Molecular Mechanisms of Immune Cell Development, Effector Function, Anti-Tumour Immunity, and Leukemogenesis.
Research in our lab centers on the molecular and transcriptional mechanisms that govern immune cell development and function, with a particular emphasis on how these processes influence innate and adaptive immunity and leukemogenesis. Our work investigates how lineage-specific transcriptional programs are established and how disruptions in these programs can lead to immune deficiencies, autoimmunity, and cancers such as acute lymphoblastic leukemia. A major focus of the laboratory is on transcription factors and their antagonists—especially E proteins and their regulators like ID and ETS family proteins—that direct the differentiation and effector functions of lymphoid cell types including B cells, T cells, natural killer (NK) cells, and innate lymphoid cells. Through genetic and genomic approaches, our group has elucidated critical roles for factors such as E2A, Notch1, LEF1, ID2/ID3, and ETS1 in lymphocyte fate decisions and functional maturation, and is advancing understanding of how these networks impact immune responses to infection and cancer as well as the mechanisms driving leukemic transformation. Current research includes a focus on how these transcriptional programs drive effective anti-tumor immune responses by natural killer cells.
University of California, San Diego
La Jolla, CA
Postdoc - Transcription/Immunology
2001
The Salk Institute
La Jolla, CA
Postdoc - Transcription
1996
University of Toronto
Toronto, Canada
Ph.D. - Immunology
1995
University of Toronto
Toronto, Canada
B.S. - Immunology
1989
Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T-ALL.
Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T-ALL. Leukemia. 2024 03; 38(3):491-501.
PMID: 38155245
TGF-ß Promotes the Postselection Thymic Development and Peripheral Function of IFN-?-Producing Invariant NKT cells.
TGF-ß Promotes the Postselection Thymic Development and Peripheral Function of IFN-?-Producing Invariant NKT cells. J Immunol. 2023 11 01; 211(9):1376-1384.
PMID: 37702745
Dual Targeting of Apoptotic and Signaling Pathways in T-Lineage Acute Lymphoblastic Leukemia.
Dual Targeting of Apoptotic and Signaling Pathways in T-Lineage Acute Lymphoblastic Leukemia. Clin Cancer Res. 2023 08 15; 29(16):3151-3161.
PMID: 37363966
Quantitative control of Ets1 dosage by a multi-enhancer hub promotes Th1 cell differentiation and protects from allergic inflammation.
Quantitative control of Ets1 dosage by a multi-enhancer hub promotes Th1 cell differentiation and protects from allergic inflammation. Immunity. 2023 07 11; 56(7):1451-1467.e12.
PMID: 37263273
Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T lymphocyte acute lymphoblastic leukemia.
Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T lymphocyte acute lymphoblastic leukemia. bioRxiv. 2023 Apr 25.
PMID: 37163059
Editorial: Molecular switches of the immune system: The E-protein/Id axis in hematopoietic development and function.
Editorial: Molecular switches of the immune system: The E-protein/Id axis in hematopoietic development and function. Front Immunol. 2022; 13:1062734.
PMID: 36405705
Genomic and Transcriptional Mechanisms Governing Innate-like T Lymphocyte Development.
Genomic and Transcriptional Mechanisms Governing Innate-like T Lymphocyte Development. J Immunol. 2022 07 15; 209(2):208-216.
PMID: 35821098
E Protein Transcription Factors as Suppressors of T Lymphocyte Acute Lymphoblastic Leukemia.
E Protein Transcription Factors as Suppressors of T Lymphocyte Acute Lymphoblastic Leukemia. Front Immunol. 2022; 13:885144.
PMID: 35514954
Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in E2a-/- T Acute Lymphoblastic Leukemia.
Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in E2a-/- T Acute Lymphoblastic Leukemia. Front Immunol. 2022; 13:845488.
PMID: 35371057
The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude.
The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude. J Exp Med. 2021 06 07; 218(6).
PMID: 33857289