Edna (Eti) Cukierman, PhD

This Fox Chase professor participates in the Undergraduate Summer Research Fellowship.
Learn more about Research Volunteering.

Marvin & Concetta Greenberg Chair in Pancreatic Cancer Research

ACS Wilmott Family Professor of Pancreatic Cancer

Co-Leader, Cancer Signaling and Microenvironment Program

Co-Director, Marvin & Concetta Greenberg Pancreatic Cancer Institute

Director, Spatial Immuno-Proteomic Initiative (Highplex Spatial Immunofluorescence)

Research Program

Cancer Signaling and Microenvironment

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
Primed 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

Caneta Brown, MSc, MD

Research Associate

W428

215-214-4218

[email protected]
Janusz Franco-Barraza, MD, PhD

Assistant Research Professor

W428

215-214-4219

[email protected]
Jaye Gardiner, PhD

Assistant Research Professor

W429

215-214-4219

[email protected]
Tiffany Luong, BS

Research Scientist (Sci Tech II)

W428

215-214-4219

[email protected]
Sergio Alcantara Dos Santos, MS, PhD

Postdoctoral Associate

W428

215-214-4219

[email protected]
Mariia Dmitrieva, BS, MS

Research Scientist (Sci Tech II)

W428

215-214-4219

[email protected]
Aleksandr Dolskii, MS, PhD

Postdoctoral Associate

W428

215-214-4219

[email protected]

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.

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

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.

Misc

Resources

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Extramural Affiliations

Selected Publications

My NCBI

Additional Publications

Google Scholar

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