Douglas Alan Marchuk

About

Douglas Alan Marchuk is the James B. Duke Distinguished Professor of Molecular Genetics and Microbiology at Duke University. He also serves as Professor of Molecular Genetics and Microbiology, Professor of Cell Biology, Director of the Duke University Program in Genetics and Genomics, Director of the Center for Experimental Genetics, and is a member of the Duke Cancer Institute. His laboratory focuses on the genetics of cardiovascular disease, utilizing both human and mouse models to study inherited diseases of vascular dysplasia. The research aims to understand the role of genes and gene products in vascular morphogenesis and the pathology of related disorders by identifying genetic loci responsible for these diseases and investigating the molecular and cellular functions of the mutant proteins involved. The lab employs biochemical, cell biological, and in vivo mouse models, including knockout and transgenic mice, to study disease mechanisms and potential therapeutic approaches. A significant portion of his work has been dedicated to Cerebral Cavernous Malformations (CCM), a congenital vascular anomaly of the brain. His lab identified two of the three known genes causing CCM and provided evidence supporting the "two-hit" mutation model for lesion formation. Mouse models for CCM genes have been developed to study lesion development and test novel therapies. Additionally, Marchuk's lab investigates Sturge-Weber Syndrome (SWS), a rare congenital vascular disorder characterized…

Research topics

• Biology
• Medicine
• Genetics
• Bioinformatics
• Neuroscience
• Pathology
• Cell biology
• Cardiology
• Internal medicine
• Cancer research

Selected publications

• PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism

  Nature · 2021 · 188 citations

  DOI

• Cerebral Cavernous Malformation: From Mechanism to Therapy

  Circulation Research · 2021 · 187 citations

  Cerebral cavernous malformations are acquired vascular anomalies that constitute a common cause of central nervous system hemorrhage and stroke. The past 2 decades have seen a remarkable increase in our understanding of the pathogenesis of this vascular disease. This new knowledge spans genetic causes of sporadic and familial forms of the disease, molecular signaling changes in vascular endothelial cells that underlie the disease, unexpectedly strong environmental effects on disease pathogenesis…

  DOI

• Novel Murine Models of Cerebral Cavernous Malformations

  Angiogenesis · 2020 · 51 citations

  Senior authorCorresponding
  DOI

• Guidelines for the Diagnosis and Clinical Management of Cavernous Malformations of the Brain and Spinal Cord: Consensus Recommendations Based on a Systematic Literature Review by the Alliance to Cure Cavernous Malformation Clinical Advisory Board Experts Panel

  Neurosurgery · 2025-05-21 · 13 citations

  articleOpen access

  BACKGROUND AND OBJECTIVES: Despite many publications about cavernous malformations (CMs), controversy remains regarding diagnostic and management strategies. To update evidence-based guidelines for the clinical management of brain and spinal cord CMs. METHODS: The Alliance to Cure CMs, the patient support group in the United States advocating on behalf of patients and research in CM, convened a multidisciplinary writing group comprising expert CM clinicians to help summarize the existing literat…

  PublisherDOI

• Arteriovenous malformation from a patient with JP-HHT harbours two second-hit somatic DNA alterations in <i>SMAD4</i>

  Journal of Medical Genetics · 2025-02-12 · 9 citations

  articleOpen accessSenior authorCorresponding

  Background Hereditary haemorrhagic telangiectasia (HHT) is an inherited disorder of vascular malformations. It is caused by inherited loss-of-function mutations in one of three genes, ENG , ACVRL1 or SMAD4 . We recently showed that HHT-associated vascular malformations from liver, lung, brain and skin develop via a two-hit genetic mechanism resulting from biallelic loss-of-function mutations in either ENG or ACVRL1 . Second-hit somatic mutations in SMAD4 have not been reported in HHT-associated…

  PublisherOA PDFDOI

Recent grants

• Signaling Aberrations and Cerebral Cavernous Malformation Pathogenesis

  NIH · $25.9M · 2015–2025

• NIH Grant R21NS091589

  NIH · $437k · 2018

• Brain Vascular Malformation Consortium: Predictor's of Clinical Course

  NIH · $39.3M · 2009–2026

Frequent coauthors

• William L. Young

  Rutgers Sexual and Reproductive Health and Rights

  197 shared

• Michael T. Lawton

  St. Joseph's Hospital and Medical Center

  142 shared

• Carol Gallione

  Duke University Hospital

  134 shared

• Ludmila Pawlikowska

  132 shared

• Pui‐Yan Kwok

  Institute of Biomedical Sciences, Academia Sinica

  119 shared

• Issam A. Awad

  University of Chicago

  115 shared

• Robert Shenkar

  University of Chicago

  112 shared

• Charles E. McCulloch

  111 shared

Labs

• Marchuk LabPI

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