Jemeen Sreedharan

Jemeen.Sreedharan@kcl.ac.uk

jemeensreed

Website

Research Interests

I am a neurologist with a research interest in TDP-43, a DNA/RNA-binding protein that is dysregulated in motor neuron disease and dementia including frontotemporal dementia and Alzheimer’s disease. TDP-43 levels in the brain are exquisitely regulated in health by autoregulation , but this mechanism is disturbed in disease. My laboratory has developed human cellular and mouse model systems to understand autoregulation with a view to normalising TDP-43 expression for therapeutic gain. We use genetic engineering technologies to create more accurate models of disease and to understand the structural, functional and molecular effects of TDP-43 misregulation on the brain. We have particular interests in axon degeneration, parvalbumin interneurons and microglial function

Most significant discovery

I was the first to identify mutations in TDP-43 as a cause of ALS thus demonstrating that TDP-43 plays a mechanistic role in disease pathogenesis. This work contributed to a
fundamental shift in the field, which now appreciates that RNA processing abnormalities
are a central tenet in the causation of ALS and the overlapping condition FTD.

Educational Interests

I teach clinical neurology to KCL medical students
I am Module 3 lead on the MSc in Clinical Neuroscience
I lecture on the MSc course in Neuroscience and MSc
in Clinical Neuropsychiatry

Top 4 Publications

White et al., 2019. Sarm1 deletion suppresses TDP-43-linked motor neuron degeneration and cortical spine loss. Acta Neuropathologica Communications.
White et al., 2018. TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD.
Sreedharan et al., 2015. Age-Dependent TDP-43-Mediated Motor Neuron Degeneration Requires GSK3, hat-trick, and xmas-2. Nature Neuroscience.
Sreedharan et al., 2008. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Current Biology.

Methods / Expertise

Clinical neurology
Murine behaviour and neuropathology
Human iPSC, derived neurons and microglia
RNA processing
CRISPR