Development &
Disease Biology
Laboratory
Research
We employ a multidisciplinary approach, using fruit flies, mammalian cell lines, and patient-derived cells, to understand the mechanisms of development and disease biology. Using techniques like CRISPR-based gene editing, molecular biology, advanced microscopy, and electrophysiological, biochemical, and genetic assays, our team investigates gene functions, assesses the pathogenicity of gene variants, and uncovers disease-driving molecular mechanisms. Some of the immediate focus areas of our lab are:
Metabolic and Mitochondrial Defects in Neurological Disorders
Mitochondria and lysosomes are central hubs for iron and lipid metabolism. Dysregulation of these pathways, including iron dyshomeostasis and altered lipid levels, has been implicated in several neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, as well as lysosomal storage diseases. This suggests a potential link between these metabolic pathways, though the underlying mechanisms remain unknown. We are investigating the mechanisms of mito-lysosomal crosstalk, the interplay between iron and lipid metabolism, and their contributions to neuronal degeneration. Additionally, we are studying how impaired mitochondrial protein import disrupts metabolic homeostasis, affects signaling pathways, and contributes to developmental and neurological diseases.
TMEM (Transmembrane) Proteins in Development and Disease
TMEM proteins are integral components of cell membranes and the membranes of various organelles, including the nucleus, mitochondria, lysosomes, and endoplasmic reticulum. Mutations that impair TMEM protein function are linked to diverse diseases, such as genetic disorders, cancer, and neurodegenerative conditions. Despite their medical significance, the in vivo functions of most TMEM proteins remain largely unexplored. We are employing a genetic approach combined with cellular and molecular studies to characterize disease-relevant TMEM proteins. We are especially interested in the role of dual-localized TMEM proteins in inter-organellar communication, organelle dynamics, and the maintenance of cellular homeostasis.
Rare/Undiagnosed Disease-Causing Gene Discovery
Undiagnosed diseases are medical mysteries in which the cause of the disease remains unknown for years, sometimes even for the patient’s entire lifetime. Standard clinical tests combined with next-generation sequencing technology can diagnose ~30-40% of patients with unknown disease etiology. Experimental evidence is therefore crucial to confirm the damaging nature of gene variants. We use "humanized" fruit flies and cellular models to evaluate the functional impact of putative disease-associated variants, study disease mechanisms, and explore therapeutic strategies. Using our expertise in fly and human genetics, we aim to identify genes that cause undiagnosed neurological diseases and are associated with mitochondrial dysfunctions.
Research Funding
