Yu Leo Lei, D.D.S., Ph.D.

Assistant Professor of Dentistry, Dept. of Periodontics and Oral Medicine
Assistant Professor of Otolaryngology- Head and Neck Surgery
U-M Rogel Cancer Center
Accepting Students


Dr. Lei is a cancer immunologist - pathologist. He is an Assistant Professor in the Cancer Biology Program at the University of Michigan Rogel Cancer Center. He is a faculty member of the PIBS Doctoral Program in Cancer Biology and Doctoral Program in Immunology. Dr. Lei received his Ph.D. training at the Lineberger Comprehensive Cancer Center, UNC-Chapel Hill and oral pathology residency training at the University of Pittsburgh Medical Center. He completed a Head and Neck Oncology research fellowship at the University of Pittsburgh Cancer Institute. He served as a research track faculty member at the Department of Otolaryngology University of Pittsburgh School of Medicine before he was recruited to Michigan.

Dr. Lei’s research program has identified main oncogenic regulators of the STING-type I interferon pathway and developed unique immunocompetent mouse models to characterize antigen-presenting cell and T-cell phenotype among tumor-infiltrating immune cells. In collaboration, his group utilizes advanced nano-engineering technologies to deliver robust immune adjuvants for cancer vaccines.Dr. Lei’s research has been published in well-respected journals, such as Immunity, Clinical Cancer Research, Oncogene and Cancer Research. He received numerous awards such as the Joseph Lister Award First Place, the Leon Barnes award from the United States and Canadian Academy of Pathology and the NIH Dentist-Scientist Pathway to Independence Award.

Research Interests

Pattern Recognition Receptors (PPRs) constitute the first line of defense against “non-self” antigens, which are encountered during microbial infections and cancer development. With the characterization of new PRR families, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs) and cGAS-STING-mediated cytoplasmic DNA-sensing molecules, novel regulatory mechanisms of PRR signaling are rapidly emerging as main cancer immune escape mechanisms. We pioneered in the identification of novel PRR regulators. Our laboratory has developed a unique collection of toolkits in the following areas.

**Mechanisms Regulating Cancer Immune Escape** Emerging evidence suggests that PRR not only detect molecular structures associated with pathogens but those linked to cellular and tissue damage. Due to increased genome instability in cancer cells and chemoradiation therapy, PRR-mediated sensing of cytoplasmic DNA, a classic danger signal for cellular damage, triggers the production of chemokines that recruit immune cells to the tumor bed. But this process is frequently suppressed by squamous cell carcinomas, leading to immune escape. We are among the first to show that oncogenic signaling in squamous cell carcinomas suppresses PRRs as a key mechanism driving T-cell exclusion.

**Immunogenomics Approaches to Identify Cold Cancer** With the emerging combinatorial strategies for cold cancer, precise identification of this group of tumors is essential for the selection of optimal treatment protocols. In collaboration with a computational geneticist, we have developed a robust and novel immune-cell deconvolution machine learning tool to map the landscape of tumor-infiltrating lymphocytes. **Immune Engineering Strategies to Sensitize Cold Cancer to Immune Checkpoint Blockade** Cold cancers are featured by insufficient elicitation of tumor-specific T-cell immunity. In order to expand the tumor-specific CD8+ T-cell repertoire, our group utilizes advanced nanotechnologies to deliver and optimize the intra-lesional immune microenvironment. For example, we have shown that our nano-vaccines can sensitize cold tumors to immunotherapy, and a combination of nano-vaccines with checkpoint blockade leads to significantly expanded tumor-specific effector T cells, reduced T-cell exhaustion and better tumor control.


Research Opportunities for Rotating Students

We have active projects to study tumor cell-immune cell interaction for rotation students, and welcome any inquiry regarding the project details.


Current Student Advisees