Dr Florian Merkle

Research Interests

The Merkle laboratory was for many years part of the IMS-MRL: but recently (2025) moved to the Department of Pharmacology.

The research group aims to uncover the mechanistic basis of human neurological diseases using human pluripotent stem cell (hPSC)-derived culture systems in order to facilitate the development of effective treatments. They use a variety of techniques including CRISPR/Cas9-based genome engineering, single-cell transcriptomics, quantitative proteomics, high content imaging, calcium imaging, and organoid and other co-culture systems. These studies are funded by the Royal Society and Wellcome Trust, the New York Stem Cell Foundation and the Chan Zuckerberg Initiative. Their research focuses on three main areas:

1) Models of obesity and neurodegeneration

2) Therapeutic translation

3) Genetic stability in human stem cells

Publications

Key publications:

Harding EC, Chen H-J C, Shepilov D,  Zhang SO,  Rowley C, Mali I, Chen J,  Stewart N,  Swinden D,  Washer SJ,  Bassett AR,  Merkle FT. Unbiased preclinical phenotyping reveals neuroprotective properties of pioglitazone. bioRxiv.  https://doi.org/10.1101/2024.08.30.610328

Harding EC, Chen H-J C, Shepilov D,  Welzer M,  Macarelli V,  Schwiening A,  Rowley C,  Aggarwal S,  Swinden D,  Kronenberg-Versteeg D,  Merkle FT. Metformin acts directly in the brain to slow features of neurodegeneration. bioRxiv.  https://doi.org/10.1101/2023.07.18.549549

Mazafferro S, Chen H-J C, Cahn O, Yang A, Shepilov D, Chen J, Alcaino C, Macarelli V, Mali I, Gribble F, Reimann F, Marioni J, Merkle FT. GLP1R agonists activate human POMC neurons. bioRxiv https://doi.org/10.1101/2024.04.02.587825

Chen H-J C, Yang A, Mazzaferro S, Mali I, Cahn O, Kentistou K, Rowley C, Stewart N, Seah JWE, Pisupati V, Kriwan P, Aggarwal S, Toyohara T, Florido MHC, Cowan CA, Quambusch L, Hyvönen M,  Livesey MR, Perry JRB,  Marioni JC,  Merkle FT. Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss. bioRxiv. https://doi.org/10.1101/2023.07.18.549357

Pantazis CB, …, Merkle FT. A reference human induced pluripotent stem cell line for large-scale collaborative studies. Cell Stem Cell. 2022 Dec 1;29(12):1685-1702.e22. doi: 10.1016/j.stem.2022.11.004. PMID: 36459969; PMCID: PMC9782786.

Kirwan P, Kay RG, Brouwers B, Herranz-Pérez V, Jura M, Larraufie P, Jerber J, Pembroke J, Bartels T, White A, Gribble FM, Reimann F, Farooqi IS, O’Rahilly S, Merkle FT. Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis. Mol Metab. Epub Aug21, 2018. DOI: 10.1016/j.molmet.2018.08.006 PMID: 30201275. PMCID:PMC6197775

Merkle FT, Ghosh S, Kamataki N, Mitchell J, Avior Y, Mello C, Kashin S, Mekhoubad S, Ilic D, Charlton M, Saphier G, Handsaker RE, Genovese G, Bar S, Benvenisty N, McCarroll S, Eggan K. Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations. Nature, E-pub. 26 April 2017. DOI 10.1038/nature22312. PMID: 28445466. PMCID:PMC5427175.

Merkle FT, Maroof A, Wataya T, Sasai Y, Studer L, Eggan K, Schier AF. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells. Development. 2015 Feb 15;142(4):633-43. doi: 10.1242/dev.117978. PMID:25670790. PMCID:PMC4325380

Additional publications are available at: http://www.ncbi.nlm.nih.gov/pubmed/?term=merkle+ft

New York Stem Cell Foundation – Robertson Investigator

Sir Henry Dale Fellow (Wellcome Trust and Royal Society)

Ben Barres Investigator (Chan Zuckerberg Institute)

Affiliate member, Cambridge Stem Cell Institute