Forschungsgruppe Dr. Zuzana Tatarova

DKTK Nachwuchsgruppe für Therapieresistenz

Systembiologie des Brustkrebses bei Therapieresistenz

Die jüngste Integration von Tumor-Devices (biotechnologischen Medizinprodukten) und hochdimensionalen Berechnungsdaten aus Studien zum Mammakarzinom der Maus hat das Konzept bekräftigt, dass die Zellen und Strukturen in der Umgebung des Krebses, das Tumormikromilieu (TME) die Wirksamkeit von Krebstherapien bestimmen kann. Wir stellen die Hypothese auf, dass für eine dauerhafte Kontrolle der Krebserkrankungen systematische Behandlungsansätze erforderlich sind, um Resistenzmechanismen zu blockieren, die aus der wechselseitigen Interaktion zwischen Tumor und TME resultieren. Es werden innovative Strategien benötigt, um all diesen Mechanismen durch die Verabreichung von Arzneimittelkombinationen entgegenzuwirken und gleichzeitig toxische Nebenwirkungen zu vermeiden, die die Lebensqualität beeinträchtigen. Bei den vielversprechenden Kombinationstherapien gegen Krebs fehlen noch immer Instrumente zur effektiven Vorhersage rationaler immun- und TME-modulierender Kombinationsbehandlungen auf personalisierter Basis.

Mit Hilfe systembiologischer Ansätze will unser Labor die vielversprechendsten integrativen computergestützten und biotechnologischen Strategien entwickeln und identifizieren, um die Komplexität des Tumormikromilieus im Hinblick auf das Ansprechen auf die Behandlung zu entschlüsseln, was letztlich zur Entdeckung neuer (i) standardisierter Biomarker mit prognostischem Wert und (ii) wirksamer Kombinationen von Immun- und konventionellen Krebstherapien führt.

Team

Gautami Gaidhani

Gautami Gaidhani

Doktorandin

Juraj Jakubik

Juraj Jakubik

Datenanalyst und Ingenieur

Leoni Moldaner

Leoni Moldaner

Doktorandin

Dr. Zuzana Tatarova

Dr. Zuzana Tatarova

Gruppenleiterin

Yishu Xu

Yishu Xu

Doktorandin

Ausgewählte Publikationen

Using the tumour microenvironment to improve therapy efficacy. 
Tatarova Z. Nat Rev Cancer. 2024 Jul;24(7):444. doi: 10.1038/s41568-024-00693-8. PMID: 38671199 

Panobinostat Induced Spatial In Situ Biomarkers Predictive of Anti-PD-1 Efficacy in Mouse Mammary Carcinoma. 
Tatarova Z, Blumberg DC, Bensen A, Mills GB, Jonas O. Cells. 2023 Jan 13;12(2):308. doi: 10.3390/cells12020308. PMID: 36672243

A multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs. 
Tatarova Z, Blumberg DC, Korkola JE, Heiser LM, Muschler JL, Schedin PJ, Ahn SW, Mills GB, Coussens LM, Jonas O, Gray JW. Nat Biotechnol. 2022 Dec;40(12):1823-1833. doi: 10.1038/s41587-022-01379-y. Epub 2022 Jul 4. PMID: 35788566

Microfluidic co-culture platform to quantify chemotaxis of primary stem cells 
Z Tatárová , J P Abbuehl, S Maerkl, J Huelsken 
Lab Chip 2016 May 21;16(10):1934-45. doi: 10.1039/c6lc00236f. Epub 2016 May 3. 
PMID: 27137768 

  • Benjamin V Stone
  • Christine A Dominas
  • Sharath K Bhagavatula
  • Sebastian W Ahn
  • Zuzana Tatarova
  • Juraj Jakubik
  • Destiny Matthew
  • Matthew Mossanen
  • Daniella Furtado
  • Kemal Tuncali
  • Michelle S Hirsch
  • Nobuhiko Hata
  • Clare Tempany
  • Oliver Jonas
  • Adam S Kibel

Novel Intraprostatic Magnetic Resonance-Guided Implantation of Multidrug-Eluting Microdevice for Testing of Systemic Therapy Agents In Situ: Proof of Concept in Intermediate-Risk and High-Risk Prostate Cancer

J Urol. 2025 Feb;213(2):173-182. doi: 10.1097/JU.0000000000004269. Epub 2024 Sep 30.ABSTRACTPURPOSE: The purpose of this study was to assess safety and feasibility of percutaneous magnetic resonance-guided placement of an implantable microdevice…

PubMed

Autor Zuzana Tatarova

Using the tumour microenvironment to improve therapy efficacy

Nat Rev Cancer. 2024 Jul;24(7):444. doi: 10.1038/s41568-024-00693-8.NO ABSTRACTPMID:38671199 | DOI:10.1038/s41568-024-00693-8

PubMed

  • Sharath K Bhagavatula
  • Sajanlal R Panikkanvalappil
  • Junichi Tokuda
  • Vincent Levesque
  • Zuzana Tatarova
  • Guigen Liu
  • John E Markert
  • Oliver Jonas

Superparamagnetic iron oxide nanoparticle enhanced percutaneous microwave ablation: Ex-vivo characterization using magnetic resonance thermometry

Med Phys. 2024 May;51(5):3195-3206. doi: 10.1002/mp.17040. Epub 2024 Mar 21.ABSTRACTBACKGROUND: Percutaneous microwave ablation (pMWA) is a minimally invasive procedure that uses a microwave antenna placed at the tip of a needle to induce lethal…

PubMed

  • Zinab O Doha
  • Xiaoyan Wang
  • Nicholas L Calistri
  • Jennifer Eng
  • Colin J Daniel
  • Luke Ternes
  • Eun Na Kim
  • Carl Pelz
  • Michael Munks
  • Courtney Betts
  • Sunjong Kwon
  • Elmar Bucher
  • Xi Li
  • Trent Waugh
  • Zuzana Tatarova
  • Dylan Blumberg
  • Aaron Ko
  • Nell Kirchberger
  • Jennifer A Pietenpol
  • Melinda E Sanders
  • Ellen M Langer
  • Mu-Shui Dai
  • Gordon Mills
  • Koei Chin
  • Young Hwan Chang
  • Lisa M Coussens
  • Joe W Gray
  • Laura M Heiser
  • Rosalie C Sears

MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer

Nat Commun. 2023 Sep 13;14(1):5665. doi: 10.1038/s41467-023-40841-6.ABSTRACTTriple-negative breast cancer (TNBC) patients have a poor prognosis and few treatment options. Mouse models of TNBC are important for development of new therapies, however,…

PubMed

  • Pierpaolo Peruzzi
  • Christine Dominas
  • Geoffrey Fell
  • Joshua D Bernstock
  • Sarah Blitz
  • Debora Mazzetti
  • Mykola Zdioruk
  • Hassan Y Dawood
  • Daniel V Triggs
  • Sebastian W Ahn
  • Sharath K Bhagavatula
  • Shawn M Davidson
  • Zuzana Tatarova
  • Michael Pannell
  • Kyla Truman
  • Anna Ball
  • Maxwell P Gold
  • Veronika Pister
  • Ernest Fraenkel
  • E Antonio Chiocca
  • Keith L Ligon
  • Patrick Y Wen
  • Oliver Jonas

Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas

Sci Transl Med. 2023 Sep 6;15(712):eadi0069. doi: 10.1126/scitranslmed.adi0069. Epub 2023 Sep 6.ABSTRACTThe lack of reliable predictive biomarkers to guide effective therapy is a major obstacle to the advancement of therapy for high-grade gliomas,…

PubMed

  • Zuzana Tatarova
  • Dylan C Blumberg
  • AeSoon Bensen
  • Gordon B Mills
  • Oliver Jonas

Panobinostat Induced Spatial In Situ Biomarkers Predictive of Anti-PD-1 Efficacy in Mouse Mammary Carcinoma

Cells. 2023 Jan 13;12(2):308. doi: 10.3390/cells12020308.ABSTRACTImmunotherapies, including anti-PD-1 immune checkpoint blocking (ICB) antibodies, have revolutionized the treatment of many solid malignancies. However, their efficacy in breast cancer…

PubMed

  • Zuzana Tatarova
  • Dylan C Blumberg
  • James E Korkola
  • Laura M Heiser
  • John L Muschler
  • Pepper J Schedin
  • Sebastian W Ahn
  • Gordon B Mills
  • Lisa M Coussens
  • Oliver Jonas
  • Joe W Gray

A multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs

Nat Biotechnol. 2022 Dec;40(12):1823-1833. doi: 10.1038/s41587-022-01379-y. Epub 2022 Jul 4.ABSTRACTSystematically identifying synergistic combinations of targeted agents and immunotherapies for cancer treatments remains difficult. In this study, we…

PubMed

  • Navid Mohammad Mirzaei
  • Zuzana Tatarova
  • Wenrui Hao
  • Navid Changizi
  • Alireza Asadpoure
  • Ioannis K Zervantonakis
  • Yu Hu
  • Young Hwan Chang
  • Leili Shahriyari

A PDE Model of Breast Tumor Progression in MMTV-PyMT Mice

J Pers Med. 2022 May 17;12(5):807. doi: 10.3390/jpm12050807.ABSTRACTThe evolution of breast tumors greatly depends on the interaction network among different cell types, including immune cells and cancer cells in the tumor. This study takes advantage…

PubMed

  • Navid Mohammad Mirzaei
  • Navid Changizi
  • Alireza Asadpoure
  • Sumeyye Su
  • Dilruba Sofia
  • Zuzana Tatarova
  • Ioannis K Zervantonakis
  • Young Hwan Chang
  • Leili Shahriyari

Investigating key cell types and molecules dynamics in PyMT mice model of breast cancer through a mathematical model

PLoS Comput Biol. 2022 Mar 16;18(3):e1009953. doi: 10.1371/journal.pcbi.1009953. eCollection 2022 Mar.ABSTRACTThe most common kind of cancer among women is breast cancer. Understanding the tumor microenvironment and the interactions between…

PubMed

  • Navid Mohammad Mirzaei
  • Sumeyye Su
  • Dilruba Sofia
  • Maura Hegarty
  • Mohamed H Abdel-Rahman
  • Alireza Asadpoure
  • Colleen M Cebulla
  • Young Hwan Chang
  • Wenrui Hao
  • Pamela R Jackson
  • Adrian V Lee
  • Daniel G Stover
  • Zuzana Tatarova
  • Ioannis K Zervantonakis
  • Leili Shahriyari

A Mathematical Model of Breast Tumor Progression Based on Immune Infiltration

J Pers Med. 2021 Oct 15;11(10):1031. doi: 10.3390/jpm11101031.ABSTRACTBreast cancer is the most prominent type of cancer among women. Understanding the microenvironment of breast cancer and the interactions between cells and cytokines will lead to…

PubMed

  • Spencer S Watson
  • Mark Dane
  • Koei Chin
  • Zuzana Tatarova
  • Moqing Liu
  • Tiera Liby
  • Wallace Thompson
  • Rebecca Smith
  • Michel Nederlof
  • Elmar Bucher
  • David Kilburn
  • Matthew Whitman
  • Damir Sudar
  • Gordon B Mills
  • Laura M Heiser
  • Oliver Jonas
  • Joe W Gray
  • James E Korkola

Microenvironment-Mediated Mechanisms of Resistance to HER2 Inhibitors Differ between HER2+ Breast Cancer Subtypes

Cell Syst. 2018 Mar 28;6(3):329-342.e6. doi: 10.1016/j.cels.2018.02.001. Epub 2018 Mar 14.ABSTRACTExtrinsic signals are implicated in breast cancer resistance to HER2-targeted tyrosine kinase inhibitors (TKIs). To examine how microenvironmental…

PubMed

  • Jean-Paul Abbuehl
  • Zuzana Tatarova
  • Werner Held
  • Joerg Huelsken

Long-Term Engraftment of Primary Bone Marrow Stromal Cells Repairs Niche Damage and Improves Hematopoietic Stem Cell Transplantation

Cell Stem Cell. 2017 Aug 3;21(2):241-255.e6. doi: 10.1016/j.stem.2017.07.004.ABSTRACTHematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and…

PubMed

  • Radoslav Janoštiak
  • Jan Brábek
  • Vera Auernheimer
  • Zuzana Tatárová
  • Lena A Lautscham
  • Tuli Dey
  • Jakub Gemperle
  • Rudolf Merkel
  • Wolfgang H Goldmann
  • Ben Fabry
  • Daniel Rösel

CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics

Cell Mol Life Sci. 2014 Feb;71(4):727-44. doi: 10.1007/s00018-013-1450-x. Epub 2013 Aug 25.ABSTRACTFocal adhesions are cellular structures through which both mechanical forces and regulatory signals are transmitted. Two focal adhesion-associated…

PubMed

  • Zuzana Tatárová
  • Jan Brábek
  • Daniel Rösel
  • Marian Novotný

SH3 domain tyrosine phosphorylation--sites, role and evolution

PLoS One. 2012;7(5):e36310. doi: 10.1371/journal.pone.0036310. Epub 2012 May 15.ABSTRACTBACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and…

PubMed

News

Nutzung der Tumormikroumgebung zur Verbesserung der Therapieeffizienz

Aktuelle Veröffentlichung in Nature Reviews Cancer

24.06.2024 Tatarova
Dr. Zuzana Tatarova

Jobs

Zur Zeit gibt es keine Stellenangebote.

Förderung

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LOEWE Exzellente Forschung für Hessens Zukunft
Frankfurt Cancer Institute