At Work: Developmental Neurobiologist Songhai Shi

Songhai Shi

Songhai Shi

Developmental neurobiologist Songhai Shi investigates the molecular and cellular mechanisms underlying mammalian neuronal development and circuit formation. We spoke with Dr. Shi shortly after he joined Memorial Sloan Kettering in 2006.

I was born in a small village in the southeastern part of China, near Nanjing, Jiangsu Province. My parents, who were farmers, always wanted me to get an education and to go onto college. In 1996, I was fortunate to be one of two students from my province to be accepted into the Department of Biological Sciences and Biotechnology at Tsinghua University in Beijing.

At Tsinghua University, one of the top universities in China, I spent the requisite five years studying mathematics, physics, chemistry, and biology, which I found particularly fascinating. Unlike chemistry and physics, where a lot is already known, I felt that biology was different. There were so many unanswered questions that you encounter every day.

During my fourth and fifth years, I was able to get into the lab and receive more first-hand research training. In my case, I was working in a plant biology lab headed by Jinyun Liu, studying the pathogen-induced immune response in rice plants. I was actually more interested in animals, but, at the time, it was one of very few labs at the school doing molecular biology work, which I found very exciting.

And it was this interest in molecular biology that led me, upon graduating in 1996, to leave China and pursue my doctorate in the Joint Genetics Program at Cold Spring Harbor Laboratory and the State University of New York at Stony Brook (SUNY-Stony Brook). At the time, the vast majority of my fellow students came to the US for our graduate degrees because of the excellent training and research environment and the availability of financial support here at US.

Synaptic Plasticity Research Yields Results

I learned so much in the first year of my graduate program at Cold Spring Harbor Laboratory and SUNY-Stony Brook. Initially, I did one rotation each in immunology and developmental biology, and two in neurobiology, the area in which I developed an immediate interest. It was in one of these two neurobiology rotations that I began to study the mechanisms of long-term potentiation (LTP), one form of synaptic plasticity, with Robert Malinow.

Synapse plasticity has been postulated to be the primary substrate for many forms of behavioral plasticity, including learning and memory. With the aid of a newly developed fluorescent imaging technique that was just brought to Cold Spring Harbor Laboratory by Karel Svoboda, we were able to demonstrate that electrical nerve-cell stimulation - similar, to a certain degree, to learning-induced nerve-cell activation — encourages proteins called glutamate receptors to move into the nerve-cell connections within the brain called synapses to strength these connections. This work was published in June 1999 issue of Science, which named it one of the top ten scientific discoveries of the year.

Unlike chemistry and physics, where a lot is already known, I felt that biology was different. There are so many unanswered questions that you encounter every day.
Songhai Shi Developmental Biologist

Wondering if these receptors moving into the synapses by nerve cell activation might be functional and thus contribute to learning and memory, we engineered a glutamate receptor, known as AMPA-type receptor (AMPA-R), that could be detected by electric recording when it was at the synapse. With this new technique, we were able to show that AMPA-R are functionally incorporated into the synaptic connections by the nerve cell activation.

Using these techniques, we discovered that AMPA-Rs with different compositions are incorporated into synapses by different types of nerve cell activity. For this work, I was fortunate to be awarded Science’s and Amersham Biosciences’ Young Scientist Prize for 2000.

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From California Back to New York

After completing my PhD at Cold Spring Harbor and SUNY-Stony Brook, I shifted my research interest into understanding the mechanisms underlying the nervous system development. I joined Lily and Yuh Nung Jan’s lab in the Department of Physiology at the Howard Hughes Medical Institute and University of California, San Francisco (UCSF). I was awarded a fellowship from the Helen Hay Whitney Foundation for my postdoctoral training, which I considered a great honor and a real help in funding my research.

After immersing myself in the study of synapses using electrophysiology and imaging in my graduate period, I wanted to expose myself to genetics, another critical approach for understanding how the brain develops and functions. I focused on identifying evolutionarily conserved mechanisms underlying three essential aspects of mammalian central nervous system development, from neuronal polarity specification, to neuronal dendrite development, to synapse maturation and plasticity.

Following the four years of fruitful postdoctoral training, I decided it was time to try and find an institution where I could create a lab of my own. I considered a number of options and the one place that rose to the top of my list was Sloan Kettering Institute (SKI). The research environment here is excellent and I was excited to work side by side with some of the biggest names in biological research.

While my lab is just beginning, our primary focus remains the desire to understand the mechanisms underlying the neural circuit assembly in mammalian central nervous systems. Specifically, we are investigating three related topics: neuronal production, polarization, and migration; dendrite development; and synapse development and plasticity.

I am very happy to be here at SKI and I have great hopes for what we can achieve.

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