James Lee, MD
Assistant Professor
Radiation Oncology
School of Medicine

I now lead a lab with a research focus on improving checkpoint inhibitors and adoptive T cell therapy using chimeric antigen receptors (CARs) to cure metastatic solid tumors. My research expertise is in the design of the next generation of CARs and combination checkpoint immunotherapy using immunocompetent mouse models that best mimic the clinic, in the setting of a tolerant/suppressive tumor microenvironment in solid malignancies and cancer metastasis.

Translating recent advancements in cellular cancer immunotherapy to metastatic solid tumors has been especially challenging, and this is highlighted by the lack of clinical response outside of the CD19 ideal antigen as the target. Current forms of therapy are likely insufficient to overcome the naturally tolerogenic microenvironment evolved to protect against autoimmunity across organ sites. Using the liver as a model organ of immune tolerance, we discovered the putative mechanisms of tumor escape to checkpoint inhibitor therapy in the setting of liver metastases and are now working on developing strategies to overcome them.

I hope to see cancer immunotherapeutics become a mainstream form of treatment that is capable of providing durable and curative responses for stage IV cancers.

Past Professional Experience:

Clinical Instructor, Memorial Sloan-Kettering Cancer Center, New York, NY. July 2012-July 2013

Clinical Instructor, University of California, San Francisco, CA. July 2013-July 2014

Education:

Medical School: Yale School of Medicine, New Haven, CT. September 2003-May 2009

Research Fellowship: Memorial Sloan-Kettering Cancer Center, New York, NY. 2006-2009.

Residency: Mount Sinai Medical Center, New York, NY. July 2009-June 2012

ABIM Board Certifications:

Internal Medicine. 2012

Medical Oncology. 2021

• ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8+ T Cell Effector and Memory Responses.
  Journal of immunology (Baltimore, Md. : 1950) 2022 Sin JH, Kashyap S, Acenas D, Cortez JT, Lee J, Marson A, Matloubian M, Waterfield MR
• XYZeq: Spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment.
  Science advances 2021 Lee Y, Bogdanoff D, Wang Y, Hartoularos GC, Woo JM, Mowery CT, Nisonoff HM, Lee DS, Sun Y, Lee J, Mehdizadeh S, Cantlon J, Shifrut E, Ngyuen DN, Roth TL, Song YS, Marson A, Chow ED, Ye CJ
• Novel circulating tumor cell-based blood test for the assessment of PD-L1 protein expression in treatment-naïve, newly diagnosed patients with non-small cell lung cancer.
  Cancer immunology, immunotherapy : CII 2019 Chen YL, Huang WC, Lin FM, Hsieh HB, Hsieh CH, Hsieh RK, Chen KW, Yen MH, Lee J, Su S, Marfatia T, Chang SE, Sundar P, Patterson B, Watson D, Mei R, Javey M
• Cytokines, Chemokines, and Other Biomarkers of Response for Checkpoint Inhibitor Therapy in Skin Cancer.
  Frontiers in medicine 2018 Bridge JA, Lee JC, Daud A, Wells JW, Bluestone JA
• Maintenance of macrophage transcriptional programs and intestinal homeostasis by epigenetic reader SP140.
  Science immunology 2017 Mehta S, Cronkite DA, Basavappa M, Saunders TL, Adiliaghdam F, Amatullah H, Morrison SA, Pagan JD, Anthony RM, Tonnerre P, Lauer GM, Lee JC, Digumarthi S, Pantano L, Ho Sui SJ, Ji F, Sadreyev R, Zhou …
• Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning
  Blood. 2012 Lee JC*, Pegram HJ*, Hayman EG, Imperato GH, Tedder TF, Sadelain M, Brentjens RJ
• Inventing New CARs: Analysis of Chimeric Antigen Receptor Gene-Targeted T cells Modified to Overcome Regulatory T cell Suppression in the Tumor Microenvironment. Yale University MD Thesis
  Inventing New CARs: Analysis of Chimeric Antigen Receptor Gene-Targeted T cells Modified to Overcome Regulatory T cell Suppression in the Tumor Microenvironment. Yale University MD Thesis. 2009 Lee, James