In pursuit of CSF homeostasis: tackling hydrocephalus
Research
We study the dynamics of cerebrospinal fluid (CSF) and its relationships with brain shape and function. Combining these insights with clinical experience, we design cellular and genetic therapies to treat hydrocephalus and other 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 is not a new idea and is supported by prior studies of how CSF ions, hormones, growth factors, and enzymes can influence neuronal function 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 collaborate to 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.
People
Cameron Sadegh
Principal Investigator
csadegh at ucdavis dot edu
I am a neurosurgeon and a laboratory scientist who is searching for every possible option to help patients today and tomorrow. I treat patients at the UC Davis Medical Center in Sacramento, California, and my laboratory is at the Institute for Pediatric Regenerative Medicine at the Shriners Hospitals for Children, Northern California.
Here, my team aims to study the composition of brain fluids and we are collaborating with colleagues to develop new treatments for hydrocephalus. The work builds on my experiences at Harvard/MIT, Massachusetts General Hospital, and Boston Children's Hospital, where I studied early brain development at a cellular level, specifically in the choroid plexus in rodent hydrocephalus models. I look forward to sharing our findings with you all, in the effort to advance our understanding of brain/fluid biology, and develop new clinical therapies.
Olga Chechneva
ochechneva at ucdavis dot edu
Originally from Russia, I completed my PhD in Germany, and completed a postdoctoral fellowship here at UC Davis. I have subsequently worked as a Project Scientist and Investigator at UC Davis, where I characterized unexpected subcellular contributions from oligodendrocytes to neurons during development. I recently joined the Sadegh lab in Oct 2023 with great interest in translational research.
My primary research interests are in the interactions of glia with one another or with neurons during the course of brain development, autoimmunity, and neurodegeneration. My current project includes exploration of the interactions of CSF with neuronal and glial development, and I am motivated by the prospect of developing novel cellular therapies with this knowledge. Outside of the lab, I like to teach art and science at local elementary schools.
Moira "Mimi" McMahon
mmmcmahon at ucdavis dot edu
I grew up in Davis and attended UC Berkeley for my undergraduate education, where I graduated with a degree in Molecular and Cell Biology. While at Berkeley, I worked in Dr. Chengji Zhou's lab at Shriners to study Wnt signaling and in the pathogenesis of spina bifida and orofacial clefts. I joined the lab in Oct 2023, and I plan to pursue a career as a physician-scientist. Outside of lab, I enjoy reading, drawing, and music, and I love spending time with my two dogs, Susie and Sasha.
Alexandra Hochstetler
Affiliate Postdoctoral Fellow
Alexandra.Hochstetler at childrens.harvard dot edu
I am a postdoctoral fellow in the laboratory of Dr. Maria Lehtinen. I completed my PhD with Dr. Bonnie Blazer-Yost on the mechanisms by which aberrant ion channels in the choroid plexus can lead to hydrocephalus. My primary research interest is in studying mechanisms of white matter damage in perinatal brain injury, with a specific focus on post-hemorrhagic hydrocephalus of prematurity.
My current project investigates the role of the choroid plexus in instructing myelination of the central nervous system. I am also studying the variations in choroid plexus transcriptomes across different species. As part of this work, I study targeted gene therapy approaches in a large animal model of hydrocephalus in collaboration with the Sadegh, Lehtinen, and Costine-Bartell Laboratories.
New lab members welcome!
We are recruiting scientists at all levels who are enthusiastic about neuroscience, neurosurgery, and translational medicine.
We welcome scholars of all backgrounds and aim to build a community of inclusion and respect.
Please email me to describe your research experiences and areas of interest.
