Isaacs Lab
Welcome to Our Advanced Translational Neurosurgery Lab
In neonatal medicine, neonatal intraventricular hemorrhage, primarily in premature infants, and perinatal sepsis represent significant challenges. It is estimated that around 30% of neonates affected by these conditions develop post-hemorrhagic or postinfectious hydrocephalus, resulting in cerebral palsy and severe neurocognitive delays in the majority of these cases. Understanding the immune response following brain injuries caused by hemorrhage or infection is crucial, as it plays a significant role in the progression to hydrocephalus and is vital for developing effective treatment strategies.
Our laboratory is dedicated to understanding complex cerebrospinal fluid-related neurological conditions, particularly neonatal post-hemorrhagic and postinfectious hydrocephalus. Our mission is to combine innovative neurosurgical research with clinical applications, aiming to develop new treatments for these serious conditions.
Research
Core Focus: Inflammation and Hydrocephalus
The Isaacs Lab is focused on understanding how inflammation drives hydrocephalus, particularly in neonates affected by intraventricular hemorrhage (PHH) or central nervous system infections (PIH). These conditions share common immune signatures that disrupt cerebrospinal fluid (CSF) flow and absorption, leading to progressive ventricular enlargement and brain injury.
We study how the immune system—especially resident and infiltrating myeloid cells—responds to injury, and why some infants recover while others develop permanent hydrocephalus. Our goal is to identify the early molecular events that tip the balance toward disease, and to use that knowledge to design interventions that can preserve brain development.
Our research approach is translational by design. We analyze:
- Human biospecimens (CSF, blood, and brain tissue) from neonates with PHH, PIH, congenital hydrocephalus, and other etiologies
- Experimental models that simulate neonatal hydrocephalus using rodent systems for both in vivo and in vitro study
This dual strategy enables us to validate findings across systems and move promising targets toward clinical application.
A major research priority is understanding why only some infants develop hydrocephalus after a hemorrhage or infection. We are investigating:
- Genetic variants that increase vulnerability to PHH
- Epigenetic signatures that may prime the immune system toward injury
- Molecular pathways that link hemorrhage, inflammation, and impaired CSF circulation
We aim to develop genetic and molecular risk scores that could one day help clinicians identify which infants are most likely to benefit from early intervention.
We are pioneering the use of CSF as a liquid biopsy in hydrocephalus. Using proteomics, RNA-seq, and nanoparticle profiling, we are:
- Identifying biomarkers of disease onset, severity, and progression
- Developing tools to guide treatment decisions and predict surgical outcomes
- Tracking response to therapy over time
Hydrocephalus also develops in children with brain tumors, either due to mass effect or altered CSF dynamics. We are studying:
- Why hydrocephalus persists in some patients even after tumor resection
- How to better predict which children will require long-term CSF diversion
- Non-invasive imaging strategies to classify unresectable or unbiopsied tumors using advanced MRI and machine learning
In parallel with our hydrocephalus work, we are studying outcomes in infants who undergo fetoscopic closure of myelomeningocele, a prenatal approach that significantly reduces hydrocephalus risk. We are investigating the molecular and anatomical factors that distinguish infants who respond well to this intervention from those who go on to need shunt surgery.
We use multi-omic data integration to understand disease networks and prioritize therapeutic targets. Our bioinformatics group develops custom pipelines to:
- Identify gene and protein modules associated with disease risk
- Explore shared pathways between different forms of hydrocephalus
- Discover new molecular candidates for intervention
Featured Publications
- Treatment of hydrocephalus following posterior fossa tumor resection: a multicenter collaboration from the Hydrocephalus Clinical Research Network
- Microstructural periventricular white matter injury in post-hemorrhagic ventricular dilatation
- Neurodevelopmental outcomes of permanent and temporary CSF diversion in posthemorrhagic hydrocephalus: a Hydrocephalus Clinical Research Network Study
- Immune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus coinfection
- Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants
Join Our Research Efforts
Whether you're a clinician, scientist, student, or family member—our work is shaped by collaboration. By bridging disciplines and working closely with patient communities, we aim to develop better diagnostics, more targeted treatments, and a deeper understanding of the pathways that lead to hydrocephalus.
Techniques
Bioinformatics & Network Discovery
We integrate large datasets—genomic, transcriptomic, proteomic, and clinical—using custom bioinformatics pipelines. Our team applies network biology approaches to uncover disease modules and prioritize therapeutic targets. Whether it’s identifying transcriptional changes in microglia or discovering protein–protein interaction networks, our analyses help bridge the gap between raw data and real insight.
High-Dimensional CSF Profiling
We are building a multi-omic map of cerebrospinal fluid (CSF) using proteomics, transcriptomics, and extracellular vesicle profiling. Our aim is to turn CSF into a dynamic diagnostic tool—capable of predicting who will develop hydrocephalus, identifying optimal windows for intervention, and monitoring disease over time. We are especially interested in how CSF composition changes in response to injury and treatment.
Disease Modeling in Hydrocephalus
We use both in vivo and in vitro rodent models to study the mechanisms underlying neonatal hydrocephalus. These models allow us to simulate post-hemorrhagic, postinfectious, and congenital forms of the disease in a controlled setting. They are central to how we test hypotheses about CSF dynamics, immune response, and neurodevelopment—and they help us evaluate new therapies before moving to clinical studies.
Genomics & Epigenomics of Susceptibility
We study the genetic and epigenetic underpinnings of hydrocephalus, with a focus on why only some neonates develop the condition after similar injuries. Using both sequencing and functional assays, we are uncovering pathways that may predispose to or protect against hydrocephalus. These discoveries are the foundation for our efforts to develop predictive tools and personalized treatment strategies.
Imaging & Computational Neuroscience
Our lab incorporates advanced neuroimaging techniques—including diffusion basis spectrum imaging (DBSI) and quantitative MRI pipelines—to assess brain injury and ventricular changes in hydrocephalus. In collaboration with computational scientists, we are building machine learning models that use imaging to classify tumor subtypes, detect early ventricular enlargement, and monitor at-risk patients noninvasively.
Nanotechnology in Neurosurgery
Our team applies nanoparticles to explore cellular communication and therapeutic delivery in the brain. We’re using these tools to track extracellular vesicles, enhance drug targeting, and probe microenvironmental changes after injury. This platform has opened new avenues for delivering precise, localized interventions that might reduce the risk of hydrocephalus after hemorrhage or infection.
Translational Neurosurgery Infrastructure
Our research is grounded in clinical reality. We maintain a dedicated biobank of CSF, blood, and brain tissue from neonates with hydrocephalus, generously contributed by families. This resource anchors our lab in the real-world diversity of pediatric hydrocephalus and fuels our translational mission—from bench to bedside and back.
Mentorship and Collaboration
The Isaacs Lab serves as a training ground for future physician-scientists, graduate students, and postdoctoral fellows. We also work closely with neurosurgeons, neonatologists, geneticists, and computational biologists across institutions. This collaborative model allows us to tackle hydrocephalus from every angle—clinical, experimental, and computational.
Interested students should complete our intake form to inquire about openings and opportunities to join our team.
Funding and Support
The Isaacs Lab is supported by a growing portfolio of federal, foundation, and institutional funding. This support allows us to pursue innovative, high-risk research aimed at improving outcomes for children with hydrocephalus and related neurological conditions.
Active Funding
- NIH/NINDS (R25 Research Education Grant)
Role of extracellular vesicles and T-cell signaling in post-hemorrhagic hydrocephalus - Hydrocephalus Association (2025–)
Epidemiologic and economic impact of non-normal pressure adult hydrocephalus in the U.S. - Lindonlight Collective (2025–)
Machine learning for imaging-based classification and monitoring of low-grade gliomas in children - Abigail Wexner Institute for Genomic Medicine
Immune response profiling in neonatal intraventricular hemorrhage
Past Funding Highlights
- Hydrocephalus Association Discovery Science Award
- CIHR Vanier Canada Graduate Scholarship
- Killam Memorial Doctoral Scholarship
We gratefully acknowledge the generosity of our sponsors, donors, and collaborating institutions whose support sustains our mission.
