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Dr Manav Pathania

Pathania Manav

      Dr Manav Pathania

       Neural stem cell heterogeneity and epigenetics in paediatric gliomas

       Departmental affiliation: Department of Pathology

       Laboratory location: The Milner Institute

Biography

Manav received a BA in Biology from Grinnell College, in Iowa, and received his PhD in Cell Biology from Yale University, in Connecticut. At Yale he investigated microRNA control of postnatal neural stem cell differentiation and survival in Professor Angelique Bordey’s lab. His first postdoctoral appointment was in Professor Josef Kittler’s lab at UCL in London, where he explored the neurobiological consequences of autism and schizophrenia candidate gene misexpression in vitro and in vivo. Following that, in his second postdoctoral appointment Manav developed in vivo models of paediatric high-grade glioma in Professor Paolo Salomoni’s lab at the UCL Cancer Institute. His current research focuses on understanding the role of chromatin remodelling in paediatric brain tumours. How does epigenetic rewiring support tumour initiation and maintenance? Do these mechanisms also contribute to the emergence of therapy resistance?

 

Pathania research

Low magnification view of an H3.3K27M tumour that has both diffusely invasive as well as focal, localised components. Green: GFP, blue: nuclear stain, red: Ki67, a marker of proliferating cells.

Research

We recently developed an in vivo paediatric brain tumour modelling approach that allows the generation of mouse models more quickly and efficiently than transgenic approaches. This system relies on delivering oncogenic insults into discrete populations of neural stem cells, either in utero or neonatally. I aim to use this approach to test the functional relevance of numerous additional co-occurring mutations that have been found at varying frequencies in paediatric brain cancers. These tumours are some of the most genetically heterogeneous human cancers and are associated with an extremely poor prognosis. Although the co-occurring mutations found within them can be used to stratify tumours into different “subtypes”, the roles that these mutations play in tumour development and relapse are unknown. The research direction I am developing is based on testing mutually exclusive subsets of these mutations for their contribution to tumorigenesis and therapy resistance. This entails developing models of clinically meaningful tumour subtypes and screening them for genetic dependencies unique to one combination of mutations vs another. Ultimately, this will allow the development of a precision medicine approach to paediatric brain tumour subtypes.

Pathania research 2

High magnification confocal immunofluorescence of Ki67- and GFP-double positive tumour cells (red and green, respectively) migrating along blood vessels. Nuclei are stained blue.

Pathania research 3

GFP immunohistochemistry and H&E staining in adjacent sections of a mouse model of H3.3K27M-driven diffuse glioma. Tumour cells can be seen proliferating and invading within the hindbrain, spreading into the cerebellum and causing extensive damage to the fourth ventricle. 

 

External links

www.pathanialab.com