Research @ Dharma Lab
Embedded Files
Overview
We are a chemical biology lab exploring oxidative lipid metabolism to drive lipid droplet accumulation. We pursue ferroptosis as a therapeutic vulnerability in cancer and neurodegeneration. Our work centers on the design of covalent chemical probes and small-molecule modulators that reprogram cellular pathways through precise protein modification. Combining chemical proteomics, mass spectrometry, and mechanism-driven screening, we uncover novel targets, decipher small molecule–protein interactions, and develop first-in-class ferroptosis inducers and inhibitors.
Our goal is to transform chemical tools into next-generation therapeutics through innovation at the chemistry–biology interface.
Targeting Ferroptosis in Cancer and Neurodegeneration
Covalent Probes for Selective Modification of Amino Acids
Small-Molecule Inducers of Lipid Droplets
Targeted Protein Degradation: PROTACs & Molecular Glues
Synthesis of Small Molecules
Synthesis of organic molecules plays a central role in our research on developing new therapeutic candidates and deciphering new biological mechanisms. We rationally design organic molecules for targeting specific mechanisms in biological systems.
Phenotypic screening of synthesized molecules, hit identification, and structure optimization are an iterative routine for our lab.
Small-Molecule Inducers of Lipid Droplets
We design and discover small molecules that induce lipid droplet (LD) formation as both chemical tools and therapeutic candidates. Lipid droplets are emerging as stress-regulated organelles involved in redox buffering, protein homeostasis, and metabolic adaptation. Our efforts uncover new chemical scaffolds and targetable proteins that modulate LD biogenesis and lipid signaling under disease-relevant conditions.
Targeting Ferroptosis in Cancer and Neurodegeneration
Ferroptosis is an iron- and lipid-dependent cell death pathway with therapeutic potential in malignancies and neurodegenerative disorders. We develop ferroptosis inducers and inhibitors that modulate lipid peroxidation, identify new druggable protein targets, GPX4 activity, and cellular antioxidant capacity. These molecules help us dissect ferroptotic signaling and exploit its vulnerabilities for selective cancer cell killing and in the protection of neuronal phenotypes.
Covalent Probes for Selective Modification of Amino Acids
Our lab designs electrophilic covalent probes that form selective bonds with target proteins. These molecules serve both as mechanistic tools and as therapeutic leads, enabling precise modulation of protein function.
Our research is anchored in chemical proteomics, including activity-based protein profiling (ABPP), clickable probe labeling, and intact mass spectrometry. This platform enables deep characterization of target engagement, selectivity, and pathway modulation across small-molecule classes. The iterative feedback between synthesis and mechanistic insight drives rapid probe-to-lead advancement.
Targeted Protein Degradation: PROTACs & Molecular Glues
We also engineer proximity-inducing molecules, including PROTACs and molecular glues, to degrade disease-relevant proteins by hijacking cellular ubiquitin–proteasome machinery. These molecules offer a powerful strategy to modulate previously “undruggable” targets and overcome limitations of occupancy-based inhibitors. We integrate structure-guided design and proteomic profiling to develop degraders with tailored specificity and potency..
Funding Support
ANRF
CSIR
BIRAC
ICMR
DBT
Page updated
Google Sites
Report abuse