Department of Cancer Biology
Zihua Gong, M.D., Ph.D.
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 445-9652
Fax: (216) 445-6269
Our laboratory is interested in understanding the molecular mechanisms underlying DNA repair pathway choice. BRCA1 and BRCA2 mutations are prevalent in familial breast and ovarian cancers. Cells with BRCA1 and BRCA2 mutations are exquisitely sensitive to PARP inhibitors (PARPi). However, treatment of BRCA mutant cancers with PARPi is not curative, and resistance to therapy is a major clinical problem. Our study investigates the mechanism on the competition and coordination of different DNA repair pathways, and uncovers key components in these pathways that we can explore to improve cancer therapy and overcome therapeutic resistance.
In other words…
Genomic instability caused by impaired DNA damage response and/or DNA repair is a triple-edged sword. On one hand, it is a driving force for tumorigenesis. On the other hand, defective DNA damage repair renders tumor cells more sensitive to DNA damaging agents, and thus allows for the use of radiation and many chemotherapeutic agents that induce DNA damage in clinic for cancer treatment. We are working on better understand the underlying mechanism on regulation of DNA repair pathway choice and resistance to PARP inhibition in BRCA1 mutant cancers, which are critical to develop new therapeutic strategies for cancer patients.
- Zhang A, Peng B, Huang P, Chen J*, Gong Z*. The p53-binding protein 1-Tudor-interacting repair regulator complex participates in the DNA damage response. J Biol Chem. 2017 Apr 21; 292 (16):6461-6467
- Chen Z, MyTran K, Tang MF, Wang W, Gong Z*, Chen J*. Proteomic Analysis Reveals a Novel MutS Partner Involved in Mismatch Repair Pathway. Molecular & Cellular Proteomics 15(4):1299-308.e-Pub 4/2016.PMID: 27037360
- Wang J, Aroumougame A, Lobrich M, Li Y, Chen D, Chen J*, Gong Z*. PTIP associates with Artemis to dictate DNA repair pathway choice. Genes Dev 28 (24): 2693-8. e-Pub 12/2014. PMID:25512557
- Wang J, Chen J*, Gong Z*. TopBP1 Controls BLM Protein Level to Maintain Genome Stability. Mol Cell 52(5): 667-78. e-Pub 11/2013.
- Gong Z, Chen J. E3 ligase RFWD3 participates in replication checkpoint control. J Biol Chem 286(25):22308-13, 6/2011. e-Pub 4/2011. PMCID: PMC3121377
- Wang J1, Gong Z1, Chen J. MDC1 collaborates with TopBP1 in DNA replication checkpoint control. J Cell Biol 193(2):267-73, 4/2011. e-Pub 4/2011. (1 these authors contributed equally to this work). PMCID: PMC3080258.
- Gong Z, Kim, JE, Leung, CC, Glover, JM, Chen J. BACH1/FANCJ acts with TopBP1 and participates early in DNA replication checkpoint control. Mol Cell 37(3):438-46, 2/2010. PMID: 20159562.
- Huang J1, Gong Z1, Ghosal G, Chen J. SOSS cooperates with RPA to maintain genomic stability. Mol Cell 5(3):384-93, 8/2009.(1 these authors contributed equally to this work). PMCID: PMC2756616.
- Gong Z, Cho YW, Kim JE, Ge K, Chen J. Accumulation of Pax2 Transactivation Domain Interaction Protein (PTIP) at Sites of DNA Breaks via RNF8-dependent Pathway Is Required for Cell Survival after DNA Damage. J Biol Chem 284(11):7284-93, 3/2009. e-Pub 1/2009. PMCID: PMC2652327