Grant Recipients

Grant Recipients and their Research

Each year, the Myocarditis Foundation awards a research grant to fund the advancement of myocarditis understanding. Read about some of our past grant recipients and learn about the research our grant program helped fund.

The Myocarditis Foundation 2023 Fellowship Grants Announced

Myocarditis Foundation Awards 2023 Fellowship Grant

One of the 2023 Fellowship Grants was awarded to Dr. Swati Sharma, of the University of North Carolina, Chapel Hill, for her work on: “The Protective Role of Platelet Protease-activated Receptor4 (PAR4) in Coxsackievirus (CVB3) Myocarditis”.

Dr. Sharma came to the United States from India, in December of 2021. Based on her pre-existing background in blood coagulation and willingness to learn about viral infections and their impact on coagulopathy, she applied to Dr.Antoniak’s lab at the University of North Carolina, Chapel Hill, to continue her scientific training. The Antoniak Lab gave her an opportunity to expand her knowledge and learn about infection induced procoagulant phenotype. Under Dr. Antoniak’s guidance she learned about myocarditis and developed an interest in this understudied field.

Dr. Sharma’s proposed work will provide an important bridge towards her own independent research interest investigating the effects of viral infections on the blood coagulation and their role in inflammatory heart diseases.

(Dr. Silvio Antoniak was the 2009 Fellowship Grant Recipient from the Myocarditis Foundation for his study on Viral Myocarditis.)

Dr. Swati Sharma’s Layman’s explanation of her Myocarditis Research Project

Inflammation of heart is one of the leading causes of sudden death in children and young adults. Inflammation can be caused by viral infections. An abnormal immune response to initial viral infection is a major driving factor. We currently lack effective treatment approaches for virus-induced heart inflammation. In infections, small circulating blood cells called platelets, that are usually involved in limiting blood loss during injury, are activated. Importantly, platelet overactivation can also lead to the formation of blood clots that cause heart attacks and strokes. In this application, I will show that platelets play an active role in preventing virus-induced inflammation of the heart by changing the immune response to the virus. Here, I intend to show that platelet activation protects against virus-induced heart inflammation. I propose that viral infection activates the platelets, through the receptor PAR4. Platelet activation is needed to release platelet components, especially small RNA fragments. One of these RNA fragments is miR223. miR223 can reduce heart inflammation by enhancing pathways that are anti-inflammatory. One of the cells responding to platelet miR223 are immune cells called macrophages. I intend to show that platelets activation limits disease by increasing macrophage miR223 levels. Thus, reducing the inflammation in the heart in a mouse model of viral-induced heart inflammation. Moreover, I will show a potential therapeutic approach by using platelets to deliver miR223 as treatment of viral-induced heart inflammation. Thus, this project will reveal a new way of protecting the heart against viral infections, preventing inflammation of the heart, and reducing the number of patients requiring heart transplantation. My research will help patients in the US to live longer and healthier lives.

Congratulations to Dr. Swati Sharma on the award for her myocarditis research study!

 

 

2023 Fellowship Grant awarded by the Myocarditis Foundation

Our second 2023 Fellowship Grants was awarded to Dr. Simon Vanhentenrijk, MD, Pharm D, of the Cleveland Clinc for his work on: “Leveraging Cutting-edge PHlP-Seq Antibody Profiling to Differentiate Autoantibody Patterns in Myocarditis”.

Dr. Vanhentenrijk came to the United States after his training as a Cardiologist in Belgium.

He always wanted to know the deeper understanding of ‘how and why’ the heart reacts to different stimuli. His particular interest in heart failure and heart muscle diseases led him to join the highly competitive research lab of Dr. Tang at the world-renowned Cleveland Clinic. Being part of the translational research group motivates him to yield scientific excellence in the field of antibody-antigen reactions at the level of the heart muscle cells. With his pharmaceutical background, Dr. Simon Vanhentenrijk also feels the urge to create new ideas on how to develop drug therapies in myocarditis.

As a dedicated father of three lovely children, Dr. Simon Vanhentenrijk says he feels deeply connected with the purpose of the Myocarditis Foundation that continuously strives to expand scientific boundaries to save the lives of young individuals. He feels humbled, and yet passionately driven, to help increase our insights on ‘how and why’ inflammation of the heart muscle often has such devastating outcome and how we can overcome this.

Dr. Simon Vanhentenrijk’s Layman explanation of his Myocarditis Research Project

The goal of his translational research project is to use a novel, state-of-the-art technique, called Phage Display Immunoprecipitation Sequencing (PhIP-Seq) in patients with myocarditis. This technique will help us understand the interplay of antibodies in cardiac autoimmune diseases by building an extensive library of distinct human peptides. The advantage of the PhIP-Seq platform is to perform an unbiased, high-throughput assessment of antibodies potentially linked to specific conditions. A previous feasibility study using PhIP-Seq was done in Dr. Tang’s lab on sera from patients with suspected autoimmune cardiomyopathy, systemic sclerosis, systemic sclerosis with heart failure with preserved ejection fraction, and healthy controls. In this pilot study with a targeted approach based on our prior work on β1-adrenergic receptor antibody epitopes (research done by former laureate of the Myocarditis Foundation grant: Dr. Yuji Nagatomo), a patient with suspected autoimmune cardiomyopathy, whose antibodies binds to both extracellular loop (ECL) 1 and 2 of b1-adrenergic receptor, showed a reduced LVEF (47%), indicating a mild dysfunction of the heart.

This project also provides the framework of the multicenter Myocarditis BioBank (that Dr. Tang is currently co-leading) that can leverage both retrospective and prospective cohorts with the following components: 1) detailed clinical phenotyping that can be extracted from Electronic Health Record and captured in REDCap; 2) extraction of review of primary data sources including advanced imaging (cardiac MRI or PET) and endomyocardial histological specimens; 3) retrospective tissue/imaging retrieval and deep phenotyping; 4) patient outreach for prospective blood sampling and longitudinal follow-up through surveys.  Procedures developed in this project will better define the myocarditis study population and will also greatly catalyze the foundation of the Myocarditis Foundation Biobank in terms of developing scalable processes of broad clinical phenotyping, patient enrollment, biospecimens collection, and longitudinal follow-up.

Dr. Simon Vanhentenrijk’s research grant is named in memory of Sarah Knight, who died of Viral Myocarditis at the age of 25 in 2011, and whose family and friends have been working on raising funds for Myocarditis research in the years since her passing.

Congratulations Dr. Simon Vanhentenrijk on the Myocarditis Foundation’s Fellowship Grant Award for your myocarditis research study!

 

 

Myocarditis Foundation 2022 Fellowship Grant Recipient Announced

Dr. Jennifer Myers, PhD

The Myocarditis Foundation is proud to announce that Dr. Jennifer Myers, PhD, of the University of Oklahoma has been awarded our 2022 Fellowship Grant Recipient for the 2023-2024 Academic Year!

Her interest in science began at an early age and for as long as she could remember, she loved looking for “clues” and solving problems. Her passion for science led her to a bachelor’s degree (summa cum laude) in biomedical sciences at the University of Oklahoma and a doctoral degree in microbiology/immunology from the University of Oklahoma Health Sciences Center.

As a graduate student, working toward her PhD, she joined the laboratory of Dr. Madeleine Cunningham. What she found intriguing in Dr. Cunningham’s laboratory, was the translational aspects of human studies in myocarditis.

The goal of her research is to understand the mechanisms and immune phenotypes governing inflammatory heart disease such as myocarditis, and the biomarkers of non-recovery and progression to subsequent heart failure. With no immunomodulatory drugs approved for treatment of myocarditis to prevent permanent heart damage and heart failure or transplant, a more comprehensive understanding of specific immune mechanisms in human myocarditis, dilated cardiomyopathy, and heart failure is needed.

Because her studies are translational, they will make a difference in the lives of those with inflammatory heart disease and lead to better identification of those who will have poor outcomes as well as provide a basis for new treatments. Dr. Myers has found that speaking with patients and their families opens lines of communication between the scientific community and the lay public and opened her eyes to the suffering caused by these devastating heart diseases that can lead to the need for heart transplantation.

It was a wonderful experience to be given the opportunity to interact with these patients and their families during a Myocarditis Foundation meeting. Outside of the laboratory, I am dedicated to my family, including my husband and two young children, and we enjoy spending time outdoors with our two Labrador retrievers and attending sporting events together.

A “layman’s summary” of Dr. Myers’ research study on “Autoimmune Mechanisms in Human Myocarditis.” is explained below.

Biomarkers to identify myocarditis patients who will not spontaneously recover heart function is an unmet clinical need to inform treatment decisions and prevent progression to dilated cardiomyopathy, heart failure, and transplant. Antibodies that target a person’s own heart (autoantibodies) have been reported for years without a full understanding of their role in disease, partly due to a lack of longitudinal studies and more focus on cellular immune responses. Our study is practical, novel, and needed to understand disease-causing heart autoantibodies in myocarditis. We plan to investigate these autoantibodies to identify patients who will have poor outcomes and to determine the genes that are altered in heart cells in response to the autoantibodies present in disease. We will investigate the hypothesis that autoantibodies against the heart protein cardiac myosin will alter genes leading to fibrosis and gene responses leading to cell death in cardiac cells. Our study will provide important new insights into autoimmune mechanisms of myocarditis and biomarkers for development of new diagnostic and treatment strategies.

Dr. Jennifer Myers Research Grant is named in memory of John Phillip Mello, a 26-year-old Viral Myocarditis victim who died in 2017. His Family and Friends have been working on raising awareness of the disease and funding for a Myocarditis Foundation Fellowship Grant in his name over the past few years since his passing.

Please join the Myocarditis Foundation in congratulating Dr. Myers and welcoming her as the Foundation’s 25th Fellowship Research Grant recipient!

Myocarditis Foundation 2021 Fellowship Grant Recipients Announced

We are proud to announce that we have two 2021 Fellowship Grant Recipients, Dr. Andrew Koenig, PhD, from Washington University in Saint Louis and Dr. Tahir Kafil, MD, from the Ottawa Heart Institute, in Canada.

Dr. Koenig’s research study is titled: “Defining the Spatial Proteomic and Transcriptomic Landscape of Myocarditis.” This Fellowship Grant will be named for Sarah Knight, a 25-year-old bi-lingual kindergarten teacher, who was a victim of Viral Myocarditis. Due to the generosity of her family and friends, this is the second grant to be named for her. They believe that myocarditis research is the key to finding the answers and putting a halt to the disease that takes so many young and otherwise healthy unsuspecting people.

Dr. Koenig’s preceptor of myocarditis research is Dr. Kory Lavine, MD, PhD, also from Washington University in Saint Louis.

Dr. Koenig is our 22nd Fellowship Grant Recipient and here is his layman’s description of his research:

Myocarditis is a life-threatening disease as an underdiagnosed cause of acute heart failure, sudden death. In addition to viral myocarditis, there are different kinds of myocarditis. They are characterized with heart damage and immune cells accumulation. It is challenging to diagnose some kinds of myocarditis with similar features using current diagnostic approaches. Furthermore, myocarditis has different features and outcomes across patients. Here in our study, we will use the recently developed novel technologies directly on patients’ biopsy samples. With the data generated by the novel technologies, we will uncover the causes and specific characters of these diseases as well as the precise differences between different patients. Importantly, this will yield new diagnostic tools that inform personalized patient management and uncover new therapeutic targets to treat these diseases and improve patients’ life quality.

Dr. Kafil’s research study is titled: “COVID-19 Vaccine-induced Inflammatory Heart Disease Registry and Prospective Cohort Study. (COVID-VIHPR)” This Fellowship Grant will be named for Ashley Burgauer, a 27-year-old registered nurse, who was a victim of Viral Myocarditis. Due to the generosity of her family and friends, this grant is being named for her. Her family have made it a passion of theirs to make people aware of this disease and support research to help stop the devastation to families that it causes.

Dr. Kafil’s preceptor of myocarditis research is Dr. Peter Liu, MD, also from the Ottawa Heart Institute.

Dr. Kafil is our 23rd Fellowship Grant recipient and here is his layman’s description of his research:

“Myocarditis and pericarditis are inflammatory conditions of the heart muscle and lining. They can occur after viral infections and can occur in patients who are infected by COVID-19. Recently, myocarditis has also been reported following mRNA vaccines for COVID-19. The mRNA vaccines are effective in preventing ICU admissions and deaths from COVID-19 infection. One of their rare side-effects can be myocarditis or pericarditis. Our study is designed to determine the natural history, diagnostic work up, immunological profile, biomarker predictors and sex differences in these conditions.”

Our congratulations to Dr. Andrew Koenig, PhD and Dr. Tahir Kafil, MD and many thanks for your work in myocarditis research!

Myocarditis Foundation Awards Another Research Grant

The Myocarditis Foundation is proud to announce that we have awarded a special 2-year research grant, to Dr. William Bobo, MD, from Mayo Clinic, Jacksonville, Florida.

Dr. Bobo, Chair of the Department of Psychiatry and Psychology at Mayo, Jacksonville, will be researching the effects of anxiety and depression on quality of life and health outcomes in people diagnosed with myocarditis and those who care for them.

Acute Myocarditis, a potentially life-threatening disease that often develops without warning, is typically associated with ongoing physical challenges among survivors, and striking emotional struggles among both survivors and their identified support givers/caregivers. While other ischemic and non-ischemic heart disease have been studied in relation to anxiety and depression, Dr. Bobo was only able to find one study on those who survived Fulminant Myocarditis and were on circulatory support. He found no reports focused on caregivers.

As such, very little is known about the impact of mental health conditions or symptoms in myocarditis survivors and their caregivers, highlighting a critical knowledge gap.

This project aims to identify people with myocarditis who are risk for clinically significant depression and anxiety.

Our congratulations to Dr. William Bobo and many thanks for his study of this in Myocarditis patents and their families!

Myocarditis Foundation 2019 Fellowship Grant Recipient Announced

We are proud to announce our 2019 Fellowship Grant Recipient, Dr. Danette Flint, MD, from Dartmouth-Hitchcock Medical Center. Dr. Flint’s research study is titled: “Immune Checkpoint Inhibitor Associated Myocarditis.” The 2019 Fellowship Grant will be named after Lee Andrew Hirsch, a 31 year old victim of Viral Myocarditis

The Myocarditis Foundation is proud to announce our 2019 Fellowship Grant Recipient, Dr. Danette Flint, MD, from Dartmouth-Hitchcock Medical Center. Dr. Flint’s research study is titled: “Immune Checkpoint Inhibitor Associated Myocarditis.” Dr. Flint’s Preceptors are Dr. Javid Moslehi, MD, from Vanderbilt University and Dr. Lauren Gilstrap, MD, from Dartmouth-Hitchcock Medical Center.

The 2019 Fellowship Grant will be named after Lee Andrew Hirsch, a 31 year old victim of Viral Myocarditis from 2015 whose mother and family have been working on raising funds for research so as to prevent others from suffering the loss that they have and to find elusive answers to stopping the disease.

Dr. Flint is our 20th Fellowship Grant Recipient and here is her layman’s description of her research.

“Immune Checkpoint Inhibitor Associated Myocarditis:”

Immune checkpoint inhibitors, or ICIs, are a newer drug therapy that target how cancer cells interact with our immune system. ICIs have been approved for treatment of multiple types of cancers and have proven to markedly increase survival for patients, even those with metastatic disease. Unfortunately, because of the way these drugs affect the body’s immune system, there are also significant side effects which can target multiple parts of the body, including the heart. When the heart is targeted, inflammation of the heart muscle results, a condition called myocarditis. The illness that results can be so severe that it leads to death. At present, the frequency of ICI associated myocarditis and other related cardiac side effects, such as heart failure and sudden cardiac death, are not well known and individual patient factors that increase or decrease the risk of these side effects have not been examined. In order to provide patients with an accurate and personalized assessment of their individual expected benefit and risk from these drugs, we plan a research project using Medicare data to both determine the rates of these side effects at a national level and identify characteristics that increase or decrease an individual patient’s likely benefit or risk with these potentially life-saving, novel therapies.

Our congratulations to Dr. Danette Flint and many thanks for her work in myocarditis research!

2018 Rhett Lundy Memorial Research Fellowship Grant Recipient: Dr. Taejoon Won, PhD

This year the Myocarditis Foundation Research Fellowship Grant is named in the honor of Rhett Lundy, a 14 year old boy who passed away due to myocarditis. Read Rhett’s Story Here.

Dr. Taejoon Won, PhD from The John Hopkins School of Medicine in Baltimore, Maryland is this year’s Myocarditis Foundation Research Grant Recipient. Dr. Won is a postdoctoral fellow in the lab of Dr. Daniela Cihakova, MD, PhD. Dr. Cihakova was the 1st Myocarditis Foundation grant recipient in 2006 and Dr. Won is our 19th recipient. Below is a layman’s description of his research study titled “Therapy for Myocarditis by Targeting Endothelial PD-L1”.

In this proposed research, we will investigate the therapeutic potential of a novel gene therapy for myocarditis treatment. Clinical management for myocarditis is currently limited to controlling symptoms, resulting in the need for new biological therapies based on understanding the pathogenetic mechanisms of myocarditis. Programmed cell death-ligand 1 (PD-L1) is a receptor expressed on immune cells and non-immune cells that suppresses excessive immune responses in peripheral organs including the heart. In some cases of cancer patients, the treatment blocking PD-L1 or its counterpart PD-1 as a cancer therapy has caused fatal myocarditis. It raised a question if myocarditis can be treated by enhancing PD-1/PD-L1 interaction in the heart. In the proposed research, I will use PD-L1 gene therapy to prevent viral myocarditis in a mouse model. Adeno-associated virus (AAV) is a novel carrier for the clinical gene therapy approach showing no adverse effects and no severe toxicity. The FDA has recently approved the first AAV-based gene therapy. Our laboratory has generated an AAV vector overexpressing PD-L1 selectively in endothelial cells, which are one of the non-immune cells in the heart covering the inside of heart chambers. We will test the therapeutic potential of our AAV-PD-L1 vector in a viral myocarditis mouse model. In addition, to investigate the importance of PD-L1 expression by endothelial cells in controlling myocarditis development, we will delete PD-L1 expression specifically in endothelial cells using the Cre-lox technology in a viral myocarditis mouse model. Developing AAV-based PD-L1 gene therapy, our work will open the door to a novel biologically based therapy for myocarditis to selectively suppress inflammation in the heart.

Post-Doctoral Grant for Myocarditis Research Co-funded with the American Heart Association 2018-2020

The Myocarditis Foundation is proud to announce that we have awarded a Post-Doctoral Research Grant, co-funded with the American Heart Association, for the Academic years of 2018-2020 to Dr. Lindsey Bazzone, MD, PhD., of the University of Massachusetts Medical School.

Dr. Bazzone’s research entitled: “The Role of ADAMS in the Immunopathogenesis of Viral Myocarditis” was reviewed by members of our Medical Advisory Board and decided on by our Board of Directors. This research is the most integrative with a human protein target in both in-vitro and mouse experiments.

A brief explanation of Dr. Bazzone’s research:

Viral myocarditis is an inflammatory disease of the heart that results in significant morbidity and mortality and may account for up to 42% of unexplained deaths in patients 35 years old or younger. Picornavirus infections are thought to be a major cause of myocarditis in humans and animals; however, the underlying pathogenesis of viral myocarditis remains largely unclear. Virus-host cell receptor interactions are implicated as important mediators of pathogenesis. This proposal will examine the role of the human protein, ADAM9, in viral myocarditis. Using functional and mechanistic studies in knockout cell lines and mouse models, we will determine the function of ADAM9 in the activation of innate antiviral immunity and disease progression to myocarditis during picornavirus infection.

Our congratulations to Dr. Lindsey Bazzone and many thanks for your work in myocarditis research!

The Myocarditis Foundation is Pleased to Announce the 2017 Sarah Knight Fellowship Grant Recipient

The Myocarditis Foundation is pleased to announce our 2017 Fellowship Grant Recipient, Dr. Paul Hanson, PhD, of the University of British Columbia/St. Paul’s Hospital, for the 2018-2019 Academic Year. Dr. Hanson’s research rose to the top of the research applications this year, with his research submission titled: “Personalizing Myocarditis Diagnostics through Novel Biomarkers.” To achieve a more accurate and personalized diagnosis for myocarditis, this lab has learned from valuable mouse models of viral myocarditis, and will be applying that knowledge to human myocarditis diagnostic development.

Dr. Hanson’s Fellowship Grant is named after a Viral Myocarditis victim, Sarah Knight, whose family has been raising funds to support research into myocarditis since she passed away from it in 2011. Read Sarah’s Real Life Story Here.

Please read more about Dr. Hanson’s work in the Layman’s Summary of his work below:

The Problem of Myocarditis: Myocarditis is a term to denote inflammation and injury of the heart muscle or myocardium. Myocarditis is a major cause of sudden and unexpected death in young people including children. Viruses that infect the heart muscle are a common cause of myocarditis, resulting in inflammation and tissue damage. This damage is significant because injured heart muscle cells cannot contract effectively, and individuals afflicted with myocarditis will develop failure of the heart pump that requires medical or surgical intervention, including heart transplantation or artificial heart pumps, for survival. Young people affected by viral myocarditis are at even greater peril as they may develop heart failure right away or decades later.

How the Diagnosis of Myocarditis Is Usually Made: To help minimize the damage and devastating outcomes, an early proper diagnosis is required. The gold standard (most certain method) for diagnosing myocarditis is via a biopsy of the heart. Tissue is snipped from the pumping chamber muscle and is examined for evidence of inflammation and tissue damage. Yet, under the current established procedures, a correct diagnosis can only be made in 30% or fewer of patients that actually have myocarditis. Not all parts of the heart muscle will be equally involved by the disease, so the biopsy may miss the inflammation and damage. Thus, the current diagnostic approach is not sufficiently sensitive. Significant advances have occurred in our understanding of the biology underlying such conditions as myocarditis since the time that the initial biopsy guidelines were developed in the 1980’s. We believe these modern diagnostic tools will dramatically improve on our ability to make the diagnosis of myocarditis, resulting in better management and outcomes for patients.

A New Approach to Diagnosis of Myocarditis: To achieve a more accurate and personalized diagnosis for myocarditis, our laboratory is learning from valuable mouse models of viral myocarditis, and applying that knowledge to human myocarditis diagnostic development. We have discovered increased amounts of certain proteins are associated with heart muscle failure -in the setting of viral infection (myocarditis) in mice when compared to the hearts of healthy uninfected mice. Importantly, these particular proteins could be detected even in sections of the heart without the characteristic inflammation and tissue damage usually considered necessary for diagnosis. Further, this pattern of increased protein expression appears to be specific to viral myocarditis as compared to other causes of heart failure. Our preliminary work in human heart muscle has revealed increased amounts of these same proteins in human myocarditis, suggesting that they are biomarkers of viral myocarditis, or in other words, biological hallmarks of this particular disease state. We are now examining whether detection of these proteins provides for improved diagnosis in myocarditis. Ultimately, if these increased proteins are part of the disease process stimulated by the virus, they could become targets for new therapies.

Important Next Steps Made Possible by the Myocarditis Foundation: Our work will start with an examination of whether staining for these biomarkers on heart biopsy tissue will consistently improve the ability of pathologists (laboratory physicians) to diagnose myocarditis after biopsy is performed. The experiments we have performed thus far suggest that this approach will be successful, possibly achieving accurate diagnosis about 80% of the time. But this needs to be rigorously demonstrated. Following on this work, we anticipate being able to detect fragments of these proteins generated during the disease process in the blood of patients with myocarditis. If this latter approach is successful, we may be able to develop blood tests that will improve our ability to diagnose myocarditis, perhaps reducing the need for an invasive heart biopsy.

Potential Impact and Significance: Perhaps the most exciting and challenging aspect of this scientific work is the potential to provide new knowledge about how the proteins function and contribute to the disease process during human myocarditis. New treatments may arise.
Currently, most treatment for myocarditis is supportive, aimed at only treating symptoms and supporting the weakened heart muscle. By better understanding the disease, we can develop more specific therapies, aimed at actually eliminating the disease before it causes severe heart damage and heart failure. Similar work in future studies will allow for each of the different causes of myocarditis to be better identified and managed, with each patient receiving the right treatment at the right time in a personalized fashion.

2016 MF Fellowship Research Grant Recipient-Dr. Guobao Chen

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The Myocarditis Foundation is pleased to announce that Dr. Guobao Chen, PhD, is the 2016 Fellowship Grant Recipient for the 2107-2018 Academic Year. Dr. Chen was the second place finalist in last year’s Fellowship Grant applicants, but came in above all the others in the 2016 submissions.Dr. Chen is from Johns Hopkins University School of Medicine and his mentor is Dr. Daniela Cihakova MD, PhD. Dr. Cihakova was the very first MF Fellowship Grant recipient in 2006. Dr. Chen is now conducting myocarditis research in Dr. Cihakova’s Lab and his research submission is entitled: “The Role of PDGFRa+ Cardiac Fibroblast in Myocarditis.”

Dr. Chen’s layman’s summary of his research project is as follows:

Despite that most patients recover from acute myocarditis, an estimated 9-16% of myocarditis cases progress to dilated cardiomyopathy, which is one of the most common causes of non-congenital heart failure in young individuals. Effective treatments for chronic dilated cardiomyopathy patients are limited, leaving heart transplantation as the only option for end stage heart failure. Thus, to stop the disease progression from myocarditis to dilated cardiomyopathy is critical for patients to recover from myocarditis.

We have adapted an experimental auto-immune myocarditis mouse model, to investigate the mechanism behind the disease progression from myocarditis to dilated cardiomyopathy. We have found a specific group of heart cells that is receiving the signaling from a pathological factor IL-17A. After receiving the signal from IL-17A, these cells will produce a number of other pathological factors to exacerbate the disease progression from myocarditis to dilated cardiomyopathy. We have also detected the same group of heart cells in human myocarditis patients and they were found to be expressing the pathological factors that were found in our mouse model. Similarly, the same specific group was also found in ischemia patient biopsies and our myocardial infarction (Heart Attack) mouse model. Thus, our discovery provides an excellent opportunity to develop specific treatment to halt the disease progression from myocarditis to dilated cardiomyopathy. We have designed delicate therapeutic methods to specifically target the immune function of this group of cells without killing them, which will minimize the side effects of systemic immune suppression and preserve other functions of these cells that might be important for the recovery from myocarditis.

A short story about how Dr. Chen joined Dr. Cihakova’s Lab at Johns Hopkins:

As previously an immunologist, I was first attracted by the sophisticated immune interactions between different cell types in the heart that were previously published by members of Dr. Cihakova’s Lab. From there, I went on to read more about myocarditis and diseases involving heart inflammation. It was after that when I became more and more interested with this topic. Later, in a routine conversation with my mum, she told me that her doctor suspected that she might have had myocarditis before, as her left ventricle was abnormally large. All these things strengthened my decision to dedicate my research career on developing treatment for myocarditis and other heart diseases.

The Myocarditis Foundation extends their best wishes to Dr. Chen for much success in his myocarditis research.  It is our prayer that we will one day find a treatment or a cure for this devastating disease, that takes so many of our young and otherwise healthy children and young adults.

The Myocarditis Foundation Welcomes Previous Fellowship Grant Recipient to the Medical Advisory Board!

Dr. Bettina Heidecker, the 2007 Myocarditis Foundation Fellowship Grant recipient, has just been appointed to the Myocarditis Foundation Medical Advisory Board. Dr. Heideckers title of her research at that time was: Gene Expression Profiling for Detection of Myocarditis.

Since that time, Dr. Heidecker, has worked with Dr. Joshua Hare at the University of Miami Interdisciplinary Stem Cell Institute as a Post-Doctoral Fellow and Co-Principal Investigator, (2007-2009) studying transcriptomic biomarkers for new onset heart failure and to further develop the diagnostic biomarker for myocarditis.

Dr. Heidecker also completed her residency training at the University of Miami in Internal Medicine (2009-2012) as well as a Cardiology fellowship at the University of California, San Francisco (2012-2015) while continuing her research in myocarditis.

Dr. Heidecker served as a member of the Scientific Advisory Board of Heart Genomics, LLC, a company that her preceptor, Dr. Joshua Hare founded. Her goal is to develop improved diagnostic accuracy in myocarditis by analyzing heart biopsies and blood samples of patients with myocarditis and to get a better understanding of the pathophysiology of this common disease She has also been an International Lecturer in Cardiology for the Aston Medical School in Birmingham, UK since 2014.

Dr. Heidecker has returned to her homeland of Austria in September 2015 and is now a non-invasive cardiologist at the University of Zurich, Switzerland, where she teaches students and fellows early recognition of myocarditis. Furthermore, she established a specialty clinic for myocarditis and is planning to start enrolling patients soon for at least two clinical studies in the field of myocarditis.
Her professional memberships include:

  • European Society of Cardiology: Working Group on Myocardial and Pericardial Diseases
  • European Acute Cardiovascular Care Association
  • American College of Cardiology
  • American Heart Association
  • American Society of Echocardiography
  • sterreichische Gesellschaft fr Innere Medizin

Dr. Heidecker has had many published articles in her field of research and has always been a supporter of the Myocarditis Foundation. She expressed in a 2015 European Heart Journal article that the Myocarditis Foundation was especially helpful for her, through its financial support and the mentorship of Drs. Leslie Cooper and DeLisa Fairweather.

We look forward to our continued association with her and utilizing her impressive achievements to help direct our future research initiatives.

Welcome Dr. Heidecker!

The Myocarditis Foundation Announces its 2015 Grant Recipient for the 2016/2017 Grant Cycle

The Myocarditis Foundation is pleased to announce that it will be funding a research fellowship grant for the 2016/2017 grant cycle. The Myocarditis Foundation will be awarding the research grant to Dr. Jon Sin of Cedars-Sinai Medical Center in the amount of $40,000. Dr. Sin is under the mentorship of Dr. Ralph Feuer of Cedars-Sinai Medical Center.

 

The Myocarditis Foundation, an international non-profit organization founded in 2005, is dedicated to increasing awareness and hastening progress in understanding this rare disease. Myocarditis is a disease that is marked by inflammation and scarring of the heart muscle, which can progress rapidly to heart failure and death or heart transplantation.

The Myocarditis Foundation announced in its third quarter of 2015 that it was accepting grant applications until December 1, 2015. The Myocarditis Foundations International Medical Advisory Board, made up of leading myocarditis researchers from around the world, voted to award a fellowship grant to Dr. Sin after selecting his application from a distinguished field of candidates.

Dr. Sins research project is titled Coxsackievirus B Subverts Host Mitophagy to Promote Viral Dissemination and Myocarditis. Below is a laymans summary of his research:

Coxsackievirus B (CVB) is a common juvenile pathogen that can cause a wide-array of inflammatory diseases including meningitis, pancreatitis, and myocarditis, all of which can be fatal. We see that CVB, which is a naked virus, can escape the cell in membrane-bound vesicles which we hypothesize are derived from autophagosomes. Not only does this blur the line between enveloped and non-enveloped viruses, but it also suggests that CVB could use these host membranes to evade the immune system. Additionally when we infect cardiomyocytes, mitochondrial networks appear to fragment, which is an early step in the autophagic degradation of mitochondria (mitophagy). Normally, these fragmented mitochondria would be targeted for destruction; however we find that in the setting of infection, mitochondrial fragments and virus are ejected from the cell in membrane-bound vesicles. If we pharmacologically block mitochondrial fission prior to infection, this results in lower viral titers in the media and fewer infected cells, suggesting that blocking the early steps in mitophagy suppresses viral escape. We hypothesize that the virus triggers mitochondrial fission and uses these fragments as bait in order to become encapsulated in autophagosomes and get ejected from the cell in order to further spread infection. Based on our preliminary findings, we are now utilizing a mouse model of CVB infection to test the efficacy of using a mitochondrial fission inhibitor to suppress vital myocarditis.

-Summary by Dr. Sin

The Myocarditis Foundation is honored to work with Dr. Sin and the Cedars-Sinai Medical Center, furthering the expansion of myocarditis research. It is the Foundations goal to build a greater understanding of the disease and find better ways to diagnose, treat and ultimately prevent myocarditis from taking more lives.

The Myocarditis Foundation would like to thank all the families, businesses, and organizations that have supported the Foundation in 2015. It is with their generosity and support that these research grants are able to be awarded each year.

For more information regarding the Myocarditis Foundation and its grant program, please visit, www.myocarditisfoundation.org.

Success in Mentoring MF Grant Recipient

The Myocarditis Foundation awards grants for one year research fellowships to study myocarditis with the aim of encouraging young PhD and MD scientists to pursue a career involving myocarditis. As well as financial support the Foundation also provides mentoring support with career advice and assistance with networking. Recently one of our grant recipients, Dr. Bettina Heidecker MD, was highlighted in an article in a prestigious scientific journal the European Heart Journal (reference Eur Heart J (2015) 36:398-403). In this article Bettina states that Myocarditis is a disease affecting many young individuals. Currently we lack sufficient understanding of its pathophysiology to improve specific treatment. With current standard diagnostic techniques a large number of patients with myocarditis remain under-diagnosed and therefore do not receive appropriate treatment. Bettinas research received funding support not only from the Myocarditis Foundation but also from the American Heart Association. She received a Samuel A. Levine Award and a Jay N. Cohn New Investigator Award based on her research findings. She mentions in her article how important funding from the MF and mentoring from Dr. Leslie Cooper MD and Dr. DeLisa Fairweather PhD, MF Board Members, was for her career success. She currently is a Cardiology Fellow at UCSF and plans to combine research, clinical work, and teaching in her career. MF grant recipients who have become Assistant Professors in Faculty positions include Dr. Daniela Cihakova MD, PhD at Johns Hopkins School of Medicine and Dr. David Marchant, PhD at the University of Alberta Canada. We are proud of the success of all of our grant recipients.
The Myocarditis Foundation Announces its 2014 Grant Recipient for the 2015/16 Grant Cycle

The Myocarditis Foundation is pleased to announce that it will be funding a research fellowship grant for the 2015/16 grant cycle. The Myocarditis Foundation will be funding a research grant awarded to Dr. Michael Bode of the University of North Carolina in the amount of $35,000. Dr. Bode is under the mentorship of Dr. Nigel Mackman of the University of North Carolina.

The Myocarditis Foundation, an international non-profit organization founded in 2005, is dedicated to increasing awareness and hastening progress in understanding this rare disease. Myocarditis is a disease that is marked by inflammation and scarring of the heart muscle, which can progress rapidly to heart failure and death or heart transplantation.

The Myocarditis Foundation announced in its third quarter of 2014 that it was accepting grant applications until December 2014. The Myocarditis Foundations international Medical Advisory Board, made up of leading myocarditis researchers from around the world, voted to award a fellowship grant to Dr. Bode after selecting his application from a distinguished field of candidates.

Dr. Bodes research project is titled Role of PAR-1 in a Mouse Model of Viral Myocarditis Below is a laymans summary of his research:

“It is estimated that myocarditis causes up to 20% of sudden death in adults less than 40 years of age, and Coxsackievirus B3 is considered to be one of the most important causes of myocarditis. I am trying to better understand the mechanisms that protect the heart from viral myocarditis. In particular, I am going to identify the role of the blood coagulation system in the regulation of the immune response against viral myocarditis. We have previously shown that a protein called PAR-1 that gets activated by the clotting system plays an important role in protecting mice from Coxsackievirus B3 infection. I recently found that especially PAR-1 in cardiomyocytes, which are the cells in the heart that are contracting, plays an important role in protecting the heart from the virus. I would now like to understand the pathways inside the cells that lead to protection, by doing cell culture experiments with cardiomyocytes. This will involve stimulating the cells with a PAR-1 activator to see if this causes them to produce proteins that can protect the cells from the virus. I will also add inhibitors of different pathways to examine which pathway is most important. In addition, I will use mice that are lacking PAR-1 in cardiomyocytes to observe the effects of the virus infection in the absence of PAR-1. I expect these mice to be sicker, to have a worse heart function, and to produce less proteins that protect them from the virus. By understanding the mechanism of viral myocarditis in detail, we may be able to improve the current therapy or establish novel therapies to protect the heart from viral infections..” -Summary by Dr. Bode

The Myocarditis Foundation is honored to work with Dr. Bode and the University of North Carolina, furthering the expansion of myocarditis research. It is the Foundations goal to build a greater understanding of the disease and find better ways to diagnose, treat, and ultimately prevent myocarditis from taking more lives.

The Myocarditis Foundation would like to thank all the families, businesses, and organizations that have supported the Foundation in 2014. It is with their generosity and support that these research grants are able to be awarded each year.

For more information regarding the Myocarditis Foundation and its grant program, please visit: www.myocarditisfoundation.org.

The Myocarditis Foundation Announces its 2013 Grant Recipient for the 2014/15 Grant Cycle

The Myocarditis Foundation is pleased to announce that it will be funding a research fellowship grant for the 2014/15 grant cycle. The Myocarditis Foundation will be funding a research grant awarded to Dr. Yuji Nagatomo of the Cleveland Clinic in the amount of $35,000. Dr. Nagatomo is under the mentorship of Dr. Wilson Tang of the Cleveland Clinic.

The Myocarditis Foundation, an international non-profit organization founded in 2005, is dedicated to increasing awareness and hastening progress in understanding this rare disease.Myocarditis is a disease that is marked by inflammation and scarring of the heart muscle, which can progress rapidly to heart failure and death or heart transplantation.

The Myocarditis Foundation announced in its third quarter 2013 that it was accepting grant applications until December 2013. Their international Medical Advisory Board, made up of leading myocarditis researchers from around the world, voted to award a fellowship grant to Dr. Nagatomo after selecting his application from a distinguished field of candidates.

Dr. Nagatomos research project is titled Autoimmunity in Suspected Myocarditis and Recent-Onset Cardiomyopathy: The significance of IgG3 autoantibody against 1 adrenergic receptors Below is a laymans summary of his research.

“Over the years, there has been extensive research work surrounding the presence of antibodies that attack the components of the adrenaline system, which may directly or indirectly affect the function of the heart. Termed autoantibodies, they may stimulate the system and activate the flight and fight response that drives the heart to get weaker over time. Preliminary findings have suggested that removal of one specific type of autoantibodies, IgG3, appears to be most effective in facilitating recovery of heart function. The objective of this study is to determine how common this subtype of autoantibody that acts against the adrenergic system is found in patients with new-onset heart failure or suspected myocarditis, and to see how these autoantibodies (and its subtype) directly influence the adrenaline system by looking at how they stimulate the blood cells. We believe that this research will provide novel insight into the pathology of myocarditis and lead to the development of new treatment modality for this potential therapeutic target.”

– Summary by Dr. Nagatomo

The Myocarditis Foundation is honored to work with Dr. Nagatomo and the Cleveland Clinic, furthering the expansion of myocarditis research. It is the Foundations goal to build a greater understanding of the disease and find better ways to diagnose, treat, and ultimately prevent myocarditis from taking more lives.

The Myocarditis Foundation has also approved to co-sponsor a research grant with the American Heart Association (AHA), but the 2013 end-of-year AHA grant applications did not match the guidelines put forth by the Myocarditis Foundation. New grant applications will be submitted in the spring of 2014, and hopefully one will meet the Myocarditis Foundations Medical Advisory Board research guidelines. It is the Myocarditis Foundations goal to award two grants for the 2014/15 grant cycle.

The Myocarditis Foundation would like to thank all the families, businesses, and organizations that have supported the Foundation in 2013. It is with their generosity and support that these research grants are able to be awarded each year.

The Myocarditis Foundation Awards Two Research Grants in 2012

The Myocarditis Foundation is pleased to announce that it will be funding two research fellowship grants for the 2013/14 grant cycle. The Myocarditis Foundation will be funding a research grant awarded to Dr. Chandirasegaran Massilamany of the University of Lincoln in the amount of $35,000 and have co-sponsored a grant with the American Heart Association awarded to Brian Avanzino of the University of California Davis in the amount of $50,000, half of which will be funded by the Myocarditis Foundation.

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Dr. Kevin Quinn of the University of California in Los Angeles
Awarded grant in 2012

Identifying Antiviral Agents to Treat Coxsackievirus Myocarditis

In support of a long-term goal of identifying potent and tolerable antiviral drugs to prevent enteroviral myocarditis, our project has the following 3 goals:

  1. To identify the compounds which most actively inhibit coxsackievirus replication in tissue culture cells
  2. To identify the mechanism of action that allows these viral inhibitors to prevent coxsackievirus from completing its lytic cycle
  3. To test the most active inhibitors in a mouse model of coxsackievirus myocarditis. Those effective in inhibiting coxsackievirus infection in animal models could in turn be evaluated towards application in human patients.

Dr. Laure Case of the University of Vermont

Awarded grant in 2012

Chromosome Y Regulates susceptibility to Coxsackievirus B3-induced Myocarditis

The experiments proposed in this fellowship will identify the critical cell types, for example, cardiomyocytes and/or immune cells, which influence myocarditis susceptibility in the consomic mice. This data will provide the necessary cellular link for future work that tests the hypothesis that ChrY-dependent regulation of genes on other chromosomes is evolutionarily conserved and that this mechanism influences myocarditis susceptibility among male mice. This is a very novel and exciting area of genetic research that will reveal ChrYs contribution to phenotypic differences that directly impact susceptibility to myocarditis and allow for the identification of genes and pathways that can be targeted for mechanistic studies and therapeutic intervention.

Dr. Alan Valaperti of the University of Health Network at the University of Toronto in Canada

Awarded grant in 2011

IL-1 Receptor-associated Kinase 4 (IRAK4) Epigenetically Modulates Nod2- and MDA5- dependent Protection in Viral Myocarditis

First we observed that the major cell population infiltrating into the inflamed heart of Coxsackie virus B3 (CVB3)-inoculated IRAK4 deficient mice were macrophages. We were able to show that upon in vitro infection with Coxsackievirus B3 (CVB3), IRAK4 down-regulated IFN- and IFN-, but not IFN-, exclusively in macrophages, but not in myeloid dendritic cells or plasmacytoid dendritic cells. Simultaneous down-regulation of IFN- and IFN-, which means up-regulation of IFN- and IFN- in IRAK4 deficient cells, was enough to dramatically reduce viral replication in infected macrophages.

In addition, IRAK4 showed unique functions that were only partially shared with its upstream molecule MyD88. In particular, IRAK4 deficiency showed better stability of MDA5, which is an important cytoplasmic receptor to recognize Coxackievirus genome to mount an interferon-dependent anti-viral response. On the contrary, CVB3-infected wild-type macrophages showed a relevant degradation of MDA5 few hours after infection, whereas MyD88 deficient cells showed degradation of MDA5 in a later stage. This resulted in higher viral protection in IRAK4 deficient cells compared to wild-type or MyD88 deficient counterparts.

Dr. Kathleen Simpson of Washington University in St. Louis, MO

Awarded grant in 2010

Autoimmunity in Pediatric Myocarditis: A Pilot Study

The relationship of autoimmunity in the pathophysiology and outcomes of pediatric myocarditis is unknown. Through the collaboration of regional pediatric hospitals encompassing the states of Missouri, Oklahoma, and Nebraska, we plan to determine the relationship of autoimmunity to outcomes in previously and newly diagnosed pediatric myocarditis. In addition, we will use MRI of the heart to determine specific findings in children and the role of MRI in disease progression and prognosis for children with myocarditis. Improving the understanding of patient immune reaction in myocarditis may lead to improvement in prognosis and treatment in children.

Dr. Byung Kwan Lim of the University of California in San Diego

Awarded grant in 2009

The Role of Dystrophin in Enterovirus Induced Viral Myocarditis

Specific Aim1. Determine whether cardiac myocyte-specific, inducible expression of enterovirus protease 2A in the dystrophin knock-in adult mouse heart can prevent myocyte sarcolemmal membrane disruption and the subsequent development of cardiomyopathy.

Hypothesis: Dystrophin knock-in can prevent mycoyte sarcolemmal membrane disruption through inhibition of dystrophin cleavage by enterovirus protease 2A.

Expected Results: We will generate DysKI/2A/MCM triple transgenic mice to determine the effect of cleavage-resistant dystrophin in cardiac-specific inducible expression of enterovirus protease 2A.

Specific Aim2. Determine whether knock-in of dystrophin that prevent protease 2A cleavage of dystrophin can protect against CVB3 infection mediated cardiac myocyte damage and myocarditis.

Hypothesis: Dystrophin knock-in reduces dystrophin cleavage and sarcolemmal membrane disruption after CVB3 infection.

Expected Results: We generated inbred Balb/C DysKI mice to determine whether DysKI mice have less sarcolemmal membrane disruption and myocyte damage in CVB3 infection. Preliminary data showed no significant difference between DysKI and littermate controls. There are similar virus titer and Evans blue dye uptake percent. However, Balb/C mice have high susceptibility to CVB3 and immune response. To prove a mechanical effect of virus infection we will generate less susceptible inbred C3H background DysKI mice.

Dr. David Marchant of the University of British Columbia in Vancouver, Canada

Awarded grant in 2009

Discovering and Understanding Virus-Host Factor Interactions for Treatment of Viral Myocarditis

We showed that virus signaling during infection originated from, and converge upon, dominant signaling nodes. This work, which employed several signaling inhibitors to investigate signaling networks, identified those targets whose inhibition most effectively inhibited viral replication; the nodes.

We concluded that by targeting the dominant signaling nodes that are required for viral replication we could, hypothetically, discover the most effective target for treatment of CVB3 infection. This is the first work of its kind and should provide new avenues for investigation of the most effective antivirals for treatment of virally induced myocarditis.

Dr. Silvio Antoniak of the University of North Carolina in Chapel Hill

Awarded grant in 2009

Thrombin-PAR-1 Signaling in Viral Myocarditis

I conclude that PAR-1 activation is essential in the early phase of virus infection to manage an effective immune response against CVB3. This response is maintained by a successful recognition of virus antigens by the TLR-3 pathway and a PAR-1 dependent NK cell activation. The altered immune reaction in PAR-1-/- mice leads to uncontrolled virus replication and later to an over-bursting immune response, aberrant cardiac remodeling leading to cardiac dysfunction after CVB3 infection.

Dr. Susan Wollersheim of the University of California in Los Angeles

Awarded grant in 2008

Cellular and Viral Determinants of Neonatal Group B Coxsackievirus Myocarditis

Sequence comparisons of more recently circulating CVB1 and CVB3 virus 5UTR and stemloop 2 folding patterns reveal that more recently circulating CVB1 and CVB3 viruses are more similar to each other than to their prototype viruses from the 1940s. The area of highest divergence from protoype of each CVB was within the stemloop 2 structure, which has previously been identified as a genomic determinant in CVB cardiovirulence [11]; this may indicate why the newer strain of CVB1 was more cardiovirulent than ever described previously. This new CVB1-Chi07 also has larger plaque size than CVB1-Conn5 which correlates with a higher viral replication and titer [12]. The CVB1-Chi07 shows a slower rate of growth and lower peak titer than all of the CVB3 viruses assessed. In vitro mouse models to compare these CVB1 viruses have been initiated with one experiment which indicates that CVB1-Chi07 is much more virulent than CVB1-Conn5, however further studies and data will be collected to verify this.

IRES transactivating protein identification is preliminary at this time, but the three proteins that have been identified are involved in cellular translation. Further studies of confirmation are underway and future experiments will be performed with mouse myocyte proteins.

Dr. Bettina Heidecker of the University of Miami

Awarded grant in 2007

Gene Expression Profiling for Detection of Myocarditis

The overall goal of this study is to improve diagnostic sensitivity for detection of myocarditis by endomyocardial biopsy derived transcriptomic biomarkers and to evaluate peripheral blood mononuclear cells as possible surrogates of heart tissue.

Dr. Daniela Cihakova of Johns Hopkins University

Awarded grant in 2007

The Role of Monocytes in Autoimmune Myocarditis

We have assembled evidence that EAM is driven in part by the Th17 pathway in the mouse; however, in the absence of IL-17A an equally severe disease can be driven through the Th1 pathway. It is not yet known whether IL-17 plays a similarly dominant role in the pathogenesis of human myocarditis. Given a lack of immunomodulatory treatments for myocarditis, blocking of the IL-23/IL-17 pathway could be very attractive option. Thus, in myocarditis different pathways can result in comparable disease (Cihakova et al., 2008)?

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