Ofer Moldavski
Researcher who worked on lysosomes and lipid signalling in Roberto Zoncu's lab at UC Berkeley and was first author of a 2021 study on how the oxysterol 4beta-hydroxycholesterol switches on fat-making genes
Department of Molecular and Cell Biology and Paul F. Glenn Center for Aging Research, University of California, Berkeley, and Cardiovascular Research Institute, UCSF (papers 2017–2021, at the time of the study)
Portrait: LinkedIn
Ofer Moldavski is a co-author of two Zoncu lab papers in this Atlas. Every cell has to decide whether it has enough raw materials to grow. mTORC1, the growth-control complex, makes that decision on the surface of the lysosome, the cell's recycling compartment, where it is switched on when nutrients are present. Amino acids were the best-known signal; CAS2017 showed that cholesterol inside the lysosome is another one. SLC38A9, a transporter-like protein already known to sense the amino acid arginine, is needed for cholesterol to switch mTORC1 on, and it uses separate cholesterol-responsive parts of the protein to do it. NPC1, the protein that moves cholesterol out of the lysosome and is faulty in Niemann-Pick type C disease, binds SLC38A9 and holds mTORC1 back. The experiments used cell lines and fibroblasts from patients, not whole animals. LAW2018 looked at the scaffold that holds the Rag GTPases on the lysosome, a protein complex called Ragulator. It found that nutrients change how tightly the Rags bind this scaffold, a switch that controls whether mTORC1 is pulled to the lysosome and turned on.
Moldavski was first author of a 2021 Journal of Lipid Research paper, with affiliations at UC Berkeley and the Cardiovascular Research Institute at UCSF. It reported that 4beta-hydroxycholesterol, an oxidised form of cholesterol, promotes fat production by switching on the master regulator SREBP1c through the liver X receptor.
No current position could be confirmed with certainty, so the affiliation shown is the one on the Atlas papers.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2017 | M | Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-Pick C1 signaling complex CAS2017 Co-author of the study showing that lysosomal cholesterol activates mTORC1 through SLC38A9 and NPC1. |
| 2018 | M | A nutrient-induced affinity switch controls mTORC1 activation by its Rag GTPase-Ragulator lysosomal scaffold LAW2018 Co-author of the study showing that nutrients flip an affinity switch between the Rag GTPases and Ragulator. |
Co-authors in the Atlas 10
People with a profile here who share at least one study with Ofer Moldavski.
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- Ashley M. Thelen Cell biologist who did graduate work in Roberto Zoncu's lysosome lab at UC Berkeley, first author of a 2017 review on the lysosome's roles in lipid metabolism, and later a postdoctoral scholar in Philip Greenberg's lab at Fred Hutch
- Brian M. Castellano Cell biologist who, in Roberto Zoncu's lab at UC Berkeley, showed that cholesterol inside the lysosome switches on mTORC1 through the SLC38A9 and NPC1 proteins
- Daniel K. Nomura Chemical biologist and professor at UC Berkeley who uses chemoproteomics to find druggable sites on proteins, including covalent handles that turn ordinary drug molecules into protein degraders
- Do Jin Kim Structural biologist, now at Denali Therapeutics, who worked in James Hurley's lab at UC Berkeley on the protein machines of autophagy and on the Rag-Ragulator complex that brings mTORC1 to the lysosome
- Douglas F. Covey Medicinal chemist and Andrew C and Barbara B Taylor Distinguished Professor of Psychiatry at Washington University in St. Louis who designs synthetic steroids and sterols to study neurosteroids, GABA-A receptors and cholesterol sensing, including in two Atlas studies on cholesterol and mTORC1
- James H. Hurley 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
- Oliver B. Davis Cell biologist who did a PhD in Roberto Zoncu's lab at UC Berkeley on how lysosomal cholesterol controls mTORC1, and first author of a 2020 study proposing NPC1-mTORC1 signalling as a drug target in Niemann-Pick type C disease
- 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
- Rosalie E. Lawrence Working in Roberto Zoncu's lab, uncovered the nutrient-driven affinity switch and the FLCN checkpoint that gate mTORC1 activation at the lysosome
- Rushika M. Perera Professor of Anatomy at UCSF whose lab studies how autophagy and the lysosome, the cell's recycling centre, help cancer cells cope with stress, and a co-author of two Science papers on how lysosomal cholesterol switches on mTORC1
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