Brent R. Stockwell

Brent R. Stockwell

Research Interest

Biological
Organic

Summary

We are using chemical and biological tools to study ferroptosis, a form of regulated cell death discovered in the Stockwell Lab. Ferroptosis is an iron-dependent form of oxidative, non-apoptotic cell death that is tightly linked to metabolism and disease.

We are exploring how ferroptosis is triggered during normal physiological processes and in disease states, and how it can be induced and inhibited for therapeutic benefit in various cancers and neurodegenerative diseases.

We cover a significant scope of chemistry and biology in our mission to define new mechanisms of cell death, to understand ferroptosis, and subsequently to discover potent therapeutics. We start with the use of computational chemistry tools to design chemical probes and drug candidates that reveal cellular and molecular mechanisms. We then use synthetic organic chemistry to produce libraries of drugs that are used in a wide range of in vitro assays to study effects on cell viability, lipid peroxidation, and gene expression. We also use metabolomics, lipidomics, CRISPR and siRNA/shRNA screening, protein expression and biochemistry, and structure elucidation. Analytical chemistry in the forms of mass spectrometry imaging and Raman spectroscopy are additionally utilized along with cell imaging to study the localization of ferroptosis inducers and inhibitors. Finally we use animal models to test our compounds in vivo.

Through the integration of biochemistry, synthetic organic chemistry, computational chemistry, biophysics, and analytical chemistry, the Stockwell Lab aims to produce potent therapeutics by determining new mechanisms of action involved in cell death and in particular, ferroptosis.

Recent Publications:

For an update to list of publications from the Stockwell Lab, please visit www.stockwelllab.org

Click here for Professor Stockwell's publications in PubMed

Reznik E, Zandkarimi F, Csuka JM, Zhu Q, Jin J, Neelakantan TV, Zheng J, Polychronidou V, Fongheiser M, Brown A, Qiu B, Rodriguez M, DeVine L, Subramaniam PS, Gu W, Califano A, Stockwell BR (2025) Lipidomic changes in persister cancer cells drive enhanced ferroptosis sensitivity, Ferroptosis and Oxidative Stress, 1:202501. 10.70401/fos.2025.0003

Cañeque T, Baron L, Müller S, Carmona A, Colombeau L, Versini A, Solier S, Gaillet C, Sindikubwabo F, Sampaio JL, Sabatier M, Mishima E, Picard-Bernes A, Syx L, Servant N, Lombard B, Loew D, Zheng J, Proneth B, Thoidingjam LK, Grimaud L, Fraser CS, Szylo KJ, Der Kazarian E, Bonnet C, Charafe-Jauffret E, Ginestier C, Santofimia-Castaño P, Estaras M, Dusetti N, Iovanna JL, Cunha AS, Pittau G, Hammel P, Tzanis D, Bonvalot S, Watson S, Gandon V, Upadhyay A, Pratt DA, Freitas FP, Friedmann Angeli JP, Stockwell BR, Conrad M, Ubellacker JM, Rodriguez R (2025) Activation of lysosomal iron triggers ferroptosis in cancer. Nature, May 7. doi: 10.1038/s41586-025-08974-4. PMID: 40335696

Liu H, Forouhar F, Saneto R, and Stockwell BR (2025) Selective small molecule activator of patient-derived GPX4 variant. ACS Chemical Biology, May 5. doi: 10.1021/acschembio.5c00158. PMID: 40325618

Sugimoto A, Saito Y, Wang G, Sun Q, Yin C, Lee KH, Geng Y, Rajbhandari P, Hernandez C, Steffani M, Qie J, Savage T, Goyal DM, Ray KC, Neelakantan TV, Yin D, Melms J, Lehrich BM, Yasaka TM, Liu S, Oertel M, Lan T, Guillot A, Peiseler M, Filliol A, Kanzaki H, Fujiwara N, Ravi S, Izar B, Brosch M, Hampe J, Remotti H, Argemi J, Sun Z, Kendall TJ, Hoshida Y, Tacke F, Fallowfield JA, Blockley-Powell SK, Haeusler RA, Steinman JB, Pajvani UB, Monga SP, Bataller R, Masoodi M, Arpaia N, Lee YA, Stockwell BR, Augustin HG, Schwabe RF (2025) Hepatic stellate cells control liver zonation, size and functions via R-spondin 3. Nature. Mar 12. doi: 10.1038/s41586-025-08677-w. Online ahead of print. PMID: 40074890

Liu H, Zask A, Forouhar F, Iketani S, Williams A, Vaz DR, Habashi D, Choi K, Resnick SJ, Hong SJ, Lovett DH, Bai T, Chavez A, Ho DD & Stockwell BR (2025) Development of small molecule non-covalent coronavirus 3CL protease inhibitors from DNA-encoded chemical library screening, Nature Communications 16: 152, published online Jan 2nd.  

Qiu B, Zandkarimi F, Saqi A, Castagna C, Tan H, Sekulic M, Miorin L, Hibshoosh H, Shinya Toyokuni S, Koji Uchida K, Stockwell BR (2024) Fatal COVID-19 pulmonary disease involves ferroptosis. Nature Communications, 15:3816. PMID: 38769293 PMCID: PMC11106344 DOI: 10.1038/s41467-024-48055-0https://doi.org/10.1038/s41467-024-48055-0 https://rdcu.be/dIrgL

Qiu B, Zandkarimi F, Bezjian CT, Reznik E, Son RK, Gu W, Jiang X, Stockwell BR (2024) Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis. Cell, 187, 1–14. PMID: 38366593 PMCID: PMC10940216 DOI: 10.1016/j.cell.2024.01.030

Tian H, Rajbhandari P, Tarolli J, Decker AM, Neelakantan TV, Angerer T, Zandkarimi F, Remotti H, Frache G, Winograd N, Stockwell BR (2024) Multi-modal mass spectrometry imaging identifies cell-type-specific metabolic and lipidomic variation in the mammalian liver. Developmental Cell, 59, 1-13.https://doi.org/10.1016/j.devcel.2024.01.025

von Krusenstiern AN, Robson RN, Qian N, Qiu B, Hu F, Reznik E, Smith N, Zandkarimi F, Estes VM, Dupont M, Hirschhorn T, Shchepinov MS, Min W*, Woerpel KA, Stockwell BR (2023) Identification of essential sites of lipid peroxidation in ferroptosis. Nature Chemical Biology, Jun;19(6):719-730. PMID: 36747055 PMCID: PMC10238648  https://rdcu.be/c403K. doi.org/10.1038/s41589-022-01249-3

Brown AR, Hirschhorn T, Stockwell BR (2024) Ferroptosis—disease perils and therapeutic promise. Science. 386, 6724, 848-849. DOI: 10.1126/science.adn7030

Rajbhandari P, Neelakantan TV, Hosny N, Stockwell BR (2023) Spatial pharmacology using mass spectrometry imaging. Trends in Pharmacology, Dec 15, https://doi.org/10.1016/j.tips.2023.11.003