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We study postnatal and adult mammalian brain stem cells to uncover fundamental developmental mechanisms and disease pathogenesis.

Newborn neurons in the olfactory bulb. Stem cells and progenitors were electroporated in the subventricular zone lining the lateral ventricle to introduce plasmid DNA encoding for a fluorescent protein that labels the membranes (purple) and another that labels nuclei (green). Seven days later they had migrated to the Olfactory Bulbs and started to differentiate into mature neurons. (Szele lab, unpublished)
Newborn neurons in the olfactory bulb. Stem cells and progenitors were electroporated in the subventricular zone lining the lateral ventricle to introduce plasmid DNA encoding for a fluorescent protein that labels the membranes (purple) and another that labels nuclei (green). Seven days later they had migrated to the Olfactory Bulbs and started to differentiate into mature neurons. (Szele lab, unpublished)

The Szele group is working on fundamental developmental neurobiological questions in health and disease.

Our main discovery platform are the two stem cell niches of the brain - the subventricular zone (SVZ) and the subgranular zone (SGZ). The SVZ and SGZ neurogenic niches contain stem cells, transit amplifying progenitors and neuroblasts. They are convenient biological systems to study fundamental developmental questions since one can easily modulate gene expression in them. We investigate the role of the SVZ and SGZ in models of neurodegeneration and neuropsychiatric disorders. We also study human neurogenesis in postmortem sections and with induced pluripotential stem cells. We are interdisciplinary and have many excellent collaborators.

Many of our studies seek to understand how the SVZ and SGZ respond to disease with the ultimate goal of using molecular insights to augment neurogenesis and enhance progenitor repair of brain injury.  We have focused on Galectin-3 (Gal-3) a pro-inflammatory protein we showed is necessary for SVZ neuroblast migration. We also found Gal-3 is necessary for angiogenesis after stroke and that it is upregulated in multiple sclerosis (MS). We are also working with Eric O'Neill on tumorigenic Gal-3 mediated signalling pathways in the SVZ. Our work on Gal-3 and microglia in the SVZ has demonstrated the SVZ is constitutively semi-inflammed in health and that compared to surrounding brain parenchyma it mounts unique immunological/inflammatory responses to disease. 

The Szele group are also pursuing novel mechanistic insights into epigenetic and lncRNA regulation of neurogenesis. Using floxed Eed and Ezh2 mice, we found that different components of the Polycomb repressive complex 2 regulate distinct neurogenic events. We showed with Keith Vance that lncRNA Paupar is necessary for SVZ/OB neurogenesis. With Hiroko Isoda we are testing the neurogenic properties of phytochemicals and nutraceuticals. 

We also have a longstanding interest in the role of abnormal neurodevelopment in neuropsychiatric disorders. We use an integrated suite of animal models, human post-mortem sections and human induced pluripotential stem cells (iPSC) to study Autism and Schizophrenia. In particular we showed how studying how dysbindin loss-of-function interacts with inflammation to regulate neurogenesis in a murine gene x environment interaction model. We demonstrated that the striatum contains fewer calretinin+ interneuron in patients with autism. Together with Hagan Bayley's group in Chemistry we are 3D printing hiPSC derived cortical cells.

The Szele lab uses a wide range of in vivo and in vitro techniques including stem cell cultures, migration assays, in vivo electroporation, over expression and knockdown, Cre-lox conditional knockouts, etc. We have used 2-photon time-lapse microscopy in slices to record and quantitatively analyse cell behaviours in the SVZ and are developing in vivo approaches of imaging neurogenesis. Together with Adam Packer in DPAG we are developing 3-photon time-lapse to image the niches in live mice.

We have bi-weekly lab meetings Thursdays from 9-10.30 AM. Please email Francis Szele if you would like to join us for one or more of these.

We welcome enquiries for collaboration, postdoctoral fellowships or studentships.

Updated 28 September, 2021

Szele lab members

Photos

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Funding Bodies

  • Oxford Martin School
  • Japan Ministry of Education 

Latest publications

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