Maryam Moarefian is developing a platform for studying neural networks in “cortical organoids,” model brain tissue grown from stem cells
September 16-20 is Postdoc Appreciation Week, when we celebrate the incredible contributions that postdoctoral scholars make to the mission of major research institutions like UC Santa Cruz. The UCSC Genomics Institute benefits from the dedication of a number of talented postdocs. This week, we are highlighting Maryam Moarefian, a postdoctoral scholar with the interdisciplinary Braingeneers research group.
An engineer by training, Maryam now works closely with colleagues in the biological sciences to create platforms for growing cerebral organoids, which are miniature, three-dimensional models of brain tissue grown from stem cells. Her contributions are helping the Braingeneers to scale up their studies on the genetics of how neural connections form, and the underpinnings of certain neurological conditions.
Maryam received her M.S. in Chemical Engineering from Tennessee Technological University and a Ph.D. in Mechanical Engineering from Virginia Polytechnic Institute and State University. She is currently an NIH IRACDA Postdoc Fellow in Professor Mircea Teodorescu’s lab at UC Santa Cruz.
Interview with Dr. Moarefian
Tell us about the platform you are building.
We are creating brain organoids, which resemble miniature human brains. We start from stem cell cultures, and then differentiate them to form organoids representing different brain regions, such as the forebrain, midbrain, and hindbrain. Our goal is to study how these regions interact and the electrical signals they produce. Essentially, it’s like performing an EEG to capture brain signals, but on a much smaller scale.
With this platform, we also have the ability to regulate the interaction between two different parts of the forebrain regions: the ventral and dorsal cortex. If mutations occur in the stem cells, we can observe how this interaction becomes dysregulated and how we can manage this dysregulation through controlled internal and external stimuli.
For example, schizophrenia is a mental disorder characterized by a range of symptoms, including disorganized thinking and cognitive functioning. While the exact cause of schizophrenia is not fully understood, researchers have identified the involvement of neurotransmitter imbalances in forebrain ventral and dorsal regions. Normally, cortical neurons experience a constant flow of organized excitatory and inhibitory synaptic inputs, which ultimately governs their postsynaptic spiking activity. GABAergic interneurons arise from the medial ganglionic eminence (MGE) and GABAergic dysfunction may contribute to the imbalance between excitatory and inhibitory neurotransmission, leading to disturbances in neural processing and has been associated with schizophrenia. Our goal is to explore how we can control the migration of inhibitory interneurons using chemical perturbations or electrical signals to restore their regulation.
It’s not just schizophrenia, though. There are a lot of neurodevelopmental diseases that we can study with these platforms because we have more control over dysregulation and we can control the balance of the interactions between different parts of the brain.
What is the potential impact of this research?
The impact of this platform could be in two different directions. It could be used for either diagnostics of disease or for testing new treatments.
For diagnostics, we analyze the electrical signals generated from neuron interactions, as well as the migration patterns and directionality of neurons and interneurons. Using live imaging over time, we can identify phenotypic dysregulation, which we then correlate with genotypic abnormalities in the stem cells.
For the treatment part, we can see if we can regulate the interactions with external stimuli such as chemical (e.g. pharmaceuticals), mechanical (e.g. acoustic or ultrasonic), or electrical stimuli. The platform allows us to test both current and novel treatment options, with the added benefit of personalizing treatments. The organoids are grown from stem cells derived from the individual receiving treatment, ensuring a tailored approach.
You have spent time in industry as a biomedical engineer for Amberstone Bioscience Inc. What did that experience teach you, and why did you decide to move back to academia?
I always knew that I wanted to return to academia. The reason I like academia is the innovation we can bring to real-world questions. In industry, there are specific projects that you work on and then you move to another specific project. In academia, we have freedom to make things and answer whatever question is in our mind. However, working in industry showed me that well-structured planning and organization in progress reports and meetings can greatly speed up achieving desired outcomes. I’ve learned how to balance ambitious, innovative projects with achievable, focused, goal-driven tasks.
I like the freedom in research, and that is one reason I came back to academia. The other main reason is the opportunity to teach and interact with students and transfer my knowledge to them. I firmly believe that gaining knowledge comes with a responsibility to give back to the community, as you’ve benefited from the time and mentorship of others who helped shape you into a researcher. I’ve gained so much from the support and guidance I’ve received from my professors and mentors, and I feel it’s important to return that support to others.
What brought you to UC Santa Cruz specifically?
I spoke with [Professor Mircea Teodorescu], and he mentioned that he was a mechanical engineer developing advanced tools to address biological challenges, which immediately clicked with me since I also have a similar background. I knew right then that he was the PI I wanted to work with. I also appreciated his personality—he cares about us not just as researchers, but as individuals.
Prof. Teodorescu introduced me to the IRACDA Postdoc Fellowship, which interested me because of its teaching component. Fortunately, I was awarded the fellowship last year. While Prof. Teodorescu is my primary PI, I also collaborate with the Sharf Lab and the Haussler-Salama Lab, as the platform we’re developing has applications for other biology labs on campus.
At UCSC, I’ve observed strong collaboration between biologists and engineers, particularly within the Braingeneers group. This is what excited me to join, as there are no barriers between engineering and biological labs. Biologists work closely with engineers, providing samples and everything needed to test the innovative platforms we’re developing. They seek a quick transition to use these platforms to address their biological questions, making it an ideal environment for me.
What do you hope to do after you finish your postdoc here?
I would like to be a faculty member. I know it’s a challenging and competitive path, but from the moment I began my PhD, this has been my dream. Even during my time in industry, I was always thinking about pursuing this goal.
Postdocs are sometimes a little less visible on campuses than students and faculty are. What do you wish more people knew about postdocs?
I believe we have several excellent postdocs at the Genomics Institute, all of whom are working incredibly hard. It’s important to recognize that postdocs bring more than just research expertise. They should be seen as a complete package, with knowledge and skills that extend far beyond their specific research projects. Postdocs have gained valuable experience and leadership abilities throughout their Ph.D.s, which can be leveraged across many areas within the Genomics Institute. They shouldn’t be overlooked—there’s so much more they can contribute! They shouldn’t be hidden!