversibly binding to proteins. The results of these pioneering studies brought to light novel functions of heme and showed that the heme “message or signal’’ orchestrates diverse and fundamental biological processes in a great variety of organisms throughout all kingdoms of life.
Our group recently discovered an unprecedented molecular mechanism allowing the heme-oxidative stress axis to regulate the activity of an E3 ubiquitin ligase to control the degradation of a heme-sensor transcription factor. We revealed how genetic mutations of this pathway in lung cancer patients critically sustain tumor progression.
Propelled by our curiosity, today’s research in our lab proceeds towards unexplored directions, which may lead us to understand fundamental mechanisms of cell biology and to design new strategies to advance cancer therapeutics.
Our main research avenues are:
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Tools and Methodologies:
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To address these questions, we use multidisciplinary approaches that leverage biochemical and molecular biology tools, together with proteomics and mouse genetics:
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We use biochemistry, cell, and molecular biology (e.g., WB, IP, PCR, qPCR, IF/IHC, confocal microscopy) to investigate at the amino acidic level the details of protein-protein interaction (PPI) and to dissect the mechanisms of protein-protein cross-regulation.
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Our lab implements mass spectrometry-based interactomic (e.g., GC-MS) analyses to reveal complex protein networks beyond individual PPI.
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We employ a wide range of high-throughput techniques to study the proteome and the transcriptome of the cells, including TMT-based whole proteome profiling, RNAseq and single cell RNAseq transcriptomic profiling.
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We have set up several in vitro cellular models, both normal and tumor cells, to understand the impact of the pathways we examine on cell biology as well as on the tumorigenic features of the cancer cells.
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We take advantage of different in vivo tumor models: (i) xenografts mouse models, to quickly analyze the results of our genetic and pharmacological approaches on tumor growth and dissemination; (ii) genetically engineered mouse models in combination with CRISPR/Cas9 editing systems, to elucidate the effects of our genetic manipulations on tumor development and progression.
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