Giovanna Rachele Mallucci (born 29 June 1963) is van Geest Professor of Clinical Neurosciences at the University of Cambridge in England and associate director of the UK Dementia Research Institute at the University of Cambridge. She is a specialist in neurodegenerative diseases.
Biography
Giovanna Mallucci attended Haberdashers' Aske's School for Girls, Elstree before studying medicine at St Hilda's College, Oxford, and University College London, then specialized in neurology. She gained her Ph.D. in 2001 from Imperial College, London, for her work on transgenic models of prion disease, after which she combined scientific and clinical careers. In 2008, she joined the MRC Toxicology Unit as Programme Leader, focusing on generic mechanisms of neurodegeneration. In 2014, she was elected van Geest Professor of Clinical Neurosciences at the University of Cambridge and in 2017 was awarded the Cambridge Centre of UK Dementia Research Institute of which she is the director. She is an Honorary Consultant Neurologist at Addenbrooke's Hospital, with a specialist interest in dementia.
Mechanisms of neurotoxicity
Her background is in modeling prion diseases in mice, looking at mechanisms of neurotoxicity, and developing new therapeutic approaches. Her group has shown that early synaptic changes in mice with prion disease can be reversed, resulting in the recovery of synaptic and cognitive function and behavioral deficits, long term neuroprotection, and lifelong survival of affected animals. Thus neurodegeneration can be prevented by reversing early synaptic deficits.
Their program uses several model systems – mice (wild type and transgenic), the primary neurons, and the nematode C. elegans, to understand the early molecular events that cause synaptic toxicity and neuronal cell death in neurodegeneration. In parallel, they are looking at the mechanisms involved in synaptic repair processes.
Her lab is interested in understanding mechanisms of neurodegeneration. The central theme is the identification of common pathways across the spectrum of these disorders (which include Alzheimer's and related diseases) that are relevant for both mechanistic insights and therapy. They focus both on 'toxic' processes that can be targeted to prevent neuronal death, and on regenerative processes that can be harnessed for repair. Using mouse models, they described the pathogenic role of the unfolded protein response (UPR) in neurodegeneration, which led to the discovery of the first small molecule - an inhibitor of this pathway - to prevent neurodegeneration in vivo. They also recently discovered the phenomenon of failure of synaptic repair processes in neurodegeneration and the underlying mechanisms: failure of another stress response involving 'cold shock' proteins, which they have successfully harnessed for neuroprotection. They aim to translate this research into new treatments for dementia.
Profession
Mallucci leads the new centre of the UK Dementia Research Institute on Cambridge Biomedical Campus tasked with finding new ways to diagnose, treat, prevent and care for people with dementia.
The centre joins others at Cardiff University, the University of Edinburgh, Imperial College London and King's College London in forming the new UK Dementia Research Institute (UK DRI).
Mallucci said: “The mission of the DRI overall is to take a transformative change in the understanding of the cellular mechanisms that make brain cells go wrong in dementia and degenerative brain disease and discovering new ways of treating based on those insights. In Cambridge we have such world-leading expertise in so many different fields so we are focusing on cross-disciplinary research, integrating chemistry and biophysics along with classic cell biologists such as myself who understand the disease. It's going to be a real dementia hub. There are lots of avenues but what you need is a couple of things that are going to change the course of the disease and Cambridge is very well-positioned for those kinds of discoveries. We have real momentum on some re-purposed drugs.”
It is in this area that a team led by Mallucci has made a potentially significant breakthrough.
Having identified a major pathway that leads to brain cell death in mice, scientists have now found two drugs that block that pathway and prevent neurodegeneration, with minimal side effects in rodents.
One of these drugs – trazodone hydrochloride – is already licensed for use in humans as an antidepressant.