Andrea Ballabio
Discovered that the transcription factor TFEB is a master switch for building lysosomes (SAR2009) and for autophagy. His lab was one of the groups that showed in 2012 that mTORC1 keeps TFEB out of the nucleus from the lysosome surface, and later (2020) that constitutive TFEB activation drives the kidney disease of Birt-Hogg-Dubé syndrome
Professor of Medical Genetics, University of Naples Federico II · founding director of the Telethon Institute of Genetics and Medicine (TIGEM), Naples (1994–2024), now principal investigator there · MD, University of Naples
Ballabio Lab, TIGEM (Naples, Italy) ↗ Lab lineage1 direct trainee → ORCID0000-0003-1381-4604 ↗
Portrait: TIGEM
Andrea Ballabio trained as a pediatrician in Naples before moving into genetics, first identifying disease genes at Baylor College of Medicine in Houston and then, from 1994, building TIGEM (founded in Milan, based in the Naples area since 2000) into one of Europe's leading rare-disease research institutes.
His lab, in parallel with the groups of Rosa Puertollano and Shawn Ferguson, showed that TFEB, a transcription factor best known for driving lysosomal and autophagy genes, is itself a direct substrate of mTORC1: when nutrients are abundant, mTORC1 phosphorylates TFEB and keeps it out of the nucleus, and during starvation TFEB moves in and switches on a program of lysosomal biogenesis and clearance. The finding reframed the lysosome as a signalling hub that talks back to mTORC1, not just a passive recycling bin.
The timeline below follows Ballabio's contributions gathered in this Atlas.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2009 | M | A gene network regulating lysosomal biogenesis and function SAR2009 Senior author: identifies TFEB as the transcription factor that binds the CLEAR motif and coordinates lysosomal gene expression and lysosome production. |
| 2011 | M | TFEB links autophagy to lysosomal biogenesis SET2011 Shows TFEB links autophagy induction to lysosomal biogenesis, with TFEB's nuclear localization controlled by ERK2-mediated phosphorylation. |
| 2012 | M | A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB SET2012 Shows mTORC1 phosphorylates TFEB at the lysosomal membrane and controls its nuclear entry, revealing a lysosome-to-nucleus signalling loop. |
| 2013 | A | TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop SET2013 Senior author: TFEB drives its own expression during starvation and controls liver lipid breakdown through PGC-1α and PPARα (mice, worms). |
| 2020 | M | A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome. NAP2020 Shows a substrate-specific mTORC1 pathway underlies Birt-Hogg-Dube syndrome, tying TFEB/TFE3 regulation to a hereditary kidney-tumour disorder. |
| 2023 | M | Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex CUI2023 First structural view of how mTORC1 actually reaches TFEB to phosphorylate it: two full Rag-Ragulator complexes present a single TFEB molecule to the mTOR active site, one in the normal Raptor-docking arrangement and a second, non-canonical one that grips TFEB's own first helix. Mutating that grip point drives TFEB straight into the nucleus (turning on autophagy/lysosome genes) without disturbing where mTORC1 itself sits. Explains, at the level of atoms, why TFEB phosphorylation needs the tumour suppressor FLCN and the GDP-loaded state of RagC in a way the authors report for no other mTORC1 substrate. Boundary: cryo-EM of a complex reconstituted from purified human proteins — a static structural snapshot, not a live cell or a real-time measurement. |
| 2025 | M | Structural basis for mTORC1 activation on the lysosomal membrane CUI2025 Resolves how mTORC1 flips from 'parked on the lysosome' to 'catalytically switched on'. Reconstituting the whole assembly on membranes from purified Rheb, Rag GTPases, Ragulator and mTORC1, cryo-EM shows the kinase reaches full activity only after two separate anchoring steps: Rag-Ragulator first pulls it to within about 100 angstroms of the membrane, then Rheb pulls it to within about 40 angstroms, and only when Raptor and mTOR itself also touch the membrane directly do the catalytic residues line up for full activity. Growth-factor input (via Rheb) and nutrient input (via the Rags) are shown converging on the same physical docking event rather than acting through separate switches. Boundary: reconstituted on synthetic membranes from purified components — a structural/biochemical model, not a measurement inside a living cell. |
| 2026 | M | A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation. ESP2026 Co-author on the TBK1/ULK1 pathway that regulates FLCN-dependent TFEB activation, linking lysosomal v-ATPase signalling to recurrent ATP6V1B2 mutations in follicular lymphoma. |
| 2026 | A | Non-canonical mTORC1-TFEB activation promotes hepatocyte plasticity and high-grade malignancy in hepatocellular carcinoma. ZHANG2026 Co-author: TSC1 loss drives non-canonical mTORC1-TFEB activation and aggressive liver cancer (mice, human HCC). |
| 2026 | A | mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation ZAU2026 Co-author on a study showing mTORC1-TFEB/TFE3 signaling state shapes bile-acid diversification during hepatic metabolic adaptation, linking his TFEB/TFE3 axis to liver bile-acid metabolism and MASLD. |
| 2026 | A | Synergistic role of TFEB/TFE3 and mTORC1 in kidney cystogenesis and tumorigenesis FER2026 Using kidney-specific mouse models that genetically uncouple mTORC1 activity from TFEB/TFE3 activity (Depdc5-KO, RagC-KO, and Flcn/RagC double-KO), the authors show mTORC1 hyperactivation -- not TFEB/TFE3 activation alone -- is the primary driver of kidney cystogenesis and tumorigenesis in Birt-Hogg-Dube and Tuberous Sclerosis Complex models. Constitutive TFEB/TFE3 activity further accelerates disease on top of mTORC1-driven pathology. |
Co-authors in the Atlas 22
People with a profile here who share at least one study with Andrea Ballabio.
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- Alessandra Esposito 4 shared studies Lysosomal signalling and TFEB regulation
- Gennaro Napolitano 4 shared studies mTORC1-TFEB lysosomal signalling
- Tuong Huynh 4 shared studies Research associate at Baylor College of Medicine in Houston and co-author on a long run of papers from Andrea Ballabio's group on TFEB, the master switch for lysosome and autophagy genes, including the work that tied TFEB to mTOR, starvation and fat metabolism
- Alessia Calcagnì 3 shared studies TIGEM researcher on the TFEB/TFE3 side of mTORC1 signalling; co-author on the lysosomal stress route to TFEB activation and on mouse models separating mTORC1 from TFEB/TFE3 in kidney cysts and tumours.
- Carmine Settembre 3 shared studies Showed, as first author in Andrea Ballabio's lab, that TFEB drives autophagy as well as lysosome production, and, in parallel with other groups, that mTORC1 phosphorylates TFEB at the lysosome to keep this program switched off when nutrients are plentiful
- James H. Hurley 3 shared studies Structural biologist who uses cryo-EM to show how protein machines assembled on membranes control autophagy and nutrient signalling. His lab solved structures of the Rag–Ragulator complex and of the whole mTORC1–TFEB–Rag–Ragulator assembly on the lysosome
- Jlenia Monfregola 3 shared studies TIGEM postdoc and co-author on the cryo-EM structure of the mTORC1–TFEB–Rag–Ragulator megacomplex and on the TBK1/ULK1 lysosomal stress route to TFEB.
- Lukas A. Huber 2 shared studies Cell biologist who studied the p14-MP1 scaffold on late endosomes, a complex later recognised as part of Ragulator (LAMTOR), the lysosomal platform that holds mTORC1 in place
- Mariana de Araujo 2 shared studies Cell biologist in Lukas Huber's group in Innsbruck who solved the crystal structure of the Ragulator (LAMTOR) complex, the lysosomal platform on which mTORC1 is switched on
- Roberto Zoncu 2 shared studies Showed as a postdoc that mTORC1 senses amino acids from inside the lysosome, through the v-ATPase and Ragulator. His Berkeley lab has since mapped how the Rag GTPases and the folliculin complex switch mTORC1 on, and how lysosomal cholesterol feeds into the same system
- Zhicheng Cui 2 shared studies Structural biologist who solved cryo-EM structures of the mTORC1–TFEB–Rag–Ragulator megacomplex and of mTORC1 switched on by RHEB and the Rags on a lipid membrane.
- Alex Zaufel Researcher studying bile acid metabolism and mTORC1 signaling in liver disease
- David M. Sabatini Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
- Diego L. Medina Cell biologist at the Telethon Institute of Genetics and Medicine in Naples who showed how TFEB, the master switch for lysosome genes, is controlled by calcium released from lysosomes, and who works on lysosomal storage diseases
- Chen Zhang Ran the liver-specific Tsc1-knockout mouse study showing that non-canonical mTORC1–TFEB activation drives hepatocyte plasticity and aggressive liver cancer
- Jörn Dengjel Mass-spectrometry proteomics specialist in autophagy and protein homeostasis; co-author on the TBK1/ULK1–TFEB lysosomal stress pathway and on the spermidine lifespan and cardioprotection study.
- Marco Ferniani First author of the study showing mTORC1 hyperactivation, not TFEB/TFE3 activity itself, is the primary driver of kidney cystogenesis and tumorigenesis in mouse models of Birt-Hogg-Dubé and Tuberous Sclerosis
- Marco Sardiello Geneticist who, in Andrea Ballabio's group, helped show that lysosomal genes share a promoter motif and are switched on together by the transcription factor TFEB; his lab now works on lysosomal storage diseases, especially the neuronal ceroid lipofuscinoses.
- Rachel M. Jansen First author of the cryo-EM structure showing how the arginine sensor CASTOR1 binds the GATOR2 cage when arginine is low and is released when arginine returns
- Taras Stasyk Protein chemist in Lukas Huber's group in Innsbruck who has spent two decades applying proteomics to the late endosomes and lysosomes where mTORC1 is controlled
- Tarek Moustafa Researcher in hepatic metabolism and bile acid signaling
- Wen-Xing Ding Studies autophagy and mitophagy in liver injury and the roles of Nrf2 and mTOR in liver disease and cancer
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On the programme
Meetings in the Atlas calendar where Andrea Ballabio is listed among the speakers or organisers.
- upcoming Keystone Symposia: Tumor and Host Metabolism – Integrating Molecular, Cellular, and Systemic Interactions 2027 ↗ 7–10 Mar 2027 ·
Princeton, NJ, USA · ★★ Add to calendar:
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