Edna (Eti) Cukierman, PhD

Edna Cukierman
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This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
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Lab Overview

The Cukierman Laboratory is focused on understanding how desmoplasia, the dense mesenchymal microenvironment surrounding solid epithelial tumors, affects tumor progression. The team uses a unique 3D culturing system that mimics the in vivo mesenchymal stroma to study the functional roles of desmoplasia in tumorigenic behaviors. They have developed Harmonic Output of Stromal Traits (HOST), a novel method for identifying tumor microenvironment (TME) cells and HOST-Factor, a numerical metric that quantifies their functional states. These tools allow the laboratory to assess the relative contribution of the main functional unit composed of cancer-associated fibroblasts (CAFs) and CAF-generated extracellular matrix (ECM), as well as the units' interaction with other TME cells (e.g., immune cells, nerves, cancer cells and more) to impart tumor-supportive or tumor-suppressive functions. They are also investigating whether HOST-Factor values can serve as TME-based prognostic indicators for patient outcomes and predict or inform on drug efficacy.

  • 3D-adhesions formed within in vivo-like fibroblast-derived extracellular matrix

  • Normal fibroblast-derived 3D culture

    Normal fibroblast-derived 3D culture

  • Primed fibroblast-derived 3D culture

    Primed fibroblast-derived 3D culture

  • Tumor-associated fibroblast-derived 3D culture

    Tumor-associated fibroblast-derived 3D culture

  • Normal fibroblasts on 2D or within normal, primed or tumor-associated 3D ECMs

  • DIC and immunofluorescence; during ECM production

  • Tracks of invasive cells moving through control or tumor-associated ECMs

  • Same cell different substrates; 2D vs. 3D adhesion structures

  • Model illustrating production of murine fibroblast-derived 3D matrices

  • Staged in vivo-like 3D stromal matrices; fibronectin (green) and collagen (red)

  • Tumor microenvironment (desmoplasia)

  • Human fibroblast within in vivo-like ECM

  • Simultaneous Multi-Channel Immunofluorescence Analysis (SMIA)

  • Cukierman lab staff, 2015

  • Human Pancreatic Cancer - NetrinG1 stroma expression

  • Some members of the M&C Greenberg Pancreatic Cancer Institute 2020

    New Target Could Starve Cancer and Activate Immune System in Fight Against Pancreatic Cancer

    Researchers at Fox Chase Cancer Center have identified a new biomarker and potential novel treatment target for pancreatic ductal adenocarcinoma (PDAC) that could help starve cancer cells and allow the immune system to attack the tumor. Read the full article here.

    Educational Background

    • Postdoctoral Fellow, Craniofacial Developmental Biology and Regeneration Branch (Mentor- Dr. Kenneth M. Yamada), NIH/National Institute of Dental and Craniofacial Research, 1997-2002
    • PhD, Molecular and Cell Biology, Technion-Israel Institute of Technology, 1997
    • MS, Biochemistry, Technion-Israel Institute of Technology, 1993
    • BS, Biology, Technion-Israel Institute of Technology, 1991

    Honors & Awards

    • ACS-Wilmott Family Professor of Pancreatic Cancer 2024 – date (Inaugural Award)
    • AACR TME Working Group Chair 2024-2026
    • Pancreatic Cancer Cure Foundation Award 2021, 2023-2024
    • DOD - Pancreatic Cancer Idea Development Award (Mentoring PI/partner)
    • Israel Binational Science Foundation (BSF) Award 2022
    • 5Senior Editor of Tumor Biology Section – Cancer research Communications (AACR Journal) 2021-date
    • American Gastroenterological Association (AGA) Inducted Fellow, 2020
    • American Society of Matrix Biology (ASMB) Elected Council Member, 2020-2023
    • Worldwide Cancer Research Foundation Award, 2020-2021
    • American Society of Matrix Biology (ASMB) Image Award (dual honor), 2019-2020
    • 5th District AHEPA Cancer Research Foundation, Inc. Award, 2019 – date
    • Distinguished Achievement Award in Cancer Research and Clinical Management –Focus in Pancreas- by the Chinese Society of Clinical Oncology (Chinese’s ASCO), 2016
    • DOD Idea Award with Special Focus in Pancreatic Cancer , 2015-2017
    • Image featured at Dulles and PLH Airports (“Life Magnified” by NIH/ASCB), 2014
    • Member of NIH/NCI’s Tumor Progression and Metastasis Study Section, 2013-2019
    • Temple-FCCC Nodal Award, 2013-2015
    • AACR Career Development Award (continuation from 2004), 2006-2007
    • Olympus BioScapes Digital Imaging Competition (Honorable Mention Award), 2006
    • W.W. Smith Charitable Trust Award, 2005-2008
    • Nikon Small World Competition (Image Distinction Award), 2005
    • AACR Career Development Award, 2004-2006
    • National Pancreas Foundation Award, 2004-2005
    • Fellows Award for Research Excellence at the NIH, 2002

    People

    Additional Staff

    Former Personnel
    Ashish Abraham
    Jennifer Alexander
    Michael Amatangelo
    Daniel Bassi
    Dorothy Beacham
    Leila Borghaei
    Kimberly Brown
    Miranda Burdiel-Herencia
    Remedios Castelló-Cros
    Lauren Cheifitz
    Gil Cukierman
    Jonte Desire
    Xiaoshen Dong
    Stephanie Elbe
    James Flaherty
    Ralph Francescone
    Sarah Goldston
    Vivekanad Gupta
    Kelci R. Holman
    David Khan
    Melissa Lech
    Raj Madhani
    Ruchi Malik
    Emily Malloy
    Charline Ogier
    Christopher Price
    Cassidy Poon
    Roderick Quiros
    Kristopher Raghavan
    Poornima Rao
    Mastan Rao Chintalapudi
    Rebecca Roth
    Dustin Rollins
    Brad Rybinski
    Neelima Shah
    Jeffery Simons
    Jerry So
    Julie Sosa
    Matthildi Valianou
    Debora B Vendramini Costa
    Fernanda Villamar
    Olga Villamar
    Corinne Watson
    Gary Wilk
    Galia Wilk
    Stephanie Wirtshafter
    Daniel Zinshteyn
    Alexander Zenin

    Research Interests

    Desmoplastic Tumor Microenvironment (TME)

    Multicolor microscopy image of human pancreatic cancer. Red areas depict cancer cells and cyan marks the desmoplastic tumor microenvironment, which is enriched in fibroblastic cells positive for 3D-adhesions (evident in cyan areas marked by lighter yellow/white colors).  Note the vast areas covered by the fibrous (cyan) desmoplasia in comparison to the modest amounts of cancer cells (red).Image credit: Neelima Shah and Edna Cukierman.
    Multicolor microscopy image of human pancreatic cancer. Red areas depict cancer cells and cyan marks the desmoplastic tumor microenvironment, which is enriched in fibroblastic cells positive for 3D-adhesions (evident in cyan areas marked by lighter yellow/white colors). Note the vast areas covered by the fibrous (cyan) desmoplasia in comparison to the modest amounts of cancer cells (red).Image credit: Neelima Shah and Edna Cukierman.

     

    • The role of desmoplasia, the dense mesenchymal microenvironment of solid tumors, in tumor progression.
    • Use of unique 3D culturing system to mimic the in vivo mesenchymal stroma and study the functional roles of desmoplasia.
    • Developing of Harmonic Output of Stromal Traits (HOST), a method for identifying TME cells, and HOST-Factor, a numerical metric that quantifies their functional states.
    • Assess the relative contribution of the main functional unit composed of cancer-associated fibroblasts (CAFs) and CAF-generated extracellular matrix (ECM) to tumor-supportive or tumor-suppressive functions.
    • A workflow that leverages automated cycling highplex immunofluorescent microscopy coupled with AI-guided image analysis to generate HOST-Factor values for each identified TME cell.
    • Query whether HOST-Factor values can serve as TME-based prognostic indicators for patient outcomes and predict or inform on drug efficacy.
    • Development of novel/future therapeutic strategies to target the TME.

     

    Lab Overview

    Cartoon depicting approaches commonly used by the Cukierman team to study desmoplastic stroma influences on tumorigenesis. Fresh surgical sample pairs of tumor and benign adjacent tissue are used to harvest fibroblastic cells, which are used to generate CDMs. The 3D cultures can be treated to extract the original cells, leaving the natural scaffold as a thin 3D coating material that can serve for culturing new cells. A plethora of cells, including fibroblasts, cancer cells, immune cells, nerves and more can
    Cartoon depicting the methodologies used to study desmoplastic stroma influences on tumorigenesis. Fresh surgical sample pairs of tumor and benign adjacent tissue are used to harvest fibroblastic cells, which are used to generate fibroblastic/ECM functional units. The 3D cultures can be treated to extract the original cells, leaving the natural scaffold as a thin 3D coating material that can serve for culturing new cells. A plethora of cells, including fibroblasts, cancer cells, immune cells, nerves and more can then be study, independently or in combination with other cells, while these reside within the fibroblastic unit-generated ECMs (known as CDMs). Results are then validated in xenografted, human or syngeneic murine, orthotopic and genetic mice models. Validations are conducted using Spatial immuno-proteomics via highplex immunofluorescence .

     

    The Cukierman Laboratory is dedicated to understanding the complex interplay between desmoplasia, the dense mesenchymal microenvironment of solid tumors, and tumor progression. Utilizing a unique 3D culturing system that mimics the in vivo mesenchymal stroma, the laboratory investigates the functional roles of desmoplasia in tumorigenic behaviors, including invasive spread, metabolic support, and immune suppression.

     

    Leveraging a multifaceted approach that integrates cell biological and bioengineering techniques, the Cukierman team has developed Harmonic Output of Stromal Traits (HOST), a novel method for identifying tumor microenvironment (TME) cells and HOST-Factor, a numerical metric that quantifies their functional states. These tools enable the laboratory to assess the relative contribution of the main functional unit composed of cancer-associated fibroblasts (CAFs) and CAF-generated extracellular matrix (ECM), as well as the units’ interaction with other TME cells to impart tumor-supportive or tumor-suppressive functions.

     

    Human pancreatic cancer pathological sample showing a pro-tumor desmoplastic phenotype. Image adapted from Alexander & Cukierman Matrix Biology 2020 and depicts central discoveries included in Franco-Barraza et al eLife 2017. Image credit Neelima Shah and Edna Cukierman
    Human pancreatic cancer pathological sample showing a pro-tumor desmoplastic phenotype. Image adapted from Alexander & Cukierman Matrix Biology 2020 and depicts central discoveries included in Franco-Barraza et al eLife 2017. Image credit Neelima Shah and Edna Cukierman

    Ongoing research within the Cukierman Laboratory seeks to uncover key mechanisms of CAF/ECM unit functions, identify new stromal targets, and develop stroma targeting modalities. Additionally, the laboratory is investigating whether HOST-Factor values can serve as TME-based prognostic indicators for patient outcomes and predict or inform on drug efficacy. Moreover, the team is exploring the potential influence of macro-environmental factors, such as residing in low socioeconomic status (nSES) neighborhoods, in exacerbating the pro-cancer TME function.

     

    In summary, the Cukierman Laboratory is at the forefront of desmoplasia research, employing a unique 3D culturing system, novel analytical tools, and a multifaceted approach to unravel the complexities of this critical TME component. The laboratory's findings hold promise for the development of novel therapeutic strategies that target the desmoplasia-tumor interactions, ultimately improving patient outcomes for solid epithelial cancers.

    Signaling NetG1 axis. Cartoon depicting the signaling pathways and resulting cell functions driven by NetG1 in CAFs as reported in Francescone & Vendramini-Costa et al Cancer Discovery 2020.
    Signaling NetG1 axis. Cartoon depicting the signaling pathways and resulting cell functions driven by NetG1 in CAFs as reported in Francescone & Vendramini-Costa et al Cancer Discovery 2021.

     

     

     

     

     

     

     

     

     

    Selected Publications

    Additional Publications

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