Other Interdiciplinary Incentives

  • Metabolism
  • Research Focus


  • Obesity
  • Pluripotent Stem Cells
  • CRISPR-Cas9
  • Drug Discovery
  • Differentiation
  • Mouse Models
  • Metabolism
  • Neurodegenerative Disease
  • Hypothalamus
  • Inflammation
  • Drug Screening
  • Clinical Conditions

  • Alzheimer's disease
  • Dementia
  • Prion diseases
  • Sleep disorders
  • Diabetes
  • Other 
  • Equipment & Techniques

  • Cell culture
  • Calcium imaging
  • Behavioural analysis
  • Fluorescence microscopy
  • Microscopy
  • Whole cell patch clamp
  • Science Culture

  • Equality, Diversity, Inclusion and Wellbeing
  • Mentorship
  • Open Access
  • Widening Participation
  • Teaching
  • Back

    Dr Florian Merkle

    University Position
    Senior Research Associate
    Dr Florian Merkle is pleased to consider applications from prospective PhD students.


    My research vision is to improve human health by identifying and targeting neurological disease mechanisms. This vision builds on my training in developmental neuroscience, where I identified the lineage and potential of adult neural stem cells and overturned dogma that stem cells are homogenous. My later work in human pluripotent stem cell (hPSC) genomics provided open-access resources for rational cell line selection, revealed recurrent mutations in p53 that profoundly impacted the fields of stem cell biology and regenerative medicine, identified a ‘reference’ hiPSC line to promote reproducibility in the field and enable large-scale studies, and showed how common genetic variants influence gene expression in a cell type- and disease state-dependent manner. I was an early adopter of CRISPR/Cas9 for hPSCs to knock out genes and introduce reporters, and employed these tools to study hPSC-derived hypothalamic POMC neurons that are key regulators of appetite. My research team showed how human POMC respond nutrients, hormones, and drugs, including the leading weight loss drug Semaglutide/Ozempic, and have revealed new potential mechanisms and drugs that suppress appetite. We pursue the fundamental biology of the three man research areas below, with the ultimate goal of developing new treatments: 1) improving the utility and reproducibility of hPSC-based disease models, 2) understanding how key appetite-regulatory hypothalamic neurons respond to metabolic signals and could be targeted to suppress appetite 3) illuminating the mechanistic links between metabolic and neurodegenerative disease to reveal novel neuroprotective strategies We achieve these goals by collaborating extensively and fostering inclusivity, curiosity, and personal development in an interdisciplinary research team. I encourage outstanding graduate students or postdoctoral candidates interested in contributing to this work to contact me at fm436[at]

    Appetite-regulatory human hypothalamic neurons, differentiated from pluripotent stem cells

    Key Publications

    Metformin may reduce dementia risk through neuroprotection not mitigation of diabetes

    E-pub date: 1 Aug 2023
    Authors: EC Harding, H-JC Chen, A Schwiening, S Aggarwal, C Rowley, D Swinden, FT Merkle

    Profiling human hypothalamic neurons reveals a candidate combination drug therapy for weight loss

    E-pub date: 19 Jul 2023
    Authors: H-JC Chen, A Yang, S Mazzaferro, I Mali, O Cahn, K Kentistou, C Rowley, N Stewart, JWE Seah, V Pisupati, P Kirwan, S Aggarwal, T Toyohara, MHC Florido, CA Cowan, L Quambusch, M Hyvönen, MR Livesey, JRB Perry, JC Marioni, FT Merkle

    Whole-genome analysis of human embryonic stem cells enables rational line selection based on genetic variation.

    Journal: Cell Stem Cell
    E-pub date: 3 Mar 2022
    Authors: FT Merkle, S Ghosh, G Genovese, RE Handsaker, S Kashin, D Meyer, KJ Karczewski, C O'Dushlaine, C Pato, M Pato, DG MacArthur, SA McCarroll, K Eggan

    A reference induced pluripotent stem cell line for large-scale collaborative studies

    E-pub date: 1 Aug 2021
    Authors: C Pantazis, A Yang, E Lara, J McDonough, C Blauwendraat, L Peng, H Oguro, J Kanaujiya, J Zou, D Sebesta, G Pratt, E Cross, J Blockwick, P Buxton, L Kinner-Bibeau, C Medura, C Tompkins, S Hughes, M Santiana, F Faghri, M Nalls, D Vitale, S Ballard, Y Qi, D Ramos, K Anderson, J Stadler, P Narayan, J Papademetriou, L Reilly, M Nelson, S Aggarwal, L Rosen, P Kirwan, V Pisupati, S Coon, S Scholz, T Priebe, M Öttl, J Dong, M Meijer, LJM Janssen, V Lourenco, R van der Kant, D Crusius, D Paquet, A-C Raulin, G Bu, A Held, B Wainger, RMC Gabriele, J Casey, S Wray, D Abu-Bonsrah, C Parish, M Beccari, D Cleveland, E Li, IVL Rose, M Kampmann, CC Aristoy, P Verstreken, L Heinrich, M Chen, B Schüle, D Dou, ELF Holzbaur, MC Zanellati, R Basundra, M Deshmukh, S Cohen, R Khanna, M Raman, Z Nevin, M Matia, JV Lent, V Timmerman, B Conklin, KJ Chase, K Zhang, S Funes, D Bosco, L Erlebach, M Welzer, D Kronenberg-Versteeg, G Lyu, E Arenas, E Coccia, L Sarrafha, T Ahfeldt, J Marioni, W Skarnes, M Cookson, M Ward, F Merkle

    Population-scale single-cell RNA-seq profiling across dopaminergic neuron differentiation

    E-pub date: 22 May 2020
    Authors: J Jerber, DD Seaton, ASE Cuomo, N Kumasaka, J Haldane, J Steer, M Patel, D Pearce, M Andersson, MJ Bonder, E Mountjoy, M Ghoussaini, MA Lancaster, JC Marioni, FT Merkle, O Stegle, DJ Gaffney

    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.

    Journal: Mol Metab
    E-pub date: 1 Nov 2018
    Authors: P Kirwan, RG Kay, B Brouwers, V Herranz-Pérez, M Jura, P Larraufie, J Jerber, J Pembroke, T Bartels, A White, FM Gribble, F Reimann, IS Farooqi, S O'Rahilly, FT Merkle

    Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations.

    Journal: Nature
    E-pub date: 11 May 2017
    Authors: FT Merkle, S Ghosh, N Kamitaki, J Mitchell, Y Avior, C Mello, S Kashin, S Mekhoubad, D Ilic, M Charlton, G Saphier, RE Handsaker, G Genovese, S Bar, N Benvenisty, SA McCarroll, K Eggan

    Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells.

    Journal: Development
    E-pub date: 15 Feb 2015
    Authors: FT Merkle, A Maroof, T Wataya, Y Sasai, L Studer, K Eggan, AF Schier

    Mosaic organization of neural stem cells in the adult brain.

    Journal: Science
    E-pub date: 20 Jul 2007
    Authors: FT Merkle, Z Mirzadeh, A Alvarez-Buylla


    Regulation of the length of neuronal primary cilia and its potential effects on signalling.

    Journal: Trends Cell Biol
    E-pub date: 1 Nov 2023
    Authors: V Macarelli, E Leventea, FT Merkle

    An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis

    E-pub date: 1 Aug 2023
    Authors: S Jörgensen, A Karnošová, S Mazzaferro, O Rowley, H-JC Chen, S Robbins, S Christofides, F Merkle, L Maletínská, D Petrik

    Differentiation, Transcriptomic Profiling, and Calcium Imaging of Human Hypothalamic Neurons.

    E-pub date: 5 Jun 2023
    Authors: H-JC Chen, S Mazzaferro, T Tian, I Mali, FT Merkle

    MKRN3 inhibits puberty onset via interaction with IGF2BP1 and regulation of hypothalamic plasticity.

    Journal: JCI Insight
    E-pub date: 24 Apr 2023
    Authors: L Naulé, A Mancini, SA Pereira, BM Gassaway, JR Lydeard, JC Magnotto, HK Kim, J Liang, C Matos, SP Gygi, FT Merkle, RS Carroll, AP Abreu, UB Kaiser

    The consequences of recurrent genetic and epigenetic variants in human pluripotent stem cells.

    Journal: Cell Stem Cell
    E-pub date: 1 Dec 2022
    Authors: PW Andrews, I Barbaric, N Benvenisty, JS Draper, T Ludwig, FT Merkle, Y Sato, C Spits, GN Stacey, H Wang, MF Pera

    Functional heterogeneity of POMC neurons relies on mTORC1 signaling.

    Journal: Cell Rep
    E-pub date: 12 Oct 2021
    Authors: N Saucisse, W Mazier, V Simon, E Binder, C Catania, L Bellocchio, RA Romanov, S Léon, I Matias, P Zizzari, C Quarta, A Cannich, K Meece, D Gonzales, S Clark, JM Becker, GSH Yeo, X Fioramonti, FT Merkle, SL Wardlaw, T Harkany, F Massa, G Marsicano, D Cota

    Nitric Oxide Synthase Neurons in the Preoptic Hypothalamus Are NREM and REM Sleep-Active and Lower Body Temperature.

    Journal: Front Neurosci
    E-pub date: 1 Aug 2021
    Authors: EC Harding, W Ba, R Zahir, X Yu, R Yustos, B Hsieh, L Lignos, AL Vyssotski, FT Merkle, TG Constandinou, NP Franks, W Wisden

    Proopiomelanocortin Processing in the Hypothalamus Is Directly Regulated by Saturated Fat: Implications for the Development of Obesity.

    Journal: Neuroendocrinology
    E-pub date: 1 Aug 2020
    Authors: DS Razolli, TM de Araújo, MR Sant Apos Ana, P Kirwan, DE Cintra, FT Merkle, LA Velloso

    Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities.

    Journal: Sci Rep
    E-pub date: 3 Jun 2020
    Authors: T Sonoyama, LKJ Stadler, M Zhu, JM Keogh, E Henning, F Hisama, P Kirwan, M Jura, BK Blaszczyk, DC DeWitt, B Brouwers, M Hyvönen, I Barroso, FT Merkle, SM Appleyard, GA Wayman, IS Farooqi

    The Genetic Architecture of DNA Replication Timing in Human Pluripotent Stem Cells

    E-pub date: 10 May 2020
    Authors: Q Ding, MM Edwards, ML Hulke, AN Bracci, Y Hu, Y Tong, X Zhu, J Hsiao, CJ Charvet, S Ghosh, RE Handsaker, K Eggan, FT Merkle, J Gerhardt, D Egli, AG Clark, A Koren

    POMC neurons functional heterogeneity relies on mTORC1 signaling

    E-pub date: 26 Mar 2020
    Authors: N Saucisse, W Mazier, V Simon, E Binder, C Catania, L Bellocchio, RA Romanov, I Matias, P Zizzari, S Leon, C Quarta, A Cannich, K Meece, D Gonzales, S Clark, JM Becker, GSH Yeo, FT Merkle, SL Wardlaw, T Harkany, F Massa, G Marsicano, D Cota

    Generation and Characterization of Functional Human Hypothalamic Neurons.

    Journal: Curr Protoc Neurosci
    E-pub date: 24 Oct 2017
    Authors: P Kirwan, M Jura, FT Merkle

    Comprehensive Protocols for CRISPR/Cas9-based Gene Editing in Human Pluripotent Stem Cells.

    Journal: Curr Protoc Stem Cell Biol
    E-pub date: 17 Aug 2016
    Authors: DP Santos, E Kiskinis, K Eggan, FT Merkle

    Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease.

    Journal: Sci Transl Med
    E-pub date: 13 Jul 2016
    Authors: A Burberry, N Suzuki, J-Y Wang, R Moccia, DA Mordes, MH Stewart, S Suzuki-Uematsu, S Ghosh, A Singh, FT Merkle, K Koszka, Q-Z Li, L Zon, DJ Rossi, JJ Trowbridge, LD Notarangelo, K Eggan

    Regional astrocyte allocation regulates CNS synaptogenesis and repair.

    Journal: Science
    E-pub date: 20 Jul 2012
    Authors: H-H Tsai, H Li, LC Fuentealba, AV Molofsky, R Taveira-Marques, H Zhuang, A Tenney, AT Murnen, SPJ Fancy, F Merkle, N Kessaris, A Alvarez-Buylla, WD Richardson, DH Rowitch

    Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain.

    Journal: Cell Stem Cell
    E-pub date: 11 Sep 2008
    Authors: Z Mirzadeh, FT Merkle, M Soriano-Navarro, JM Garcia-Verdugo, A Alvarez-Buylla

    Radial glia give rise to adult neural stem cells in the subventricular zone.

    Journal: Proc Natl Acad Sci U S A
    E-pub date: 14 Dec 2004
    Authors: FT Merkle, AD Tramontin, JM García-Verdugo, A Alvarez-Buylla