Publications

Breakthrough discoveries across numerous applications utilizing the IsoCode Chip.

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Publications

Daver N, Kantarjian H, Mackay S, Flynn B, Morse K, Speranza MC, Zhou J, Ramaswamy S, Mackay S, Coleman KG. TESARO Inc, Waltham, MA; IsoPlexis, Branford, CT. Polyfunctionality determined by single-cell proteomics of bone marrow-derived CD4 T cells from patients with acute myeloid leukemia identifies patients responding to anti-PD-1-based therapy and discovers profound T cell defect in mutant TP53 disease. Presented the AACR Conference 2019.

Kaufmann JK, Flynn B, Basu S, Garcia-ManeroG, Alfayez M, Konopleva M, Matthews J, Kornblau S, Jabbour E, Zhou J, Andreeff M. UT MD Anderson Cancer Ctr., Houston, TX; Isoplexis, Branford, CT. Triple checkpoint blockade targeting PD-1, TIM-3, and LAG-3 reinvigorates ovarian cancer-infiltrating T cells by increasing T cell polyfunctionality and effector function. Presented the AACR Conference 2019.

Mackay S, Chen J, Patino J, Seo YD, Pollack S, Zhou J. IsoPlexis Corporation, Branford, CT; University of Washington School of Medicine, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA. Single-cell polyfunctionality of circulating CD4+ T cells correlates with T cell receptor repertoire diversity of PBMCs, indicating potential synergistic activity and peripheral biomarker predictive of efficacy of intratumor injection of the toll-like receptor 4 agonist G100. Presented the AACR Conference 2019.

Sennino B, Conroy A, Purandare B, Litterman A, Jacoby K, Moot R, Lu W, Nguyen D, Urbinati F, Foy S, Hunter T, Dalmas O, Bethune M, Park T, Peng S, Franzusoff A, Mandl S. PACT Pharma, South San Francisco, CA; Arcus Biosciences, Hayward, CA. NeoTCR-P1, a novel neoepitope-specific adoptive cell therapy, consists of T cells with ‘younger’ phenotypes that rapidly proliferate and kill target cells upon recognition of cognate antigen. Presented the AACR Conference 2019.

Kotani H, Li Gongbo, Yao Jiqiang, Mesa TE, Chen J, Boucher JC, Yoder SJ, Zhou J, Davila ML. Aged CAR T cells exhibit enhanced cytotoxicity and effector function but shorter persistence and less memory-like phenotypes. Presented at ASH Annual Meeting 2018.

Srivastava SK, Panch SR, Jin J, Shalabi H, Shah NN, Flynn B, Zhou J, Mackay S, Highfill SL, Stroncek DF. Abbreviated T-cell activation on the automatic CliniMACS Prodigy device enhances bispecific CD19/22 Chimeric Antigen Receptor T-Cell viability and fold expansion, reducing total culture duration. Presented at ASH Annual Meeting 2018.

Mackay S, Paczkowski P, Flynn B, Morse K, Liu D, Coupet TA, Godbersen C, Sentman CL, Zhou J. Single-cell proteomic analysis of T cells stimulated by Bi-specific T cell Engagers shows a robust and unique polyfunctional secretion profile. Presented at SITC Annual Meeting 2018.

Ravindranathan S, Jajja MR, Petersen C, Bommireddy R, Selvaraj P, Yang L, El-Rayes B, Flynn B, Waller EK. Improving T cell functionality for adoptive T cell therapy in metastatic colon cancer. Presented at SITC Annual Meeting 2018.

Mackay S, Flynn B, Morse K, Paczkowski P, Chen J, Liu D, Bacchiocchi A, Heath JR, Fan R, Sznol M, Halaban R, Zhou J. Single-cell PSI of CD8+ TILs in melanoma shows uniquely sensitive correlates with response to anti-PD-1/CTLA4 therapy, where histology and serum cytokines were unable to detect significant associations. Presented at SITC Annual Meeting 2018.

Fujiwara M, Anstadt EJ, Flynn B, Morse K, Ng C, Paczkowski P, Zhou J, Mackay S, Wasko N, Nichols F, Clark RB. Enhanced TLR2 Responses in Multiple Sclerosis. Clinical and Experimental Immunology (2018).

Rossi J, Paczkowski P, Shen Y, Morse K, Flynn B, Kaiser A, Ng C, Gallatin K, Cain T, Fan R, Mackay S, Heath JR, Rosenberg SA, Kochenderfer JN, Zhou J, and Bot A. Preinfusion Polyfunctional Anti-CD19 Chimeric Antigen Receptor T Cells Associate with Clinical Outcomes in NHL. Blood (2018).

Parisi G, Saco J, Salazar F, Krystofinski P, Tsoi J, Zhang R, Puig Saus C, Zhou J, Hu-Lieskovan S, Comin-Anduix B, Wu A, Charych DH, Ribas A. Enhanced Expansion and Tumor Targeting of Adoptively Transferred T Cells with NKTR-214. Session PO.CL06.03 - Adoptive Cell Therapy 3. American Association for Cancer Research Annual Meeting 2018.

Mackay S, Flynn B, Morse K, Paczkowski P, Bacchiocchi A, Heath JR, Fan R, Halaban R, and Zhou J. Single-Cell Cytokine Profiling of Tumor-Infiltrating T Cells to Measure Patient Responses to Anti-PD-1 Therapy. Presented at TRCCC Annual Meeting 2018.

Seo YD, Zhou J, Morse K, Patino J, Mackay S, Kim EY, Conrad III EU, O'Malley RB, Cranmer L, Lu H, Hsu FJ, Xu Y, Loggers E, Hain T, Pillarisetty VG, Kane G, Riddell S, Meulen J, Jones RL, Pollack SM. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist G100 induces a clinical response and a T cell response locally and systemically. Journal of Clinical Oncology, 36, Suppl 5S (2018).

Fraietta JA, Lacey SF, Orlando E, Pruteanu J, Gohil M, Wang Y, Boesteanu A, O'Connor R, Ambrose DE, Hwang WT, Wilcox N, Bedoya F, Dorfmeier C, Chen F, Parakandi H, Gupta M, Pequignot E, Johnson FB, Kulikovskaya I, Liu L, Lundh SM, Xu J, Davis MM, Young RM, Levine BL, Siegel DL, Huang A, Wherry EJ, Zhou J, Paczkowski P, Mackay S, Brogdon J, Bitter H, Porter DL, June CH, and Melenhorst JJ. Identification of Functional Determinants of Response and Resistance to CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy of Chronic Lymphocytic Leukemia. Blood 130 (Suppl. 1) 3181 (2017).

Su Y, Wei W, Robert L, Xue M, Tsoi J, Garcia-Diaz A, Homet Moreno B, Kim J, Ng R, Lee JW, Koya RC, Comin-Anduix B, Graeber TG, Ribas A, and Heath JR. Single-Cell Analysis Resolves the Cell State Transition and Signaling Dynamics Associated with Melanoma Drug-Induced Resistance. Proc. Natl. Acad. Sci. 114 (52) 13679-13684 (2017).

Xue Q, Bettini E, Paczkowski P, Ng C, Kaiser A, McConnell T, Kodrasi O, Quigley M, Heath JR, Fan R, Mackay S, Dudley M, Kassim S, and Zhou J. Single-Cell Multiplexed Cytokine Profiling of CD19 CAR-T Cells Reveals a Diverse Landscape of Polyfunctional Antigen-Specific Response. Journal for ImmunoTherapy of Cancer, 5:85 (2017).

Rossi J, Paczkowski P, Shen Y, Morse K, Flynn B, Kaiser A, Ng C, Gallatin K, Cain T, Fan R, Mackay S, Heath JR, Rosenberg SA, Kochenderfer JN, Zhou J, and Bot A. Polyfunctional Anti-CD19 CAR T Cells Determined by Single-Cell Multiplex Proteomics Associated with Clinical Activity in Patients with Advanced Non-Hodgkin’s Lymphoma. Proc. AACR Annual Meeting 177 (13 Suppl.) 2990 (2017).

Xue Q, Bettini E, Paczkowski P, Ng C, Kaiser A, McConnell T, Kodrasi O, Quigley M, Heath JR, Fan R, Mackay S, Dudley M, Kassim S, and Zhou J. Single-Cell Proteomic Assessment of CD19 CAR-T Cells Reveals a Complex Landscape of Polyfunctional Antigen-Specific Response. Presented at FOCiS 2017.

Zhou J, Kaiser A, Ng C, Karcher R, McConnell T, Paczkowski P, Fernandez C, Zhang M, Mackay S, and Tsuji M. CD8+ T-Cell Mediated Anti-Malaria Protection Induced by Malaria Vaccines; Assessment of Hepatic CD8+ T Cells by SCBC Assay. Human Vaccines & Immunotherapeutics, 13 (7), 1625-1629 (2017).

Mackay S, Flynn B, Morse K, Paczkowski P, Bacchiocchi A, Heath JR, Fan R, Halaban R, and Zhou J. Single-Cell Cytokine Profiling of Tumor-Infiltrating T Cells to Measure Patient Responses to Anti-PD-1 Therapy. Journal of Clinical Oncology, 35 (9), Suppl. 7S (2017).

Jayatilaka H, Tyle P, Chen J, Kwak M, Ju J, Kim HJ, Lee JSH, Wu PH, Gilkes DM, Fan R, and Wirtz D. Synergistic IL-6 and IL-8 Paracrine Signalling Pathway Infers a Strategy to Inhibit Tumour Cell Migration. Nature Communications, 8, 15584 (2017).

Xue M, Wei W, Su Y, Johnson D, and Heath JR. Supramolecular Probes for Assessing Glutamine Uptake Enable Semi-Quantitative Metabolic Models in Single Cells. Journal of the American Chemical Society, 138 (9), 3085-3093 (2016).

Poovathingal SK, Kravchenko-Balasha N, Shin YS, Levine RD, and Heath JR. Critical Points in Tumorigenesis: A Carcinogen-Initiated Phase Transition Analyzed via Single-Cell Proteomics. Small, 12 (11), 1613-6829 (2016).

Wei W, Shin YS, Xue M, Matsutani T, Masui K, Yang H, Ikegami S, Gu Y, Herrmann K, Johnson D, Ding X, Hwang K, Kim J, Zhou J, Su Y, Li X, Bonetti B, Chopra R, James CD, Cavenee WK, Cloughesy TF, Mischel PS, Heath JR, and Gini B. Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma. Cancer Cell, 29:4 563-573 (2016).

Xue Q, Bettini E, Paczkowski P, Ng C, Kaiser A, McConnell T, Kodrasi O, Quigley M, Heath JR, Fan R, Mackay S, Dudley M, Kassim SH, and Zhou J. Novel Multiplexing Technologies for Comprehensive Functional Characterizations of CAR-T Final Products. Presented at BioMAN Workshop 2016.

Heath JR, Ribas A, and Mischel PS. Single-Cell Analysis Tools for Drug Discovery and Development. Nature Reviews Drug Discovery, 15, 204-216 (2016).

Kleppe M, Kwak M, Koppikar P, Riester M, Keller M, Bastian L, Hricik T, Bhagwat N, Abdel-Wahab OI, Marubayashi S, Chen JJ, Romanet V, Fridman JS, Bromberg J, Murakami M, Radimerski T, Michor F, Fan R, and Levine RL. JAK-STAT Pathway Activation in Malignant and Non-Malignant Cells Contributes to MPN Pathogenesis and Therapeutic Response. Cancer Discovery, 5 (3), 316-31 (2015).

Xue M, Wei W, Su Y, Kim J, Shin YS, Mai WX, Nathanson DA, and Heath JR. Chemical Methods for the Simultaneous Quantitation of Metabolites and Proteins from Single Cells. Journal of the American Chemical Society, 137 (12), 4066–4069 (2015).

Xue Q, Lu Y, Eisele MR, Sulistijo E, Fan R, and Miller-Jensen K. Analysis of Single-Cell Secretion Reveals a Role for Paracrine Signaling in Coordinating Macrophage Response to TLR4 Stimulation. Science Signaling, 8, 381 (2015).

Lu Y, Xue Q, Eisele MR, Sulistijo E, Brower K, Han L, Amir ED, Pe’er D, Miller-Jensen K, and Fan R. Highly Multiplexed Profiling of Immune Effector Functions Reveals Deep Functional Heterogeneity in Response to Pathogenic Ligands. Proc. Natl. Acad. Sci., 112 (7), 607-615 (2015).

Kravchenko-Balasha N, Wang J, Remacle F, Levine RD, and Heath JR. Glioblastoma Cellular Architectures are Predicted Through the Characterization Of Two-Cell Interactions. Proc. Natl. Acad. Sci., 111, 6521- 26 (2014).

Zhao JL, Ma C, O'Connell RM, Mehta A, Diloreto R, Heath JR, and Baltimore D. Conversion of Danger Signals into Cytokine Signals by Hematopoietic Stem and Progenitor Cells for Regulation of Stress-Induced Hematopoiesis. Cell Stem Cell, 14(4), 445-459 (2014).

Yu J, Zhou J, Sutherland A, Wei W, Shin YS, Xue M, and Heath JR. Microfluidics-Based Single-Cell Functional Proteomics for Fundamental and Applied Biomedical Applications. Annual Reviews of Analytical Chemistry, 7, 275-295 (2014).

Lin L, Ma C, Wei B, Aziz N, Rajalingam R, Yusung S, Erlich HA, Trachtenberg EA, Targan SR, McGovern DPB, Heath JR, and Braun J. Human NK Cells Licensed by Killer Ig Receptor Genes have an Altered Cytokine Program that Modifies CD4+ T Cell Function. Journal of Immunology, 193, 940-9 (2014).

Elitas M, Brower K, Lu Y, Chen JJ, and Fan R. A Microchip Platform for Interrogating Tumor-Macrophage Paracrine Signaling at the Single-Cell Level. Lab on a Chip, 14, 3582 (2014).

Ma C, Cheung AF, Chodon T, Koya RC, Wu Z, Ng C, Avramis E, Cochran AJ, Witte ON, Baltimore D, Chmielowski B, Economou JS, Comin-Anduix B, Ribas A, and Heath JR. Multifunctional T Cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy. Cancer Discovery, 3, 418 (2013).

Wei W, Shi Q, Remacle F, Qin L, Shackelford DB, Shin YS, Mischel PS, Levine RD, and Heath JR. Hypoxia Induces a Phase Transition within a Kinase Signaling Network in Cancer Cells. Proc. Natl. Acad. Sci., 110 (15), (2013).

Wei W, Shin YS, Ma C, Wang J, Elitas M, Fan R, and Heath JR. Microchip Platforms for Multiplex Single-Cell Functional Proteomics with Applications to Immunology and Cancer Research. Genome Medicine, 5, 75 (2013).

Lu Y, Chen JJ, Mu L, Xue Q, Wu Y, Wu PH, Li J, Vortmeyer AO, Miller-Jensen K, Wirtz D, and Fan R. High-throughput Secretomic Analysis of Single Cells to Assess Functional Cellular Heterogeneity. Analytical Chemistry, 85 (4), 2548– 2556 (2013).

Wang J, Tham D, Wei W, Shin YS, Ma C, Ahmad H, Shi Q, Yu J, Levine RD, and Heath JR. Quantitating Cell-Cell Interaction Functions with Applications to Glioblastoma Multiforme Cancer Cells. Nano Letters, 12 (12), 6101-6106 (2012).

Shi QH, Qin LD, Fan R, Wei W, Guo DL, Shin YS, Hood L, Mischel P, and Heath JR. Single Cell Proteomic Chip for Profiling Intracellular Signaling Pathways in Single Tumor Cells. Proc. Natl. Acad. Sci., 109 (2), 419-424 (2012).

Ma C, Fan R, Ahmad H, Shi Q, Comin-Anduix B, Chodon T, Koya RC, Liu CC, Kwong GA, Radu CG, Ribas A, and Heath JR. A Clinical Microchip for Evaluation of Single Immune Cells Reveals High Functional Heterogeneity in Phenotypically Similar T Cells. Nature Medicine, 17, 738-743 (2011).

Shin YS, Remacle F, Fan R, Hwang K, Wei W, Ahmad H, Levine RD, and Heath JR. Protein Signaling Networks from Single Cell Fluctuations and Information Theory Profiling. Biophysical Journal, 100, 2378-2386 (2011).

Shin YS, Ahmad H, Shi Q, Kim H, Pascal TA, Fan R, Goddard III WA, and Heath JR. Chemistries for Patterning Robust DNA Microbarcodes Enable Multiplex Assays of Cytoplasm Proteins from Single Cancer Cells. Chem. Phys. Chem, 11 (14), 3063-3069 (2010).

Fan R, Vermesh O, Srivastava A, Yen BKH., Qin LD., Ahmad H, Kwong GA, Liu CC, Gould J, Hood L, and Heath JR. Integrated Barcode Chips for Rapid, Multiplexed Analysis of Proteins in Microliter Quantities of Blood. Nature Biotechnology 26, 1373-1378 (2008).

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