Carmine Settembre
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
Full Professor of Histology, Univ. of Naples Federico II · PI, TIGEM (since 2013) · postdoc, Columbia University & Baylor College of Medicine · PhD, University of Naples Federico II (2008, with Ballabio)
Settembre Lab, TIGEM (Telethon Institute of Genetics and Medicine) (Naples, Italy) ↗ Lab lineagetrained under Andrea Ballabio → ORCID0000-0002-5829-8589 ↗
Portrait: TIGEM (Telethon Institute of Genetics and Medicine)
As first author in Ballabio's lab (SET2011), showed that TFEB, already known as the master regulator of lysosome-building genes, also turns on autophagy genes, coordinating both programs. A year later (SET2012), in parallel with other groups, identified the sensor: mTORC1 phosphorylates TFEB directly on the lysosome, trapping it in the cytoplasm when nutrients are abundant.
Since 2013 at TIGEM, extended the mechanism into disease: hyperactive mTORC1 in lysosomal storage disorders stunts bone growth via autophagy suppression in cartilage; more recently contributed to a study, led by Davide Tampellini's group, linking synaptic activity to TFEB-mediated tau clearance in neurodegeneration models.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2011 | M | TFEB links autophagy to lysosomal biogenesis SET2011 First-authored the paper showing that TFEB also drives autophagy genes, linking autophagy to lysosomal biogenesis. |
| 2012 | M | A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB SET2012 mTORC1 sits on the lysosome and phosphorylates TFEB there. |
| 2013 | A | TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop SET2013 First author: TFEB drives its own transcription during starvation and controls liver lipid catabolism through PGC-1α and PPARα. |
Co-authors in the Atlas 5
People with a profile here who share at least one study with Carmine Settembre.
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- Andrea Ballabio 3 shared studies 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
- Tuong Huynh 3 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
- 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
- Roberto Zoncu 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
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