Principal Investigator Dr. med. Dieter A. Wolf

• Dr. med. Dieter A. Wolf (PI)
• Yanzhu Hu (PhD student)
• Dan Su (PhD student)

Our research focusses on basic mechanisms of protein and energy homeostasis, their role in tumorigenesis, and their utility as cancer drug targets. Our work has concentrated on conserved pathways regulating protein homeostasis and associated stress response pathways. We have been pursuing these lines of investigation in human cell lines as well as in genetic models ranging from yeast to the mouse. Current projects are geared toward deciphering energy and protein metabolism as mutually intertwined processes critical for the generation of biomass from nutrients – and thus the growth and proliferation of cancer cells. We concentrate on mitochondrial complex I and the translation initiation factor eIF3, two macromolecular complexes at the cross-roads of these processes. Much remains to be learned about their exact functions and integration in cancer. Our goal over the next 5 – 10 years is to advance our functional understanding of these complexes to the point where we can develop strategies for rationally interfering with their essential roles in tumorigenesis.

• Jain S, Hu C, Kluza J, Ke W, Bleilevels A, Tian G, Giurgiu M, Campos AR, Charbono A, Stickeler E, Maurer J, Holinski-Feder E, Vaisburg A, Bureik M, Luo G, Marchetti P, Cheng Y, Wolf DA. Targeting cancer metabolism through a ubiquinone uncompetitive inhibitor of mitochondrial complex I. (2022) Cell Chemical Biology, 29:436-450
• Tian G, Hu Cheng, Yun Y, Yang W, Dubiel W, Cheng Y, Wolf DA. Dual roles of HSP70 chaperone HSPA1 in promoting quality control of nascent and newly synthesized proteins. (2021) EMBO J., e106183
• Wang J, Dubiel D, Wu Y, Cheng Y, Wolf DA, Dubiel W. CSN7B defines a variant COP9 signalosome complex with distinct function in DNA damage response. (2021) Cell Reports, 34: 108662
• Lin Y, Li F, Huang L, Polte C, Duan H, Fan J, Sun L, Xing X, Tian G, Cheng Y, Ignatova Z, Yang X, Wolf DA. eIF3 associates with 80S ribosomes to promote translation elongation, mitochondrial homeostasis, and muscle health. (2020) Molecular Cell 79, 1-13
• Wolf DA, Lin YY, Duan H, Cheng Y eIF-Three to tango: Emerging functions of translation initiation factor eIF3 in protein synthesis and disease. (2020) Journal of Molecular Cell Biology 12, 403-409
• Shah M, Su D, Scheliga JS, Pluskal T, Boronat S, Shah M, Motamedchaboki K, Campos AR, Qi F, Yanagida M, Wolf DA. A transcript-specific eIF3 complex mediates global translational control of energy metabolism (2016), Cell Reports 16:1891-1902
• Wolf DA. Is reliance on mitochondrial respiration a "chink in the armor" of therapy-resistant cancer? (2014), Cancer Cell 26:788-795