UH stadium

We are a group of researchers from the fields of chemistry, biology, and biophysics. We strive to develop experimental and computational techniques to explore the protein behaviors in cells at the single-cell and single-molecule levels, as well as to understand catalysis of plasmonic nano materials. Our research projects routinely use Single-molecule In-cell-imaging of Genome-edited HESC-derived Target (SIGHT) assay, which comprises multiple modern techniques including super-resolution imaging (PALM), in-cell oligomer simulation (IOS), CRISPR/ Cas9 genetic editing, and human embryonic stem cell (hESCs). By exploiting SIGHT, we aim to explore cellular function from both chemical and biological perspectives.

Mechanism for Neuronal Cu Homeostasis

Understanding responsive mechanisms of metalloproteins is key to elucidate biological functions of copper (Cu) and to identify the causes of diseases resulting from abnormal metal homeostasis. The cellular Cu uptake and secretion require relevant metalloproteins to adjust in a spatiotemporally coordinated manner to assure proper cellular Cu level. However, in the Cu field, little is known about how metalloproteins are individually regulated nor systematically cooperate with each other in their native environment, i.e., in cells. Our research goal is to understand the responsive mechanisms of Cu-uptake and secretory metalloproteins in human neurons, with specific focuses on how metalloproteins adjust their behaviors such as spatial distributions, oligomeric states, inter-protein and inter-domain interactions for proper Cu balance in a spatiotemporally defined manner.

Using CTR1 and ATOX1-ATP7A/B as the initial examples of uptake and secretory metalloproteins, our lab aims to (1) quantify Cu-dependent oligomeric state distribution and identify the Cu-responsive moiety of CTR1; (2) define the preferential interaction of ATOX1 to ATP7A and ATP7B and how mutations in ATP7B affect Cu homeostasis in cellular Cu defending. The comparison between hESC-derived healthy and diseased neurons will inform how disease mutations disrupt cellular Cu balance.


Protein Oligomers and Neurodegenerative Disease

Soluble oligomers of aggregating protein have been suggested to be the toxic species to initiate a cascade of events that ultimately lead to neural death in many neurodegenerative diseases in recent years. Knowledge about where the toxic oligomers begin to form, how they induce neurotoxicity, and what environmental factors trigger the oligomer formation is still unavailable. Here, we use Cu, Zn superoxide dismutase (SOD1), whose aggregation is a hallmark of amyotrophic lateral sclerosis (ALS), as a model system to address these important questions.

By exploiting the SIGHT, we plan to examine the formation mechanism of SOD1 trimer and its impact on wild-type SOD1 in healthy and diseased neurons.We aim to identify the formation mechanism of SOD1 trimers by examining the pH and oxidative level-dependent trimer populations at cytosol, mitochondria, and lysosome. We will identify mechanisms of SOD1 trimers impacting the wild-type SOD1 (WT-SOD1) by studying the cellular activities of SOD1 trimers and WT-SOD1 simultaneously. The research will shift quantifications of specific protein behaviors from in vitro to physiologically relevant human cells and offer a new avenue for uncovering therapeutic interventions.


Photoenhanced Reactivity of Plasmoic Array

Charge-carrier-mediated reactions through plasmonic metal nanostructures offer potential effective catalytic conversion of solar to chemical energy. It remains unclear how the spatial heterogeneity of plasmonic enhancements correlates with spatial patterns of catalytic events and how the hot carrier and thermal effects contribute to the catalytic results as a function of structures of plasmonic nanocatalysts. To maximize the energy efficiency of chemical transformations, experimentally distinguishing the relative importance of each mechanism to the final catalytic results at the single-molecule level, even though challenging, is required.

Using nanoporous gold disk (NPGD) as our model catalyst, we aim to elucidate catalytic reaction mechanisms and the structure-reactivity relationships of plasmonic nanocatalysts.

Using single-molecule super-resolution and fluorescence polarization anisotropy microscopy, we will resolve the reaction activities and temperature on single NPGDs with tens nanometer resolution. We aim to define the primary mechanism for photocatalysis of NPGD with different sizes and inter-disk distance. The outcomes will contribute to the knowledge base helping devise strategies to improve the photocatalytic efficiency of NPGD.