Research Summary

I have a research focus in adoptive T cell therapy using chimeric antigen receptors (CARs) and checkpoint inhibitors. My current interest is on the design of next generation of CARs and combination checkpoint immunotherapy in the setting of a tolerant/suppressive tumor microenvironment in solid malignancies.

Translating recent advancements in cellular cancer immunotherapy to metastatic solid tumors has been especially challenging, and this is highlighted by the lack clinical response outside of the CD19 ideal antigen as target. Current forms of therapy is 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.

My hope is to see cancer immunotherapeutics become a mainstream form 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

Education

  • Medical School, Yale University
  • Internal Medicine Residency, The Mount Sinai Hospital
  • Medical Oncology Fellowship, UC San Francisco

Honors & Awards

  • Parker Institute for Cancer Immunotherapy Bridge Fellow Award, 2021-2024
  • Parker Institute for Cancer Immunotherapy Project Award, 2019-2021
  • A.P. Giannini Fellowship Award, 2017-2020
  • NIH Immunology T32, 2016-2017
  • American Cancer Society of Connecticut Research Award, 2008-2009
  • Farr Scholar Award for Leadership and Excellence in Biomedical Research, Yale University, 2007-2008
  • American Medical Association Seed Grant, 2006-2007
  • American Society of Hematology Trainee Award, 2006-2007

Selected Publications

  1. Sin JH, Kashyap S, Acenas D, Cortez JT, Lee J, Marson A, Matloubian M, Waterfield MR. ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8+ T Cell Effector and Memory Responses. J Immunol. 2022 03 01; 208(5):1155-1169.  View on PubMed
  2. Huppert LA, Green MD, Kim L, Chow C, Leyfman Y, Daud AI, Lee JC. Tissue-specific Tregs in cancer metastasis: opportunities for precision immunotherapy. Cell Mol Immunol. 2022 01; 19(1):33-45.  View on PubMed
  3. Lee JC, Green MD, Huppert LA, Chow C, Pierce RH, Daud AI. The Liver-Immunity Nexus and Cancer Immunotherapy. Clin Cancer Res. 2022 01 01; 28(1):5-12.  View on PubMed
  4. Lee JC, Mehdizadeh S, Smith J, Young A, Mufazalov IA, Mowery CT, Daud A, Bluestone JA. Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis. Sci Immunol. 2020 10 02; 5(52).  View on PubMed
  5. Levine LS, Mahuron KM, Tsai KK, Wu C, Mattis DM, Pauli ML, Oglesby A, Lee JC, Spitzer MH, Krummel MF, Algazi AP, Rosenblum MD, Alvarado M, Daud AI. Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma. Ann Surg Oncol. 2020 Oct; 27(11):4122-4130.  View on PubMed
  6. 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. 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 Immunol Immunother. 2019 Jul; 68(7):1087-1094.  View on PubMed
  7. Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, Lee J, Bluestone JA, Anderson M, Herold KC. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes. 2018 08; 67(8):1471-1480.  View on PubMed
  8. Loo K, Tsai KK, Mahuron K, Liu J, Pauli ML, Sandoval PM, Nosrati A, Lee J, Chen L, Hwang J, Levine LS, Krummel MF, Algazi AP, Pampaloni M, Alvarado MD, Rosenblum MD, Daud AI. Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy. JCI Insight. 2017 Jul 20; 2(14).  View on PubMed
  9. Holohan DR, Lee JC, Bluestone JA. Shifting the Evolving CAR T Cell Platform into Higher Gear. Cancer Cell. 2015 Oct 12; 28(4):401-402.  View on PubMed
  10. Lee JC*, Pegram HJ*, Hayman EG, Imperato GH, Tedder TF, Sadelain M, Brentjens RJ . Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood. 2012; 18(119):4133-41.  View on PubMed
  11. Lee JC, Hayman E, Pegram HJ, Santos E, Heller G, Sadelain M, Brentjens R. In vivo inhibition of human CD19-targeted effector T cells by natural T regulatory cells in a xenotransplant murine model of B cell malignancy. Cancer Res. 2011 Apr 15; 71(8):2871-81.  View on PubMed
  12. Santos EB, Yeh R, Lee J, Nikhamin Y, Punzalan B, Punzalan B, La Perle K, Larson SM, Sadelain M, Brentjens RJ. Sensitive in vivo imaging of T cells using a membrane-bound Gaussia princeps luciferase. Nat Med. 2009 Mar; 15(3):338-44.  View on PubMed
  13. Lee, James. 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.  View on PubMed
  14. Lee J, Sadelain M, Brentjens R. Retroviral transduction of murine primary T lymphocytes. Methods Mol Biol. 2009; 506:83-96.  View on PubMed

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