Jonathan M. Irish, Ph.D.
Assistant Professor of Cancer Biology
Assistant Professor of Pathology, Microbiology and Immunology
740B Preston Research Building
2220 Pierce Avenue
Nashville, TN 37232-6840
Jonathan M. Irish, Ph.D. is Assistant Professor of Cancer Biology and Pathology, Microbiology and Immunology at Vanderbilt University. The Irish Lab uses new tools and computational approaches to do basic and translational research in human cancer and immunology.
A specialty of the Irish lab is tracking and targeting rare populations of cells in human tissues. Close collaborations between the Irish lab and clinicians in the VICC enable Irish lab members to bring patient biopsy samples directly from the bedside into the laboratory for analysis by 'next generation' research techniques. For example, using mass cytometry Irish lab members can detect and characterize every cell in a patient's biopsy sample -- including cancer cells, immune cells, and stem cells. Dr. Irish is leading the development of mass cytometry at Vanderbilt, one of the first 15 institutions worldwide to acquire the technology. The long term goal of the Irish lab is to use single cell approaches and new knowledge of biology to detect disease earlier, create safe and effective new therapies, and to monitor and guide personalized medicine.
Ultimately, by better understanding biological systems which control cell biology 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.
The Irish lab is grateful for outstanding support from the VICC, including the VICC Ambassadors, a passionate group of volunteers and advocates dedicated to fighting cancer by supporting research: https://viccambassadors.vicc.org/
The goal to study control of signaling networks in healthy and malignant cells forms the basis of an NIH/NCI R00 grant that supports the Irish lab (5R00CA143231-04).
Research Background and Training
Dr. Irish received his Ph.D. from the Cancer Biology program at Stanford for studies in the laboratory of Dr. Garry Nolan, Ph.D., and previously earned B.S. degrees in Chemistry, Biochemistry, and Biology from the University of Michigan. For his postdoctoral fellowship, Dr. Irish worked with Dr. Ronald Levy, M.D., at Stanford until founding his lab at Vanderbilt in 2012. Together with Nolan lab alumni Dr. Nikesh Kotecha and Dr. Peter Krutzik, Dr. Irish created Cytobank, a big data analytics platform used by thousands of researchers worldwide to manage, analyze, and share data from high dimensional single cell research.
During his Ph.D. research with Dr. Nolan, Dr. Irish created a new technique to measure signaling responses in individual cancer cells and applied it to the study of 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.
In his postdoctoral research with Dr. Levy, Dr. Irish applied this 'single cell signaling profiles' technique to dissect B cell signaling in follicular lymphoma (Blood 2006) and healthy B cell development (J Immunol 2006). This project culminated in the identification of new type of lymphoma B cell termed lymphoma negative prognostic (LNP) cells. LNP cells are closely associated with progression to aggressive disease and lower overall survival (PNAS 2010). With collaborators, Dr. Irish has now shown that LNP cells exist in other B cell cancers (BMC Cancer, Br J Haematol 2012), are distinguished by a set of genetic driver mutations (Blood 2013), and suppress tumor infiltrating T cell signaling via PD-1 (Blood 2013).
- B.S., B.S., and B.S., Chem. - University of Michigan, 1998
- Ph.D. - Stanford University, 2004
- Fellowship - Stanford University, 2011
A central goal of our 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 the Irish Lab, we use new tools and computational approaches to do basic and translational research in human cancer and immunology.
In addition to making discoveries at the frontier of human genetics and immunology, we 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.
Featured recent publications:
- Characterizing phenotypes and signaling networks of single human cells by mass cytometry. Leelatian N, Diggins KE, Irish JM, Methods Mol Bio. 2015.
- Cutting Edge: Redox Signaling Hypersensitivity Distinguishes Human Germinal Center B cells. Polikowsky HG, Wogsland CE, Diggins KE, Huse K, Irish JM, J Immunol. 2015.
- Methods for discovery and characterization of cell subsets in high dimensional mass cytometry data. Diggins KE, Ferrell PB, Irish JM, Methods. 2015.
- Beyond the age of cellular discovery. Irish JM, Nat Immunol. 2014.
- High-dimensional single-cell cancer biology. Irish JM and Doxie DB, Curr Top Microbiol Immunol. 2014.
- Simmons AJ, Banerjee A, McKinley ET, Scurrah CR, Herring CA, Gewin LS, Masuzaki R, Karp SJ, Franklin JL, Gerdes MJ, Irish JM, Coffey RJ, Lau KS. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-a-induced apoptosis in vivo. Mol. Syst. Biol. 2016 Aug 8/29/2016; 12(8): 881. PMID: 27574014, PMCID: PMC5119492, ISSN: 1744-4292.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/27574014.
- Greenplate AR, Johnson DB, Roussel M, Savona MR, Sosman JA, Puzanov I, Ferrell PB, Irish JM. Myelodysplastic Syndrome Revealed by Systems Immunology in a Melanoma Patient Undergoing Anti-PD-1 Therapy. Cancer Immunol Res [print-electronic]. 2016 Mar 3/10/2016; PMID: 26966176, PII: 2326-6066.CIR-15-0213, DOI: 10.1158/2326-6066.CIR-15-0213, ISSN: 2326-6074.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26966176.
- Chong KM, Leelatian N, Deguire SM, Brockman AA, Earl D, Ihrie RA, Irish JM, Bachmann BO, Sulikowski GA. The use of fluorescently-tagged apoptolidins in cellular uptake and response studies. J. Antibiot [print-electronic]. 2016 Mar 3/9/2016; PMID: 26956792, PII: ja201622, DOI: 10.1038/ja.2016.22, ISSN: 0021-8820.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26956792.
- Johnson DB, Estrada MV, Salgado R, Sanchez V, Doxie DB, Opalenik SR, Vilgelm AE, Feld E, Johnson AS, Greenplate AR, Sanders ME, Lovly CM, Frederick DT, Kelley MC, Richmond A, Irish JM, Shyr Y, Sullivan RJ, Puzanov I, Sosman JA, Balko JM. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Nat Commun. 2016; 7: 10582. PMID: 26822383, PMCID: PMC4740184, PII: ncomms10582, DOI: 10.1038/ncomms10582, ISSN: 2041-1723.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26822383.
- Shah AT, Diggins KE, Walsh AJ, Irish JM, Skala MC. In Vivo Autofluorescence Imaging of Tumor Heterogeneity in Response to Treatment. Neoplasia. 2015 Dec; 17(12): 862-70. PMID: 26696368, PII: S1476-5586(15)00143-8, DOI: 10.1016/j.neo.2015.11.006, ISSN: 1476-5586.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26696368.
- Nicholas KJ, Greenplate AR, Flaherty DK, Matlock BK, Juan JS, Smith RM, Irish JM, Kalams SA. Multiparameter analysis of stimulated human peripheral blood mononuclear cells: A comparison of mass and fluorescence cytometry. Cytometry A [print-electronic]. 2015 Nov 11/24/2015; PMID: 26599989, DOI: 10.1002/cyto.a.22799, ISSN: 1552-4930.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26599989.
- Polikowsky HG, Wogsland CE, Diggins KE, Huse K, Irish JM. Cutting Edge: Redox Signaling Hypersensitivity Distinguishes Human Germinal Center B Cells. J. Immunol [print-electronic]. 2015 Aug 8/15/2015; 195(4): 1364-7. PMID: 26157177, PMCID: PMC4530023, PII: jimmunol.1500904, DOI: 10.4049/jimmunol.1500904, ISSN: 1550-6606.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26157177.
- Diggins KE, Ferrell PB, Irish JM. Methods for discovery and characterization of cell subsets in high dimensional mass cytometry data. Methods [print-electronic]. 2015 Jul 7/1/2015; 82: 55-63. PMID: 25979346, PMCID: PMC4468028, PII: S1046-2023(15)00199-1, DOI: 10.1016/j.ymeth.2015.05.008, ISSN: 1095-9130.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/25979346.
- Green MR, Kihira S, Liu CL, Nair RV, Salari R, Gentles AJ, Irish J, Stehr H, Vicente-Dueñas C, Romero-Camarero I, Sanchez-Garcia I, Plevritis SK, Arber DA, Batzoglou S, Levy R, Alizadeh AA. Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Mar 3/10/2015; 112(10): E1116-25. PMID: 25713363, PMCID: PMC4364211, PII: 1501199112, DOI: 10.1073/pnas.1501199112, ISSN: 1091-6490.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/25713363.
- Karr JR, Guturu H, Chen EY, Blair SL, Irish JM, Kotecha N, Covert MW. NetworkPainter: dynamic intracellular pathway animation in Cytobank. BMC Bioinformatics. 2015; 16: 172. PMID: 26003204, PMCID: PMC4491883, PII: 10.1186/s12859-015-0602-4, DOI: 10.1186/s12859-015-0602-4, ISSN: 1471-2105.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26003204.
- Leelatian N, Diggins KE, Irish JM. Characterizing Phenotypes and Signaling Networks of Single Human Cells by Mass Cytometry. Methods Mol. Biol. 2015; 1346: 99-113. PMID: 26542718, PMCID: PMC4656023, DOI: 10.1007/978-1-4939-2987-0_8, ISSN: 1940-6029.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26542718.
- Simmons AJ, Banerjee A, McKinley ET, Scurrah CR, Herring CA, Gewin LS, Masuzaki R, Karp SJ, Franklin JL, Gerdes MJ, Irish JM, Coffey RJ, Lau KS. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-a-induced apoptosis in vivo. Mol. Syst. Biol. 2015; 11(10): 835. PMID: 26519361, PMCID: PMC4631206, ISSN: 1744-4292.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26519361.
- Irish JM. Beyond the age of cellular discovery. Nature immunology. 2014 Dec; 15(12) Sect. 1095,7.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/25396342.
- Irish JM, Doxie DB. High-dimensional single-cell cancer biology. Curr. Top. Microbiol. Immunol. 2014; 377: 1-21. PMID: 24671264, PMCID: PMC4216808, DOI: 10.1007/82_2014_367, ISSN: 0070-217X.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/24671264.
- Pyne S, Lee SX, Wang K, Irish J, Tamayo P, Nazaire MD, Duong T, Ng SK, Hafler D, Levy R, Nolan GP, Mesirov J, McLachlan GJ. Joint modeling and registration of cell populations in cohorts of high-dimensional flow cytometric data. PLoS ONE. 2014; 9(7): e100334. PMID: 24983991, PMCID: PMC4077578, PII: PONE-D-13-55136, DOI: 10.1371/journal.pone.0100334, ISSN: 1932-6203.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/24983991.
- 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 [print-electronic]. 2013 Feb 2/28/2013; 121(9): 1604-11. PMID: 23297126, PMCID: PMC3587323, PII: blood-2012-09-457283, DOI: 10.1182/blood-2012-09-457283, ISSN: 1528-0020.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23297126.
- 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 [print-electronic]. 2013 Feb 2/21/2013; 121(8): 1367-76. PMID: 23297127, PMCID: PMC3578953, PII: blood-2012-04-421826, DOI: 10.1182/blood-2012-04-421826, ISSN: 1528-0020.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23297127.
- 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 [letter]. Br. J. Haematol [print-electronic]. 2012 Dec; 159(5): 604-8. PMID: 23043253, PMCID: PMC3767388, DOI: 10.1111/bjh.12073, ISSN: 1365-2141.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23043253.
- Blix ES, Irish JM, Husebekk A, Delabie J, Forfang L, Tierens AM, Myklebust JH, Kolstad A. Phospho-specific flow cytometry identifies aberrant signaling in indolent B-cell lymphoma. BMC Cancer. 2012; 12: 478. PMID: 23072591, PMCID: PMC3519597, PII: 1471-2407-12-478, DOI: 10.1186/1471-2407-12-478, ISSN: 1471-2407.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23072591.
- 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 [print-electronic]. 2010 Jul 7/20/2010; 107(29): 12747-54. PMID: 20543139, PMCID: PMC2919949, PII: 1002057107, DOI: 10.1073/pnas.1002057107, ISSN: 1091-6490.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/20543139.
- Kotecha N, Krutzik PO, Irish JM. Web-based analysis and publication of flow cytometry experiments. Curr Protoc Cytom. 2010 Jul; Chapter 10: Unit10.17. PMID: 20578106, PMCID: PMC4208272, DOI: 10.1002/0471142956.cy1017s53, ISSN: 1934-9300.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/20578106.
- 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 [print-electronic]. 2009 Oct 10/15/2009; 114(16): 3431-8. PMID: 19641184, PMCID: PMC2765679, PII: blood-2009-05-223958, DOI: 10.1182/blood-2009-05-223958, ISSN: 1528-0020.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19641184.
- 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. 2009 Feb; 7(1): 44-55. PMID: 19187010, PMCID: PMC2956679, PII: 10.1089/adt.2008.174, DOI: 10.1089/adt.2008.174, ISSN: 1540-658X.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19187010.
- 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. 2008 Oct 10/7/2008; 14(4): 335-43. PMID: 18835035, PMCID: PMC2647559, PII: S1535-6108(08)00293-6, DOI: 10.1016/j.ccr.2008.08.014, ISSN: 1878-3686.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/18835035.
- Van Meter ME, Díaz-Flores E, Archard JA, Passegué 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 [print-electronic]. 2007 May 5/1/2007; 109(9): 3945-52. PMID: 17192389, PMCID: PMC1874575, PII: blood-2006-09-047530, DOI: 10.1182/blood-2006-09-047530, ISSN: 0006-4971.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17192389.
- Irish JM, Anensen N, Hovland R, Skavland J, Børresen-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 [print-electronic]. 2007 Mar 3/15/2007; 109(6): 2589-96. PMID: 17105820, PII: blood-2006-02-004234, DOI: 10.1182/blood-2006-02-004234, ISSN: 0006-4971.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17105820.
- 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 [print-electronic]. 2006 Nov 11/1/2006; 108(9): 3135-42. PMID: 16835385, PMCID: PMC1895530, PII: blood-2006-02-003921, DOI: 10.1182/blood-2006-02-003921, ISSN: 0006-4971.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16835385.
- 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. 2006 Aug 8/1/2006; 177(3): 1581-9. PMID: 16849466, PII: 177/3/1581, ISSN: 0022-1767.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16849466.
- Irish JM, Kotecha N, Nolan GP. Mapping normal and cancer cell signalling networks: towards single-cell proteomics. Nat. Rev. Cancer. 2006 Feb; 6(2): 146-55. PMID: 16491074, PII: nrc1804, DOI: 10.1038/nrc1804, ISSN: 1474-175X.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16491074.
- Irish JM, Hovland R, Krutzik PO, Perez OD, Bruserud Ø, Gjertsen BT, Nolan GP. Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell. 2004 Jul 7/23/2004; 118(2): 217-28. PMID: 15260991, PII: S0092867404006282, DOI: 10.1016/j.cell.2004.06.028, ISSN: 0092-8674.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/15260991.
- 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. 2004 Mar; 110(3): 206-21. PMID: 15047199, PII: S1521661603003097, DOI: 10.1016/j.clim.2003.11.009, ISSN: 1521-6616.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/15047199.
- 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. 2002 Mar; 9(3): 252-63. PMID: 11859408, DOI: 10.1038/sj.cdd.4400959, ISSN: 1350-9047.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/11859408.