Lehtinen Laboratory Research | Overview
We are committed to understanding the fundamental mechanisms that regulate the development and maintenance of the mammalian brain. The brain is bathed by cerebrospinal fluid (CSF), which also fills the brain’s ventricles or cavities. In the developing brain, neural precursor cells divide immediately adjacent to CSF-filled ventricles. We found that the CSF proteome is both elaborate and dynamic, and that the CSF provides a rich and adaptive library of secreted factors that help coordinate neurogenesis and brain development.
We are fascinated by how the CSF instructs brain development and heath. Recent work in the lab has focused on investigating how the CSF proteome is regulated. Most CSF is produced by the choroid plexus, a tissue located in each ventricle in the brain. We have estimated the choroid plexus secretome, using next-generation sequencing and proteomics tools. In the process, we uncovered that the choroid plexus has a distinct identity in different ventricles, which leads to the secretion of unique CSF proteomes into the brain’s ventricular system in an age-dependent manner. These findings raise exciting questions about regionalization and regulation of the entire choroid plexus-CSF system during healthy development, and spark new hypotheses for how the system is involved in neurodevelopmental as well as age-associated neurologic conditions.
We employ a multi-tiered approach that draws on molecular and developmental neurobiology, and imaging to investigate:
- Contributions of early CSF to forebrain development
- Mechanisms regulating the choroid plexus-CSF system
- CSF-based signaling in neuropathological conditions, including hydrocephalus
Our laboratory is located in the Department of Pathology, Boston Children’s Hospital. We are affiliated with the following centers/programs:
- Neurobiology Program, Boston Children’s Hospital (Neuro)
- Intellectual and Developmental Disabilities Center, Boston Children’s Hospital (IDDRC)
- Harvard University Graduate Program in Biological and Biomedical Sciences (BBS)
- Harvard University Graduate Program in Biophysics (Biophysics)
- Harvard University Graduate Program in Neuroscience (PIN)
- Harvard Brain Initiative (HBI)
- Harvard Stem Cell Institute (HSCI)
- Broad Institute (BI)