̽��ֱ�� of Cambridge - Menna Clatworthy

Professor Duncan Richards appointed as Head of Department of Medicine

Anonymous — Fri, 06 Dec 2024 16:59:07 +0000

Professor Richards joins Cambridge from the ̽��ֱ�� of Oxford, where he has been since 2019. His particular research interest is the demonstration of clinical proof of concept of novel therapeutics through the application of experimental medicine techniques, especially human challenge studies.

As Climax Professor of Clinical Therapeutics, director of the Oxford Clinical Trial Research Unit (OCTRU), and the NIHR Oxford Clinical Research Facility, he led a broad portfolio focused on new medicines for multiple conditions. His focus has been the acceleration of promising new drug treatments through better decision-making in early phase clinical trials.

Professor Richards also brings with him a wealth of experience in a number of Pharmaceutical R&D clinical development roles. In 2003 he joined GSK and held a number of roles of increasing responsibility, latterly as Head of Clinical Pharmacology and Experimental Medicine, including directorship of GSK’s phase 1 and experimental medicine unit in Cambridge (CUC).

Commenting on his appointment, Professor Richards said: “As a clinical pharmacologist, I have been fortunate to work across a broad range of therapeutic areas over the years. I am excited by the breadth and depth of expertise within the Department of Medicine and look forward to working with the first-class scientific team. My goal is to work with the Department team, the Clinical School, and hospitals to maximise the impact of the important work taking place in Cambridge.”

Members of the department’s leadership team are looking forward to the continued development of the department under Professor Richards, building on its legacy of collaboration and groundbreaking translational research to drive our future success.

Professor Mark Wills, Interim Head of Department of Medicine, said: “Duncan brings to his new role a fantastic breadth of experience, which encompasses his clinical speciality in pharmacology, extensive experience of working within the pharmaceutical industry R&D at senior levels and most recently establishing academic clinical trials units and human challenge research facilities.

“I am very excited to welcome Duncan to the Department and looking forward to working with him, as he takes on the role of delivering of the Department of Medicine’s vision to increase the efficacy of translation of its world class fundamental research, and its impact upon clinical practice and patient wellbeing.”

Menna Clatworthy, Professor of Translational Immunology and Director of the Cambridge Institute for Therapeutic Immunology and Infectious Disease (CITIID), said: "Duncan has a wealth of leadership experience in biomedicine, in both academia and pharma. That skillset will be invaluable in ensuring the Department of Medicine continues to deliver world-leading research to transform patient outcomes."

Charlotte Summers, Professor of Intensive Care Medicine and Director of the Victor Phillip Dahdaleh Heart & Lung Research Institute, said: “Duncan’s exemplary track record of translating fundamental scientific discoveries into therapies that benefit patients will help us further increase the impact of our research as we continue our mission to improve human health.”

̽��ֱ��appointment underpins the recently announced five-year collaboration between GSK and the ̽��ֱ�� of Cambridge, the Cambridge-GSK Translational Immunology Collaboration (CG-TIC). ̽��ֱ��£50 million investment will accelerate research and development in kidney and respiratory diseases to improve patient outcomes.

Professor Richards will assume the role in February 2025, replacing Interim Head of Department Dr Mark Wills who was appointed after the departure of Professor Ken Smith in January 2024. Dr Wills will continue as Director of Research and Deputy Head of the Department of Medicine as well as leading his research group.

Professor Richards trained in medicine at Oxford ̽��ֱ�� and after junior doctor roles in London, he returned to Oxford as Clinical Lecturer in Clinical Pharmacology. His DM thesis research was on a translational model using platelet ion flux to interrogate angiotensin biology and he is author of the Oxford Handbook of Practical Drug Therapy and the 3rd edition of Drug Discovery and Development.

Professor Richards has been a core member of the UK COVID-19 Therapeutics Advisory Panel. He is a member of the Oxford Bioescalator Management Board, UK Prix Galien Prize Committee, and the therapeutic advisory committee of several national platform clinical trials.

Professor Duncan Richards has today been announced as the new Head of the Department of Medicine at the ̽��ֱ�� of Cambridge.

I am excited by the breadth and depth of expertise within the Department of Medicine and look forward to working with the first-class scientific team

Duncan Richards

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Underactive immune response may explain obesity link to COVID-19 severity

cjb250 — Mon, 20 Mar 2023 12:00:14 +0000

Scientists at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) and Wellcome Sanger Institute showed that following SARS-CoV-2 infection, cells in the lining of the lungs, nasal cells, and immune cells in the blood show a blunted inflammatory response in obese patients, producing suboptimal levels of molecules needed to fight the infection.

Since the start of the pandemic, there have been almost 760 million confirmed cases of SARS-CoV-2 infection, with almost 6.9 million deaths. While some people have very mild – or even no – symptoms, others have much more severe symptoms, including acute respiratory distress syndrome requiring ventilator support.

One of the major risk factors for severe COVID-19 is obesity, which is defined as a body mass index (BMI) of over 30. More than 40% of US adults and 28% of adults in England are classed as obese.

While this link has been shown in numerous epidemiological studies, until now, it has not been clear why obesity should increase an individual’s risk of severe COVID-19. One possible explanation was thought to be that obesity is linked to inflammation: studies have shown that people who are obese already have higher levels of key molecules associated with inflammation in their blood. Could an overactive inflammatory response explain the connection?

Professor Menna Clatworthy is a clinician scientist at the ̽��ֱ�� of Cambridge, studying tissue immune cells at CITIID alongside caring for patients at Addenbrooke’s Hospital, part of Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust. She said: “During the pandemic, the majority of younger patients I saw on the COVID wards were obese. Given what we know about obesity, if you’d asked me why this was the case, I would have said that it was most likely due to excessive inflammation. What we found was the absolute opposite.”

Clatworthy and her team analysed blood and lung samples taken from 13 obese patients with severe COVID-19 requiring mechanical ventilation and intensive care treatment, and 20 controls (non-obese COVID-19 patients and ventilated non-COVID-19 patients). These included patients admitted to the Intensive Care Unit at Addenbrooke’s Hospital.

Her team used a technique known as transcriptomics, which looks at RNA molecules produced by our DNA, to study activity of cells in these key tissues. Their results are published in the American Journal of Respiratory and Critical Care Medicine.

Contrary to expectations, the researchers found that the obese patients had underactive immune and inflammatory responses in their lungs. In particular, when compared to non-obese patients, cells in the lining of their lungs and some of their immune cells had lower levels of activity among genes responsible for the production of two molecules known as interferons (INF) – interferon-alpha and interferon-gamma – which help control the response of the immune system, and of tumour necrosis factor (TNF), which causes inflammation.

When they looked at immune cells in the blood of 42 adults from an independent cohort, they found a similar, but less marked, reduction in the activity of interferon-producing genes as well as lower levels of IFN-alpha in the blood.

Professor Clatworthy said: “This was really surprising and unexpected. Across every cell type we looked at, we found that that the genes responsible for the classical antiviral response were less active. They were completely muted.”

̽��ֱ��team was able to replicate its findings in nasal immune cells taken from obese children with COVID-19, where they again found lower levels of activity among the genes that produce IFN-alpha and IFN-gamma. This is important because the nose is one of the entry points for the virus – a robust immune response there could prevent the infection spreading further into the body, while a poorer response would be less effective.

One possible explanation for the finding involves leptin, a hormone produced in fat cells that controls appetite. Leptin also plays a role in the immune response: in individuals who are normal weight, levels of the hormone increase in response to infection and it directly stimulates immune cells. But obese people already have chronically higher levels of leptin, and Clatworthy says it is possible that they no longer produce sufficient additional leptin in response to infection, or are insensitive to it, leading to inadequate stimulation of their immune cells.

̽��ֱ��findings could have important implications both for the treatment of COVID-19 and in the design of clinical trials to test new treatments.

Because an overactive immune and inflammatory response can be associated with severe COVID-19 in some patients, doctors have turned to anti-inflammatory drugs to dampen this response. But anti-inflammatory drugs may not be appropriate for obese patients.

Co-author Dr Andrew Conway Morris from the Department of Medicine at the ̽��ֱ�� of Cambridge and Honorary Consultant on the intensive care unit at Addenbrooke’s Hospital said: “What we’ve shown is that not all patients are the same, so we might need to tailor treatments. Obese subjects might need less anti-inflammatory treatments and potentially more help for their immune system.”

Clinical trials for potential new treatments would need to involve stratifying patients rather than including both severe and normal weight patients, whose immune responses differ.

̽��ֱ��research was largely supported by Wellcome, the Medical Research Council and the National Institute of Health and Care Research, including via the NIHR Cambridge Biomedical Research Centre.

Reference
Guo, SA, Bowyer, GS, Ferdinand, JR, Maes, M & Tuong, ZK et al. Obesity associated with attenuated tissue immune cell responses in COVID-19. Am J Resp Critical Care Med; 1 Mar 2023; DOI: 10.1164/rccm.202204-0751OC

Individuals who are obese may be more susceptible to severe COVID-19 because of a poorer inflammatory immune response, say Cambridge scientists.

During the pandemic, the majority of younger patients I saw on the COVID wards were obese... I would have said that it was most likely due to excessive inflammation. What we found was the absolute opposite

Menna Clatworthy

Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust

Intensive care unit at Addenbrooke's Hospital

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cambridge researchers elected as members of European Molecular Biology Organisation

cjb250 — Wed, 06 Jul 2022 12:00:22 +0000

Five Cambridge researchers join the community of more than 1,900 leading life scientists in Europe and beyond today as the European Molecular Biology Organisation announces its newly-elected Members.

Why it takes guts to protect the brain against infection

cjb250 — Wed, 04 Nov 2020 16:01:47 +0000

̽��ֱ��brain is arguably the most important organ in the body, as it controls most other body systems and enables reasoning, intelligence, and emotion. Humans have evolved a variety of protective measures to prevent physical damage to the brain: it sits in a solid, bony case – the skull – and is wrapped in three layers of watertight tissue known as the meninges.

What has been less clear is how the body defends the brain from infection. Elsewhere in the body, if bacteria or viruses enter the bloodstream, our immune system kicks in, with immune cells and antibodies that target and eliminate the invader. However, the meninges form an impermeable barrier preventing these immune cells from entering the brain.

In research published today in Nature, a team led by scientists at the ̽��ֱ�� of Cambridge, UK, and the National Institute of Health, USA, have found that the meninges are home to immune cells known as plasma cells, which secrete antibodies. These cells are specifically positioned next to large blood vessels running within the meninges allowing them to secrete their antibody ‘guards’ to defend the perimeter of the brain. When the researchers looked at the specific type of antibody produced by these cells, they got a surprise – the antibody they observed is normally the type found in the intestine.

Plasma cells are derived from a particular type of immune cell known as a B cell. Every B cell has an antibody on its surface that is unique to that cell. If an antigen (the part of a bacterium or virus that triggers an immune response) binds to that surface antibody, the B cell becomes activated: it will divide to make new offspring that also recognise that same antigen.

During division, the B cell introduces a mutation into the antibody gene so that one amino acid is changed and its binding characteristics are slightly different. Some of these B cells will now produce antibodies that enable better binding to the pathogen – these go on to expand and multiply; B cells whose antibodies are less good at binding die off. This helps ensure the body produces the best antibodies for targeting and destroying particular antigens.

Normally, the antibodies found in the blood are a type known as Immunoglobulin G (IgG), which are produced in the spleen and bone marrow – these antibodies protect the inside of the body. However, the antibodies found in the meninges were Immunoglobulin A (IgA), which are usually made in the gut lining or in the lining of the nose or lungs – these protect mucosal surfaces, the surfaces that interface with the outside environment.

̽��ֱ��team were able to sequence the antibody genes in B cells and plasma cells in the gut and meninges and show that they were related. In other words, the cells that end up in the meninges are those that have been selectively expanded in the gut, where they have recognised particular pathogens.

“ ̽��ֱ��exact way in which the brain protects itself from infection, beyond the physical barrier of the meninges, has been something of a mystery, but to find that an important line of defence starts in the gut was quite a surprise,” said lead scientist Professor Menna Clatworthy from the Department of Medicine and CITIID at the ̽��ֱ�� of Cambridge and the Wellcome Sanger Institute.

“But actually, it makes perfect sense: even a minor breach of the intestinal barrier will allow bugs to enter the blood stream, with devastating consequences if they’re able to spread into the brain. Seeding the meninges with antibody-producing cells that are selected to recognise gut microbes ensures defence against the most likely invaders.”

̽��ֱ��team made the discovery using mice, which are commonly used to study physiology as they share many characteristics similar to those found in the human body. They showed that when the mice had no bacteria in their gut, the IgA-producing cells in the meninges were absent, showing that these cells actually originate in the intestine where they are selected to recognise gut microbes before taking up residence in the meninges. When the researchers removed the plasma cells in the meninges – and hence no IgA was present to trap bugs – microbes were able to spread from the bloodstream into the brain.

̽��ֱ��team confirmed the presence of IgA cells in the human meninges by analysing samples that were removed during surgery, showing that this defence system is likely to play an important role in defending humans from infections of the central nervous system – meningitis and encephalitis.

Professor Clatworthy is a Fellow of Pembroke College.

Reference
Fitzpatrick, Z et al. Gut-educated IgA plasma cells defend the meningeal venous sinuses. Nature; 4 Nov 2020; DOI: 10.1038/s41586-020-2886-4

Image
Confocal micrograph showing the superior saggital sinus (a dural venous sinus) in the mouse. Immune cells are shown in green lining this tube, and blood vessels in red. (Credit: Zach Fitzpatrick)

̽��ֱ��brain is uniquely protected against invading bacteria and viruses, but its defence mechanism has long remained a mystery. Now, a study in mice, confirmed in human samples, has shown that the brain has a surprising ally in its protection: the gut.

̽��ֱ��exact way in which the brain protects itself from infection, beyond the physical barrier of the meninges, has been something of a mystery, but to find that an important line of defence starts in the gut was quite a surprise

Menna Clatworthy

Zach Fitzpatrick

Confocal micrograph showing the superior saggital sinus in the mouse. Immune cells are shown in green lining this tube, and blood vessels in red

Yes

̽��ֱ��Academy of Medical Sciences announces new Fellows for 2020

sc604 — Wed, 13 May 2020 01:00:00 +0000

̽��ֱ��new Fellows have been chosen for their exceptional contributions to advancing biomedical science via world-leading research discoveries, running national science communication and engagement programmes and translating scientific advances into benefits for patients and the public.

̽��ֱ��value of medical science has never been more apparent than during the current coronavirus global health crisis. From testing and vaccine development, to public health and behavioural science, to addressing the impacts of lockdown measures on mental health, biomedical and health scientists are helping to guide the UK through unprecedented challenges.

Several new Fellows have redirected their research efforts to tackle the effects of the pandemic, such as Professor Ludovic Vallier FMedSci, a stem cell expert from the ̽��ֱ�� of Cambridge, who has refocussed part of his team to study the effects of coronavirus on the liver. Professor Tamsin Ford CBE FMedSci, a Professor of Psychiatry at Cambridge, has channelled her expertise into looking at mental health impacts of the pandemic on children and young people.

Professor Sir Robert Lechler PMedSci, President of the Academy of Medical Sciences said: “This year our new Fellows announcement happens amidst a global health crisis. Never has there been a more important time to recognise and celebrate the people behind ground-breaking biomedical and health research, working harder than ever to further knowledge and protect patients and the public.

“It brings me great pleasure to congratulate the new Fellows, and see our Fellowship grow to even greater heights of evidence-based advice, leadership and expertise.”

̽��ֱ�� ̽��ֱ�� of Cambridge Fellows elected in 2020 are:

Professor Menna Clatworthy FLSW, NIHR Research Professor and Professor of Translational Immunology, ̽��ֱ�� of Cambridge and Associate Faculty, Wellcome Sanger Institute, Fellow, Pembroke College

Dr Helen Firth, Consultant Clinical Geneticist, Cambridge ̽��ֱ�� Hospitals, Honorary Faculty Member, Wellcome Sanger Institute, Bye-Fellow, Newnham College

Professor Tamsin Ford CBE, Professor of Child and Adolescent Psychiatry, ̽��ֱ�� of Cambridge, Fellow, Hughes Hall

Professor Ziad Mallat, Professor of Cardiovascular Medicine, ̽��ֱ�� of Cambridge

Dr Nitzan Rosenfeld, Senior Group Leader, Cancer Research UK Cambridge Institute, ̽��ֱ�� of Cambridge

Professor Ludovic Vallier, Professor of Regenerative Medicine, Wellcome - MRC Cambridge Stem Cell Institute, ̽��ֱ�� of Cambridge, Fellow, St Edmund’s College

̽��ֱ��new Fellows will be formally admitted to the Academy on 25 June 2020.

Six affiliates of the ̽��ֱ�� of Cambridge are among 50 world-leading UK researchers who have been elected to the prestigious Fellowship of the Academy of Medical Sciences.

Big T Images for Academy of Medical Sciences

Academy of Medical Sciences

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Teaching celebrated across the ̽��ֱ��

ta385 — Wed, 21 Jun 2017 23:00:00 +0000

̽��ֱ��winners include a veterinary anaesthetist praised for developing an acclaimed Clinical Skills Centre, a pioneer of interdisciplinary Gender Studies programmes, and a Classicist as passionate about outreach as Ovid.

While the prizes reveal the diversity of teaching at Cambridge, certain themes emerge, in particular a focus on the individual student, the value of research-led teaching, the continuing importance of one-to-one teaching, innovation in teaching practice, interdisciplinary approaches, and above all, dedication to students.

̽��ֱ��Pilkington Prizes were initiated by Sir Alastair Pilkington – graduate of Trinity College, engineer, businessman and the first Chairman of the Cambridge Foundation – who passionately believed that teaching excellence was crucial to Cambridge’s future success.

̽��ֱ��Pilkington Prizes are organised by ̽��ֱ��Cambridge Centre for Teaching and Learning, which supports staff by providing training, developing networks, hosting events and encouraging and funding innovation. ̽��ֱ��Centre also provides a focus for strategic priorities within Cambridge and for engaging with national and international developments in higher education.

New films about teaching at Cambridge

̽��ֱ�� ̽��ֱ�� has produced a series of films about five of this year’s Pilkington Prize winners. These films go behind the scenes to show Cambridge teaching in action as well as inviting winners to explain their passion for teaching and reveal some of their trade secrets. ̽��ֱ��films feature Lecturer in German Thought, Martin Ruehl; Physics Lecturer Lisa Jardine-Wright; Sociologist Mónica Moreno Figueroa; Zoologist Andrew Balmford; and Design Engineer James Moultrie. Watch the films.

Dr Martin Ruehl said:

"I was an undergraduate here myself so I want to give back some of what I received. I had a number of very charismatic teachers who inspired me back then. I think the trick is always to find something that’s growing out of your own research."

Dr Lisa Jardine-Wright said:

"It is only when you start teaching a subject that you really start to understand it and all of its nuances. ̽��ֱ��most important thing for me is that my students are willing to make mistakes, and learn from them."

This year’s winners in full are:

Dr Anthony Ashton (Department of Mathematics)
Dr Jackie Brearley (Department of Veterinary Medicine)
Dr Jude Browne (Department of Politics and International Studies)
Dr Menna Clatworthy (School of Clinical Medicine)
Dr Richard Davies (School of Clinical Medicine)
Dr Ingo Gildenhard (Faculty of Classics)
Dr Nigel Kettley (Institute of Continuing Education)
Professor Jochen Runde (Judge Business School)
Dr Martin Ruehl (Faculty of Modern and Medieval Languages)
Dr Lisa Jardine-Wright (Department of Physics)
Dr Mónica Moreno Figueroa (Department of Sociology)
Professor Andrew Balmford (Department of Zoology)
Dr James Moultrie (Department of Engineering)

Read more about the 2017 Pilkington Prize winners here.

Thirteen Cambridge academics have been recognised for their outstanding teaching in the ̽��ֱ��'s Pilkington Prizes.

"I was an undergraduate here myself so I want to give back some of what I received. I think the trick is always to find something that’s growing out of your own research."

Dr Martin Ruehl, Faculty of Modern and Medieval Languages

Teaching celebrated across the ̽��ֱ��

Dr Martin Ruehl, Faculty of Modern and Medieval Languages, ̽��ֱ�� of Cambridge

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes