Yunhua Liu, Ph.D.
980 W. Walnut Street
Indianapolis, IN 46202
Phone: (317) 278-8194
Research Program Membership
Department of Medical and Molecular Genetics
IU School of Medicine
Dr. Liu's research interests include:
I started my research career as a graduate student at the Institut Pasteur of Shanghai, Chinese Academy of Sciences. During my graduate study, I successfully completed several projects to identify the novel molecular mechanisms of tumorigenesis of Kaposi’s sarcoma herpesvirus (KSHV). My graduate research resulted in several publications in major research journals and the scientific results provide novel insights to the research field of viral oncology (Virology 380 (2), 264-275; J Virol. 84 (4), 2047-2062; J Virol 86 (3), 1372-1381). After graduation, I joined the University of Texas, M.D. Anderson Cancer Center for postdoctoral training. During the first few years, I have been studying the roles of non-coding RNAs in homeostasis, the DNA damage response and tumorigenesis (Cell Signal 25(5):1086-95, 2013; Cell Rep 3(6):2100-12, 2013; EMBO J 32(21):2833-47, 2013; Cell Rep 8 (5), 1447-60, 2014). Recently, I have been working on the identification and development of therapeutic strategies for human cancers with hemizygous loss of TP53, which is frequently inactivated by mutation or deletion in a majority of human tumors. A tremendous effort has been made to restore p53 activity in cancer therapies. However, no effective p53-based therapy has been successfully translated into clinical cancer treatment due to the complexity of p53 signaling. Our recent studies demonstrated that concomitant deletion of POLR2A with TP53 creates a therapeutic vulnerability and targeting POLR2A provides an effective treatment strategy (Nature 520 (7549), 697-701, 2015). I anticipate that inhibiting POLR2A will be a novel therapeutic approach for all human cancers harboring such common genomic alterations (BioEssays. 2015;37(12):1277-86; Future Oncol. 2015;11(23):3101-4.). There is already a discussion regarding the potential for initiation of a clinical trial based on my work. This study was also highlighted and commented in several prestigious journals, including Nat. Rev. Cancer, Nat. Rev. Clin. Oncol., and Cancer Discov. In addition, my study was also featured and commented in “Cancer Currents Blog”, a National Cancer Institute (NCI)-based Cancer Research Blog. Based on what we achieved in the last few years, I will, in future, continue to identify and develop novel strategies to target human cancers with common tumor suppressor alterations, such TP53, PTEN, SMAD4 and NF1. I anticipate that my studies will provide a novel and effective therapeutic strategy in human colorectal cancer treatment. The principle of collateral vulnerability to the POLR2A inhibition is also applicable to other types of human tumors possessing hemizygous loss of TP53, such as liver (62.7%), ovarian (74.9%), pancreas (53.8%), lung (59.6%), breast (60.4%), esophageal (45.1%) and stomach (36.6%) cancer. In particular, I will aim to further develop and optimize our current strategy (alpha-amanitin-based-antibody-drug conjugates, AADCs) to treat over half of human cancers with TP53 loss either alone or in combination with chemo- or immune-therapy.
Post-doctoral Fellowship - MD Anderson Cancer Center, Houston, TX 11/2011-06/2017
Ph.D. - Insitut Pasteur of Shangahi, Chinese Academy of Sciences 09/2006-08/2011