Our lab works at the intersection between chemistry and biology. Many important biological questions cannot be fully addressed due to the lack of proper methodologies. We aspire to tackle these questions by developing and applying novel chemical tools.
The main focus in the lab is to understand biological processes that involve local desolvation and/or conformational contraction, using chemical compounds whose excited states are dependent on these micro-environmental changes. By exploring and expanding the functional excited states of molecules, we aim to probe, dissect, and control these biological processes in live cells.
We are currently focused on protein misfolding and aggregation that occur in a deficient proteostasis in the presence of cellular stress. These molecular events have been associated with a variety of diseases that are termed as protein misfolding diseases. It is now appreciated that amyloid toxicity results not necessarily from insoluble aggregates or fibrils, but primarily from soluble, misfolded conformational species that accumulate in cells during the aggregation cascade of amyloidogenic proteins. We aim to understand the biochemical nature of this species and their mechanism of action in disease initiation and progression.
Currently, we attempt to address the following questions:
1) How can we quantify proteostasis deficiency during cellular stress in real time?
2) What is the biochemical nature of soluble, misfolded proteins in live cells?
3) How do soluble, misfolded proteins lead to disease initiation and progression?
We achieve this goal through the development and utilization of chemical tools that allow for the real-time visualization of these species and the direct dissection of their interaction partners in living cells. These methods can be generally applicable to a variety of pathogenic proteins whose misfolding and aggregation lead to diseases. Further, we employ synthetic chemistry and physical chemistry to discern how molecular interactions control function of excited states. We hope these chemical knowledge can be applied to better the development of materials whose function is dependent on their excited states.