As an undergraduate in the Sengupta Lab at Brigham and Women’s Hospital, I contributed to developing a 3D tumor co-culture system to study tumor-endothelial interactions. Using this, we  discovered that metastatic cancer cells preferentially make cytoskeletal contacts, termed nanoscale conduits, with the endothelium. These conduits facilitated the transfer of intercellular contents, including miRNAs, leading to pathological transformation of the endothelium and associated metastatic angiogenesis. We showed that blocking this intercellular transfer using Taxol protected the endothelium and demonstrated the importance of conduits in breast cancer in vivo using mouse models. We also developed a mathematical model to predict tumor-endothelial interactions and established an epithelial-endothelial dissociation index as a robust predictor for tumor grade. This early work demonstrated the successful integration of quantitative modeling and in vivo data to understand cellular mechanics and disease progression. 

Read more about this here, and here

I adopted a clever mosaic genetic labeling tool called CoinFLP developed the Hariharan lab to track and label polyploid cells in the Drosophila brain, and demonstrate how they become polyploid (cell cycle re-entry instead of cell fusion). Since CoinFLP works in a probabliistic way, depending on when, how and for how long you induce the labelling, it can be used to mark and follow polyploid cells, and even be used to discover new polyploid cell types! Read more here and see how  else it can be used here

I also initiated a community resource project: The Polyploidy Atlas, a library of various reports of polyploid cell types across Eukarya. Mining this dataset, I authored a comprehensive review summarizing and classifying all recorded instances of cell cycle re-entry in the nervous system across the animal kingdom, offering historical perspective and a modern outlook on its implications for neurodegenerative diseases like Alzheimer's. 

I discovered that individual fat body cells in Drosophila are paired through ring canals, forming a bi-cellular syncytium via incomplete cytokinesis. Using a live imaging technique I developed, we showed that specific organellar cargo such as ER and Golgi vesicles (but not mitochondria or lipid droplets) are transported through these ring canals, demonstrating transport specificity. Crucially, disruption of ring canals resulted in higher levels of ER stress, aberrant cell size, and cell lethality under exogenous stress. This points to a critical role for syncytialization in stress tolerance and larval development—a feature conserved in metabolically active mammalian tissues like cardiomyocytes and hepatocytes. 

To learn more, watch me speak about this in the SDB EBH Postdoctoral Seminar Series

We found that epithelial proliferation, differentiation, and endoreplication are crucial processes that reshape the mosquito midgut in response to challenges like maturation, bacterial infection, and blood feeding. Our results showed that these stimuli trigger increases in cellular turnover and, notably, a shift toward higher ploidy levels in midgut cells, which we hypothesize facilitates increased metabolic activity. For instance, we observed a sharp increase in mitosis following oral bacterial infection, and a species-specific increase in cell proliferation and ploidy after blood feeding. To assess these dynamics, we employed flow cytometry to quantify the ploidy of cell populations in the posterior midgut epithelium, an essential method that allowed us to detect and measure this fundamental shift in cell size and DNA content under the different physiological states. Read more here

In the FlyStressLab We recently discovered that the master regulator of the Integrated Stress Response (ISR) pathway, ATF4, is regulated by a functional, conserved micropeptide (μPATF4) encoded by an upstream open reading frame (uORF) within the same mRNA. μPATF4 negatively regulates ATF4 protein levels in trans. I developed biochemical and imaging-based reporters in mammalian cell culture and genetic tools in Drosophila to demonstrate this novel regulatory mechanism. In Drosophila, overexpression of μPATF4 results in altered developmental timing, increased lipid storage, and might even play a role in collective cell migration. Stay tuned for multiple publications on this work in coming months!