Research

The Vasculitis Foundation is the largest private funder of research on vasculitis and collaborates with researchers around the world to fund the most promising studies. The program is guided by the VF Scientific Advisory Board which reviews, critiques and ranks the applications and provides guidance to the VF Board of Directors on the selection of studies to fund.

The VF Research Program is funded by donations, honors, memorials and special fundraising events.

The VF hosted the 2nd International Vasculitis Research Consensus Conference on April 20, 2012. The purpose of the conference was to utilize the combined skills and experience of leading experts in vasculitis from different subspecialties and other scientific fields to evaluate the VF’s Research Program and explore new areas of inquiry that the Foundation should support over the next five years. Click here to read the VF Research Consensus Conference Report 2012.

To learn more about the VF Research Program, please click here.


2014 Grants

Vinuesa Study GroupCarola-19 Dec-2 (2)Awardee: Carola G. Vinuesa, MD, MSc, PhD
Head, Dept of Pathogens and Immunity, Group Leader, Humoral Immunity and Autoimmunity
Elizabeth Blackburn NHMRC Research Fellow, John Curtin School of Medical Research
The Australian National University, Canberra City, Australia
Award:  $50,000 for one year
Topic:  The Role of micro RNA in a Novel Mouse Model of Vasculitis

While researching how gene mutations lead to autoimmune disease, Vinuesa and her team discovered that mice carrying mutations in two genes of the same family spontaneously develop medium- to large-vessel vasculitis. Mouse models of spontaneous medium- to large-vessel vasculitis are rare, and understanding how these mice develop vasculitis will hopefully translate into how these genes, and the immune cells they affect, can be targeted to improved management of vasculitis. For researchers Vinuesa’s work may provide an important step in understanding how interactions between the limbs of the immune system drive the vasculitis disease process. The new mouse model of spontaneous vasculitis may offer new insights into how T cell abnormalities, changes in a specific microRNA, and post transcriptional regulation of expression of genes encoding autoantigens that are a central feature of human vasculitis, lead to severe disease. The grant provides essential support in driving an exciting discovery forward.


Sibley-Cailin

Awardees:  Lindsay Lally, MD, principal investigator, Rheumatology Fellow;
Robert Spiera, MD, co-investigator
Hospital for Special Surgery
Award:  $50,000 for one year

Topic:  Rho-kinase Activity in Large Vessel Vasculitis

Dr._Robert_SpieraHEADSHOT[1]

Rho/Rho kinase (ROCK) are a group of proteins involved in regulating blood vessels. In a small pilot study, Lally et al found increased levels of ROCK in the temporal artery biopsies of patients with GCA compared to patients without GCA. The higher levels of ROCK were seen even in biopsies that were negative by routine conventional analysis of the tissue. The team will look at a larger number of biopsies to see if staining for ROCK activity is useful in enhancing the diagnostic potential in negative biopsies, and if this may be a new therapeutic target. The findings may help identify patients who have GCA despite a negative biopsy for vessel inflammation, and prevent patients without GCA from getting unnecessary treatment with high doses of corticosteroids. ROCK may also represent a pathway that has not yet been extensively explored in inflammatory vascular disease. The funding enables Lally to move forward with this important project quickly.


LiangKimMDAwardee: Kimberly P. Liang, MD, Assistant Professor of Medicine
Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA
Award:  $50,000 for one year
Topic:  Microbubble Contrast-Enhanced Vascular Ultrasonography: A Novel Method of Detecting Large Vessel Vasculitis?

Monitoring disease activity is crucial for effective patient care and better outcomes, yet a key unmet need is the ability to differentiate active vasculitic disease activity from vessel damage in patients with large vessel vasculitides (LVV), like giant cell arteritis and Takayasu’s arteritis. In LVV, the inflammatory process appears to begin at the outer layer of the vessel’s blood supply, with inflammation and new vessel formation occurring. Liang’s team uses microbubble-contrast-enhanced carotid ultrasonography (CU), a novel non-invasive imaging technique, to detect changes in inflammation and new vessel formation in the outer vessel layer. CU may be able to help distinguish between active vasculitis and damage in patients with LVV. Liang’s research will look at LVV patients with clinically active and inactive disease, and compare them to patients with rheumatoid arthritis and people with no history of autoimmune disease. The results could help physicians tailor long-term treatment in LVV patients.

Click here to watch an interview with Dr. Liang as she discusses her research with Ed Becker, producer of the VF Extraordinary Stories Project.


2013 Grants

Paul Brogan, FRCPCH, reader in vasculitis and honorary consultant pediatric rheumatologist, UCL Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London
Award: $99,206 for two years
Topic: Circulating microparticles as therapeutic targets of plasma exchange in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis

Inspired by a patient whose Microscopic polyangiitis was diagnosed too late, Brogan began studying ANCA vasculitis and other forms of vasculitis in children in 1997. His work centers on the novel biomarkers contained within the “blood dust”, which could be targets for therapeutic plasma exchange.

“We now know that ANCA cause little pieces of white blood cell ‘shrapnel’ to be released when they bind to neutrophils,” he explains. “In test tube experiments these neutrophil microparticles do bad stuff to endothelium, causing it to be activated and sticky and encouraging more white blood cells to bind, amplifying the vasculitis. We also know that these microparticles may contribute to blood clotting, and are found at higher levels in the blood of children who go on to have thrombotic complications of vasculitis.”

Brogan’s study will determine if this is also true in patients with ANCA vasculitis, and if removing the “shrapnel” by plasma exchange improves patient outcomes. He hopes his study will help identify which blood parameters are most important to remove to achieve disease control.

VF grants help clinician scientists like Brogan who are working at the interface of science and clinical practice for rare diseases.

“It undoubtedly facilitates the flow of knowledge from benchside research to the clinic for patient benefit,” he says. “This sort of support is essential to further our knowledge of such rare diseases.”


Ritu Chakravarti, Ph.D., research associate, Department of Pathobiology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio
Award: $49,000 for one year
Topic:  To Understand the Role of14-3-3In Giant Cell Arteritis (GCA)

Chakravarti’s interest in GCA is simple: It is the most common form of vasculitis where the causative agent is not known.

Her research studies the agent causing inflammation of the aorta that manifests as GCA and affects 1 in 500 adults inAmerica. The current therapy primarily uses steroids to suppress immune function causing significant morbidity.

“We hope that our results will facilitate early detection and better treatments for GCA patients,” Dr. Chakravarti says. “Our proposed work is the first step in identifying the causative agent and we would continue to test specificity of known targets. We will possibly look for novel targets involved in the disease. The next big step would be to facilitate non-invasive test for the early detection of GCA.”

The grant will help Chakravarti build a research base and will facilitate generation of useful results.

“It’s a very important bridge needed to find novel direction and sufficient data needed to develop future therapeutics,” she says.


Susanne Schinke, MD, research fellow, Department of Rheumatology and Clinical Immunology, The University of Lübeck, Lübeck, Germany
Award: $50,000 for one year
Topic: Disease-specific dysregulation of miRNA in Granulomatosis with Polyangiitis (GPA/Wegener’s) 

Schinke began researching vasculitis while in medical school. Her MD thesis studied a special subgroup of ANCA directed against BPI, bactericidal/permeability-increasing protein associated with ANCA and chronic inflammation. Despite decades of research, scientists still don’t know the causes of ANCA and vasculitis. That intrigued Schinke and inspired her to investigate in vasculitis the regulation of genetic code by microRNA (MiRNA), an aspect of research that emerged only recently.

MiRNA shows that the genome we are born with is not a fixed setting. Gene expression can be profoundly changed by regulatory processes such as miRNA,” she explains. “MiRNA are influenced by environmental factors and therefore might explain the development of autoimmunity better than genetic or epidemiological studies that until now have not been able to explain why vasculitis develops in some patients and not in others. I hope to find a distinct pattern revealing a specific dysregulation of miRNA that only occurs in GPA patients–and not in healthy people. Hopefully this will give a hint to what causes this granulomatous and necrotizing vasculitis.”

The VF grant will help Schinke quantify miRNA expression in a set of GPA tissue samples and sera. This is essential for further study and will be the basis for future development of miRNA- based therapeutic interventions.

“For young researchers with new ideas the VF grant allows us to transfer these ideas into practice without being established in the researcher community with a high-ranked publication,” Schinke says. “This is so essential in order to generate the first results further studies can be based on and research can continue.


BenselerSusanne Benseler, MD, pediatric rheumatologist, associate professor of paediatrics, The Hospital for Sick Children, University of Toronto
Award: $40,128.10 for one year
Topic: Development of a uniform histology scoring systems for Small Vessel CNS Vasculitis in adulthood and childhood

Benseler was inspired to study CNS vasculitis in pediatric patients after seeing previously healthy children present with severe neurological deficits including seizures, stroke, loss of vision of speech, inability to concentrate and more devastating symptoms. “Until about 10 years ago, brain vessel inflammation, or CNS vasculitis, remained unrecognized and untreated,” she says. “Children often died of their vasculitis without anybody making the diagnosis while they were alive.”

She began looking for a way to discover the underlying disease more quickly, reducing negative impacts and increasing quality of life.

“The mean age of a child with CNS vasculitis is 10, so an early diagnosis can alter their lives immensely,” Benseler explains. “If we can start treatment earlier and make it more tailored, chances of long-term brain damage are increasingly low and patients have a chance to recover completely and return to the life they lived before.”

Her team is developing a standardized  approach to use the most reliable tests to expedite and confirm diagnosis and prevent permanent brain injury..

“This grant will help us to identify what is specific and instrumental for the diagnosis of CNS vasculitis on brain biopsy. New tests will help to identify possible new targets for treatment, which will be more targeted with fewer side-effects.”


2012 Grants

Sharon Chung, MD, MAS, assistant adjunct professor, Division of Rheumatology, University of California, San Francisco
Award: $50,000 for one year
Topic: Exome sequencing in granulomatosis with polyangiitis (GPA, Wegener’s)

Sharon Chung became interested in researching vasculitis while caring for patients with GPA and other vasculitis diseases during her internal medicine residency at Johns Hopkins University. “I was fascinated by how these diseases could have so many different manifestations, and how the underlying trigger for these diseases was unknown,” she notes. That prompted her to study the genetics of the disease, to see if she can identify genes and genetic mutations that predispose individuals to developing GPA in an effort to better understand how the disease develops. “Identifying genes that are associated with GPA can reveal biologic pathways that are important in developing this disease, and those pathways may provide novel targets for less toxic treatments and better diagnostic tests,” Chung continues.

Her proposed project is an advancement over current genetic studies, since she will be focusing on rare genetic mutations instead of the common genetic mutations that are usually studied. The VF funding is crucial the undertaking, but its patient network also is critical. Genetic research like this is completely dependent on patients who are willing to participate in genetic studies and provide DNA samples. “When more individuals participate, more powerful studies can be conducted, and thus, we are more likely to identify the genes involved in this disease,” she explains. “Participation in genetic studies is an easy, low-risk way of helping move research forward for these diseases.”

To learn more information about participating in a vasculitis genetics study, please click here.


Shadi Swaidani, Ph.D.,  research associate, immunology, Cleveland Clinic Lerner Research Institute
Award:  $50,000 for one year
Topic: Investigating the molecular mechanism for IL-25-driven Act1-dependent eosinophilic vasculitis

Little is known about what drives hypereosinophilia — an abnormal increase in white blood cells — in eosinophilic vasculitis in Churg-Strauss Syndrome (CSS). But Shadi Swaidani is hoping to change that. “One of my major research interests is to better understand the immunological and molecular pathways that lead to hypereosinophilic syndromes,” he says. Building on existing research from the Cleveland Clinic, he will investigate whether and how two particular proteins are involved in this form of vasculitis.

“This research project will help us understand the underlying causes and mechanisms that contribute to the development of eosinophilic vasculitis,” Swaidani explains. Of particular interest is the role of one protein, IL-25, in promoting eosinophilic vasculitis and its potential use as a therapeutic target for CSS. “Such understanding will hopefully bring a future where we can better prevent, diagnose, and treat this disease.”

By supporting his project at its early and preliminary phase, the VF grant will help Swaidani conduct the research, publish the study and hopefully expand into future research projects relating to eosinophilic vasculitis.

Says Swaidani, “Supporting basic research studies is crucial for driving new ideas and concepts to the medical field to improve the way we prevent, diagnose and treat human disease.”


Cornelia Weyand, MD, Ph.D, professor of medicine, Stanford University School of Medicine
Award: $50,000 for one year
Topic: Small molecule therapeutics in Giant Cell Arteritis

For the last 15 years, Cornelia Weyand’s research has focused on large vessel vasculitis with a special emphasis on giant cell arteritis (GCA), which is caused by immune cells that invade and attack arterial wall cells. With her latest project, she hopes to pave the way for introducing a new class of therapies.

“In this study we will examine how the immune cells are activated in the first place; how they respond to activation and how immune activation translates into the injury in the blood vessel,” Weyand explains. The study gives special attention to a new type of immuno-modulatory drugs, called the JAK inhibitors, which can suppress cellular activation. Experiments will explore the potential of such new inhibitors as a new treatment approach in GCA.

The new therapies will be tested in a model system created by grafting human arteries into a mouse model and infusing the blood cells from the patients into the mouse. “Through this system we can create ‘GCA in a dish’, with real patient cells and real human arteries,” she explains. “Doing so with the cells from a specific patient, we can test how this patient would react to the therapy.”

The VF grant will allow investigators to do a pilot study to create the necessary first data set that helps direct further research. “Support that comes through the Vasculitis Foundation is critical in securing that research programs can continue their work,” she concludes.


2011 Award

Felipe Andrade, Assistant Professor of Medicine in the Division of Rheumatology
Award:  $75,000 for one year
Topic:  Defining an animal model for the study of Wegener’s Granulomatosis

“If we can confirm or discard a role of proteinase 3 in Wegener’s, that would be a big step in understanding this disease.”
Felipe Andrade, Assistant Professor of Medicine in the Division of Rheumatology

Even as a child, Felipe Andrade wanted to be a doctor. “I knew I would be a doctor from age 5 or 6, but I have no idea why,” laughs Andrade, the son of a tailor and a homemaker. “I used to work with my father a lot, and I learned a lot of things – I’m very good at ironing. I know well the anatomy of clothes. I’m good on the sewing machine, and even hand-sewing.” But despite these talents, he was set on a career in medicine.

“When I was young, I thought about being a doctor because you see doctors and they’re always nice and helpful,” he recalls. “Then you grow up and see diseases and become interested in treating them and the people who have them.”

In the Clinic
And so began his journey to become a clinician. Andrade earned his MD from the National Autonomous University of Mexico. He remained in Mexico City to complete his internal medicine training at the National Medical Center, and his rheumatology training at the National Institute of Nutrition. Later, he earned his doctorate at Johns Hopkins University, where he is now an Assistant Professor of Medicine in the Division of Rheumatology.

“As a clinician, the most rewarding is to interact with patients, but the worst part is that you can’t offer them something else when the treatments don’t work,” he says.

At the Bench
The desire to pioneer new diagnostics and therapies took him out of the clinic and into the lab five years ago. “Now that I’m doing bench work, I like the possibility that I might be able to find something to help patients to feel better. They need an opportunity to be cured and I can work toward that.”

Andrade’s research centers on an assay commonly used to diagnose Wegener’s (WG): antineutrophil cytoplasmic autoantibodies (ANCA) that recognize human proteinase 3 (PR3) of neutrophil granules. “Understanding their pathogenic role in vivo is a high priority,” he says. “They may be more than markers.”

His research team hopes to find out if human PR3 actually plays a role in the development of WG. This is done using “knock-in mice”, so called because their own PR3 was removed and replaced with human PR3. This enables the test mice to express human PR3, and allows researchers to see if WG develops in the presence of anti-human PR3-ANCAS. Initial funding was from The Lowe Family Scholars program. Recently the VF awarded Andrade a $75,000 grant to continue his research. “If projects like this work,” he says, “it will be amazing.”

On the Horizon

“Supporting the VF is so important because these are diseases which are not so frequent, so it’s hard to find a big institution that will support research,” he asserts. “The VF is the one who’s going to support those projects that are risky, less certain, but also have a high ‘risk’ of success. The VF is giving the basis for many investigators to start with new ideas. Otherwise we’d never be supported.”

Andrade is excited about the possibilities the funding gives him – and WG patients.

“As a researcher, I think there’s a solution for any problem — even a very bad, horrible disease like Wegeners – you just need to find it,” he asserts. “We’ll find a solution. It’s there. But if you don’t look and work for it, you won’t find it. I might be able to do something. This is my beginning.”


 

To learn more about the VF Research Program, please click here.

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Participation in Clinical Trials is one way you can help advance research into finding better treatments and perhaps even a cure for vasculitis!
Learn how you can participate in clinical trials - National Institutes of Health

Vasculitis Foundation Fellowship Program

The Vasculitis Foundation Fellowship provides the opportunity for one- or two- year tracks designed to support the training of physician scientists who wish to gain clinical expertise in vasculitis and who may also wish to pursue an investigational career in this field. The fellowship will be conducted through Vasculitis Centers where there has been a track record of training individuals in vasculitis.

"The Vasculitis Foundation is committed to creating greater awareness and interest in vasculitis," said Joyce Kullman, executive director of the VF. "We hope that our new Vasculitis Foundation Fellowship will encourage medical professionals to pursue careers in patient care and research linked to vasculitis."

The Vasculitis Foundation Fellowship is possible thanks to the generous support of Genentech, Inc., and Biogen Idec and many other generous individual and corporate donors. For more information on how you may donate to the Vasculitis Foundation Fellowship, visit the donate page.

Medical Institutions

The Vasculitis Foundation encourages vasculitis patients to seek expert medical care for diagnosis and treatment of the disease. The VF works closely with vasculitis experts and centers around the world to ensure patients have access to the most up-to-date medical care.

The Vasculitis Clinical Research Consortium (VCRC) is an integrated group of academic medical centers, patient support organizations, and clinical research resources dedicated to conducting clinical research in different forms of vasculitis and improving the care of patients with vasculitis.