Atherosclerosis, thrombosis & inflammation
(Prof. Christian M. Matter, MD)
Christian Matter is Professor of Cardiology at the University Hospital Zurich. He completed Medical School at the University of Zurich and is a board-certified internist and cardiologist with clinical training in Lucerne, Zurich and Boston. After a postdoctoral fellowship at the Brigham and Women's Hospital in Boston he returned to the University Heart Center in Zurich.
There he now heads Translational Research and the Cardio-oncology service and works as a non-invasive clinical cardiologist. His research focuses on the effects of inflammation and caloric restriction on atherosclerosis and thrombosis using cell culture and mouse models. These experimental findings are complemented with clinical studies in patients with myocardial infarction, acute heart failure and cancer.
Ongoing Research Lines
The group focused on the following basic and translational research topics:
Characterize immuno-metabolic pathways in atherothrombosis. His experimental research has addressed the role of PARP1, JNK2, sirtuins 1, 3 and 6 in endothelial function, atherosclerosis, and thrombosis – using genetic loss-of-function mouse models and pharmacological interventions. He is currently extending these models to mice with mutations of clonal hematopoiesis of indeterminate potential (CHIP) in mice.
Test novel prognostic biomarkers in patients with ACS. The translation of above experimental aim to patients with atherothrombosis, i.e. acute coronary syndromes (ACS) provided the basis for the Special Program University Medicine ACS-inflammation for which Christian Matter was the Co-PI. Since 2009 this multicenter Swiss cohort has recruited about 5’000 patients with detailed baseline data, outcome and a biobank. We test the role of immmunometabolic prognostic biomarkers. Together with Joachim Buhmann’s group from the ETH Zurich, they developed a machine learning-based risk score for 1 year mortality prediction in ACS patients. Moreover, we plan to apply an anti-cytokine strategy in patients with acute large myocardial infarctions.
Standardized digital patient data for research and clinical use. The SwissHeart Failure Network (SHFN, funded by SAMW) constitutes an extension of our SPUM consortium build together with the Cardiology departments in Basel, Bern and Geneva. The SHFN is supported by the Swiss Personalized Health Network (SPHN) and ETH-related Personalized Health and Related Technologies (PHRT), Christian Matter is the main applicant of this collaborative project of the Swiss Precision Health Network (SPHN) together with Joachim Buhmann (main applicant PHRT) who coordinates experts in bioinformatics and machine learning for this joint Driver project. The SWISSHEART Failure Registry collects clinical, drug and laboratory values together with raw data from electrocardiograms and transthoracic echocardiography data of patients at risk for heart failure (ACS patients) and patients hospitalized for acute heart failure. These multi-dimensional patient data will be integrated into machine learning-based diagnostic and risk scores. This project aims to improve prediction, prevention and eventually treatment of patients with heart failure. The mid-to long-term goal is to automatically extract structured dataset not only for research, but with real-time feedback loops back to the treating doctor.
Figure: Scheme of the SwissHeart Failure Network (SHFN) to build IT infrastructure (Aim 1), a Swiss Heart Failure Registry (Aim 2) and apply machine learning (ML) tools in heart failure (HF patients (Aim 3).
Improve understanding of inflammation / immunity in cardio-oncology focusing on immune check point inhibitors. Retro- and prospective analyses are performed with Dermatology (Reinhard Dummer’s team) with Isabella Sudano and Andreas Flammer. Moreover, we plan to elucidate interactions between exogenous damage (e.g., risk factors, infectious agents), the patient’s immune response to injury that is modulated by intestinal microbes and the subsequent organ damage which determines the phenotypes of cardiovascular disease. For this purpose, teaming up with Burkhard Ludewig and Michael Scharl will be crucial given their expertise in immunology and intestinal microbes, respectively.
Research Team
Yu-Jen Wang, PhD student
Tanja Engels, study nurse
Carolin Gänssle – with Clinical Study Group of Barbara Stähli
Annie Srdic. BSc
Michael A. Matter – With Catheter Study Group of Christian Templin and Barbara Stähli
Valentina Rossi – with Isabella Sudano and Andreas Flammer
Funding
Swiss Academy of Medical Sciences (SAMW)
Swiss Heart Foundation
Novartis Foundation
Sanofi-Regeneron, Amgen