In vivo Forward Genetic Screens to Identify Immunotherapy Resistance Mechanisms and Synergistic Treatment Combinations for Cancer

2021 Emerging Leader Award

Hao Zhu, MD, Children’s Medical Center Research Institute at UT Southwestern

Hao Zhu, MD

Dr. Zhu’s lab develops mouse models of hepatobiliary cancers. He has pioneered in vivo pooled CRISPR screening approaches to identify novel biological pathways, with the goal of dissecting the relationship between cancer and regeneration. With this project, he is applying these technologies to the problem of resistance to immune checkpoint inhibitors. This work focuses on identifying genes that promote or inhibit immune clearance of tumors in the presence of immune checkpoint inhibitors. By performing iterative screens with understudied candidate pools and subsequently validating the most promising hits, Dr. Zhu hopes to identify therapeutic approaches to increase the effectiveness of immune checkpoint inhibitors across different types of cancer.

Dr. Zhu earned his bachelor’s degree in biology from Duke University, followed by an MD from Harvard Medical School and MIT. He underwent training in internal medicine at University of California, San Francisco and medical oncology at the Dana-Farber Cancer Institute. Dr. Zhu’s lab is focused on understanding the connections between tissue injury, regeneration, and cancer.


Jia Y, Li L, Lin Y, Gopal P, Shen S, Zhou K, Yu X, Sharma T, Zhang Y, Siegwart DJ, Ready DM, Zhu H. In vivo CRISPR screening identifies BAZ2 chromatin remodelers as druggable regulators of mammalian liver regeneration. Cell Stem Cell. 2022.

Karalis JD, Yoon LY, Hammer STG, Hong C, Zhu M, Nassour I, Ju MR, Xiao S, Castro-Dubon EC, Agrawal D, Suarez J, Reznik SI, Mansour JC, Polanco PM, Yopp AC, Zeh HJ 3rd, Hwang TH, Zhu H, Porembka MR, Wang SC. Lenvatinib inhibits the growth of gastric cancer patient-derived xenografts generated from a heterogeneous population. J Transl Med. 2022.

Zhang D, Wang G, Yu X, Wei T, Farbiak L, Johnson LT, Taylor AM, Xu J, Hong Y, Zhu H, Siegwart DJ. Enhancing CRISPR/Cas gene editing through modulating cellular mechanical properties for cancer therapy. Nat Nanotechnol. 2022.

Wang Z, Zhu S, Jia Y, Wang Y, Kubota N, Fujiwara N, Gordillo R, Lewis C, Zhu M, Sharma T, Li L, Zeng Q, Lin YH, Hsieh MH, Gopal P, Wang T, Hoare M, Campbell P, Hoshida Y, Zhu H. Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease. Cell. 2023.

Lin YH, Wei Y, Zeng Q, Wang Y, Pagani CA, Li L, Zhu M, Wang Z, Hsieh MH, Corbitt N, Zhang Y, Sharma T, Wang T, Zhu H. IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration. Cell Stem Cell. 2023.

Rong R, Wei Y, Li L, Wang T, Zhu H, Xiao G, Wang Y. Image-based quantification of histological features as a function of spatial location using the Tissue Positioning System. EBioMedicine. 2023.

Lin YH, Zeng Q, Jia Y, Wang Z, Li L, Hsieh MH, Cheng Q, Pagani CA, Livingston N, Lee J, Zhang Y, Sharma T, Siegwart DJ, Yimlamai D, Levi B, Zhu H. In vivo screening identifies SPP2, a secreted factor that negatively regulates liver regeneration. Hepatology. 2023.