Bio


Zinaida Good, Ph.D. is a postdoctoral fellow working at the intersection of systems biology and cancer immunotherapy at Stanford University. Good’s research with Crystal L. Mackall and Sylvia K. Plevritis is focused on investigating why engineered cellular immunotherapies succeed or fail in patients. Leveraging multimodal single-cell analysis, tumor microenvironment imaging, and data integration, she aims to identify features of optimal engineered T cells from patient data. Good earned her doctorate in computational and systems immunology from Stanford University in 2018, where she trained with Garry P. Nolan and Sean C. Bendall. Her background is in immunology — with bachelor’s and master’s degrees from the University of British Columbia — and oncology, having worked for two years in discovery oncology at Genentech. Good is an inventor on two patent applications, has co-authored 12 papers, published four first-author manuscripts (Good and Sarno et al. Nature Medicine, 2018; Good et al. Nature Biotechnology, 2019; Good et al. Trends in Immunology, 2019; Good and Spiegel et al. Nature Medicine, 2022), and has been named a Parker Institute for Cancer Immunotherapy Scholar, a Stanford Cancer Institute Fellow, and an Arthur and Sandra Irving Cancer Immunology Fellow. Good’s long-term goal is to understand and enhance engineered cellular immunotherapies for patients with cancer.

Academic Appointments


  • Instructor, Stanford Institutes of Medicine

Honors & Awards


  • In-Kind Pilot Project Support: July 6, 2022 – July 5, 2023, 10x Genomics and Parker Institute for Cancer Immunotherapy (2022 – 2023)
  • Arthur and Sandra Irving Fellow, Arthur and Sandra Irving Cancer Immunology Symposium (2022)
  • NK and Irene Cheung Family Scholar, Keystone Symposia (2022)
  • Stanford Cancer Institute Fellow: July 1, 2020 – June 30, 2021, Stanford Cancer Institute (2020 – 2021)
  • ASH 2019 Abstract Achievement Award, American Society of Hematology (2019)
  • Best Q1 2019 Paper (1 of 3 papers selected), Parker Institute for Cancer Immunotherapy (2019)
  • Parker Institute for Cancer Immunotherapy Scholar: April 22, 2018 – May 30, 2020, Parker Institute for Cancer Immunotherapy (2018 – 2020)
  • Keystone Symposium Scholar, Keystone Symposia (2018)
  • CYTO Image Analysis Challenge Finalist, International Society for Advancement of Cytometry (2017)
  • Stanford Biosciences Travel Grant (3 times), Stanford University (2016 – 2018)
  • CYTO Student Travel Award (2 times), International Society for Advancement of Cytometry (2016 – 2017)
  • CYTO Exceptional Student Award Finalist, International Society for Advancement of Cytometry (2016)
  • Featured Wikipedia Editor (2 times), Wikimedia Foundation (2012 – 2013)
  • 4th Prize in Speed Poster Competition, ImmunoVancouver Conference (2011)
  • Member of the DARPA Shredder Challenge Winning Team “All Your Shreds Are Belong to Us”, Defense Advanced Research Projects Agency (2011)
  • 2nd Prize in the Life Sciences Institute Junior Poster Competition, University of British Columbia (2009)
  • Graduate Entrance Scholarship, University of British Columbia (2008)

Boards, Advisory Committees, Professional Organizations


  • Member, Society for Immunotherapy of Cancer (2021 - Present)
  • Member, American Society of Hematology (2019 - Present)
  • Member, Parker Institute for Cancer Immunotherapy (2017 - Present)
  • Associate Member, American Association for Cancer Research (2016 - Present)
  • Member, International Society for the Advancement of Cytometry (2016 - 2018)
  • Member, International Society for Stem Cell Research (2015 - 2016)
  • Member, Canadian Society for Immunology (2009 - 2012)
  • Member, American Association for the Advancement of Science (2009 - 2011)
  • Member, Canadian Student Biotechnology Network (2005 - 2011)

Professional Education


  • Doctor of Philosophy, Stanford University, IMMUN-PHD (2018)
  • Master of Science, University of British Columbia, Microbiology & Immunology (2012)
  • Bachelor of Science, University of British Columbia, Microbiology & Immunology (2008)

Stanford Advisors


All Publications


  • Post-infusion CAR T-Reg cells identify patients resistant to CD19-CAR therapy NATURE MEDICINE Good, Z., Spiegel, J. Y., Sahaf, B., Malipatlolla, M. B., Ehlinger, Z. J., Kurra, S., Desai, M. H., Reynolds, W. D., Lin, A., Vandris, P., Wu, F., Prabhu, S., Hamilton, M. P., Tamaresis, J. S., Hanson, P. J., Patel, S., Feldman, S. A., Frank, M. J., Baird, J. H., Muffly, L., Claire, G. K., Craig, J., Kong, K. A., Wagh, D., Coller, J., Bendall, S. C., Tibshirani, R. J., Plevritis, S. K., Miklos, D. B., Mackall, C. L. 2022

    Abstract

    Approximately 60% of patients with large B cell lymphoma treated with chimeric antigen receptor (CAR) T cell therapies targeting CD19 experience disease progression, and neurotoxicity remains a challenge. Biomarkers associated with resistance and toxicity are limited. In this study, single-cell proteomic profiling of circulating CAR T cells in 32 patients treated with CD19-CAR identified that CD4+Helios+ CAR T cells on day 7 after infusion are associated with progressive disease and less severe neurotoxicity. Deep profiling demonstrated that this population is non-clonal and manifests hallmark features of T regulatory (TReg) cells. Validation cohort analysis upheld the link between higher CAR TReg cells with clinical progression and less severe neurotoxicity. A model combining expansion of this subset with lactate dehydrogenase levels, as a surrogate for tumor burden, was superior for predicting durable clinical response compared to models relying on each feature alone. These data credential CAR TReg cell expansion as a novel biomarker of response and toxicity after CAR T cell therapy and raise the prospect that this subset may regulate CAR T cell responses in humans.

    View details for DOI 10.1038/s41591-022-01960-7

    View details for Web of Science ID 000852940800007

    View details for PubMedID 36097223

  • Advancing T cell-based cancer therapy with single-cell technologies. Nature medicine Bucktrout, S. L., Banovich, N. E., Butterfield, L. H., Cimen-Bozkus, C., Giles, J. R., Good, Z., Goodman, D., Jonsson, V. D., Lareau, C., Marson, A., Maurer, D. M., Munson, P. V., Stubbington, M., Taylor, S., Cutchin, A. 2022; 28 (9): 1761-1764

    View details for DOI 10.1038/s41591-022-01986-x

    View details for PubMedID 36127419

  • Identification of cell types in multiplexed in situ images by combining protein expression and spatial information using CELESTA. Nature methods Zhang, W., Li, I., Reticker-Flynn, N. E., Good, Z., Chang, S., Samusik, N., Saumyaa, S., Li, Y., Zhou, X., Liang, R., Kong, C. S., Le, Q., Gentles, A. J., Sunwoo, J. B., Nolan, G. P., Engleman, E. G., Plevritis, S. K. 2022

    Abstract

    Advances in multiplexed in situ imaging are revealing important insights in spatial biology. However, cell type identification remains a major challenge in imaging analysis, with most existing methods involving substantial manual assessment and subjective decisions for thousands of cells. We developed an unsupervised machine learning algorithm, CELESTA, which identifies the cell type of each cell, individually, using the cell's marker expression profile and, when needed, its spatial information. We demonstrate the performance of CELESTA on multiplexed immunofluorescence images of colorectal cancer and head and neck squamous cell carcinoma (HNSCC). Using the cell types identified by CELESTA, we identify tissue architecture associated with lymph node metastasis in HNSCC, and validate our findings in an independent cohort. By coupling our spatial analysis with single-cell RNA-sequencing data on proximal sections of the same specimens, we identify cell-cell crosstalk associated with lymph node metastasis, demonstrating the power of CELESTA to facilitate identification of clinically relevant interactions.

    View details for DOI 10.1038/s41592-022-01498-z

    View details for PubMedID 35654951

  • GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature Majzner, R. G., Ramakrishna, S., Yeom, K. W., Patel, S., Chinnasamy, H., Schultz, L. M., Richards, R. M., Jiang, L., Barsan, V., Mancusi, R., Geraghty, A. C., Good, Z., Mochizuki, A. Y., Gillespie, S. M., Toland, A. M., Mahdi, J., Reschke, A., Nie, E., Chau, I. J., Rotiroti, M. C., Mount, C. W., Baggott, C., Mavroukakis, S., Egeler, E., Moon, J., Erickson, C., Green, S., Kunicki, M., Fujimoto, M., Ehlinger, Z., Reynolds, W., Kurra, S., Warren, K. E., Prabhu, S., Vogel, H., Rasmussen, L., Cornell, T. T., Partap, S., Fisher, P. G., Campen, C. J., Filbin, M. G., Grant, G., Sahaf, B., Davis, K. L., Feldman, S. A., Mackall, C. L., Monje, M. 2022

    Abstract

    Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMG) are universally lethal paediatric central nervous system tumours1. We previously discovered that the disialoganglioside GD2 is highly expressed on H3K27M-mutant glioma cells and demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells2, providing the rationale for a first-in-human Phase 1 clinical trial (NCT04196413). Because CAR T-cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure, and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutant DIPG/DMG treated with GD2-CAR T cells (GD2-CART) at dose level 1 (1e6 GD2-CAR T cells/kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T infusions administered intracerebroventricularly3. Toxicity was largely related to tumor location and reversible with intensive supportive care. On-target, off-tumor toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Proinflammatory cytokines were increased in plasma and cerebrospinal fluid (CSF). Transcriptomic analyses of 65,598 single cells from CAR T cell products and CSF elucidate heterogeneity in response between subjects and administration routes. These early results underscore the promise of this approach for H3K27M+ DIPG/DMG therapy.

    View details for DOI 10.1038/s41586-022-04489-4

    View details for PubMedID 35130560

  • SINGLE CELL RNA SEQUENCING FROM THE CSF OF SUBJECTS WITH H3K27M+DIPG/DMG TREATED WITH GD2 CAR T-CELLULAR THERAPY Mochizuki, A., Ramakrishna, S., Good, Z., Patel, S., Chinnasamy, H., Yeom, K., Schultz, L., Richards, R., Campen, C., Reschke, A., Mahdi, J., Toland, A., Baggot, C., Mavroukakis, S., Egeler, E., Moon, J., Landrum, K., Erickson, C., Rasmussen, L., Barsan, V., Tamaresis, J., Marcy, A., Kunicki, M., Celones, M., Ehlinger, Z., Kurra, S., Cornell, T., Partap, S., Fisher, P., Grant, G., Vogel, H., Davis, K., Feldman, S., Sahaf, B., Majzner, R., Mackall, C., Monje, M. OXFORD UNIV PRESS INC. 2021: 39
  • Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling. Science (New York, N.Y.) Weber, E. W., Parker, K. R., Sotillo, E., Lynn, R. C., Anbunathan, H., Lattin, J., Good, Z., Belk, J. A., Daniel, B., Klysz, D., Malipatlolla, M., Xu, P., Bashti, M., Heitzeneder, S., Labanieh, L., Vandris, P., Majzner, R. G., Qi, Y., Sandor, K., Chen, L., Prabhu, S., Gentles, A. J., Wandless, T. J., Satpathy, A. T., Chang, H. Y., Mackall, C. L. 2021; 372 (6537)

    Abstract

    T cell exhaustion limits immune responses against cancer and is a major cause of resistance to chimeric antigen receptor (CAR)-T cell therapeutics. Using murine xenograft models and an in vitro model wherein tonic CAR signaling induces hallmark features of exhaustion, we tested the effect of transient cessation of receptor signaling, or rest, on the development and maintenance of exhaustion. Induction of rest through enforced down-regulation of the CAR protein using a drug-regulatable system or treatment with the multikinase inhibitor dasatinib resulted in the acquisition of a memory-like phenotype, global transcriptional and epigenetic reprogramming, and restored antitumor functionality in exhausted CAR-T cells. This work demonstrates that rest can enhance CAR-T cell efficacy by preventing or reversing exhaustion, and it challenges the notion that exhaustion is an epigenetically fixed state.

    View details for DOI 10.1126/science.aba1786

    View details for PubMedID 33795428

  • Molecular Imaging of Chimeric Antigen Receptor T Cells by ICOS-ImmunoPET. Clinical cancer research : an official journal of the American Association for Cancer Research Simonetta, F., Alam, I. S., Lohmeyer, J. K., Sahaf, B., Good, Z., Chen, W., Xiao, Z., Hirai, T., Scheller, L., Engels, P., Vermesh, O., Robinson, E., Haywood, T., Sathirachinda, A., Baker, J., Malipatlolla, M. B., Schultz, L. M., Spiegel, J. Y., Lee, J. T., Miklos, D. B., Mackall, C. L., Gambhir, S. S., Negrin, R. 2020

    Abstract

    PURPOSE: Immunomonitoring of chimeric antigen receptor (CAR) T cells relies primarily on their quantification in the peripheral blood, which inadequately quantifies their biodistribution and activation status in the tissues. Non-invasive molecular imaging of CAR T cells by positron emission tomography (PET) is a promising approach with the ability to provide spatial, temporal and functional information. Reported strategies rely on the incorporation of reporter transgenes or ex vivo biolabeling, significantly limiting the application of CAR T cell molecular imaging. In the present study, we assessed the ability of antibody-based PET (immunoPET) to non-invasively visualize CAR T cells.EXPERIMENTAL DESIGN: After analyzing human CAR T cells in vitro and ex vivo from patient samples to identify candidate targets for immunoPET, we employed a syngeneic, orthotopic murine tumor model of lymphoma to assess the feasibility of in vivo tracking of CAR T cells by immunoPET using the 89Zr-DFO-anti-ICOS tracer we previously reported.RESULTS: Analysis of human CD19-CAR T cells during activation identified the Inducible T-cell COStimulator (ICOS) as a potential target for immunoPET. In a preclinical tumor model, 89Zr-DFO-ICOS mAb PET-CT imaging detected significantly higher signal in specific bone marrow-containing skeletal sites of CAR T cell treated mice compared with controls. Importantly, administration of ICOS-targeting antibodies at tracer doses did not interfere with CAR T cell persistence and function.CONCLUSIONS: This study highlights the potential of ICOS-immunoPET imaging for monitoring of CAR T cell therapy, a strategy readily applicable to both commercially available and investigational CAR T cells.

    View details for DOI 10.1158/1078-0432.CCR-20-2770

    View details for PubMedID 33087332

  • Reversal of epigenetic aging and immunosenescent trends in humans. Aging cell Fahy, G. M., Brooke, R. T., Watson, J. P., Good, Z., Vasanawala, S. S., Maecker, H., Leipold, M. D., Lin, D. T., Kobor, M. S., Horvath, S. 2019: e13028

    Abstract

    Epigenetic "clocks" can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many age-related diseases, and a mean epigenetic age approximately 1.5years less than baseline after 1year of treatment (-2.5-year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from -1.6year/year from 0-9month to -6.5year/year from 9-12month. The GrimAge predictor of human morbidity and mortality showed a 2-year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention.

    View details for DOI 10.1111/acel.13028

    View details for PubMedID 31496122

  • Computational and Systems Immunology: A Student's Perspective. Trends in immunology Good, Z., Glanville, J., Gee, M. H., Davis, M. M., Khatri, P. 2019

    Abstract

    The big data revolution has transformed the landscape of immunology research. As inaugural students of Stanford's new Computational and Systems Immunology PhD track, we share our experiences and advice with other institutions considering a similar program.

    View details for DOI 10.1016/j.it.2019.06.006

    View details for PubMedID 31288986

  • Proliferation tracing with single-cell mass cytometry optimizes generation of stem cell memory-like T cells. Nature biotechnology Good, Z., Borges, L., Vivanco Gonzalez, N., Sahaf, B., Samusik, N., Tibshirani, R., Nolan, G. P., Bendall, S. C. 2019

    Abstract

    Selective differentiation of naive T cells into multipotent T cells is of great interest clinically for the generation of cell-based cancer immunotherapies. Cellular differentiation depends crucially on division state and time. Here we adapt a dye dilution assay for tracking cell proliferative history through mass cytometry and uncouple division, time and regulatory protein expression in single naive human T cells during their activation and expansion in a complex ex vivo milieu. Using 23 markers, we defined groups of proteins controlled predominantly by division state or time and found that undivided cells account for the majority of phenotypic diversity. We next built a map of cell state changes during naive T-cell expansion. By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype. This method for tracing cell fate across division states and time can be broadly applied for directing cellular differentiation.

    View details for PubMedID 30742126

  • c-Jun overexpression in CAR T cells induces exhaustion resistance. Nature Lynn, R. C., Weber, E. W., Sotillo, E. n., Gennert, D. n., Xu, P. n., Good, Z. n., Anbunathan, H. n., Lattin, J. n., Jones, R. n., Tieu, V. n., Nagaraja, S. n., Granja, J. n., de Bourcy, C. F., Majzner, R. n., Satpathy, A. T., Quake, S. R., Monje, M. n., Chang, H. Y., Mackall, C. L. 2019

    Abstract

    Chimeric antigen receptor (CAR) T cells mediate anti-tumour effects in a small subset of patients with cancer1-3, but dysfunction due to T cell exhaustion is an important barrier to progress4-6. To investigate the biology of exhaustion in human T cells expressing CAR receptors, we used a model system with a tonically signaling CAR, which induces hallmark features of exhaustion6. Exhaustion was associated with a profound defect in the production of IL-2, along with increased chromatin accessibility of AP-1 transcription factor motifs and overexpression of the bZIP and IRF transcription factors that have been implicated in mediating dysfunction in exhausted T cells7-10. Here we show that CAR T cells engineered to overexpress the canonical AP-1 factor c-Jun have enhanced expansion potential, increased functional capacity, diminished terminal differentiation and improved anti-tumour potency in five different mouse tumour models in vivo. We conclude that a functional deficiency in c-Jun mediates dysfunction in exhausted human T cells, and that engineering CAR T cells to overexpress c-Jun renders them resistant to exhaustion, thereby addressing a major barrier to progress for this emerging class of therapeutic agents.

    View details for DOI 10.1038/s41586-019-1805-z

    View details for PubMedID 31802004

  • Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse. Nature medicine Good, Z., Sarno, J., Jager, A., Samusik, N., Aghaeepour, N., Simonds, E. F., White, L., Lacayo, N. J., Fantl, W. J., Fazio, G., Gaipa, G., Biondi, A., Tibshirani, R., Bendall, S. C., Nolan, G. P., Davis, K. L. 2018; 24 (4): 474–83

    Abstract

    Insight into the cancer cell populations that are responsible for relapsed disease is needed to improve outcomes. Here we report a single-cell-based study of B cell precursor acute lymphoblastic leukemia at diagnosis that reveals hidden developmentally dependent cell signaling states that are uniquely associated with relapse. By using mass cytometry we simultaneously quantified 35 proteins involved in B cell development in 60 primary diagnostic samples. Each leukemia cell was then matched to its nearest healthy B cell population by a developmental classifier that operated at the single-cell level. Machine learning identified six features of expanded leukemic populations that were sufficient to predict patient relapse at diagnosis. These features implicated the pro-BII subpopulation of B cells with activated mTOR signaling, and the pre-BI subpopulation of B cells with activated and unresponsive pre-B cell receptor signaling, to be associated with relapse. This model, termed 'developmentally dependent predictor of relapse' (DDPR), significantly improves currently established risk stratification methods. DDPR features exist at diagnosis and persist at relapse. By leveraging a data-driven approach, we demonstrate the predictive value of single-cell 'omics' for patient stratification in a translational setting and provide a framework for its application to human cancer.

    View details for PubMedID 29505032

  • Automated mapping of phenotype space with single-cell data NATURE METHODS Samusik, N., Good, Z., Spitzer, M. H., Davis, K. L., Nolan, G. P. 2016; 13 (6): 493-?

    Abstract

    Accurate identification of cell subsets in complex populations is key to discovering novelty in multidimensional single-cell experiments. We present X-shift (http://web.stanford.edu/~samusik/vortex/), an algorithm that processes data sets using fast k-nearest-neighbor estimation of cell event density and arranges populations by marker-based classification. X-shift enables automated cell-subset clustering and access to biological insights that 'prior knowledge' might prevent the researcher from discovering.

    View details for DOI 10.1038/NMETH.3863

    View details for Web of Science ID 000377480100015

    View details for PubMedID 27183440

    View details for PubMedCentralID PMC4896314

  • Lymph node-independent liver metastasis in a model of metastatic colorectal cancer NATURE COMMUNICATIONS Enquist, I. B., Good, Z., Jubb, A. M., Fuh, G., Wang, X., Junttila, M. R., Jackson, E. L., Leong, K. G. 2014; 5

    Abstract

    Deciphering metastatic routes is critically important as metastasis is a primary cause of cancer mortality. In colorectal cancer (CRC), it is unknown whether liver metastases derive from cancer cells that first colonize intestinal lymph nodes, or whether such metastases can form without prior lymph node involvement. A lack of relevant metastatic CRC models has precluded investigations into metastatic routes. Here we describe a metastatic CRC mouse model and show that liver metastases can manifest without a lymph node metastatic intermediary. Colorectal tumours transplanted onto the colonic mucosa invade and metastasize to specific target organs including the intestinal lymph nodes, liver and lungs. Importantly, this metastatic pattern differs from that observed following caecum implantation, which invariably involves peritoneal carcinomatosis. Anti-angiogenesis inhibits liver metastasis, yet anti-lymphangiogenesis does not impact liver metastasis despite abrogating lymph node metastasis. Our data demonstrate direct hematogenous spread as a dissemination route that contributes to CRC liver malignancy.

    View details for DOI 10.1038/ncomms4530

    View details for Web of Science ID 000334302800003

    View details for PubMedID 24667486

  • Biomarkers of Residual Disease, Disseminated Tumor Cells, and Metastases in the MMTV-PyMT Breast Cancer Model PLOS ONE Franci, C., Zhou, J., Jiang, Z., Modrusan, Z., Good, Z., Jackson, E., Kouros-Mehr, H. 2013; 8 (3)

    Abstract

    Cancer metastases arise in part from disseminated tumor cells originating from the primary tumor and from residual disease persisting after therapy. The identification of biomarkers on micro-metastases, disseminated tumors, and residual disease may yield novel tools for early detection and treatment of these disease states prior to their development into metastases and recurrent tumors. Here we describe the molecular profiling of disseminated tumor cells in lungs, lung metastases, and residual tumor cells in the MMTV-PyMT breast cancer model. MMTV-PyMT mice were bred with actin-GFP mice, and focal hyperplastic lesions from pubertal MMTV-PyMT;actin-GFP mice were orthotopically transplanted into FVB/n mice to track single tumor foci. Tumor-bearing mice were treated with TAC chemotherapy (docetaxel, doxorubicin, cyclophosphamide), and residual and relapsed tumor cells were sorted and profiled by mRNA microarray analysis. Data analysis revealed enrichment of the Jak/Stat pathway, Notch pathway, and epigenetic regulators in residual tumors. Stat1 was significantly up-regulated in a DNA-damage-resistant population of residual tumor cells, and a pre-existing Stat1 sub-population was identified in untreated tumors. Tumor cells from adenomas, carcinomas, lung disseminated tumor cells, and lung metastases were also sorted from MMTV-PyMT transplant mice and profiled by mRNA microarray. Whereas disseminated tumors cells appeared similar to carcinoma cells at the mRNA level, lung metastases were genotypically very different from disseminated cells and primary tumors. Lung metastases were enriched for a number of chromatin-modifying genes and stem cell-associated genes. Histone analysis of H3K4 and H3K9 suggested that lung metastases had been reprogrammed during malignant progression. These data identify novel biomarkers of residual tumor cells and disseminated tumor cells and implicate pathways that may mediate metastasis formation and tumor relapse after therapy.

    View details for DOI 10.1371/journal.pone.0058183

    View details for Web of Science ID 000318679900052

    View details for PubMedID 23520493

    View details for PubMedCentralID PMC3592916

  • Heterotrimeric G(i)/G(o) proteins modulate endothelial TLR signaling independent of the MyD88-dependent pathway AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Dauphinee, S. M., Voelcker, V., Tebaykina, Z., Wong, F., Karsan, A. 2011; 301 (6): H2246-H2253

    Abstract

    The innate immune recognition of bacterial lipopolysaccharide (LPS) is mediated by Toll-like receptor 4 (TLR4) and results in activation of proinflammatory signaling including NF-κB and MAPK pathways. Heterotrimeric G proteins have been previously implicated in LPS signaling in macrophages and monocytes. In the present study, we show that pertussis toxin sensitive heterotrimeric G proteins (Gα(i/o)) are involved in the activation of MAPK and Akt downstream of TLR2, TLR3, and TLR4 in endothelial cells. Gα(i/o) are also required for full activation of interferon signaling downstream of TLR3 and TLR4 but are not required for the activation of NF-κB. We find that Gα(i/o)-mediated activation of the MAPK is independent of the canonical MyD88, interleukin-1 receptor-associated kinase, and tumor necrosis factor receptor-associated factor 6 signaling cascade in LPS-stimulated cells. Taken together, the data presented here suggest that heterotrimeric G proteins are widely involved in TLR pathways along a signaling cascade that is distinct from MyD88-TRAF6.

    View details for DOI 10.1152/ajpheart.01194.2010

    View details for Web of Science ID 000298325200009

    View details for PubMedID 21949112

  • Understanding the Mechanism of Virus Removal by Q Sepharose Fast Flow Chromatography During the Purification of CHO-Cell Derived Biotherapeutics BIOTECHNOLOGY AND BIOENGINEERING Strauss, D. M., Lute, S., Tebaykina, Z., Frey, D. D., Ho, C., Blank, G. S., Brorson, K., Chen, Q., Yang, B. 2009; 104 (2): 371-380

    Abstract

    During production of therapeutic monoclonal antibodies (mAbs) in mammalian cell culture, it is important to ensure that viral impurities and potential viral contaminants will be removed during downstream purification. Anion exchange chromatography provides a high degree of virus removal from mAb feedstocks, but the mechanism by which this is achieved has not been characterized. In this work, we have investigated the binding of three viruses to Q sepharose fast flow (QSFF) resin to determine the degree to which electrostatic interactions are responsible for viral clearance by this process. We first used a chromatofocusing technique to determine the isoelectric points of the viruses and established that they are negatively charged under standard QSFF conditions. We then determined that virus removal by this chromatography resin is strongly disrupted by the presence of high salt concentrations or by the absence of the positively charged Q ligand, indicating that binding of the virus to the resin is primarily due to electrostatic forces, and that any non-electrostatic interactions which may be present are not sufficient to provide virus removal. Finally, we determined the binding profile of a virus in a QSFF column after a viral clearance process. These data indicate that virus particles generally behave similarly to proteins, but they also illustrate the high degree of performance necessary to achieve several logs of virus reduction. Overall, this mechanistic understanding of an important viral clearance process provides the foundation for the development of science-based process validation strategies to ensure viral safety of biotechnology products.

    View details for DOI 10.1002/bit.22416

    View details for Web of Science ID 000269846900015

    View details for PubMedID 19575414