Research

Current research focus

The lab is interested in investigating molecular mechanisms underlying protein phase separation, aggregation, and misfolding of proteins. Current research focuses on understanding intrinsically disordered proteins (IDPs) and the consequences of multivalency in biological regulation. 

The primary domain of the lab is the formation of nuclear biomolecular condensates during transcription and DNA damage repair processes. We focus on understanding the underlying sequence grammar involved in the formation of nuclear condensates. The emergent properties of biomolecular condensates are studied using a combinatorial approach of in vitro, cytomimetic, and in vivo techniques. 

The long-term goal is to integrate molecular biology, biochemistry, live-cell imaging, and computational modeling to dissect how intrinsically disordered regions and multivalent interactions shape gene expression and genome stability.

The research outcomes are expected to contribute significantly to understanding the physiological functions and pathological malfunctions of proteins in diseases such as cancer and neurodegeneration.

Publication:  

Navalkar A*, Arunagiri A*, Tovaria Kee T, Panchal K, Dick K. (2025). Protein Aggregates and Biomolecular Condensates: Implications for Human Health and Disease, Frontiers in Molecular Biosciences, 12, 1719678. DOI: 10.3389/fmolb.2025.1719678. (*corresponding author).

Postdoctoral research

Doctoral research

The research focused on p53 amyloids implicated in cancer pathogenesis. We successfully demonstrated the presence of p53 amyloids in clinical biopsies along with their isolation from human cancer tissues. In vitro aggregation of the p53 DNA-binding domain and its cancer-associated mutants was studied. 

An inducible in-cell p53 amyloid formation model using fibrillar seeds of p53 was designed.  This model was used to establish the prion-like cell-to-cell transmission of p53 amyloids.  Characterized the structure of p53 core domain aggregates by electron microscopy along with atomistic & coarse-grained molecular dynamics.

Using a multi-faceted approach, we establish that wild-type p53 amyloid formation can impart oncogenic properties to non-cancerous cells, eventually leading to tumorigenesis in vivo.  Further, my research demonstrates the systemic level changes in cellular signalling pathways due to p53 amyloids using microarray and proteomic profiling. We highlight the critical genes in the cell cycle and proliferative pathways leading to p53 amyloid-mediated transformation of cells. Furthermore, as the last part of my project, I am extensively working on the prion-like infectious nature of p53 amyloids demonstrated via direct fibril injections in mice, leading to tumor-like lesions. This study will pioneer the research in characterizing cancer as a prion disease.

Publications:

1. Navalkar A, Pandey S, Singh N, Patel K, Datta D, Mohanty B, Jadhav S, Chaudhari P, Maji SK (2021). Direct evidence of cellular transformation by prion-like p53 amyloid infection. Journal of Cell Science, 134 (11), jcs258316. DOI: 10.1242/jcs.258316.

2. Lima I, Navalkar A, Maji SK, Silva JL, Oliveira G and Cino E (2019). Biophysical characterization of p53 core domain aggregates. Biochemical Journal, 17;477(1):111-120; DOI: 10.1042/bcj20190778.

3. Navalkar A*, Ghosh S, Pandey S, Paul A, Datta D and Maji SK* (2019). Prion-like p53 amyloids in cancer. Biochemistry, 59, 2, 146–155. DOI: 10.1021/acs.biochem.9b00796 (*corresponding author).   This article has been featured as a part of the cover art of the journal.

4. Ghosh S#, Salot S#, Sengupta S#, Navalkar A#, Ghosh D, Jacob RS, Das S, Kumar R, Jha NN, Sahay S, Mehra S, Mohite GM, Ghosh SK, Kombrabail M, Krishnamoorthy G, Chaudhari P, and Maji SK (2017), p53 amyloid formation leading to its loss of function: Implications in cancer pathogenesis. Nature Cell Death and Differentiation, 24:1784–1798; DOI:10.1038/cdd.2017.105 (#equal contribution first author).