My lab studies how breast cancer cells survive chemotherapy and eventually relapse and contribute to poor patient survival. We use mouse models and human tumor data to examine how the programs used by tumor cells to respond to chemotherapy, such as cellular senescence, enable evasion of intrinsic (e.g., apoptosis) and extrinsic, (e.g., immune mediated) mechanisms of cell death.
The Jackson Lab studies why some breast cancers respond poorly to treatment. Recent studies from our lab have shown that chemotherapy treated patients with breast cancers that were wild type for the tumor suppressor TP53 have much worse survival than patients with TP53 mutant tumors (Ungerleider et al, 2018). We showed that TP53 wild type tumors enter a program of arrest and cellular senescence that prevents the tumor cells from dying by apoptosis or mitotic catastrophe (Tonnessen-Murray et al, 2019-1; Jackson et al, 2012). Further research by our lab identified a novel phenotype used by some chemotherapy treated cells to survive and persist: senescent tumor cells engulf and break down neighboring cells (Tonnessen-Murray et al 2019-2; Frey et al 2022). We have recently identified how breast cancers activate programs of immune evasion to survive chemotherapy (Shahbandi et al, 2022).
1. Shahbandi A, Chiu FY, Ungerleider NA, Kvadas R, Mheidly Z, Sun MJS, Tian D,Waizman DA, Anderson AY, Machado HL, Pursell ZF, Rao SG, and Jackson JG. Breast cancer cells survive chemotherapy by activating targetable immune-modulatory programs characterized by PD-L1 or CD80. Nat Cancer 3, 1513–1533 (2022). https://doi.org/10.1038/s43018-022-00466-y
• Featured in Cancer Immunol Res (2023) 11 (4): 401–404
https://doi.org/10.1158/2326-6066.CIR-23-0051
• Spotlight article, Cancer Cell (2023) 41 (5) 831-833
https://doi.org/10.1016/j.ccell.2023.03.013
• Comment in npj Aging 9, 8 (2023). https://doi.org/10.1038/s41514-023-00105-52.
2. Frey WD, Anderson AY, Lee H, Nguyen JB, Cowles EL, Lu H, and Jackson JG. Phosphoinositide species and filamentous actin formation mediate engulfment by senescent tumor cells.PLoS Biology. (2022) Oct 24;20(10):e3001858. doi: 10.1371/journal.pbio.3001858.Online ahead of print. PMID: 36279312
3. Shahbandi A*, Rao SG*, Anderson AY, Frey WD, Olayiwola J, Ungerleider NA, and Jackson JG. BH3 mimetics selectively eliminate chemotherapy-induced senescent cells and improve response in TP53 wild-type breast cancer. Cell Death &Differentiation, (2020) 27: 3097–3116; online May 26, 2020;doi.org/10.1038/s41418-020-0564-6, PMID: 32457483 PMC7560696 *equal contribution
4. Tonnessen-Murray CA, Frey WD, Rao SG, Shahbandi A, Ungerleider NA, OlayiwolaJO, Murray LB, Vinson BT, Chrisey DB, Lord CJ, and Jackson JG .Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival. Journal of Cell Biology, (2019) Vol. 218, No. 11 3827–3844; Sept 17[Epub ahead of print]; PMID: 31530580 pii: jcb.201904051. DOI:10.1083/jcb.201904051.
• Covered by more than 24 news outlets
• Featured in a “Spotlight” article in Journal of Cell Biology, Oct 18, 2019,DOI: 10.1083/jcb.201910040
• Featured in Nature “News and Views” article, Oct 28, 2019; Nature 574, 635-636(2019); doi: 10.1038/d41586-019-03271-3
• Featured in “Spotlight” article in Trends in Cancer, November 05, 2019, doi:10.1016/j.trecan.2019.10.008
• Featured in an invited “Author’s View”, Molecular and Cellular Oncology, (DOI:10.1080/23723556.2019.1688601)
• Featured in Scientific American (By Kelso Harper, Jeffery Del Viscio on September 30, 2019)
• Featured in the NIH Director’s blog (Posted on October 29th, 2019 by Dr.Francis Collins)
TP53, p53, senescence, chemotherapy, breast cancer, mouse models, immunotherapy, resistance
