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Herndler-Brandstetter Lab

  1. Center for Cancer Research
  2. Research Focuses
  3. Cellular and Molecular Tumor Biology
  4. Dietmar Herndler-Brandstetter

Dietmar Herndler-Brandstetter, Mag.pharm., PhD

Research Focus

Identifying novel immunotherapies for colorectal cancer

1. Humanized mouse models for translational cancer research and immunotherapy
We use next-generation humanized mice (immunodeficient mice reconstituted with a human immune system), which represent highly innovative models for translational research and personalized medicine, as they allow in vivo modeling and therapy of human diseases, in particular cancer.

2. Long noncoding RNA regulation of adaptive immunity
Long noncoding RNAs (lncRNAs) play a key role in regulating tumor growth and immune cell responses. By using deep RNA-seq we identified novel lncRNAs regulated during adaptive immunity. By using CRISPR/Cas9-mediated genome engineering, we generated knockout mice to understand how these lncRNAs regulate adaptive immunity.

3. Stromal regulation of immune cell development and anti-tumor immunity
Stromal cells support hematopoietic stem cells (HSC) and provide lineage-instructive differentiation signals for lymphoid progenitors. We have developed reporter and conditional knockout mice to investigate the role of distinct subsets of stromal cells for immune cell development and the regulation of immune cell responses.

Selected Publications

A GATA6-centred gene regulatory network involving HNFs and ΔNp63 controls plasticity and immune escape in pancreatic cancer
Kloesch B, Ionasz V, Paliwal S, Hruschka N, Martinez de Villarreal J, Öllinger R, Mueller S, Dienes HP, Schindl M, Gruber ES, Stift J, Herndler-Brandstetter D, Lomberk GA, Seidler B, Saur D, Rad R, Urrutia RA, Real FX, Martinelli P.
Gut. 2022 Apr; 71(4):766-777. doi: 10.1136/gutjnl-2020-321397.

IDO1+ Paneth cells promote immune escape of colorectal cancer
Pflügler S, Svinka J, Scharf I, Crncec I, Filipits M, Charoentong P, Tschurtschenthaler M, Kenner L, Awad M, Stift J, Schernthanner M, Bischl R, Herndler-Brandstetter D, Glitzner E, Moll HP, Casanova E, Timelthaler G, Sibilia M, Gnant M, Lax S, Thaler J, Müller M, Strobl B, Mohr T, Kaser A, Trajanoski Z, Heller G, Eferl R.
Commun Biol. 2020 May 22; 3(1):252. doi: 10.1038/s42003-020-0989-y.

KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity
Herndler-Brandstetter D*, Ishigame H*, Shinnakasu R, Plajer V, Stecher C, Zhao J, Lietzenmayer M, Kroehling L, Takumi A, Kometani K, Inoue T, Kluger Y, Kaech SM, Kurosaki T, Okada T, Flavell RA.;
Immunity. 2018 Apr 17;48(4):716-729.e8. doi: 10.1016/j.immuni.2018.03.015. Epub 2018 Apr 3. (* joint first authors)

Anti-SIRPa antibody immunotherapy enhances neutrophil and macrophage antitumor activity
Ring NG*, Herndler-Brandstetter D*, Weiskopf K*, Shan L, Volkmer JP, George BM, Lietzenmayer M, McKenna KM, Naik TJ, McCarty A, Zheng Y, Ring AM, Flavell RA, Weissman IL.;
Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10578-E10585. doi: 10.1073/pnas.1710877114. Epub 2017 Nov 20. (* joint first authors)

Humanized mouse model supports development, function, and tissue residency of human natural killer cells
Herndler-Brandstetter D*, Shan L*, Yao Y, Stecher C, Plajer V, Lietzenmayer M, Strowig T, de Zoete MR, Palm NW, Chen J, Blish CA, Frleta D, Gurer C, Macdonald LE, Murphy AJ, Yancopoulos GD, Montgomery RR, Flavell RA.;
Proc Natl Acad Sci U S A. 2017 Nov 7;114(45):E9626-E9634. doi: 10.1073/pnas.1705301114. Epub 2017 Oct 25. (* joint first authors)

Hematopoietic stem cell niches produce lineage-instructive signals to control multipotent progenitor differentiation
Cordeiro Gomes A*, Hara T*, Lim VY*, Herndler-Brandstetter D, Nevius E, Sugiyama T, Tani-Ichi S, Schlenner S, Richie E, Rodewald HR, Flavell RA, Nagasawa T, Ikuta K, Pereira JP.;
Immunity. 2016 Dec 20;45(6):1219-1231. doi: 10.1016/j.immuni.2016.11.004. Epub 2016 Nov 29. (* joint first authors)

All Publications

PubMedDatabase

Biography

Dietmar Herndler-Brandstetter studied pharmacy in Innsbruck, where he also got his PhD in Immunology / Biogerontology (2007). As a FLARE Postdoc Fellow, he continued his research on human T cell biology and aging at the Institute for Biomedical Aging Research in Innsbruck (Beatrix Grubeck-Loebenstein) and the University of Birmingham, UK (Janet M Lord). In 2011 he joined the Richard Flavell lab at Yale University (New Haven, USA) as an Erwin Schrödinger Postdoc Fellow, where he analyzed the plasticity of effector T cells and used humanized mouse models to study cancer immunotherapies. In 2018 he joined the Center for Cancer Research in Vienna as a junior group leader, where his lab is using humanized mouse models and patient-derived colorectal cancers (PDX) to study the human tumor-immune microenvironment and to identify effective combination cancer immunotherapies.

Financial Support