Periodic Reporting for period 4 - CSI-Fun (Chronic Systemic Inflammation: Functional organ cross-talk in inflammatory disease and cancer)
Período documentado: 2022-12-01 hasta 2024-05-31
The main goal of this project was to gain a better understanding of Chronic Systemic Inflammation (CSI), implicated in several common diseases, such as Psoriasis, Arthritis and Cancer, which are serious health issues. To achieve this goal, we focussed on whole body physiology. As there is no good understanding of the mechanisms behind these diseases, it is important to conduct experiments in model systems, from the petri dish to samples donated by patients. The final aim is to find new ways (biomarkers) to detect these diseases early, when they have the highest chance to be treatable, and to direct the medical community towards new methods to treat and even prevent the disease. We worked along three angles:
1. Inflammatory Skin Diseases (ISD): Atopic Dermatitis (AD) and Psoriasis (Ps) are chronic skin conditions that can lead to a significant deterioration of life quality: 5–30% of children and 2–10% of adults develop AD, while Ps affects 3-5% of the population. AD and Ps are caused by perturbations in the communications between the immune system and keratinocytes, the most important skin cells. We carefully studied how the immune system and the skin interact during ISD, to understand what goes wrong and why. We made several discoveries using our model systems that were communicated to the scientific community and the public. These will certainly help establishing novel biomarkers/treatments that can be further tested and validated in the clinic.
2. Inflammatory Joint Diseases (IJD): Psoriatic Arthritis (PsA) affects up to 30% of Ps patients and leads to joint pain, stiffness and swelling. Debilitating joint degeneration also occurs in Osteoarthritis (OA), the most common joint disease affecting millions of people. OA, where the cartilage is slowly eroded, is a disease affecting the entire joint, with an important role for inflammation. We studied how inflammation/immune system perturbations affect joint degeneration and metabolism in OA and how perturbations in skin-immune system interactions lead to distant effects on the joints in PsA, but also surprisingly in some forms of AD. We discovered important commonalities and differences by comparing different joint diseases and proposed new molecules that could be used as biomarkers after clinical validation. We also made unanticipated discoveries that could be useful for the management of bone cancer (osteosarcoma).
3. Cancer associated Cachexia (CAC): is a disorder of the whole body affecting 50-80% of cancer patients, characterized by involuntary loss of body weight due to wasting of muscles and fat. CAC is detrimental to cancer patients’ quality of life and considered the immediate cause of death for a third of of cancer patients. It is therefore very important to find biomarkers to predict which patient is likely to develop CAC to adapt treatment and lifestyle to prevent or delay cachexia as much as possible. We studied how uncontrolled inflammation, perturbed hormone balance and the nervous system operate and interact during CAC using model systems that mimic the patient situation. We experimentally demonstrated that inflammation and the beta-adrenergic system are important players that should be closely monitored in patients. In addition, we showed how immune cells interact with the sympathetic nervous system during CAC and unravelled unanticipated implications of inflammation in skin and liver cancer. Once validated by clinicians, our findings will likely translate into new biomarkers that will help improve CAC and more generally cancer prevention and treatment.
In conclusion, the CSI-fun project not only allowed us to gain a better understanding of Chronic Systemic Inflammation, but also led to discoveries that will help improve the management of Atopic Dermatitis, Psoriasis, Arthritis and Cancer and decrease the societal burden of these common, but very detrimental diseases.
1. Inflammatory Skin Diseases (ISD): Atopic Dermatitis (AD) and Psoriasis (Ps) are chronic skin conditions that can lead to a significant deterioration of life quality: 5–30% of children and 2–10% of adults develop AD, while Ps affects 3-5% of the population. AD and Ps are caused by perturbations in the communications between the immune system and keratinocytes, the most important skin cells. We carefully studied how the immune system and the skin interact during ISD, to understand what goes wrong and why. We made several discoveries using our model systems that were communicated to the scientific community and the public. These will certainly help establishing novel biomarkers/treatments that can be further tested and validated in the clinic.
2. Inflammatory Joint Diseases (IJD): Psoriatic Arthritis (PsA) affects up to 30% of Ps patients and leads to joint pain, stiffness and swelling. Debilitating joint degeneration also occurs in Osteoarthritis (OA), the most common joint disease affecting millions of people. OA, where the cartilage is slowly eroded, is a disease affecting the entire joint, with an important role for inflammation. We studied how inflammation/immune system perturbations affect joint degeneration and metabolism in OA and how perturbations in skin-immune system interactions lead to distant effects on the joints in PsA, but also surprisingly in some forms of AD. We discovered important commonalities and differences by comparing different joint diseases and proposed new molecules that could be used as biomarkers after clinical validation. We also made unanticipated discoveries that could be useful for the management of bone cancer (osteosarcoma).
3. Cancer associated Cachexia (CAC): is a disorder of the whole body affecting 50-80% of cancer patients, characterized by involuntary loss of body weight due to wasting of muscles and fat. CAC is detrimental to cancer patients’ quality of life and considered the immediate cause of death for a third of of cancer patients. It is therefore very important to find biomarkers to predict which patient is likely to develop CAC to adapt treatment and lifestyle to prevent or delay cachexia as much as possible. We studied how uncontrolled inflammation, perturbed hormone balance and the nervous system operate and interact during CAC using model systems that mimic the patient situation. We experimentally demonstrated that inflammation and the beta-adrenergic system are important players that should be closely monitored in patients. In addition, we showed how immune cells interact with the sympathetic nervous system during CAC and unravelled unanticipated implications of inflammation in skin and liver cancer. Once validated by clinicians, our findings will likely translate into new biomarkers that will help improve CAC and more generally cancer prevention and treatment.
In conclusion, the CSI-fun project not only allowed us to gain a better understanding of Chronic Systemic Inflammation, but also led to discoveries that will help improve the management of Atopic Dermatitis, Psoriasis, Arthritis and Cancer and decrease the societal burden of these common, but very detrimental diseases.
The 1st year of the project was devoted to relocate the laboratory at the Medical University of Vienna (MUV), before COVID restrictions forced us to work at a modest capacity for 18 months. The last 42 months (including a 12-months extension) were dedicated to experimental work and results dissemination to the general & scientific community.
Despite COVID-related issues, experiments along all 3 Goals progressed well and 22 research papers were published to date. 15 are directly linked to project core while 7 publications either incorporated data/material produced within the ERC project and/or were initially outside project core, but generated project-relevant knowledge. One additional research paper, a perspective article and 2 collaborative articles are currently under peer-review, while 4 research manuscripts are very close to submission and will be added to the project’s scientific output. These publications unravelled several new candidate biomarkers and/or therapeutic targets in Psoriasis, Atopic Dermatitis and Cancer.
All our published research is open access and the related OMIC datasets deposited in public databases. These scientific publications have received considerable attention despite their young age and they were already cited 570 times in other scientific papers (source: Dimensions). When additionally considering citations in news feeds & media (more than a 100), social media appearances (over a million X followers hit by a primary post) and science popularisation journals and websites, our research papers reached high attention scores in Altmetric, a web resource that tracks and quantifies interest for published research. More than half of the CSI-fun scientific research papers are ranked in the top 5% of all research outputs scored by Altmetric. We actively disseminated our ERC-funded research by participating to scientific meetings & public events and publishing articles for the large public and/or medical doctors. Our research papers have been the direct topic of 10 MUV-endorsed press releases and almost 200 social media posts. Our engagement in dissemination is also exemplified in 7 published abstracts in scientific reviews supplements corresponding to oral/poster presentations where ERC funding was acknowledged, 4 publications in journals or magazines read by scientists outside the field and/or medical doctors and 1 article in EU research, the most highly regarded dissemination publication in Europe. The PI has been particularly engaged in sharing the project results with the public, but also advertising the exceptional value of the ERC support. His interventions at the Austrian National Television (ORF), at the European Forum Alpbach, his talk on the importance of research and research funding at public events organised by/at the Medical University of Vienna, or at the Cardinal Innitzer Appreciation Prize ceremony, are some examples. The PI’s election in 2021 as International Member of the National Academy of Sciences, USA has also put the ERC and its excellent support to research in the centre of attention (https://www.nasonline.org/directory-entry/erwin-f-wagner-xhfni8/). As a matter of fact, all 3 Austrian life scientists that are currently International NAS members have been awarded ERC grants.
Despite COVID-related issues, experiments along all 3 Goals progressed well and 22 research papers were published to date. 15 are directly linked to project core while 7 publications either incorporated data/material produced within the ERC project and/or were initially outside project core, but generated project-relevant knowledge. One additional research paper, a perspective article and 2 collaborative articles are currently under peer-review, while 4 research manuscripts are very close to submission and will be added to the project’s scientific output. These publications unravelled several new candidate biomarkers and/or therapeutic targets in Psoriasis, Atopic Dermatitis and Cancer.
All our published research is open access and the related OMIC datasets deposited in public databases. These scientific publications have received considerable attention despite their young age and they were already cited 570 times in other scientific papers (source: Dimensions). When additionally considering citations in news feeds & media (more than a 100), social media appearances (over a million X followers hit by a primary post) and science popularisation journals and websites, our research papers reached high attention scores in Altmetric, a web resource that tracks and quantifies interest for published research. More than half of the CSI-fun scientific research papers are ranked in the top 5% of all research outputs scored by Altmetric. We actively disseminated our ERC-funded research by participating to scientific meetings & public events and publishing articles for the large public and/or medical doctors. Our research papers have been the direct topic of 10 MUV-endorsed press releases and almost 200 social media posts. Our engagement in dissemination is also exemplified in 7 published abstracts in scientific reviews supplements corresponding to oral/poster presentations where ERC funding was acknowledged, 4 publications in journals or magazines read by scientists outside the field and/or medical doctors and 1 article in EU research, the most highly regarded dissemination publication in Europe. The PI has been particularly engaged in sharing the project results with the public, but also advertising the exceptional value of the ERC support. His interventions at the Austrian National Television (ORF), at the European Forum Alpbach, his talk on the importance of research and research funding at public events organised by/at the Medical University of Vienna, or at the Cardinal Innitzer Appreciation Prize ceremony, are some examples. The PI’s election in 2021 as International Member of the National Academy of Sciences, USA has also put the ERC and its excellent support to research in the centre of attention (https://www.nasonline.org/directory-entry/erwin-f-wagner-xhfni8/). As a matter of fact, all 3 Austrian life scientists that are currently International NAS members have been awarded ERC grants.
The project has already led to important discoveries. We expect that our findings and those that will be published in the project’s follow up phase will help clinicians’ in the near future to elaborate new treatment regimens and new therapeutic targets for Psoriasis, PsA, OA, Cancer and CAC.