Mark N. Lee, MD, PhD
Research & Publications
Biography
Locations
Research Summary
The Lee lab develops and applies high-throughput genomic technologies to interrogate the function of infiltrating immune cells in tumors and in autoimmune/alloimmune patient specimens. Work in the lab lies at the intersection of human immunology, immunogenetics, and functional genomics. The lab collaborates with physicians and partners with patients to collect primary samples; characterizes variation in immune genes using next-generation and single-cell sequencing; and uses a combination of high-throughput functional genomics, immunology, and molecular biology to interrogate gene and variant function down to the molecular level. Major goals of the lab include: uncovering the pathophysiology of autoimmune diseases by identifying self-reactive antigens, designing new T cell receptor-based therapies for cancer patients, and designing novel antigen-based therapies for patients with alloimmune diseases.
Coauthors
Research Interests
Antigenic Variation; Antigens; Autoimmune Diseases; Hematologic Diseases; Immune System Diseases; Immunologic Memory; Immunotherapy; Lymphocyte Activation; Major Histocompatibility Complex; Neoplasms; Neoplastic Processes; Pathology; Pathology, Clinical; Gene Rearrangement, T-Lymphocyte; Autoimmunity; Genomics; T-Cell Antigen Receptor Specificity; Adaptive Immunity; Immune Evasion; Tumor Microenvironment; Clonal Selection, Antigen-Mediated; Molecular Medicine; Biological Variation, Individual; Immune Checkpoint Inhibitors; Translational Science, Biomedical
Selected Publications
- Antigen identification for HLA class I- and HLA class II-restricted T cell receptors using cytokine-capturing antigen-presenting cells.Lee MN, Meyerson M. Antigen identification for HLA class I- and HLA class II-restricted T cell receptors using cytokine-capturing antigen-presenting cells. Science Immunology 2021, 6 PMID: 33483338, PMCID: PMC8320540, DOI: 10.1126/sciimmunol.abf4001.
- Genetic analysis of isoform usage in the human anti-viral response reveals influenza-specific regulation of ERAP2 transcripts under balancing selection.Ye CJ, Chen J, Villani AC, Gate RE, Subramaniam M, Bhangale T, Lee MN, Raj T, Raychowdhury R, Li W, Rogel N, Simmons S, Imboywa SH, Chipendo PI, McCabe C, Lee MH, Frohlich IY, Stranger BE, De Jager PL, Regev A, Behrens T, Hacohen N. Genetic analysis of isoform usage in the human anti-viral response reveals influenza-specific regulation of ERAP2 transcripts under balancing selection. Genome Research 2018, 28: 1812-1825. PMID: 30446528, PMCID: PMC6280757, DOI: 10.1101/gr.240390.118.
- Systematic STAT3 sequencing in patients with unexplained cytopenias identifies unsuspected large granular lymphocytic leukemia.Morgan EA, Lee MN, DeAngelo DJ, Steensma DP, Stone RM, Kuo FC, Aster JC, Gibson CJ, Lindsley RC. Systematic STAT3 sequencing in patients with unexplained cytopenias identifies unsuspected large granular lymphocytic leukemia. Blood Advances 2017, 1: 1786-1789. PMID: 29296824, PMCID: PMC5728102, DOI: 10.1182/bloodadvances.2017011197.
- Parsing the Interferon Transcriptional Network and Its Disease Associations.Mostafavi S, Yoshida H, Moodley D, LeBoité H, Rothamel K, Raj T, Ye CJ, Chevrier N, Zhang SY, Feng T, Lee M, Casanova JL, Clark JD, Hegen M, Telliez JB, Hacohen N, De Jager PL, Regev A, Mathis D, Benoist C. Parsing the Interferon Transcriptional Network and Its Disease Associations. Cell 2016, 164: 564-78. PMID: 26824662, PMCID: PMC4743492, DOI: 10.1016/j.cell.2015.12.032.
- Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in LeukocytesRaj T, Rothamel K, Mostafavi S, Ye C, Lee MN, Replogle JM, Feng T, Lee M, Asinovski N, Frohlich I, Imboywa S, Von Korff A, Okada Y, Patsopoulos NA, Davis S, McCabe C, Paik HI, Srivastava GP, Raychaudhuri S, Hafler DA, Koller D, Regev A, Hacohen N, Mathis D, Benoist C, Stranger BE, De Jager PL. Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes. Science 2014, 344: 519-523. PMID: 24786080, PMCID: PMC4910825, DOI: 10.1126/science.1249547.
- Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic CellsLee MN, Ye C, Villani AC, Raj T, Li W, Eisenhaure TM, Imboywa SH, Chipendo PI, Ran FA, Slowikowski K, Ward LD, Raddassi K, McCabe C, Lee MH, Frohlich IY, Hafler DA, Kellis M, Raychaudhuri S, Zhang F, Stranger BE, Benoist CO, De Jager PL, Regev A, Hacohen N. Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells. Science 2014, 343: 1246980. PMID: 24604203, PMCID: PMC4124741, DOI: 10.1126/science.1246980.
- Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach.Lee MN, Roy M, Ong SE, Mertins P, Villani AC, Li W, Dotiwala F, Sen J, Doench JG, Orzalli MH, Kramnik I, Knipe DM, Lieberman J, Carr SA, Hacohen N. Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach. Nature Immunology 2013, 14: 179-85. PMID: 23263557, PMCID: PMC3838897, DOI: 10.1038/ni.2509.