Skip to main content
Deutsch

Winkler Lab

  1. Center for Cancer Research
  2. Research Focuses
  3. Tumor Progression and Metastasis
  4. Juliane Winkler

Juliane Winkler, PhD

Research Focus

The main challenge in oncology remains the effective treatment of metastasis.

Current cancer treatment is most effective in attacking the primary tumor but has little effect on metastatic cells. This is a substantial problem because metastases account for the vast majority of cancer-related deaths. During the multistep process of metastasis, tumor cells adapt to various microenvironments that are distinct from their site of origin, but our understanding of the processes that lead to these adaptations is limited. Moreover, phenotypic alterations of metastatic cells may also cause resistance to therapeutics that cannot be accounted for by genotypic changes alone.

So why do some patients develop metastasis while others do not? Tumors consist of individual tumor cells that can vary in their genetic modifications (genetic intra-tumoral heterogeneity) as well as display very different phenotypes (phenotypic intra-tumoral heterogeneity). The individual tumor cells interact with their environment including a variety of non-malignant stromal and immune cells in a unique way that impacts their ability to metastasize.

The Lab of Tumor Heterogeneity and Metastasis is focused on achieving a better understanding of how tumor heterogeneity impacts metastatic behavior, how individual tumor cells interact with the microenvironment (Winkler et al. Nature Communications 2020), and in particular, how the innate immune system modulates (pre-) metastatic niches in distant organ sites.

We are using technology-driven systems-oncology approaches that lead to meaningful insights into the complex biology of metastasis. We co-developed MULTI-Seq (McGinnis et al. Nature Methods 2019), a novel multiplexing approach for single-cell RNA-sequencing (scRNA-Seq), which enables a cost-effective increase in sample size, reduction of batch effects, and the recovery of challenging cell populations.

In the Winkler Lab, we apply this scRNA-Seq technology together with other single-cell omics and spatial applications to understand the implications of tumor heterogeneity on:

  1. the formation and progression of metastasis
  2. the tumor-immune cell axis
  3. the therapy resistance of metastasis.

Selected Publications

Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes
Winkler J#, Tan W, Diadhiou CMM, McGinnis CS, Abbasi A, Hasnain S, Durney S, Atamaniuc E, Superville D, Awni L, Lee JV, Hinrichs JH, Wagner PS, Singh N, Hein MY, Borja M, Detweiler A, Liu SY, Nanjaraj A, Sitarama V, Rugo HS, Neff N, Gartner ZJ, Pisco AO#, Goga A#, Darmanis S# & Werb Z.
# corresponding author
J. Clin. Invest. (2024) 134, e164227. doi: 10.1172/JCI164227 

The temporal progression of lung immune remodeling during breast cancer metastasis
McGinnis CS, Miao Z, Superville D, Yao W, Goga A, Reticker-Flynn NE, Winkler J*#, Satpathy AT*#
# corresponding author * equal contribution
Cancer Cell (2024) 42(6), 1018-1031.e6. doi:10.1016/j.ccell.2024.05.004

The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans
Tabula Sapiens Consortium*
*Winkler J (Tabula Sapiens Consortium member)
Science. 2022 May 13;376(6594):eabl4896. doi: 10.1126/science.abl4896.

Bisphenol A replacement chemicals, BPF and BPS, induce pro-tumorigenic changes in human mammary gland organoid morphology and proteome
Winkler J#, Liu P, Phong K, Hinrichs JH, Ataii N, Williams K, Hadler-Olsen E, Samson S, Gartner ZJ, Fisher S#, Werb Z.
# corresponding author
Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2115308119. doi: 10.1073/pnas.2115308119.

Concepts of Extracellular Matrix Remodelling in Tumour Progression and Metastasis
Winkler J#, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z.
# corresponding author
Nat Commun 2020 Oct 9;11(1):5120. doi: 10.1038/s41467-020-18794-x.

MULTI-seq: sample multiplexing for single-cell RNA sequencing using lipid-tagged indices
McGinnis CS, Patterson DM, Winkler J, Conrad DN, Hein MY, Srivastava V, Hu JL, Murrow LM, Weissman JS, Werb Z, Gartner Z.
Nat Methods. 2019 Jul;16(7):619-626. doi: 10.1038/s41592-019-0433-8.

Alle Publikationen

Google Scholar

Financial Support

PhD position available

Dissecting tumor-immune interactions in organ-specific metastasis using single-cell and spatial omics approaches

What we do:

Metastasis is the leading cause of cancer related deaths. Specific cancers have a prevalence to metastasize to specific organs. The underlying mechanisms for this organotropism are poorly understood. In this project you will investigate how tumor and metastatic cells and their immune-microenvironment are different in different host organs and how malignant cells remodel distant tissue niches. We are focusing on finding ways to empower the immune system to combat metastasis using cutting-edge single-cell and spatial omics technologies. We use clinically highly relevant disease models of metastasis and patient samples to investigate the complex interplays of tumor and immune cells in metastasis. The use of modern omics technologies makes it possible to discover new tumor immune cell interactions in metastasis that have not been described before. By studying these interactions between metastatic cancer cells and immune cells, we hope to uncover new insights that could lead to improved treatments for cancer patients.

What we offer:

Fully funded PhD position! Our interdisciplinary approach combines different expertise to tackle the complex interplay of tumor and immune cells in metastasis including experimental and computational biology, as well as translational research. As a member of our dynamic team, you will receive training in both experimental and computational biology that are equally important skill sets for modern cancer researchers. You will be trained to generate and analyze single-cell and spatial omics data using the latest technologies, learn how to generate scientific hypothesis and to validate your hypothesis in appropriate advanced in vitro organoid and in vivo metastasis model systems. You will have the opportunity to present your work at conferences and collaborate with researchers from around the world, helping you grow professionally and make valuable connections in the field.

As part of the unique SHIELD PhD program, you will have access to coordinated courses and workshops and a network of experts in immunology and cancer, providing even more opportunities for learning and collaboration.

What we are looking for:

  • Master in Biochemistry, Molecular biology, Immunology, Computational Biology or equivalent.
  • Experience in computational biology and/or immunology are desirable
  • Excitement to work both computationally (analyzing single-omics and spatial omics data) and experimentally (e.g. working with mouse models)
  • Strong team spirit and high motivation to push the boundaries of metastatic research to improve patient outcomes.

Keywords: AI/ML, Animal research, Human research, Wet lab, Computer lab, Bioinformatics, Cancer, Immunology

Join our team and do your PhD in vibrant Vienna - one of the most livable cities worldwide!

More info here : winklerlab.org or email juliane.winkler@meduniwien.ac.at.

 Apply by 25.04.2025, 23:55 CET

Interested in joining our team?

We are always looking for extraordinary passionate researchers across all levels who are as excited about tumor heterogeneity and metastasis as we are.

For inquiries please send your CV, a cover letter describing your interest in our research and previous research experience (max one page), transcripts, and contact information of 2 references. For undergraduate volunteers, please additionally indicate the specific skills that you would like to learn so we can determine a potential fit. We are committed to building an inclusive, diverse, and collaborative team and assessing candidates based on their excellence.

Please omit your picture, date of birth, gender, nationality, and family status in your CV.

 E-Mail to Juliane Winkler

Bibliography

Dr. Juliane Winkler is a trained Pharmacist and received her Ph.D. from the University of Heidelberg (jointly EMBL, German Cancer Research Center, and Institute of Pathology), where she studied how nuclear transport alterations promote aggressive hepatocellular carcinoma (HCC). In her postdoc at the University of California San Francisco, Dr. Winkler worked with the late Zena Werb and Andrei Goga on the impact of tumor heterogeneity on breast cancer metastasis. She received multiple awards for her research and mentoring (e.g. EMBO long-term Fellow, AACR Scholar-in-Training Award, Dean’s Award for Excellence in Mentoring, honorable mention). The motivation for her research comes from years of caring for cancer patients as a trained oncology consultant in the public pharmacy, and her desire to improve treatment options for patients with metastasis.