Edna Cukierman

Last updated
Eti Cukierman
Edna Cukierman CDMRP photo.jpg
Cukierman in a Congressionally Directed Medical Research Programs (CDMRP) photo, 2018
Born
Edna Cukierman

Alma mater Technion – Israel Institute of Technology
Scientific career
Fields Tumor microenvironment
Cancer associated fibroblasts
Extracellular matrix
Pancreatic cancer
Desmoplasia [1]
Institutions National Institute of Dental and Craniofacial Research
Fox Chase Cancer Center
Thesis Molecular characterization of an ARF directed GTPase activating protein  (1997)
Doctoral students Jaye Gardiner
Website www.foxchase.org/edna-cukierman OOjs UI icon edit-ltr-progressive.svg

Edna "Eti" Cukierman is a Mexican biochemist who is a professor at the Fox Chase Cancer Center. [1] [2] She serves as co-director of the Marvin & Concetta Greenberg Pancreatic Cancer Institute. Her research investigates pancreatic cancer and the tumor microenvironment.

Contents

Early life and education

Cukierman was born in Mexico City. [3] She emigrated to Israel in 1986. [3] She joined Technion – Israel Institute of Technology for her doctoral research, where she studied ARF directed GTPase. [4] [5]

Research and career

After her PhD, Cukierman was awarded a postdoctoral fellowship in 1997, and joined the National Institute of Dental and Craniofacial Research. [3] She developed a multilayered fibroblastic cell-derived extracellular matrix, which became widely used in biomaterials research. [6] [7]

Cukierman joined the Fox Chase Cancer Center in 2002. [3] She studies pancreatic cancer, with a specific focus on the tumor microenvironment and the identification of strategies that can change the tumor microenvironment. [8] Desmoplasia, which is the growth of connective tissue, shows similarities to wound healing pathologies (e.g. chronic inflammation). [9] [10] She believes it will be possible to stall the growth of tumors by transforming the microenvironment into one which harnesses anti-tumor functions. [11]

In 2005, Cukierman demonstrated that desmoplastic extracellular matrices could induce a myofibroblastic phenotype on naïve fibroblastic cells. [12] This work involved the realization of a human mimetic three-dimensional stroma system, which allowed Cukierman to understand the extracellular factors that determine the function of fibroblasts. [12] Through multi-cellular culturing, Cukierman has shown how cancer-associated fibroblasts impart immunosuppressive influences, communicate and provide nutrition to cancer cells. [12] She identified that cancer communication involved the TGF beta signaling pathway, extracellular matrix and integrin signalling pathway and the reorganization of cytoskeletal elements. [13] She demonstrated that the glutamatergic presynaptic protein Netrin G1 promoted tumorgenesis by providing nutritional support and immunity to cancer-associated fibroblasts. [14] She has shown that anti-Netrin G1 antibodies can halt tumorgenesis. [9]

Cukierman joined the American Gastroenterological Association in 2010. [8] At the time, this was considered novel because the association is mainly a medical association, and Cukierman is not a physician. [8] In 2017, she established the Marvin and Concetta Greenberg Pancreatic Cancer Institute. [15]

Awards and honors

Academic service

Cukierman has supported the development of early career researchers, and has developed a philosophy around teaching and mentoring. She is a member of the American Cancer Society, and on the editorial board of Matrix Biology . [19]

Selected publications

Related Research Articles

<span class="mw-page-title-main">Fibroblast</span> Animal connective tissue cell

A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals.

<span class="mw-page-title-main">Fibronectin</span> Protein involved in cell adhesion, cell growth, cell migration and differentiation

Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. It is approved for marketing as a topical solution in India by Central Drugs Standard Control organization in 2020 under the brand name FIBREGA for chronic wounds. Fibronectin also binds to other extracellular matrix proteins such as collagen, fibrin, and heparan sulfate proteoglycans.

<span class="mw-page-title-main">Extracellular matrix</span> Network of proteins and molecules outside cells that provides structural support for cells

In biology, the extracellular matrix (ECM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.

<span class="mw-page-title-main">Netrin</span> Class of proteins involved in axon guidance

Netrins are a class of proteins involved in axon guidance. They are named after the Sanskrit word "netr", which means "one who guides". Netrins are genetically conserved across nematode worms, fruit flies, frogs, mice, and humans. Structurally, netrin resembles the extracellular matrix protein laminin.

<span class="mw-page-title-main">Radioimmunotherapy</span>

Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell. It is a form of unsealed source radiotherapy. In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells. The ability for the antibody to specifically bind to a tumor-associated antigen increases the dose delivered to the tumor cells while decreasing the dose to normal tissues. By its nature, RIT requires a tumor cell to express an antigen that is unique to the neoplasm or is not accessible in normal cells.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 4</span> Mammalian protein found in Homo sapiens

SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, which act as mediators of TGF-β signal transduction. The TGFβ family of cytokines regulates critical processes during the lifecycle of metazoans, with important roles during embryo development, tissue homeostasis, regeneration, and immune regulation.

<span class="mw-page-title-main">Syndecan</span>

Syndecans are single transmembrane domain proteins that are thought to act as coreceptors, especially for G protein-coupled receptors. More specifically, these core proteins carry three to five heparan sulfate and chondroitin sulfate chains, i.e. they are proteoglycans, which allow for interaction with a large variety of ligands including fibroblast growth factors, vascular endothelial growth factor, transforming growth factor-beta, fibronectin and antithrombin-1. Interactions between fibronectin and some syndecans can be modulated by the extracellular matrix protein tenascin C.

<span class="mw-page-title-main">Netrin 1</span> Protein-coding gene in the species Homo sapiens

Netrin-1 is a protein that in humans is encoded by the NTN1 gene.

<span class="mw-page-title-main">MMP21</span> Protein-coding gene in the species Homo sapiens

Matrix metalloproteinase-21 (MMP-21) is an enzyme that in humans is encoded by the MMP21 gene.

<span class="mw-page-title-main">Desmoplasia</span> Growth of fibrous or connective tissue

In medicine, desmoplasia is the growth of fibrous connective tissue. It is also called a desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.

Pancreatic stellate cells (PaSCs) are classified as myofibroblast-like cells that are located in exocrine regions of the pancreas. PaSCs are mediated by paracrine and autocrine stimuli and share similarities with the hepatic stellate cell. Pancreatic stellate cell activation and expression of matrix molecules constitute the complex process that induces pancreatic fibrosis. Synthesis, deposition, maturation and remodelling of the fibrous connective tissue can be protective, however when persistent it impedes regular pancreatic function.

<span class="mw-page-title-main">Tumor microenvironment</span> Surroundings of tumors including nearby cells and blood vessels

The tumor microenvironment (TME) is a complex ecosystem surrounding a tumor, composed of a variety of non-cancerous cells including blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). Mutual interaction between cancer cells and the different components of the TME support its growth and invasion in healthy tissues which correlates with tumor resistance to current treatments and poor prognosis. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.

A 3D cell culture is an artificially created environment in which biological cells are permitted to grow or interact with their surroundings in all three dimensions. Unlike 2D environments, a 3D cell culture allows cells in vitro to grow in all directions, similar to how they would in vivo. These three-dimensional cultures are usually grown in bioreactors, small capsules in which the cells can grow into spheroids, or 3D cell colonies. Approximately 300 spheroids are usually cultured per bioreactor.

Zena Werb was a professor and the Vice Chair of Anatomy at the University of California, San Francisco. She was also the co-leader of the Cancer, Immunity, and Microenvironment Program at the Hellen Diller Family Comprehensive Cancer Center and a member of the Executive Committee of the Sabre-Sandler Asthma Basic Research Center at UCSF. Her research focused on features of the microenvironment surrounding cells, with particular interest in the extracellular matrix and the role of its protease enzymes in cell signaling.

<span class="mw-page-title-main">Fractone</span>

In biology, fractones are structures consisting primarily of laminin and heparan sulfate proteoglycan (HSPG) first discovered in the extracellular matrix niche of the subventricular zone of the lateral ventricle (SVZa) in the mouse brain. Recent research has suggested its importance in adult neurogenesis, gliogenesis, and angiogenesis.

A cancer-associated fibroblast (CAF) is a cell type within the tumor microenvironment that promotes tumorigenic features by initiating the remodelling of the extracellular matrix or by secreting cytokines. CAFs are a complex and abundant cell type within the tumour microenvironment; the number cannot decrease, as they are unable to undergo apoptosis.

Fibroblastic and myofibroblastic tumors (FMTs) develop from the mesenchymal stem cells which differentiate into fibroblasts and/or the myocytes/myoblasts that differentiate into muscle cells. FMTs are a heterogeneous group of soft tissue neoplasms. The World Health Organization (2020) defined tumors as being FMTs based on their morphology and, more importantly, newly discovered abnormalities in the expression levels of key gene products made by these tumors' neoplastic cells. Histopathologically, FMTs consist of neoplastic connective tissue cells which have differented into cells that have microscopic appearances resembling fibroblasts and/or myofibroblasts. The fibroblastic cells are characterized as spindle-shaped cells with inconspicuous nucleoli that express vimentin, an intracellular protein typically found in mesenchymal cells, and CD34, a cell surface membrane glycoprotein. Myofibroblastic cells are plumper with more abundant cytoplasm and more prominent nucleoli; they express smooth muscle marker proteins such as smooth muscle actins, desmin, and caldesmon. The World Health Organization further classified FMTs into four tumor forms based on their varying levels of aggressiveness: benign, intermediate, intermediate, and malignant.

<span class="mw-page-title-main">Jaye Gardiner</span> American cancer researcher

Jaye Cassandra Gardiner is an American cancer researcher at the Fox Chase Cancer Center. Her research considers the microenvironment that surrounds tumors, with a particular focus on pancreatic ductal adenocarcinoma. In 2022, she was the inaugural awardee of the Black in Cancer Postdoctoral Fellowship.

Valerie M. Weaver is a professor and the director of the Center for Bioengineering and Tissue Regeneration in the department of surgery and co-director Bay Area Center for Physical Sciences and Oncology at the University of California San Francisco (USA). She has been working and leading oncology research for more than 20 years. Her scientific contributions have been recognised by different awards. She was the first woman to receive the Shu Chien Award from the Biomedical Engineering Society in 2022, which honours contributions in the cellular and molecular bioengineering field.

Maddy Parsons is a British cell biologist who is a professor and Associate Dean for Impact & Innovation at King's College London. She is the Director of the Nikon Imaging Centre. Her research looks to understand the fundamental mechanisms that underpin cell adhesion and migration. She is Chair of the Medical Research Council Molecular & Cellular Medicine Board.

References

  1. 1 2 Edna Cukierman publications indexed by Google Scholar OOjs UI icon edit-ltr-progressive.svg
  2. Edna Cukierman publications from Europe PubMed Central
  3. 1 2 3 4 5 "Edna Cukierman Elected to Council of the American Society for Matrix Biology". foxchase.org. 2020-01-07. Retrieved 2022-11-06.
  4. "איפיון וניקוי של חלבון ממברנת הפלסמה של הטפיל ליישמניה דונובני | WorldCat.org". worldcat.org. Retrieved 2022-11-06.
  5. "Molecular characterization of an ARF directed GTPase activating protein | WorldCat.org". worldcat.org. Retrieved 2022-11-06.
  6. 1 2 "3-D Vision Brings New Perspectives". American Association for Cancer Research (AACR). Retrieved 2022-11-06.
  7. Madhusoodanan, Jyoti (2019-02-26). "Matrix mimics shape cell studies". Nature. 566 (7745): 563–565. Bibcode:2019Natur.566..563M. doi: 10.1038/d41586-019-00681-1 . PMID   30809069. S2CID   71147041.
  8. 1 2 3 4 "Cukierman Named Fellow of the American Gastroenterological Association". foxchase.org. 2020-02-14. Retrieved 2022-11-06.
  9. 1 2 3 4 "Edna (Eti) Cukierman". foxchase.org. 2015-11-03. Retrieved 2022-11-06.
  10. "Exploring how a tumour's environment helps it grow". Worldwide Cancer Research. Retrieved 2022-11-06.
  11. 1 2 "Fox Chase Researcher Receives Grant for Study of Biology of Pancreatic Cancer". foxchase.org. 2020-01-27. Retrieved 2022-11-06.
  12. 1 2 3 Amatangelo, Michael D.; Bassi, Daniel E.; Klein-Szanto, Andrés J. P.; Cukierman, Edna (August 2005). "Stroma-derived three-dimensional matrices are necessary and sufficient to promote desmoplastic differentiation of normal fibroblasts". The American Journal of Pathology. 167 (2): 475–488. doi:10.1016/S0002-9440(10)62991-4. ISSN   0002-9440. PMC   1603576 . PMID   16049333.
  13. Franco-Barraza, Janusz; Francescone, Ralph; Luong, Tiffany; Shah, Neelima; Madhani, Raj; Cukierman, Gil; Dulaimi, Essel; Devarajan, Karthik; Egleston, Brian L; Nicolas, Emmanuelle; Katherine Alpaugh, R; Malik, Ruchi; Uzzo, Robert G; Hoffman, John P; Golemis, Erica A (2017-01-31). Ivaska, Johanna (ed.). "Matrix-regulated integrin αvβ5 maintains α5β1-dependent desmoplastic traits prognostic of neoplastic recurrence". eLife. 6: e20600. doi: 10.7554/eLife.20600 . ISSN   2050-084X. PMC   5283834 . PMID   28139197.
  14. Francescone, Ralph; Barbosa Vendramini-Costa, Débora; Franco-Barraza, Janusz; Wagner, Jessica; Muir, Alexander; Lau, Allison N.; Gabitova, Linara; Pazina, Tatiana; Gupta, Sapna; Luong, Tiffany; Rollins, Dustin; Malik, Ruchi; Thapa, Roshan J.; Restifo, Diana; Zhou, Yan (2021-02-01). "Netrin G1 Promotes Pancreatic Tumorigenesis through Cancer-Associated Fibroblast–Driven Nutritional Support and Immunosuppression". Cancer Discovery. 11 (2): 446–479. doi:10.1158/2159-8290.CD-20-0775. ISSN   2159-8274. PMC   7858242 . PMID   33127842.
  15. "Edna Cukierman: How Fox Chase is Becoming a Hub for Pancreatic Research". foxchase.org. 2018-07-19. Retrieved 2022-11-06.
  16. "Edna Cukierman". Nikon's Small World. Retrieved 2022-11-06.
  17. "Pollen grains | 2005 Photomicrography Competition". Nikon's Small World. Retrieved 2022-11-06.
  18. "Officers". asmb.net. Retrieved 2022-11-06.
  19. "Dr. Edna Cukierman, PhD - Editorial Board - Matrix Biology - Journal - Elsevier". journals.elsevier.com. Retrieved 2022-11-06.
  20. Cukierman E; Pankov R; Stevens DR; Yamada KM (23 November 2001). "Taking cell-matrix adhesions to the third dimension". Science . 294 (5547): 1708–12. Bibcode:2001Sci...294.1708C. doi:10.1126/SCIENCE.1064829. ISSN   0036-8075. PMID   11721053. Wikidata   Q29615214.
  21. Kenneth M Yamada; Edna Cukierman (1 August 2007). "Modeling tissue morphogenesis and cancer in 3D". Cell . 130 (4): 601–610. doi:10.1016/J.CELL.2007.08.006. ISSN   0092-8674. PMID   17719539. Wikidata   Q34667330.
  22. Erik Sahai; Igor Astsaturov; Edna Cukierman; et al. (24 January 2020). "A framework for advancing our understanding of cancer-associated fibroblasts". Nature Reviews Cancer . 20 (3): 174–186. doi:10.1038/S41568-019-0238-1. ISSN   1474-175X. PMC   7046529 . PMID   31980749. Wikidata   Q92932998.