Leducq Foundation awards $7 million for vascular malformation research

Luisa Iruela-Arispe, PhD, the Stephen Walter Ranson Professor of Cell Biology and chair of Cell and Developmental Biology, is the North American coordinator for an international collaboration that has received a five-year, $7 million Transatlantic Networks of Excellence Program award from the Leducq Foundation.

An international collaboration for which Luisa Iruela-Arispe, PhD, the Stephen Walter Ranson Professor of Cell Biology and chair of Cell and Developmental Biology, serves as North American coordinator, has received a five-year, $7 million Transatlantic Networks of Excellence Program award from the Leducq Foundation.

The Leducq Foundation was founded in 1996 to support international, collaborative research in cardiovascular and neurovascular disease with an emphasis on the training of early-career scientists.

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The aim of the project, titled "Recalibrating Mechanotransduction in Vascular Malformations" is to advance the basic understanding of – and develop pharmacological therapeutics for – vascular abnormalities that lead to stroke, edema, hemorrhages and deformities associated with severe chronic pain.

Project investigators will research the molecular mechanisms through which vascular cells respond to the mechanical stimulus of blood flow – or mechanotransduction – and how mutations disrupt mechanotransduction and cause vascular malformations.

We aim to advance the most promising preclinical approaches into patient studies by the end of the funding period. This work will benefit patients with a wide range of vascular anomalies for which corrective treatments are urgently needed."

Luisa Iruela-Arispe, PhD, the Stephen Walter Ranson Professor of Cell Biology and Chair of Cell and Developmental Biology

Miikka Vikkula, MD, PhD, co-director and professor of Human Genetics at the Institut de Duve (Belgium) is the European Coordinator. Network members also include Ondine Cleaver, PhD, University of Texas Southwestern Medical Center; Josef Penninger, MD, University of British Columbia (Canada); Salim Seyfried, PhD, University of Potsdam (Germany); and Elisabeth Tournier-Lasserve, MD, Paris Diderot University-INSERM U1141 Research Lab (France).

The interdisciplinary team of basic research scientists and clinicians combine expertise in genetics, cell biology, biochemistry, molecular biology and stem cell biology.

"The program brings together a highly synergistic group of investigators with strong track records of interactions whose complementary scientific skills will facilitate the advancement of studies that individually would not be possible," said Arispe, who is also co-leader of the Tumor Environment and Metastasis (TEAM) Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

In addition to monthly virtual meetings, the network will meet in person for two to three days every six months. Frequent team interactions will also occur through an online scientific communication hub that enables real-time access to data, protocols, documents and discussions, according to Arispe.

The network will directly train clinical investigators, pre- and postdoctoral fellows in each member lab and will collectively engage a total of 49 trainees at different stages of professional advancement through the broader communication hub. The cohort will be encouraged to develop interdisciplinary research interests through team science and the transfer of skills among trainees across institutions.

Network investigators will also mentor trainees in scientific reasoning and methods to enhance rigor, transparency and reproducibility, Arispe added.

The alliance will also launch two calls for applications (in years 2 and 4) to support four emerging scientists not currently affiliated with a project member.

"Our objective is to capture raw talent – up-and-coming bright investigators – and cultivate their scientific interests towards solving problems related to vascular malformations," said Arispe.

The Leducq Foundation funded four Transatlantic Networks of Excellence Program awards in the 2021 cycle. Northwestern investigators have received several awards in recent years and four are currently active:

Elizabeth McNally, MD, PhD, the Elizabeth J. Ward Professor and director of the Center for Genetic Medicine, is the North American Coordinator of the "Editing the Failing Heart" project. McNally is also a professor of Medicine in the Division of Cardiology and of Biochemistry and Molecular Genetics.

Hossein Ardehali, MD, PhD, the Thomas D. Spies Professor of Cardiac Metabolism and director of the Feinberg Cardiovascular and Renal Research Institute’s Center for Molecular Cardiology, is the North American Coordinator of the "Targeted Approaches for Prevention and Treatment of Anthracycline-Induced Cardiotoxicity" study. Ardehali is also professor of Medicine in the Division of Cardiology and of Pharmacology.

Paul Burridge, PhD, assistant professor of Pharmacology, is also a member of the network.

Alfred George, Jr., MD, the Magerstadt Professor and chair of Pharmacology, is a member of the team investigating "The sodium channel as a therapeutic target for prevention of lethal cardiac arrhythmias." George is also director of the Center for Pharmacogenomics.

John Rogers, PhD, the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery, is a member of the project team investigating: "Repolarization HeterogeneitY imaging for personalised Therapy of Heart ArrhythMia (RHYTHM)." Rogers is also director of the Simpson Querrey Institute for Bioelectronics.

Past Leducq Foundation award recipients include:

Guillermo Oliver, PhD, the Thomas D. Spies Professor of Lymphatic Metabolism and director, Feinberg Cardiovascular and Renal Research Institute’s Center for Vascular and Developmental Biology. Oliver is also professor of Medicine in the Division of Nephrology and Hypertension.

Kathleen Green, PhD, the Joseph L. Mayberry, Sr., Professor of Pathology and Toxicology, and professor of Dermatology.

Lisa Godsel, PhD, research assistant professor of Pathology and of Dermatology.