Research in the Wang laboratory is focused on the cell death response to genotoxic stress.
Our previous work focused on how nuclear ABL tyrosine kinase and the retinoblastoma tumor suppressor (RB) regulate the cell-death response to stress. Using molecular cell biology, functional genomics and mouse genetics approaches, we have established that nuclear ABL tyrosine kinase stimulates apoptosis whereas RB suppresses apoptosis in response to DNA damage and tumor necrosis factor. Our findings challenge the dogma that oncoproteins, such as ABL, only promote cell proliferation/survival, whereas tumor suppressors, such as RB, only promote cell death, while providing ex vivo and in vivo evidence for the concept that signal transducers (ABL) and transcription regulators (RB) do not have deterministic functions, instead, they are designed to support a variety and at times contradictory signal outputs, dictated by the context in which they are recruited to serve.
Currently, we focus on two lines of research: (a) to investigate how replication-associated DNA damage triggers cell death, and (b) to investigate how cancer cells suppresses the translation of pro-apoptosis proteins to escape therapy-induced death.
Research Focus Areas:
Signal Transduction | DNA Replication and Repair
Guo E, Ishii Y, Mueller J, Srivatsan A, Gahman T, Putnam CD, Wang JYJ, Kolodner RD. FEN1 endonuclease as a therapeutic target for human cancers with defects in homologous recombination. Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19415-19424. doi: 10.1073/pnas.2009237117. Epub 2020 Jul 27. PMID: 32719125; PMCID: PMC7431096.
Wang JYJ. Cell Death Response to DNA Damage. Yale J Biol Med. 2019 Dec;92(4):771-779. eCollection 2019 Dec. Review. PMID: 31866794; PMCID: PMC6913835.
Rastogi S, Hwang A, Chan J, Wang JYJ. Extracellular vesicles transfer nuclear Abl-dependent and radiation-induced miR-34c into unirradiated cells to cause bystander effects. Mol Biol Cell. 2018 Sep 1;29(18):2228-2242. doi: 10.1091/mbc.E18-02-0130. Epub 2018 Jul 5. PMID: 29975106; PMCID: PMC6249796.
Tu CC, Zhong Y, Nguyen L, Tsai A, Sridevi P, Tarn WY, Wang JY. The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage. Sci Signal. 2015 Jun 30;8(383):ra64. doi: 10.1126/scisignal.aaa4468. PMID: 26126715; PMCID: PMC4499470.
Wang JY. The capable ABL: what is its biological function?. Mol Cell Biol. 2014 Apr;34(7):1188-97. doi: 10.1128/MCB.01454-13. Epub 2014 Jan 13. Review. PMID: 24421390; PMCID: PMC3993570.