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Where Passion Meets Discovery: Yi Bao, PhD’s Path to Research Investigator

By Lynn McCain | March 3

Dr. Yi Bao“I watched a family member go through chemotherapy for lung cancer. It was incredibly painful for them, and ultimately, the treatment only extended their life for a few months. A few years ago, I watched them pass away from the disease. That experience drove me to pursue a PhD in cancer biology.”

Yi Bao, PhD, completed his undergraduate education at South China Agricultural University and then earned a Master of Science degree at the University of Sheffield in England. Afterward, he relocated to Singapore and worked as a research officer for 3 or 4 years. His family member’s passing solidified his commitment to cancer research, and he began his PhD training at the National University of Singapore, graduating in 2020. “My major was cancer biology. I’ve been focused on cancer research since my time as a research officer.”

During his PhD, Bao joined the lab of Dr. Qiang Yu, a breast cancer researcher, where he studied HER2-positive breast cancer. He discovered that the tumor suppressor EZH2 is epigenetically downregulated by PP2R2B. “If you target that epigenetic regulation by inhibiting EZH2 using a clinically available EZH2 inhibitor, PP2R2B is restored. As a result, HER2+ breast cancer cells become susceptible to anti-HER2 treatments both in vitro and in vivo, slowing tumor growth. Bao’s work was published in Nature Communications, one of the leading research journals.

Near the end of his PhD program, Dr. Yu introduced him to his close friend and collaborator, Dr. Arul Chinnayan. “Dr. Yu suggested I reach out about joining his lab for postdoctoral training. He welcomed me in 2021.” In the Chinnaiyan lab, Bao focused on immunology and epigenetics. “Immunotherapies are promising, and some patients experience durable responses. But we still don’t fully understand why many patients remain resistant. Our work aims to overcome that resistance so more patients can benefit from immunotherapy, experience a durable response, and have long-term survival.”

To advance these efforts, Bao began collaborating with Dr. Weiping Zou. Together, they discovered that cancer cells often downregulate MHC-I to evade antitumor immunity. Further, therapeutically targeting PIKfyve to upregulate surface expression of MHC-I in cancer cells enhances the response to immunotherapies across various cancer types, including those that are often unresponsive, such as pancreatic cancer. This is an extremely exciting finding with great potential for cancer patients (Bao et al., 2023).

Their work continued to uncover new immunotherapy regulators. They found that elevated levels of ubiquitin-like modifier-activating enzyme 1 (UBA1) predict immunotherapy resistance and poor survival. Inhibition of UBA1 with TAK-243 markedly suppressed tumor growth. Moreover, inactivation of UBA1 significantly improved responses to cancer immunotherapies. (Bao et al. J Can Res 2025)

Dr. Yi Bao performs an experiment.They also discovered that inactivation of CDK12/13 triggers STING-mediated antitumor immunity. STING activation drives T cell infiltration and an immune-hot tumor microenvironment in CDK12 mutant cancers. This work suggests that dual CDK12/13 inhibitors or degraders activate antitumor immunity and enable responses to immunotherapies (Bao et al., JCI, 2025)

In October 2025, Bao completed his postdoctoral training and was promoted to Research Investigator. “In addition to conducting my research, I now train PhD students and other trainees. I guide their experiments, attend meetings, and teach them how to design experiments and think like scientists. I’m also preparing three grant applications due in the next month and writing several manuscripts.” He recently filed a US patent application and expects to submit multiple additional grants in the coming years. “Hopefully, we will secure funding soon. That is essential for growing my team and advancing our work. My goal is to become an Assistant Professor and start my own lab in the next two to three years.”

Bao takes great pride in his trainees’ accomplishments. “During my PhD, I trained two master’s students. One is now a PhD candidate at an excellent university, and the other is doing very well in industry.”

Outside the lab, Bao enjoys soccer and photography. “I have less time now, but I still enjoy going to my favorite coffee shop in the morning before work. And I love eating fruit with salt on it – a strange habit to many.”

Bao is modest in calling soccer a hobby. In high school, he represented his city on the provincial team in China and was among the top players in his region. He also enjoys basketball and often spends time with his colleague and fellow basketball enthusiast, Jie Luo, PhD. “He often invites me to his home for dinner and to hang out. He’s a really nice guy.”

Please join us in welcoming Dr. Yi Bao to our faculty ranks!

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Citations:

Bao, Y., Oguz, G., Lee, W.C. et al. EZH2-mediated PP2A inactivation confers resistance to HER2-targeted breast cancer therapy. Nat Commun 11, 5878 (2020). https://doi.org/10.1038/s41467-020-19704-x

  1. Bao, Y. Qiao, J.E. Choi, Y. Zhang, R. Mannan, C. Cheng, T. He, Y. Zheng, J. Yu, M. Gondal, G. Cruz, S. Grove, X. Cao, F. Su, R. Wang, Y. Chang, I. Kryczek, M. Cieslik, M.D. Green, W. Zou, A.M. Chinnaiyan. Targeting the lipid kinase PIKfyve upregulates surface expression of MHC class I to augment cancer immunotherapy, Proc. Natl. Acad. Sci. U.S.A.120 (49) e2314416120, https://doi.org/10.1073/pnas.2314416120 (2023).

Yi Bao, Gabriel Cruz, Yuping Zhang, Yuanyuan Qiao, Rahul Mannan, Jing Hu, Fan Yang, Mahnoor Gondal, Miraian Shahine, Sarah Kang, Somnath Mahapatra, Alec Chu, Jae Eun Choi, Jiali Yu, Heng Lin, Stephanie J. Miner, Dan R. Robinson, Yi-Mi Wu, Yang Zheng, Xuhong Cao, Fengyun Su, Fui Wang, Noshad Hosseini, Marcin Cieslik, Ilona Kryczek, Ulka Vaishampayan, Weiping Zou, Arul M. Chinnaiyan. The UBA1-STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade. Cancer Discov 15(2):363-381 (2025). https://doi.org/10.1158/2159-8290.CD-24-0435

Yi Bao, Yu Chang, Jean Ching-Yi Tien, Gabriel Cruz, Fan Yang, Rahul Mannan, Somnath Mahapatra, Radha Paturu, Xuhong Cao, Fengyun Su, Rui Wang, Yuping Zhang, Mahnoor Gondal, Jae Eun Choi, Jonathan K. Gurkan, Stephanie J. Miner, Dan R. Robinson, Yi-Mi Wu, Licheng Zhou, Zhen Wang, Ilona Kryczek, Xiaoju Wang, Marcin Cieslik, Yuanyuan Qiao, Alexander Tsodikov, Weiping Zou, Ke Ding, Arul M. Chinnaiyan. CDK12/13 Inactivation Triggers STING-Mediated Antitumor Immunity in Preclinical Models. J Clin Invest. 135(18):e193745 (2025) https://doi.org/10.1172/JCI193745

 
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