“How do diverse neural circuits precisely form during development?”
“How are neural circuits disrupted by genetic mutations or disease?”
It is commonly known that complex neural circuits form within the brain to control basic biological processes and behavior. Similarly, neurons’ axons innervate varied organs in the peripheral nervous system, carrying signals that regulate the organs’ physiological functions. Understanding the architecture of these neural structures is important to understanding their function. Yet capturing a complete architecture poses unique challenges. When a single neuron’s numerous, sub-micron thin projections can extend across the entire brain and beyond in multiple directions, how can that neuron and its associated circuitry be investigated in detail in its entirety?
To tackle this challenge, we develop and apply novel three-dimensional imaging methods in our lab (the iDISCO family of tissue clearing) which we combine with genetic approaches. This platform allows us to image intact organs and embryos to examine their internal neural structures in true three dimensions. With this platform, we study how neural circuits assemble in the developing mouse embryo. This model helps us answer questions about how healthy circuitry is established and how neural wiring can go wrong. We also study adult animals to characterize the fully established circuitry and to investigate how ongoing changes in circuitry structure may play a role in aging and disease processes. Understanding the structural changes that occur will hopefully give us insights into how we may restore function in human individuals suffering from genetic mutations or disease.
We are a vibrant, inclusive, and synergistic team with multidisciplinary expertise (genetics and modern histology, cellular and molecular biology, advanced volumetric imaging, and big-data analysis using machine learning), to facilitate our highly collaborative research spanning basic systematic profiling of the brain to pathological discovery with animal models and human patient samples. Our motivation is to contribute to the development of both tools/resources and biological insights, as well as to engage in community effort for the education and training of scientists to lead future brain research.
Biography
Zhuhao obtained a PhD in Neuroscience from the Johns Hopkins Medical Institute, working on cellular and molecular mechanisms mediating the initial sensory circuitry assembly using Drosophila genetics in Dr. Alex Kolodkin’s laboratory. During his postdoc at the Rockefeller University with Dr. Marc Tessier-Lavigne and Dr. Jeffrey Friedman, he further studied how brain circuitries are precisely formed under guidance signaling regulations, and how they may get disrupted in mutant and injury.
To facilitate studying complex biological tissues and neural structures, he developed advanced tissue clearing and imaging techniques (iDISCO, iDISCO+, and Adipo-Clear) to visualize fine molecular and anatomical patterns in large intact organs. He set up his lab at Mount Sinai in 2019, moved to WCM in late 2022, continuing both technical development and biological exploration to reveal the secretes of brain development and disease.
