Recent Publications
"Methods for Physical Characterization of Phase Separated Bodies and Membrane-Less Organelles".
- Journal of Molecular Biology (2018)
Membrane-less organelles form through phase separation, compartmentalizing macromolecules to regulate cellular processes. This enhances local concentration and modulates structure and dynamics. Understanding their structure, material properties, and function requires interdisciplinary approaches across vast length and time scales. This review explores diverse methods used to study the morphology, rheology, structure, and dynamics of membrane-less organelles in vitro and in live cells.
"Fluorescence quenching by lipid encased nanoparticles shows that Amyloid-β has a preferred orientation in the membrane".
- Chemical Communication (2017)
​
​
"​Emerging structural details of transient Amyloid-β oligomers suggest designs for effective small molecule modulators".
- Chemical Physics Letter (2017)​
​
​
"Stereoisomers Probe Steric-Zippers in Amyloid-β".
- Journal of Physical Chemistry B (2017)
​​
​
​
"​Curcumin dictates divergent fates for the central salt-bridges in Amyloid-β40 and Amyloid-β42".
- Biophysical Journal (2017)
​​
​
​
​"Major Reaction Coordinates Linking Transient Amyloid-β Oligomers to Fibrils Measured at Atomic Level".
- Biophysical Journal (2017)
​
​
​"Significant structural differences between transient Amyloid-β oligomers and less-toxic fibrils in regions known to harbor familial Alzheimer’s mutations".
​​
​
​
​
​"Perturbation of the F19-L34 Contact in Amyloid β (1-40) Fibrils Induces Only Local Structural Changes but Abolishes Cytotoxicity".
- The journal of physical chemistry letters (2017)
​
​
​​
"Defining the condensate landscape of fusion oncoproteins".
- Nature Communications (2023).
Fusion oncoproteins (FOs) result from chromosomal translocations in ~17% of cancers and often drive oncogenesis. While some FOs promote cancer via liquid-liquid phase separation (LLPS), its generality remains unclear. Testing 166 FOs in HeLa cells, we found 58% formed condensates with distinct physicochemical features, grouping by subcellular localization and function. Using Machine Learning, we predicted 67% of ~3000 additional FOs form condensates, with 35% linked to gene expression and 47% of condensate-negative FOs associated with cell signaling. Our datasets and reagents provide valuable resources for future FO condensation research.
"The Role of Phase Separated Condensates in Fusion Oncoprotein Driven Cancers".
- Annual Reviews of Cancer Biology (2023).
Fusion oncoproteins (FOs) from in-frame chromosomal translocations drive aggressive cancers with poor outcomes. Many function within biomolecular condensates via liquid-liquid phase separation (LLPS). Two FO classes emerge: nuclear condensates altering chromatin and gene expression, and cytoplasmic condensates promoting aberrant signaling like RAS/MAPK. Their sequences contain LLPS-prone intrinsically disordered regions and folded domains that facilitate condensate formation. This review explores LLPS in FO oncogenicity, highlights FOs disrupting normal LLPS, and examines sequence features linked to LLPS enrichment in FOs.
"Phase Separation mediates NUP98 Fusion Oncoprotein Leukemic Transformation".
- Cancer Discovery (2022)
NUP98 fusion oncoproteins (FOs) drive pediatric leukemias, with many transforming hematopoietic cells. Most contain an intrinsically disordered region from NUP98 prone to liquid-liquid phase separation (LLPS). A major class, including NUP98-HOXA9 (NHA9), retains DNA-binding domains, while others bind chromatin differently. Although NUP98 FOs form nuclear puncta, their role in leukemogenesis remained unclear. We show that NHA9 condensates rely on homotypic and heterotypic interactions to form puncta, driving aberrant transcription and cell transformation. Three additional NUP98 FOs also form puncta and transform cells, highlighting LLPS as a key mechanism in NUP98-driven leukemogenesis.