Chi Yan, PhD

Research summary

My lab develops novel therapeutic strategies to improve outcomes for patients with metastatic melanoma, triple-negative breast cancer (TNBC), and other aggressive solid tumors. A central challenge in cancer treatment is overcoming resistance to immune checkpoint blockade (ICB; e.g., anti-PD1/CTLA4/LAG3) and targeted therapies. We investigate how rational combination therapies can remodel the tumor-immune microenvironment to enhance antitumor immunity while suppressing escape mechanisms.

Our translational approach integrates patient-derived models (xenografts, organoids) with immunocompetent and humanized mouse models to bridge preclinical and clinical research. Current projects explore:

• CD40 agonism to overcome ICB resistance by reinvigorating immune responses
• Small-molecule inhibitors targeting oncogenic pathways (e.g., RAS/RAF/MEK, PI3K/AKT/mTOR) and their synergy with ICB
• Cytokine/chemokine pathways (e.g., CXCR2) in modulating ICB response and resistance
• The development and immunosuppressive role of regulatory B cells (Bregs) in therapy-resistant tumors and inflammatory diseases.

By elucidating resistance mechanisms and identifying actionable targets, we aim to develop more durable therapies for hard-to-treat cancers and inflammatory diseases.

Dr. Chi Yan is an assistant professor in the Department of Immunology at the University of Manitoba and a member of the Paul Albrechtsen Research Institute at CancerCare Manitoba. His translational research focuses on overcoming resistance to cancer immunotherapy through innovative combination therapies.

Dr. Yan earned his MSc in molecular biology and bioinformatics at Saint Mary's University and his PhD in cancer immunology at Dalhousie University. As a Postdoctoral Fellow in Dr. Ann Richmond's lab at Vanderbilt University (2018-2020), he pioneered research on rigosertib, a RAS-pathway inhibitor, demonstrating its synergy with immune checkpoint blockade (ICB) in melanoma. This work, published in Molecular Cancer (2021), led to an investigator-initiated Phase IIb trial (NCT05764395) for ICB-resistant melanoma, for which he leads correlative studies through a Vanderbilt-Ingram Cancer Center Support Grant.

During his appointments as research instructor (2020) and research assistant professor (2021) in the Department of Pharmacology at Vanderbilt, Dr. Yan identified that residual disease persists due to incomplete ERK inhibition, securing a Henry J. Lloyd Foundation Career Development Grant (2022-2024) to explore MEK inhibition strategies. As a junior faculty, he established an independent program investigating the crosstalk between CD40 agonism and regulatory B cells (Bregs), with potential applications in both cancer and inflammatory diseases, while publishing 12 first/senior-author papers in high-impact journals (e.g., Molecular Cancer, Journal of Clinical Investigation, Cancer Letters).

At UM (2025–present), Dr. Yan’s team investigates next-generation molecular and cellular targets for cancer and inflammatory diseases through cross-disciplinary collaborations with clinicians, pathologists, biostatisticians, and industry partners. The lab employs cutting-edge platforms:

• Multi-omics profiling (scRNA-Seq, TCR-Seq, RPPA, protein arrays)
• Spatial biology (GeoMx IO proteome atlas, multiplex IHC)
• High-dimensional immunophenotyping (30+ parameter flow cytometry)

By bridging preclinical discovery and clinical translation, Dr. Yan’s research program aims to transform resistant cancers into treatable diseases through rationally designed immunotherapy combinations.

Education

• Research Assistant Professor, Vanderbilt University (2021)
• Research Instructor, Vanderbilt University (2020)
• Postdoctoral Fellowship, Vanderbilt University (2018)
• Postdoctoral Fellowship, Dalhousie University (2017)
• Doctor of Philosophy in Cancer Immunology, Dalhousie University (2017)
• Master of Science in Molecular Biology and Bioinformatics, Saint Mary's University (2011)
• Bachelor of Engineering in Biology, HuaZhong Agricultural University (2008)

Awards

NIH/NCI R01 CA116021 (09/01/2023-09/30/2025). New strategies for treatment of NRAS mutant melanoma after progression on immune checkpoint inhibitors

NIH/NCI R01 CA243326 (09/01/2023-05/31/2025). Optimizing response to immune checkpoint inhibitor therapy for breast cancer

Vanderbilt-Ingram Cancer Center and The Reynolds Foundation Support Grant 30CA068485 (05/01/2023-06/30/2025). Rigosertib and pembrolizumab in anti-PD-1 refractory melanoma

Lloyd Foundation Melanoma Research Career Development Grant (06/01/2022-05/30/2024). Rigosertib plus trametinib in metastatic melanoma refractory to immune checkpoint blockade

AAI Early Career Faculty Travel Grant (2022, 2024)

Doctoral Thesis Award for “the Best Doctoral Thesis in the 2017 Calendar Year”, Dalhousie University (2018)

Graduate Fellowship from IWK Health Center (2013-2015)

Graduate Fellowship from CRTP-BHCRI in Cancer Research at CIHR (2011-2013)

Graduate Fellowship, Saint Mary's University (2009-2011)