Research Interests
Our research seeks to understand how cells dynamically build, remodel, and dismantle the actin cytoskeleton at the right place and time. These actin networks are essential for cell movement, division, membrane remodeling, intracellular transport, and force generation, and their disruption is closely associated with cancer, cardiomyopathies, neurological disorders, immune dysfunction, and infectious diseases. At the heart of our work is a fundamental question: how does an actin filament integrate multiple, often competing, regulatory signals to determine its fate?

We investigate this problem by viewing actin filaments not as passive polymers, but as dynamic molecular decision-making platforms where regulatory proteins cooperate and compete to control growth, branching, stabilization, remodeling, and disassembly. A major focus has been the Arp2/3 complex, a key actin nucleator whose activity shapes diverse cellular architectures. By dissecting how Arp2/3 complex and its regulators work together, we aim to uncover the molecular principles that govern cytoskeletal organization across different cellular contexts.

This naturally extends to an important evolutionary and biomedical dimension: fungi use distinct actin-regulatory strategies that support polarized growth, endocytosis, and virulence, potentially revealing fungus-specific therapeutic vulnerabilities. Using cryo-electron microscopy, cryo-electron tomography, biochemical reconstitution, biophysical approaches, molecular dynamics simulations, and cellular validation, our goal is to connect molecular structure to cellular function and disease, thereby revealing fundamental principles of life while creating opportunities for future discoveries in human health and infection biology.

Google Scholar page https://scholar.google.com/citations?hl=en&user=6-Tk-uUAAAAJ

Selected Publications

Francis J, Pathri AK, Shyam KT, Sripada S, Mitra R, Narvaez-Ortiz HY, Eliyan KV, Nolen BJ, Chowdhury S. Activation of Arp2/3 complex by a SPIN90 dimer in linear actin-filament nucleation. Nat Struct Mol Biol. 2025 Nov;32(11):2272-2284. doi: 10.1038/s41594-025-01673-8. Epub 2025 Sep 15. PMID: 40954370

Yang S, Tang Y, Liu Y, Brown AJ, Schaks M, Ding B, Kramer DA, Mietkowska M, Ding L, Alekhina O, Billadeau DD, Chowdhury S, Wang J, Rottner K, Chen B. Arf GTPase activates the WAVE regulatory complex through a distinct binding site. Sci Adv. 2022 Dec 14;8(50):eadd1412. doi: 10.1126/sciadv.add1412. Epub 2022 Dec 14. PMID: 36516255

Ding B, Yang S, Schaks M, Liu Y, Brown AJ, Rottner K, Chowdhury S, Chen B. Structures reveal a key mechanism of WAVE regulatory complex activation by Rac1 GTPase. Nat Commun. 2022 Sep 16;13(1):5444. doi: 10.1038/s41467-022-33174-3. PMID: 36114192

Ding B, Narvaez-Ortiz HY, Singh Y, Hocky GM, Chowdhury S, Nolen BJ. Structure of Arp2/3 complex at a branched actin filament junction resolved by single-particle cryo-electron microscopy. Proc Natl Acad Sci U S A. 2022 May 31;119(22):e2202723119. doi: 10.1073/pnas.2202723119. Epub 2022 May 27. PMID: 35622886

Shaaban M, Chowdhury S, Nolen BJ. Cryo-EM reveals the transition of Arp2/3 complex from inactive to nucleation-competent state. Nat Struct Mol Biol. 2020 Nov;27(11):1009-1016. doi: 10.1038/s41594-020-0481-x. Epub 2020 Aug 24. PMID: 32839613