Spotlight publications

1. HUMAN CANCER: In this study, multiplex immunofluorescence was used to analyze the staining patterns of 61 antigens on colon cancer samples from 747 patients. Results revealed tumor heterogeneity and offered the ability to map the TOR and MAPK pathways at the single-cell level. This data has served as a source for the development of analysis algorithms currently in use.*

Gerdes MJ, Sevinsky CJ, Sood A, et al. Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11982-7.
http://www.pnas.org/content/110/29/11982.full.pdf

*Note that sophisticated analyses were not available at the time of publication. Single-cell segmentation then cluster analysis was performed. Visualization was done with in house

2. MOUSE STEM CELL: The Coffey lab at Vanderbilt University was an early adopter of Cell DIVE imaging in their work with mouse models to understand stem cell differentiation in the gut. This paper focuses on the tuft cell, a strange cell, which was mostly uncharacterized until this paper. Researchers used Cell DIVE to analyze tuft cell numbers in the small intestine and colon and found two new tuft cell markers. Then used physiological perturbations to characterize tuft cell phenotype.

McKinley ET, Sui Y, Al-Kofahi Y, et al. Optimized multiplex immunofluorescence single-cell analysis reveals tuft cell heterogeneity. JCI Insight. 2017 Jun 2;2(11). pii: 93487.
https://insight.jci.org/articles/view/93487

3. HUMAN CANCER, GLIOMA: This study used different modes of analysis, including genomic sequencing, magnetic resonance imaging (MRI), and multiplexed immunofluorescence, to better understand IDH1 mutant gliomas. These results demonstrate the utility of Cell DIVE in being paired with other modes of study to characterize tumor heterogeneity. Better tumor characterization can lead to an increased understanding of treatment response in genetically different gliomas.

Berens ME, Sood A, Barnholtz-Sloan JS, et al. Multiscale, multimodal analysis of tumor heterogeneity in IDH1 mutant vs wild-type diffuse gliomas. PLoS One. 2019 Dec 27;14(12):e0219724.
https://www.ncbi.nlm.nih.gov/pubmed/31881020

4. HUMAN METASTATIC CANCER: This paper examines the antitumor immune response, identifying homogenous and heterogenous cell patterns within the tumor microenvironment. This work resulted in the development of mathematic and spatial analysis tools with two algorithms to reveal cell interplay within the tumor microenvironment. A correlation between HLA-1 expression in the tumor and cytotoxic T lymphocyte infiltration into the tumor was observed. The use of Cell DIVE imaging in this study allowed for automated selection of regions of interest within the tumors for further analysis with other markers. Tumor microenvironment expression characteristics were found to be associated with patient outcomes. In the future this type of study is essential for the analysis of the response following immunotherapy.

Yan Y, Leontovich AA, Gerdes MJ, et al. Understanding heterogeneous tumor microenvironment in metastatic melanoma. PLoS One. 2019 Jun 5;14(6):e0216485.
https://www.ncbi.nlm.nih.gov/pubmed/31166985

5. HUMAN CANCER: This paper examines samples from relapsed thymoma and thymic carcinoma patients treated with avelumab. Two patients had a positive response and two had a partial response. All experienced adverse events when taking the drug. Cell DIVE imaging was used to characterize the tissues from patients with partial response (pre-treatment and post-treatment).

Rajan A, Heery CR, Thomas A, et al. Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma. J Immunother Cancer. 2019 Oct 21;7(1):269.
https://www.ncbi.nlm.nih.gov/pubmed/31639039

Publications and presentations

  1. Gerdes MJ, Sevinsky CJ, Sood A, et al. Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue. Histopathology. 2013 Jul 16;110(29):11982-7.
    http://www.pnas.org/content/110/29/11982.full.pdf
  2. Clarke GM, Zubovits JT, Shaikh KA, et al. A novel, automated technology for multiplex biomarker imaging and application to breast cancer. Proc Natl Acad Sci U S A. 2014 Jan;64(2):242-55.
    http://onlinelibrary.wiley.com/doi/10.1111/his.12240/full
  3. Surrette C, Shoudy D, Corwin A, et al. Microfluidic Tissue Mesodissection in Molecular Cancer Diagnostics. SLAS Technol. 2017 Aug;22(4):425-430.
    https://journals.sagepub.com/doi/10.1177/2211068216680208
  4. Can A, Bello MO, Cline HE, et al. Multi-modal imaging of histological tissue sections. Published in: 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro. 1008; 288-291.
    http://dx.doi.org/10.1109/ISBI.2008.4540989
  5. Kumar VS, Williams JW, Aggour KS, et al. Collaborative Analysis of High-Content Image Data. In NIST BioImage Informatics Conference. 2015.
    https://isg.nist.gov/BII_2015/webPages/pages/2015_BII_program/PDFs/Day_1/Session_2/Abstract_Kumar_Vijay.pdf
  6. Larriera A, et al. MultiOmyx characterization of embryonic stem cells. Paper presented at: Am. Soc. Cell Biology. December 2014; Philadelphia, PA.
  7. Dinn S, et al. Measurement of multiple biomarkers using a novel fluorescence immunohistochemistry multiplexing technique. In Drug Discovery & Development of Innovative Therapeutics World Congress. 2014; 4–7.
  8. Lazare M. Novel image processing technique allows immunofluorescence signals to resemble traditional H&E stain and enable multiple biomarker visualizations on a single slide. Paper presented at: US & Canadian Academy of Pathology Annual Meeting (USCAP). Mar 2–8 2013; Baltimore, MD.
  9. McCulloch C, et al. System variability study of multiplexed immunofluorescence using cell line microarrays. Paper presented at: Joint Statistical Meetings (JSM). Jul 28–Aug 2 2013; San Diego, CA.
  10. Li Q. et al. Proof of principle: Colocalization of pan cytokeratins (AE1/AE3), pan cytokeratin (PCK26), and cytokeratin 8/18 using an Integrated Sequential Staining and Imaging Device. Paper presented at: International Academy of Digital Pathology (IADP). Aug 3–5, 2011; Quebec City, Canada.
  11. Zubovits J, et al. Novel multiplexing technology in tissue-based biomarker discovery. Paper presented at: Florida Oncology Symposium: Clinical Pathways to Personalized Medicine. May 5–7 2011; Naples, FL.
  12. Rittscher J, et al. (2011). Methods and algorithms for extracting high-content signatures from cells, tissues, and model organisms. Paper presented at: IEEE International Symposium on Biomedical Imaging: From Nano to Macro. Mar 30–Apr 2 2011; Chicago, IL.
  13. Corwin AD, et al. An automated system for performing multiplexed immunohistochemistry. Paper presented at: Materials Research Society (MRS) Fall Meeting. Nov 29–Dec 3 2010; Boston, MA.
  14. Sevinsky C, et al. Multiplexed immunofluorescence in formalin- fixed paraffin-embedded prostate cancer. In Clin Cancer Res 16, (Suppl 2; A28). Paper presented at: AACR International Conference on Translational Cancer Medicine. Jul 11–14 2010; San Francisco, CA.
  15. Manhard CT, et al. Profiling active protein expression in salivary gland using multiplex methodsPaper presented at: American Association for Dental Research (AADR) Annual Meeting. Mar 3–6 2010; Washington, DC.
  16. Li Q, et al. Visualization the heterogeneity of cancer tissue at the molecular level in situ. Paper presented at: EORTC-NCIASCO Annual Meeting on ‘Molecular Markers in Cancer’. Oct 15–17 2009; Brussels, Belgium.
  17. Barash E, et al. Quantitative analysis of protein multiplexes in tissues using multispectral fluorescence imaging. Paper presented at: International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI). Sep 20–24 2009; London, UK.
  18. Dinn S, et al. Measurement of multiple biomarkers using a novel fluorescence immunohistochemistry multiplexing technique. Paper presented at: Annual World Congress on Drug Discovery & Development of Innovative Therapeutics. Aug 4–7 2008; Boston, MA.
  19. Sevinsky CJ, et al. Measurement of multiple biomarkers using a novel fluorescence immunohistochemistry multiplexing technique. Paper presented at: New York State Histotechnological Society (NYSHS) Annual Meeting. Mar 7–8 2008; Saratoga Springs, NY.
  20. Barnhardt NE, et al. Antibody validation: how do we determine speci city? Paper presented at: National Society for Histotechnology. Oct 26–31, 2007; Denver, CO.
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  1. Graf, J.F. and Zavodszky, M.I. Characterizing the heterogeneity of tumor tissues from spatially resolved molecular measures. PloS one, 12 (11),e0188878 (2017). http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188878
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  1. Santamaria-Pang A, Padmanabhan R, Sood A, et al. Robust single cell quantification of immune cell subtypes in histological samples. 2017 IEEE EMBS International Conference on Biomedical & Health Informatics (BHI). 2017; 121-124; Orlando, FL.
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  7. Badve SS, et al. Impact of heterogeneity of DCIS on immune cell infiltrations. Paper presented at San Antonio Breast Cancer Symposium. 2016, November; San Antonio, TX.
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  9. Mansfield AS, et al. Multiplexed immunofluorescence demonstrates tumor infiltrating lymphocytes localize to periphery of primary melanomas but not metastases. Paper presented at: American Soc. Clinical Oncology. May 29–June 2 2015; Chicago, IL.
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  11. . Adams A, et al. MultiOmy: A Novel Chemistry and Visualization Tools To Aid Resolution Of Discrepant Hodgkin Lymphoma Cases-A Single Slide Multiplex Assay For The Evaluation Of Classical Hodgkin Lymphoma. In Blood, 122(21). Paper presented at American Society of Hematology (ASH). Abstract #2994; 2013, December; New Orleans, LA.
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  1. Simmons AJ, Banerjee A, McKinley ET, et al. Cytometry‐based single‐cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF‐α‐induced apoptosis in vivo. Mol Syst Bio. 2015 Oct; 11(10).
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  3. Sevinsky CJ, et al. Multiplexed immunofluorescence imaging and single-cell analysis of MAPK and mTOR signaling in a large cohort of colorectal cancer subjects. Paper presented at Ninth AACR-JCA Joint Conference: Breakthroughs in Basic and Translational Cancer Research. 2013, Feb; Maui, HI.
  4. Sevinsky C, et al. Multiplexed immunofluorescence analysis of hypoxia and tumor microenvironment in localized colorectal cancer. Paper presented at Keystone Symposia Conference, Advances in Hypoxic Signaling: From Bench to Bedside. 2012, Feb. Alberta Canada.
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  1. Gerdes MJ, Gökmen-Polar Y, Sui Y, et al. Single-cell heterogeneity in ductal carcinoma in situ of breast. Mod Pathol. 2018;31(3):406–417.
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  5. Lazare M, et al. New visualization technique enables HER2 immuno uorescence staining to resemble traditional chromogenic DAB stain. Paper presented at: US & Canadian Academy of Pathology Annual Meeting (USCAP). 2013, Mar; Baltimore, MD.
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  1. Sevinsky C. et al. In situ phenotyping of prostate cancer tissue using multiplexed immunouorescent staining and quantitation technology. Paper presented at: WIN Symposium. Abstract P4.02. 2013, July; Paris, France.
  1. Zhang J., et al. Characterization of glioblastoma (GBM) vasculature and protein expression of surrounding tumor cells on single FFPE sections with a multi-cycle multiplexed in situ immunouorescent staining technology. Paper presented at: American Society of Clinical Oncology (ASCO) Annual Meeting. May 31–Jun 4 2013: Chicago, IL . J Clin Oncol; Abstract 2097.
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