My life’s goal is to truly understand the brain, its organization, its inner workings, and how it gives rise to thought, perception, and behavior. As a neuroscientist, I’ve interrogated brain function using a range of techniques aimed at understanding different properties of the brain – functional imaging in humans, single unit recordings during behavior, and whole-cell electrophysiology. You can read more about my experience and how it shaped me as a scientist over here.
Recently, I’ve been thinking about the diversity of cell types in the human brain. During development, each of us begins as a single-celled zygote, which divides and eventually gives rise to every neuron in the brain (not to mention every other cell in our body), each with an identical genetic code. Yet, despite identical genetics, the neurons in our brain are remarkably diverse at the molecular level – diversity that defines unique cellular properties (think morphology, localization, projection profile, and neurotransmitter type for example) that can be used to classify the mature cell into a category of cell-type. Once selected, a given neuron’s cell-type identity remains remarkably constant throughout life. This cellular diversity is absolutely foundational to the organization of neural networks in our brain, those that underlie perception and thought and make us human – all this from cells with identical genetic starting material. To me, the determination of cellular identity is then the ultimate question of genetics versus environment. How might we understand the development of cellular identity at the molecular level?
To answer this question, I have turned to the in vitro differentiation of pluripotent stem cells into neurons. Using this system, I believe that we can interrogate the epigenetic changes that accompany cell-fate decisions during development at a molecular level in single cells. The ability to study the single cell is critical to determine the relative contributions of the environment, deterministic genetic programs, and stochasticity at critical choice-points during the selection of cellular identity. My long-term goals are to take this pursuit beyond the basic science. Once we truly understand how cellular identity is determined, we can leverage that knowledge to direct the differentiation of human pluripotent stem cells into defined cell types – even recapitulating canonical neural circuits in vitro. This access to human neural circuits, combined with cellular reprogramming of patient-derived cells, opens up the possibility of directly interrogating the mechanisms of neuropsychiatric disease at a cellular level for the first time.