Biomedical Research Education & Training
Faculty Member

Irish, Jonathan, Ph.D.
Assistant Professor of Cancer Biology
Assistant Professor of Pathology, Microbiology and Immunology

Lab Url: http://my.vanderbilt.edu/irishlab/

Phone Number: (615) 936-3460

Email Address: jonathan.irish@vanderbilt.edu

Irish, Jonathan's picture
Academic history
B.S., University of Michigan
B.S., University of Michigan
B.S., Chem., University of Michigan
Ph.D., Stanford University

Office Address   Mailing Address

740B PRB

740B Preston Research Building Irish Lab, Vanderbilt University 37232-6840


Research Keywords
Cell biology, cancer, signaling, computational and systems biology, immunology, personalized medicine, pharmacology and screening, single cell analysis, flow cytometry, mass cytometry

Research Specialty
Single cell systems biology for translational cancer and immunology research

Research Description
My background is in cancer biology, cell signaling, immunology, and computational biology. A central goal of my research at Vanderbilt is to understand how changes at the single cell level alter signaling in healthy cells and lead to therapy resistant populations in human diseases.

In addition to making discoveries at the frontier of human genetics and immunology, I aspire to use knowledge of cell signaling to create therapeutic technologies and to guide clinical decisions. In the long term, great potential exists to detect disease earlier and to tailor a patient's therapy to the biological alterations detected in the cells of their disease. By better understanding biological systems which control development and cell-cell interactions in healthy and diseased contexts, we can learn to program cells to become therapeutic agents or target malignant signaling events to specifically kill cancer cells.

Environment
I aim to foster a diverse and exciting research atmosphere in my lab by recruiting students working on integrative, interdisciplinary projects. I'm especially interested in training students whose projects will combine elements of:
- basic cancer biology or immunology
- computational & systems biology
- pharmacology & drug screening
- clinical translational research
- new technology or techniques
- primary human samples

Training
My experimental approach has focused on measuring signaling events in individual cells from primary tissues, including human tumors. Before coming to Vanderbilt, I trained at Stanford University with Garry Nolan and Ronald Levy. There I created a new approach that measures signaling in individual cancer cells and applied it to the study of acute myelogenous leukemia patient clinical outcomes (Cell 2004). An advantage of this single cell approach is that signaling can be characterized in rare populations of cancer cells and contrasted with the bulk cancer cell population or with tumor-infiltrating non-malignant cells. I later applied this technique to healthy B cells (J Immunol 2006) and malignant B cells in follicular lymphoma (Blood 2006). In follicular lymphoma, signaling identified a subset of tumor B cells that were present at diagnosis only in patients with a lower overall survival (p < 0.0001) and that increased over time as the patient's cancer progressed (PNAS 2010). Systems biology tools we created to manage and analyze single cell signaling data were critical to this work (Curr Protoc Cytometry 2010).

Technology
Key technologies in my laboratory include phospho-specific flow cytometry (phospho-flow) and mass cytometry. Phospho-flow combines lineage and phospho-specific antibodies to measure intracellular signaling in individual cells (Nature Reviews Cancer 2006). Mass cytometry is a next generation analytical flow cytometry technology capable of measuring 34+ features of individual cells - a dramatic leap forward from the present technology, which routinely measures only 3 to 8 features per cell. The form of single cell proteomics enabled by mass cytometry provides unique opportunities for mechanistic understanding of signaling in primary tumors and healthy human tissues.

My laboratory is also interested in computational biology, bioinformatics, and modeling and develops tools for our research that:
1) Identify and compare individual cells in heterogeneous primary tissue samples
2) Are cloud based and connected to online tools and communities
3) Capture key experiment annotations and relate them to the raw data files
4) Integrate pathway modeling and visualization tools into the data analysis workflow

Publications
Green, MR, Gentles, AJ, Nair, RV, Irish, JM, Kihira, S, Liu, CL, Kela, I, Hopmans, ES, Myklebust, JH, Ji, H, Plevritis, SK, Levy, R, Alizadeh, AA. Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. Blood, 2013

Myklebust, JH, Irish, JM, Brody, J, Czerwinski, DK, Houot, R, Kohrt, HE, Timmerman, J, Said, J, Green, MR, Delabie, J, Kolstad, A, Alizadeh, AA, Levy, R. High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells. Blood, 2013

Blix, ES, Irish, JM, Husebekk, A, Delabie, J, Forfang, L, Tierens, A, Myklebust, JH, Kolstad, A. Phospho-specific flow cytometry identifies aberrant signaling in indolent B-cell lymphoma. BMC Cancer, 12(1), 478, 2012

Blix, ES, Irish, JM, Husebekk, A, Delabie, J, Tierens, AM, Myklebust, JH, Kolstad, A. Altered BCR and CD40 signalling are associated with clinical outcome in small lymphocytic lymphoma/chronic lymphocytic leukaemia and marginal zone lymphoma patients. Br J Haematol, 2012

Irish, JM, Myklebust, JH, Alizadeh, AA, Houot, R, Sharman, JP, Czerwinski, DK, Nolan, GP, Levy, R. B-cell signaling networks reveal a negative prognostic human lymphoma cell subset that emerges during tumor progression. Proc Natl Acad Sci U S A, 107(29), 12747-54, 2010 PMCID:2919949

Kotecha, N, Krutzik, PO, Irish, JM. Web-based analysis and publication of flow cytometry experiments. Curr Protoc Cytom, Chapter 10, Unit10.17, 2010

Hammer, MM, Kotecha, N, Irish, JM, Nolan, GP, Krutzik, PO. WebFlow: a software package for high-throughput analysis of flow cytometry data. Assay Drug Dev Technol, 7(1), 44-55, 2009 PMCID:2956679

Houot, R, Goldstein, MJ, Kohrt, HE, Myklebust, JH, Alizadeh, AA, Lin, JT, Irish, JM, Torchia, JA, Kolstad, A, Chen, L, Levy, R. Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion. Blood, 114(16), 3431-8, 2009 PMCID:2765679

Kotecha, N, Flores, NJ, Irish, JM, Simonds, EF, Sakai, DS, Archambeault, S, Diaz-Flores, E, Coram, M, Shannon, KM, Nolan, GP, Loh, ML. Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates. Cancer Cell, 14(4), 335-43, 2008 PMCID:2647559

Irish, JM, Anensen, N, Hovland, R, Skavland, J, B??rresen-Dale, AL, Bruserud, O, Nolan, GP, Gjertsen, BT. Flt3 Y591 duplication and Bcl-2 overexpression are detected in acute myeloid leukemia cells with high levels of phosphorylated wild-type p53. Blood, 109(6), 2589-96, 2007 PMCID:1874575

Van Meter, ME, D?-az-Flores, E, Archard, JA, Passegu??, E, Irish, JM, Kotecha, N, Nolan, GP, Shannon, K, Braun, BS. K-RasG12D expression induces hyperproliferation and aberrant signaling in primary hematopoietic stem/progenitor cells. Blood, 109(9), 3945-52, 2007 PMCID:1874575

Irish, JM, Czerwinski, DK, Nolan, GP, Levy, R. Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells. Blood, 108(9), 3135-42, 2006 PMCID:1895530

Irish, JM, Czerwinski, DK, Nolan, GP, Levy, R. Kinetics of B cell receptor signaling in human B cell subsets mapped by phosphospecific flow cytometry. J Immunol, 177(3), 1581-9, 2006 PMCID:1874575

Irish, JM, Kotecha, N, Nolan, GP. Mapping normal and cancer cell signalling networks: towards single-cell proteomics. Nat Rev Cancer, 6(2), 146-55, 2006 PMCID:1895530

Irish, JM, Hovland, R, Krutzik, PO, Perez, OD, Bruserud, ??, Gjertsen, BT, Nolan, GP. Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell, 118(2), 217-28, 2004 PMCID:1895530

Krutzik, PO, Irish, JM, Nolan, GP, Perez, OD. Analysis of protein phosphorylation and cellular signaling events by flow cytometry: techniques and clinical applications. Clin Immunol, 110(3), 206-21, 2004 PMCID:1895530

Armstrong, JS, Steinauer, KK, Hornung, B, Irish, JM, Lecane, P, Birrell, GW, Peehl, DM, Knox, SJ. Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line. Cell Death Differ, 9(3), 252-63, 2002 PMCID:1895530


Postdoctoral Position Available
N/A

Postdoctoral Position Details
N/A

Updated Date
03/05/2013