Members
Cameron Sadegh
Assistant Professor
Pediatric Neurological Surgery
csadegh@ucdavis.edu
Education
- 2006 B.S., Biology; Chemical Engineering, MIT
- 2013 Ph.D., Neurobiology, Harvard University
- 2015 M.D., Harvard-MIT Program in Health Sciences and Technology
- 2020 Postdoctoral research, Boston Children’s Hospital
- 2022 Clinical training (Neurosurgery residency), Mass. General Hospital
- 2023 Clinical training (Pediatric Neurosurgery fellowship), Harvard Boston Children’s Hospital
Studying cerebrospinal fluid (CSF) composition and relationship to brain shape and function. Combining these insights with clinical experience, we design cellular and genetic therapies to treat hydrocephalus and conditions causing intellectual disability.
- Gene therapy for hydrocephalus
People of all ages can develop hydrocephalus and related brain injury. But hydrocephalus is not inevitable. Some patients can escape it, using the brain’s natural defense mechanisms of CSF homeostasis. How does that work? How can we tell which person is at risk? How can we augment these defense mechanisms in vulnerable patients?
Gene therapy can target and support the critical brain epithelial cells that work to prevent hydrocephalus. We use advanced imaging tools (MRI), hydrodynamic profiling, and animal models of acquired hydrocephalus to study the optimal conditions for such a therapy to work in patients. - Indirect neuromodulation
Our hypothesis is that CSF influences brain function, by fine-tuning the activity of neurons. This idea is supported by prior studies showing how CSF composition (ions, hormones, growth factors, enzymes, extracellular vesicles) can influence neuronal and brain function. Therefore, strategies to bioengineer the composition of CSF could enable a different and indirect form of modulating brain activity.
Neurosurgeons routinely access CSF, and we collect clinical samples to study how CSF influences neuronal activity in animal models. With the hope of restoring brain function after perturbation, we aim to better understand what normally nurtures brain function, what limits brain function in disorders, and how we can design treatments for conditions affecting intellectual ability. - Early brain development
There is no better way to identify cures for neurologic disorders than by understanding how the fetal brain develops its diversity of cell types and fluid environments over time. The interaction of CSF with these early cell types is avidly debated, and we hypothesize that the tiny choroid plexus plays an outsized role.
The choroid plexus is a neglected part of the brain. Bearing no resemblance to its neighboring neurons and glia, the choroidal cells hide their common heritage. The same early stem cells that produce the hippocampus also generate the choroidal tissue, although with an entirely different purpose. The choroidal tissue does for the brain what the endocrine system, pancreas, liver, and kidneys do for the rest of the body. And there is a lot more to discover.
Please see: Dr. Sadegh’s laboratory website for more information.
2023
Sadegh C, Xu H, Sutin J, Fatou B, Gupta S, Pragana A, Taylor M, Kalugin PN, Zawadzki ME, Alturkistani O, Shipley FB, Dani N, Fame RM, Wurie Z, Talati P, Schleicher RL, Klein EM, Zhang Y, Holtzman MJ, Moore CI, Lin PY, Patel AB, Warf BC, Kimberly WT, Steen H, Andermann ML, Lehtinen MK. Choroid plexus-targeted NKCC1 overexpression to treat post-hemorrhagic hydrocephalus. Neuron. 2023 May 17;111(10):1591-1608.e4. doi: 10.1016/j.neuron.2023.02.020. Epub 2023 Mar 8. PubMed PMID: 36893755; PubMed Central PMCID: PMC101988102022
2021
Xu H, Fame RM, Sadegh C, Sutin J, Naranjo C, Della Syau, Cui J, Shipley FB, Vernon A, Gao F, Zhang Y, Holtzman MJ, Heiman M, Warf BC, Lin PY, Lehtinen MK. Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development. Nat Commun. 2021 Jan 19;12(1):447. doi: 10.1038/s41467-020-20666-3. PubMed PMID: 33469018; PubMed Central PMCID: PMC7815709.
2020
Shipley FB, Dani N, Xu H, Deister C, Cui J, Head JP, Sadegh C, Fame RM, Shannon ML, Flores VI, Kishkovich T, Jang E, Klein EM, Goldey GJ, He K, Zhang Y, Holtzman MJ, Kirchhausen T, Wyart C, Moore CI, Andermann ML, Lehtinen MK. Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface. Neuron. 2020 Nov 25;108(4):623-639.e10. doi: 10.1016/j.neuron.2020.08.024. Epub 2020 Sep 21. PubMed PMID: 32961128; PubMed Central PMCID: PMC7847245
2016
Sances S, Bruijn LI, Chandran S, Eggan K, Ho R, Klim JR, Livesey MR, Lowry E, Macklis JD, Rushton D, Sadegh C, Sareen D, Wichterle H, Zhang SC, Svendsen CN. Modeling ALS with motor neurons derived from human induced pluripotent stem cells. Nat Neurosci. 2016 Apr;19(4):542-53. doi: 10.1038/nn.4273. Review. PubMed PMID: 27021939; PubMed Central PMCID: PMC5015775