Lynsey Meikle

Researcher in David Kwiatkowski's tuberous sclerosis lab at Brigham and Women's Hospital who built a mouse model of TSC in the brain and showed that mTOR blockers rescue it

Division of Translational Medicine, Brigham and Women's Hospital and Harvard Medical School, Kwiatkowski lab (papers 2005–2009, at the time of the study)

In tuberous sclerosis complex (TSC), loss of the TSC1 or TSC2 gene removes the brake on mTORC1, the growth-control complex, and the brain is often hit hardest, with seizures, learning problems and autism. Lynsey Meikle, working in David Kwiatkowski's lab in Boston, first built a mouse in which most nerve cells of the cerebral cortex lose Tsc1 during development. Published in 2007, these mice had enlarged, misplaced neurons, delayed myelination, seizures and a median survival of only 35 days, which made them a model of the human brain disease.

In the Atlas paper (MEI2008), Meikle and colleagues treated these mice with rapamycin and the related drug RAD001 (everolimus). The drugs switched off the overactive mTORC1 signal, restored Akt signalling, and greatly improved survival and brain function. This mouse work was part of the evidence that led to testing mTOR blockers in people with TSC, where everolimus is now used for brain and kidney tumours and for seizures.

Meikle also contributed to a 2009 study with Mustafa Sahin's group showing that neurons lacking the TSC complex suffer high stress in the endoplasmic reticulum, a protein-folding compartment, which rapamycin reversed. No later papers or current position could be found, so the affiliation shown is the one on the Atlas paper.

Milestones in the Atlas

A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.

Co-authors in the Atlas 1

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