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
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.
Iris Martinez
Lab Manager
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 and spending time with my dogs, Osito and Loki.
Tarek Bacha
Junior Specialist
tabacha at ucdavis dot edu
I grew up in Lebanon in the Middle East and moved to the US at the age of 17. I attended UC Davis for my undergraduate education and had the opportunity to get involved in undergraduate cancer research as part of the UC Davis CURE Program. I also had the amazing chance to conduct a summer internship at the Fred Hutchinson Cancer Center in Seattle, WA, during my undergraduate education. After graduating, I briefly conducted research at the National Institutes of Health in Bethesda, Maryland, before deciding to return to UC Davis to join the Sadegh Lab, hoping to gain further experience in pursuit of my goal of becoming a physician-scientist. My hobbies include soccer, jogging, religious studies, and spending quality time with family
Yuxin Ren
Junior Specialist
yxren at ucdavis dot edu
I grew up in Shenzhen, China, and graduated from UC Davis with a double major in NPB and CS. I joined the Sadegh Lab in March 2024. My primary research interest is in indirect neuromodulation through cerebrospinal fluid and its application in disease treatments. Outside the lab, I enjoy cycling along the American River.
Moira "Mimi" McMahon
PhD Rotation Student
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.
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.
Dabney Warner
Undergrad Research Assistant
dwarner at ucdavis dot edu
I am currently a third-year undergraduate student at UC Davis studying Neurobiology with an interest in pediatric neurology. I work as an EMT, am a member of the UC Davis mock trial team, and love to read in my free time.
Varsha Vijayakartik
Undergrad Research Assistant
varvijay at ucdavis dot edu
I am a third year pre-medical undergraduate student at UC Davis, majoring in Human Biology. I am highly interested in how chemically modifying membrane ion channels within the lymphatic and glymphatic systems can impact neuroinflammatory responses and improve CSF-related symptoms of hydrocephalus. I am also currently working in immunohistochemistry and imaging to quantify protein uptake and gene expression into the choroid plexus to shed light on the understudied role of the ChP in hydrocephalus. Outside of the lab, I enjoy hiking, creative writing, and I also play the saxophone in various wind ensembles at UC Davis
Yuvan Raghupathy
Undergrad Research Assistant
yraghupathy at ucdavis dot edu
I am a third year undergraduate majoring in Neurobiology, Physiology and Behavior. I grew up in Mumbai then came to the United States for my college education because I want to see the world. I believe that learning can’t happen if one doesn’t explore the world. I joined Sadegh Lab as an Undergraduate Researcher in August 2024. Outside the lab I love watching new movies, gaming, going to the gym, spending time with friends and trying new cuisines.
Aman Panigrahi
Research Assistant
apanigrahi at ucdavis dot edu
I just graduated from UC Davis with a B.S. in Biological Sciences. I am passionate about the outdoors and when I'm not in the lab, I enjoy nature, playing videogames, and reading books.
Florian Mayrhofer
Volunteer
I love science and learning about how the brain develops and functions. I'm especially interested in studying how cells in the brain communicate and support each other to stay healthy. I hope that our research will contribute meaningfully to the advancement of neuroscientific knowledge and translate into new therapies to improve the lives of people. I joined the lab as a volunteer in 2024
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.
Alumni
Daniel Weber
Medical Student Volunteer
daniel.weber.med at dartmouth dot edu
I am a 2nd year medical student at Dartmouth with an interest in clinical and translational neurosurgical research. While I’m involved in a variety of clinical research projects at my home institution, my work here has been primarily translational, investigating differences in clotting ability of intraventricular bleeds for juvenile vs. adult mice.As an east-coaster born and raised, I’m excited to experience the variety of hiking, beaches, sight-seeing, and city life that California has to offer.
Karina Leticia Zepeda
Administrative Assistant
Cheryl A Williams
Administrative Assistant
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.
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
Contact
The Sadegh Lab opened in October 2023 at the Shriners Hospitals for Children, Northern California.
We welcome donations to the lab efforts. For more information about how you can support our work and ways to give, please contact Jennifer Navarro (Senior Director of Development, Neurosciences)
at 916-871-6991 / jmhnavarro at ucdavis.edu