The paper identifies distinct proteostasis programs in fetal, neonatal, and adult hematopoietic stem cells, showing how proteostasis changes during development and impacts stem cell function.

bioRxiv · Dec 15, 2025 · PreprintDevelopmental Biology

Proteostasis Stress Drives Stem Cell Aging, Clonal Hematopoiesis and Leukemia

Fanny Zhou, Michelle K. Le, Helen C. Wang, Wei Yang, Huan‐You Wang, Arukshita Tiwari, Xinjian Cen, Mary Jean Sunshine, Jeffrey A. Magee, Robert A. J. Signer

This study identifies proteostasis stress as a driver of stem cell aging, clonal hematopoiesis, and leukemia by showing Hsf1's role in both physiological adaptation and pathological clonal expansion.

bioRxiv · Nov 27, 2025 · PreprintCancer Biology

The Proteostasis Network is a Therapeutic Target in Acute Myeloid Leukemia

Kentson Lam, Yoon Joon Kim, Evelyn L. Tan, Carlo M. Ong, Andrea Zoey Liu, Fanny Zhou, Mary Jean Sunshine, Bernadette Anne Chua, Silvia Vicenzi, Katelyn Chen, Helena Yu, Pierce W. Ford, Jiehua Zhou, Yuning Hong, Eric J. Bennett, , Robert A. J. Signer

This study shows that proteasome inhibitors are ineffective in AML due to activation of HSF1 and autophagy, and that combining autophagy and proteasome inhibition effectively kills AML cells.

Blood · Oct 20, 2025Peer-reviewedCancer Biology