Lehtinen Laboratory

We are committed to understanding the fundamental mechanisms that regulate the development and life-long health of the mammalian brain. The brain is bathed by cerebrospinal fluid (CSF), which 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, adaptive library of secreted factors that help coordinate neurogenesis and brain development.

We are fascinated by how CSF production and its composition are regulated. Most CSF is produced by the choroid plexus, an epithelial tissue located in each ventricle in the brain. We have estimated the choroid plexus secretome using transcriptomics 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. Imaging technologies allow tracking secretion in real time.

The choroid plexus also forms a critical brain barrier that helps protect the brain from peripheral challenges. We are applying new technologies to better understand the interplay between central and peripheral cues that regulate brain barrier permeability and inflammation.

Collectively, our work sparks new hypotheses for how the choroid plexus - CSF system can be harnessed to treat neurologic conditions including by corrective gene therapy-based approaches.

Research Areas

We employ a multi-tiered, collaborative approach that draws on molecular, cellular, and computational neuroscience, and imaging to investigate:

• Contributions of early CSF and maternal-fetal interactions to brain development
• Regulation of CSF production and composition
• Mechanisms regulating permeability and neuroinflammation at the choroid plexus brain barrier
• Signaling in neuropathological conditions including hydrocephalus and brain cancer
• CSF-based therapeutics approaches including gene therapy

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)