Research

Research Interests

Approximately ~ 10000 rare (or orphan) diseases have been identified in humans, and the number is raising weekly. Around 70-80% of these diseases are monogenic, while the molecular mechanisms and effective treatments for a majority of the rare diseases have not been clearly defined and developed. The nematode Caenorhabditis elegans contains orthologs of the majority of disease genes. Precision modeling of pathogenic gene variants of rare diseases in C. elegans has uncovered a better understanding of the cellular and molecular mechanisms as well as revealed novel therapies based on drug and genetic suppressor screens. In my lab, we aim to identify genetic modifiers of patient-specific alleles, including those associated with the mechanosensor PIEZO, the lipid-droplet protein SEIPIN, and other neuromuscular and metabolic disorders associated variants. We leverage CRISPR/Cas9 genome editing, whole-genome sequencing, and machine-learning based bioinformatic pipeline to conduct large genetic screens and identify these genetic modifiers in a short time period. These screens will identify novel interactors or genetic pathways that can suppress or alleviate the defective phenotypes of the patient-specific missense alleles. Lastly, these studies will help determine the functions of these putative suppressors and their relationship with disease-associated genes, as well as their contributions to physiological processes in other model systems.

Research Directions

Mechanobiology

Regulation of mechanosensors (including PIEZOs) by the cytoskeleton
Relationship between mechanosensors (TACAN & PIEZOs) and fatty acid metabolism
Mechanosensor membrane trafficking

Lipid and Metabolic Biology

Seipin-mediated lipid metabolism and lipid transfer
Lipid droplet (LD) morphology, and contacts between organelles (ER, mitochondria, and cortical granules)
Genetic regulation of the fatty acid synthase (FASN-1).
Modeling the PMM2-Congenital Disorders of Glycosylation (PMM2-CDG).

Live Imaging and Cell Biology

Establish high-resolution and temporal imaging pipeline
Ca²⁺ and cytoskeleton imaging, and data analysis (AI-based imaging analysis tools)

Genetics, High-throughput Sequencing, Bioinformatics, and Multi Omics Assays

Optimization of CRISPR/Cas9 gene editing
Forward genetic and chemical screens
Whole genome sequencing combined with machine-learning bioinformatic tools to identify single nucleotide variations (SNVs)
RNA-seq to decipher the gene regulation network
Proximity-labeling pull-down assays