Li Lab

Hundreds of millions of years ago, single cells started to adhere to each other, assemble into groups, and live together cooperatively. These ancient collaborations rewarded the multicellular pioneers with profound evolutionary advantages and seeded the flourishing world of multicellular organisms. Inter-cellular adhesion and communication, which is the foundation of multicellularity, happen at the cellular interface and rely on cell-surface molecules. Cell-surface signaling thus controls almost every aspect of the development and physiology of multicellular organisms. The evolution of multicellular systems is tightly coupled with the diversification and selection of cell-surface molecules, resulting in the complexity of cell-surface signaling that we see today. Apart from the timescale of millions of years, the "evolution" of cell-surface milieu is happening every minute for almost every cell in our body: from division to differentiation and ultimately death, the cell-surface molecular composition is constantly changing to serve the physiological function of a cell.

Our lab studies the operating principles of cell-surface signaling in two "sense-n’-response" systems — the nervous and immune systems — and their crosstalk. Both systems detect physical or chemical cues, process the information, and make proper responses so that the body can adapt to the ever-changing environment and survive. These two systems operate in distinct modes: in mammals, the nervous system is highly centralized with neurons fixed in their positions lifelong; conversely, the immune system is distributed, featuring constantly patrolling immune cells. Nevertheless, cell-surface signaling plays a central role in the development and physiology of both. To obtain novel mechanistic insights, our lab innovates new methods and tools for analyzing cell-surface signaling at systems, cellular, and molecular levels. We collaborate with chemists, engineers, and computational biologists to build cross-disciplinary approaches and tackle originally intractable biological questions.

Our current research directions include:

• Method development for quantitatively profiling the cell-surface milieu and molecular interactions at high spatiotemporal resolution.
• Advanced imaging (volume electron microscopy, cryo-electron tomography) for analyzing cellular structures and cell-surface molecules in situ.
• Systems and mechanistic investigation of cell-surface signaling in the nervous and immune systems, as well as their crosstalk.