Sadegh Lab

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

Project Scientist

ochechneva at ucdavis dot edu

Originally from Russia, I earned my PhD in Neurobiology at Otto-von-Guericke University Magdeburg in Germany and completed postdoctoral training at UC Davis. I have worked as a Project Scientist at UC Davis and Investigator at Shriners Children’s Northern California. My primary research interests revolve around understanding the interactions of glia with one another or with neurons during brain development, function, and disease. My recent research has been predominantly focused on material transfer from oligodendroglia to neurons, stemming from an unexpected observation.

I joined the Sadegh lab in October 2023, driven by a keen interest in translational research on cerebrospinal fluid physiology and cerebral palsy, exploring the interactions of CSF with neuronal and glial cells in development and disease. I am highly motivated by the potential to develop novel cellular therapies with this knowledge. Beyond the lab, I enjoy teaching art and science at local elementary schools. As a mother of four, I am also actively involved in the teaching and support of children with developmental delays.

Moira "Mimi" McMahon

Junior Specialist

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 (starting at an MD-PhD program this summer!). Outside of lab, I enjoy reading, drawing, and music, and I love spending time with my two dogs, Susie and Sasha.

Iris Martinez

Staff Research Associate

irimartinez at ucdavis dot edu

I grew up in Napa, Ca and attended UC Davis for my undergraduate education, where I graduated with a degree in Biochemistry and Molecular Biology. I joined the Sadegh Lab in March 2024. Outside of the lab, I enjoy music, shopping, watching new shows and spending time with my dogs, Osito and Loki.

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.

Venina Kalistratova

Medical Student Research Assistant

vskalistratova at ucdavis dot edu

I am a third-year medical student at UC Davis interested in neuro-oncology and neurosurgery. I am completing a medical student research fellowship at Aghi Lab in UCSF, studying the interactions between metastatic breast cancer and the brain microenvironment. My primary research interest at Sadegh Lab focuses on the role of the choroid plexus as a regulator of the brain microenvironment in the event of primary and metastatic brain tumors. I am also very interested in the potential role of the choroid plexus as a mediator of chemotherapeutic toxicity in brain tumors. In my free time, I enjoy baking, swimming, and learning the basics of beekeeping. I am currently working towards my Master Beekeeper certificate.

Sophia Baltasar

Undergrad Research Assistant

svbaltasar at ucdavis dot edu

I am from the Bay Area and currently a third-year undergraduate student at UC Davis majoring in Global Disease Biology. I joined the Sadegh lab this January, and I plan to apply to medical school after I graduate in the fall. In my free time, I like to swim, cook, and go to concerts!

Ryan Li

Undergrad Research Assistant

rxlli at ucdavis dot edu

I am a second-year undergraduate student at UC Davis majoring in Environmental Science and Management. I am particularly interested in discovering more about how dyssynchrony of CSF pulsations within the ventricular system in the brain can lead to various types of hydrocephalus. I hope that through helping to develop this novel model of hydrocephalus, more effective treatment methods than shunts can be created and implemented.

Florian Mayrhofer

Volunteer

I am passionate about studying developmental neurobiology and oligodendroglia-neuronal materal transfer, and have joined the lab as a volunteer in 2024.