HONG LAB Investigating Genetic Mechanisms and Developing Precision Therapies for Hemorrhagic Neurovascular Diseases
Genetic Mechanism : Identifying somatic mutations of CNS vascular malformations.
Disease Model : Establishing cellular, organoid, and animal models of vascular malformations, cerebral amyloid angiopathy, and intracerebral hemorrhage.
Novel Therapies : Developing novel drugs, gene therapies, cell therapies, and bioengineered treatments for hemorrhagic neurovascular diseases.
Clinical Research : Conducting prospective cohorts and clinical trials to evaluate new treatments.
ABOUT OUR LAB
Principal Investigator
Tao Hong, M.D.
Professor of Neurosurgery
Vice President, Xuanwu Hospital Capital Medical University
Deputy Director, National Center for Neurological Disorders (Xuanwu Hospital)
Dr. Tao Hong is a neurosurgeon and physician scientist specializing in hemorrhagic vascular diseases of the brain and spinal cord. His research identified the KRAS/BRAF and MAP3K3/PIK3CA somatic mutations driving sporadic arteriovenous and cavernous malformations, establishing genotype-matched models that advanced thalidomide into clinical trials. He currently leads TIME-ICH, a national randomized trial investigating the earliest treatment window in intracerebral hemorrhage.
Hong Lab
The Hong Lab is a multidisciplinary team of clinicians, biologists, engineers, and data scientists based at National Center for Neurological Disorders (Xuanwu Hospital, Capital Medical University), with research platforms at the Chinese Institute for Brain Research, Beijing (CIBR).We investigate the genetic and endothelial mechanisms of CNS vascular malformations, as well as the pathophysiology and treatment of intracerebral hemorrhage.By integrating patient-derived data with multi-omics, organoids, animal models, bioengineering, and clinical trials, we aim to translate mechanistic discoveries into precision therapies.
MEET OUR TEAMMAJOR DISCOVERIES
Our research focuses on hemorrhagic cerebrovascular diseases, particularly central nervous system vascular malformations, intracranial hemorrhage, and cerebral amyloid angiopathy.
Reveal Somatic Genetic Drivers of CNS Vascular Malformations
We identified somatic KRAS/BRAF mutations in 87.1% of sporadic brain and spinal AVMs and MAP3K3/PIK3CA mutations in 91% of sporadic cerebral and spinal CMs. These findings established somatic mosaicism as a central genetic mechanism and provided a basis for molecular subtyping and targeted therapy.
Somatic variants of MAP3K3 are sufficient to cause cerebral and spinal cord cavernous malformations. Brain DOI: 10.1093/brain/awad104.
Here we analysed whole-exome sequencing data for patients with CCM and found that ∼40% of them have a single, specific MAP3K3 mutation [c.1323C>G (p.Ile441Met)] but not any other known mutations in CCM-related genes.
High prevalence of KRAS/BRAF somatic mutations in brain and spinal cord arteriovenous malformations. Brain DOI: 10.1093/brain/awy307.
We investigated the genetic basis of brain and spinal cord arteriovenous malformations (BAVMs/SAVMs) in a cohort of 31 patients using ultradeep targeted next-generation sequencing and droplet digital PCR. On this basis, we found a high prevalence (87.1%) of somatic KRAS/BRAF mutations across CNS AVMs, with mutation frequencies negatively correlating with nidus volume.
Establish Genotype-Specific Models of AVMs and CMs
Our work established mouse models of KRAS- and BRAF-driven AVMs and MAP3K3- and PIK3CA-driven CMs. These models reproduce key features of human disease and enable studies of lesion formation, hemorrhage, molecular heterogeneity, and treatment response.
Inhibition of Angiopoietin-2 rescues sporadic brain arteriovenous malformations by reducing pericyte loss. Angiogenesis DOI: 10.1007/s10456-024-09957-1.
In this study, we introduce a new bAVM model by inducing a brain endothelial-specific BrafV600E mutation using the Slc1o1c1(BAC)-CreER driver line. The pathological characteristics of this model resemble human bAVMs, including dilated and hyperpermeable vessels, as well as parenchymal hemorrhage.
Somatic BrafV600E mutation in the cerebral endothelium induces brain arteriovenous malformations. Angiogenesis DOI: 10.1007/s10456-024-09918-8.
Here we developed a novel mouse model of sporadic bAVM that is consistent with clinical manifestations in humans. Mice with BrafV600E mutations in brain Endothelial cells developed bAVM closely resembled that of human lesions.
Develop Mechanism-Based Drug Therapies
Using patient samples and disease models, we identified actionable pathways and demonstrated the therapeutic effects of rapamycin in MAP3K3-driven CM and dabrafenib in BRAF-driven AVM. These findings supported a phase IIa trial of thalidomide for AVMs (ChiCTR1900021901) and a prospective clinical study of CMs (ChiCTR2200063445).
Effect of thalidomide on sporadic central nervous system arteriovenous malformations. Science Bulletin DOI: 10.1016/j.scib.2026.05.076.
In this study, we demonstrate that thalidomide attenuates lesion progression and hemorrhage in sporadic central nervous system arteriovenous malformations in mice and patients. Mechanistically, thalidomide suppresses ETS1 to downregulate ANGPT2, counteracting endothelial KRASG12V-induced mural cell deficiency and promoting pericyte-mediated vascular maturation.
Angiogenic switching in cerebral cavernous malformations driven by MAP3K3-PIK3CA synergy. Brain DOI: 10.1093/brain/awag017.
This study reveals a collaborative MAPK/PI3K mechanism in cerebral cavernous malformations, where MAP3K3-driven inflammation and PIK3CA-driven cell cycle progression synergistically hyperactivate PI3K–AKT–mTOR signaling to trigger a tumor-like angiogenic switch.
Define Natural History and Advance Precision Surgery
Through large clinical cohorts, we defined the natural history of spinal AVMs and CMs and provided evidence for timely surgical intervention. Our work also developed intraoperative residual-lesion imaging and precision surgical strategies that increased the cure rate for spinal AVMs from 32% to 41%, together with safer surgical approaches for spinal CMs.
The efficacy and deficiency of contemporary treatment for spinal cord arteriovenous shunts. Brain DOI: 10.1093/brain/awab237.
We reviewed the clinical course of the largest multicenter cohort of 463 patients with spinal cord arteriovenous shunts. The overall cure rate was 40.6% (58.5% after microsurgery and 26.4% after embolization), and the annual clinical deterioration rate fell from 32.5% before treatment to 9.3% after intervention, supporting individualized strategies based on angioarchitectural features.
Natural History and Clinical Outcomes of Paravertebral Arteriovenous Shunts. Stroke DOI: 10.1161/STROKEAHA.120.033963.
In a two-center cohort of 64 paravertebral arteriovenous shunts, we classified lesions according to whether intradural veins participated in drainage and showed that shunts with intradural drainage deteriorated far more rapidly, supporting early intervention and surgical disconnection of refluxing radicular veins for incompletely obliterated lesions.
WHAT'S NEW
Stay updated with our latest research breakthroughs, events, and announcements.
Jun 30, 2026
Congratulations to four HongLab members on earning their doctoral degrees
Jun 6, 2026
Effect of thalidomide on sporadic central nervous system arteriovenous malformations
New publication in Science Bulletin
Effect of thalidomide on sporadic central nervous system arteriovenous malformations
We evaluated thalidomide's therapeutic efficacy in sporadic central nervous system arteriovenous malformations.
Endothelial KRASG12V mutation upregulated ANGPT2 and induced mural cell deficiency, while thalidomide suppressed ETS1 to downregulate ANGPT2. This restored pericyte coverage and attenuated lesion progression and hemorrhage in mice and patients.
Our findings uncover a translational mechanism involving ETS1–ANGPT2 axis inhibition and mural cell-mediated vascular maturation.
Jan 19, 2026
Angiogenic switching in cerebral cavernous malformations driven by MAP3K3-PIK3CA synergy
New publication in Brain
Angiogenic switching in cerebral cavernous malformations driven by MAP3K3-PIK3CA synergy
We explored the cooperative effects between MAP3K3 and PIK3CA mutations from multiple perspectives.
MAP3K3 mutation activated inflammatory and angiogenic programs in brain endothelial cells, while PIK3CA mutation promoted cell cycle and DNA replication. Double mutations of MAP3K3 and PIK3CA synergistically hyperactivated PI3K–AKT–mTOR signaling and triggered a tumor-like angiogenic switch.
Our findings uncover a convergent mechanism involving MAPK and PI3K pathway activation in cerebral cavernous malformations pathogenesis.
CONTACT US
Contact
Shikun Zhang, Ph.D.
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