Chandra Bappaditya

Currently, I am a postdoc in Richard Kriwacki’s lab at St. Jude Children’s Research Hospital. Education: Ph.D. in Biophysics: Department of Chemical Science; Tata Institute of Fundamental Research (TIFR), Mumbai, India Thesis title: “Understanding amyloid aggregation in terms of its distal folding contacts.” 2018 M.Sc. in Chemistry: Department of Chemistry; Indian Institute of Technology Madras (IIT M), Chennai, India Thesis title: “Synthetic efforts towards new bodipy based derivative and pyridine based multichromophoric system.” 2011 Research: During my doctoral studies, my thesis aimed to understand the structural basis of protein misfolding, aggregation, and possible toxicity links. Combining fast fluorescence-based techniques, such as FCS and FRET and structure deciphering technique of solid-state NMR, I showed how small alterations in the molecular conformation of an intrinsically disordered protein, amyloid-beta, can alter the formation of macromolecular assemblies and lead to alteration in function. During my current postdoctoral studies in Richard Kriwacki’s lab, I have focused on investigating the role of liquid-liquid phase-separation on NUP98 fusion oncoproteins (FOs) driven Leukemia. NUP98 FO-driven pediatric AML is characterized by poor prognosis, and there are no targeted therapies. My studies address critical open questions regarding the mechanism(s) through which NUP98 FOs transform cells and drive leukemogenesis. My current studies showed that sticky NUP98 driven phase separation synergizes with DNA binding of the fusion partner, can cause the formation of membrane-less bodies at HoxA9-specific sites on chromatin and lead to aberrant gene transcription. Personal Statement: "Simplicity is the ultimate sophistication." - Leonardo da Vinci. I chose the field of structural biology and biophysics as a life pursuit because I wish to probe how the simple molecular building blocks drive complex hierarchical biological processes. During my doctoral studies, I was intrigued by the fact that a slight alteration in the molecular conformation of intrinsically disordered proteins (IDPs) can alter the formation of macromolecular assemblies and lead to a wide range of neurodegenerative diseases. Combining fast fluorescence-based techniques, such as FCS and FRET, and the structure deciphering technique of solid-state NMR, I showed how minor alterations in the molecular conformation of an IDP, amyloid-beta, can alter the formation of macromolecular assemblies and lead to alteration in its function and the progression of Alzheimer's disease. My passion for working with disordered proteins was reinforced during my postdoctoral studies in Richard Kriwacki's lab when I got the opportunity to observe the radical changes in the IDP field with the introduction of a new phenomenon called "phase separation." Recent evidence shows that phase separation is a critical component in a wide range of cancers. In recent years, the observation that many IDPs undergo phase separation has established a new paradigm regarding their functions; they drive the formation of biomolecular condensates associated with diverse biological processes through the process of phase separation. Since I joined the Kriwacki lab, I started probing the phase separation behavior of acute myeloid leukemia (AML)-associated fusion oncoproteins contrived of IDPs fused with DNA binding/histone modifying domains. I have focused on investigating the role of liquid-liquid phase-separation in NUP98 fusion oncoproteins (FOs) driven leukemias. NUP98 FO-driven pediatric AML is characterized by poor prognosis, and there are no targeted therapies. These studies address critical open questions regarding the mechanism(s) through which NUP98 FOs transform cells and drive leukemogenesis. My recently published work showed that sticky NUP98-driven phase separation synergizes with DNA binding of the fusion partner, causing the formation of membrane-less bodies at HOXA9-specific sites on chromatin leading to aberrant gene expression. I am keen to contribute to this field as a leading scientist and to perform independent research in the future to unveil novel approaches to drug discovery targeting aberrant gene regulation in adult cancer. I seek to become a professor or independent research scientist in the US.