CIS Program Event: GuangJun Zhang

DNA damage repair defects and its therapeutic potential in MPNST tumorigenesis

Dr. GuangJun Zhang, John T. and Winifred M. Hayward Professor, in the Department of Comparative Pathobiology at Purdue University, will be a speaker for the PICR Seminar Series.

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive sarcomas with poor prognosis and a strong tendency for metastasis and relapse. Surgical removal remains the mainstay of treatment but is frequently ineffective or impractical. Currently, no effective targeted therapy exists for this type of malignancy, highlighting the urgent need for novel and efficient therapeutic targets. Using a zebrafish model, we have identified smarcad1 as a new tumor suppressor gene, and it plays important roles in DNA damage repair in both zebrafish and human cells. In addition, we found that there is increased PRMT5 expression and activity in MTAP loss MPNSTs. PRMT5 inhibition led to DNA damage accumulation following G2/M cell cycle arrest in MTAP-low MPNST cell lines. Furthermore, we found that the combination treatment of PRMT5 inhibitors with doxorubicin and gemcitabine presented synergistic effects, respectively. Therefore, these findings suggested that Smarcad1 and PRMT5 are potential therapeutic targets for MPNSTs.

The event is hosted by Majid Kazemian.