My research encompasses both technology development and biological discovery. We integrate diverse approaches including molecular engineering, imaging, chemical synthesis, molecular and cell biology. Our efforts in method and probe development centers around our interests in understanding hormone secretion and signaling in pancreatic islets.

 

Develop photonic probes for biological applications

We focus on engineering molecular probes that can be applied to live cells under non- or minimum invasive conditions. Besides photoactivatable or “caged” molecules, we are particularly interested in developing fluorescent sensors for investigating the spatiotemporal characteristics of cellular biochemistry, exploiting the superb sensitivity of fluorescence detection.

Related to our interests in islets biology, we are exploring new ways to monitor islet b-cells in live animals. In type 2 diabetes, b-cells are gradually lost. The capability of following the change in b-cell mass or function in vivo remains a crucial yet unmet need in both clinical diagnostics and in diabetes research. Searching for biomarkers and labels that can be applied to b-cell imaging in live animals represents a grand challenge and opportunity in probe engineering.

 

Hormone secretion in pancreatic islets

 The islets of Langerhans contain diverse endocrine cells (a, b, d, etc) that release distinctive hormones. While it has been appreciated that the appropriate coordination of these secretory events is important for maintaining euglycemia, little is known about the pattern, timing and sites of hormone release in intact islets at the cellular and subcellular levels. To better understand the regulation and function of these dynamic events in the context of paracrine and autocrine signaling, we are interested in mapping the spatiotemporal characteristics of hormone release in pancreatic islets in three dimensions. Over the long term, we believe these imaging studies should lead us to perform detailed mechanistic investigations on stimulus-secretion coupling under either physiological or pathological settings, which should in turn aid us to better understand the cause of abnormal hormone release when diabetes develops.

 

Functional analysis of microRNAs

MicroRNAs (miRNAs) are small noncoding RNAs ~22 nucleotide long that play diverse roles in development, physiology and human diseases. The questions of how a miRNA recognizes its targets and where miRNAs are localized in cells have perplexed the RNA field for a long time. We are interested in developing new probes to tackle the challenge. Further, since antisense oligonucleotides can potently inhibit the activity of complementary miRNAs, we have been developing new antimirs (or antagomirs) using the nematode C. elegans as a test bed.