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Immunology, Infection and Inflammation@DKFZ SEMINAR SERIES

I3@dkfz

 

Thursday 14.10.2021 Guest Lecture

Prof. Andrea Ablasser, Group Leader at the École Polytechnique Fédérale de Lausanne, Switzerland.

Sensing DNA as a danger signal inside cells. 

She has extensive experience in the field of innate immunity and Pattern Recognition Receptor(PRRs) systems. The research of her lab focuses on studying the cGAS-STING signaling pathway in innate DNA sensing with a special emphasis on defining its function in physiological contexts that fall outside its classical, infection-associated realm. She has been the recipient of the German Cancer Prize and the Dr. Josef Steiner Cancer Research Award.

 

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Or ask fsp-d@dkfz-heidelberg.de for the link.

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PAST SEMINARS

Dr. Ed Green (D170) The 2 dollar TCR: how D170's innovations in DNA synthesis, screening and modular cloning enables low cost, high throughput screening for personalised therapeutics.

Dr Matthias Bossa (F160) Non-Integrating DNA Vectors for T cell engineering.

Dr. Patrick Schmidt (D120) Accelerating the translation of CAR-T therapies

Dr Michael Dill (F240) Versatile modeling of cholangiocarcinome to dissect oncogenic influences on the microenvironment.

Molecular programs defining T-cell differentiation and dysfunction in tumors.

Dr. Andrea Schietinger, Group Leader at the Sloan Kettering Institute in the Memorial Sloan Kettering Cancer Center.
Her lab has extensive experience in studying T-cell responses and how they detect cancer cells over the course of tumor development. A primary focus of her team is on understanding the dynamics of how immune cells become unresponsive to tumors and mechanisms that regulate T-cell differentiation.

 

Single-Cell Proteoics and Multiplexed Imaging reveal the Metabolic Regulation of Anti-Tumor Immunity

Dr. Felix Hartmann, who is currently a Postdoctoral fellow at Stanford University.
We are very happy to inform you that he will join the DKFZ in October as a Junior PI. We would like to use this seminar as an opportunity for the DKFZ fraternity to get to know him and his research and stem potential collaborations.
His research combines novel single-cell and imaging proteomic technologies to study interactions of immune cells with the local environment in human cancer. His recent publication outlined a method to characterize the metabolic regulome of single cells together with their phenotypic identity – scMEP (https://doi.org/10.1038/s41587-020-0651-8)

 

Dr. Nina Weisshaar (D140) Discovery of a new immune check-point

Prof. Dr. Mathias Heikenwälder (F180) Stratifying hepatic immune cells: Consequences for liver cancer therapy.

 

     Theresa Kordaß (D210): Controlling the immune suppressor: how miRNAs regulate CD73/NT5E

     Julian Mochayedi (D200): An autochthorous preclinical pancreatic cancer model for immuno-oncology research

 

      Dr. Ilka Wahl (D130): Human T-follicular helper cell response to Plasmodium falciparum circumsporozoite protein.

     Meiqi Ren (D180): Cytidine deaminases hape the genome of germinal center B-cell derived lymphoma

 

Cytosolic DNA sensing s a driver of autoimmunity 
 
Prof. Dr. med Axel Roers, Director of the Institute of Immunology at TU, Dresden.

His team has extensive experience in studying mechanisms of uncontrolled autoimmune and Type-II immune responses. In his talk, he will discuss their work on how chronic innate response due to uncontrolled activation of cytosolic DNA sensor pathways leads to autoimmunity.

Hedgehog signaling in immune cells

Dr. Maike de La Roche, a Group Leader at the CRUK-CI, Uni. of Cambridge.

Her team studies differentiation, migration and function of CD8 T cells during the adaptive anti-tumor response. In her talk, she will provide an overview of the different avenues in her laboratory engaged towards defining the roles of Hedgehog signaling in immune cells which may enable novel therapeutic opportunities.

Fuwei Shang (D110): Deconvoluting Hematopoiesis by PolyExpress Barcoding

Beatrice Casati (D150): COVID-19 pandemic: another case for SHERLOCK

Rapid selection, characterization and clinical development of fully-human antibodies against emerging infectious diseases.
How Pandemics change us | What history has taught us | How we can profit from it today
Clinical aspects of SARS-CoV-2 infection and patient management.
Studies of SARS-CoV-2 - host cell interactions
SARS-COV-2 - immune system interaction and status quo on immunological research on COVID-19.
Kevin Bode: Dectin-1 binding to annexins on apoptotic cells induces peripheral immune tolerance via NADPH oxidase-2

Riccardo Pecori: RNA editing modulates pathways critical to B cell lymphomagenesis

iReceptor plus: Federated Infrastructure for AIRR-seq Data
Using functional genetics to understand immune regulation in cancer

 

Panta rhei: Cellular flows in immune responses, hematopoiesis and leukemia

AWARDS

Congratulations to Prof. Dr. Dirk Jäger, recipient of the 2020 Team Science Award of SITC, which recognizes teams of scientists that have made a long-standing contribution to the field to cancer immunotherapy over the past 35 years. Dirk Jäger received the award as part of The Lloyd J. Old Lab Family.

https://www.sitcancer.org/funding/awards/anniversaryawards/sitc2020/2020teamscience

 

Congratulations to Dr. Guoliang Cui who received the Georges-Köhler Prize from the German Society for immunology e.V.

https://dgfi.org/dgfi-en/awards/koehler-prize/?noredirect=en_US

 

Congratulations to Dr Riccardo Pecori, recipient of 2019 Young Scientist in IO Award by the Bristol-Myers Squibb Foundation for Immuno-oncology.
The work awarded was presented at the German Cancer Congress (DKK) in February 2020, where the award ceremony took place. (https://twitter.com/Stiftung_IO/status/1230163917961334786?s=20)
We congratulate Dr. Lukas Bunse, who received the Swiss Bridge Award (250.000 CHF) to develop immunotherapies for brain cancer patients.

More information (in German only) can be found here: https://www.dkfz.de/de/presse/pressemitteilungen/2019/dkfz-pm-19-49c-Preis-fuer-die-Weiterentwicklung-von-zellulaeren-Immuntherapien.php

Dr. Rajagopal Murugan received the Werner-Müller-Award (2000 €) - Congratulations!

The price was awarded for Dr. Murugans work on immune responses to Plasmodium falciparum (causative agent of malaria) antigens. 

Details can be found under

https://dgfi.org/ausgezeichnet-deutsche-gesellschaft-fuer-immunologie-dgfi-ehrt-herausragende-nachwuchswissenschaftler-2/ (in German only)

and

in Murugan, Buchauer et al., Science Immunology 2018 as well was Scally, Murugan et al., Journal of Experimental Medicine 2018.

Congratulations to Dr. Theresa Bunse, who received the Herbert-Fischer-Award for Neuroimmunologie (1.500 €).
 
The price was awarded for Dr. Bunses research about how brain tumors are recognized by the immune system. She could show that a mutation in the IDH1 protein represents a promising therapeutic target for glioblastoma.

More information can be found under https://dgfi.org/ausgezeichnet-deutsche-gesellschaft-fuer-immunologie-dgfi-ehrt-herausragende-nachwuchswissenschaftler-2/ (in German only) and

in Schumacher, Bunse et al., Nature 2014 and Bunse, Pusch, Bunse et al., Nature Medicine 2018.

JOURNAL CLUB CANCER IMMUNOTHERAPY

The weekly Journal Club organized by S. Eichmüller, focuses on "Cancer Immunotherapy" and takes place on Mondays at 9.00 a.m. with participants from different departments and research programs of the DKFZ and NCT.

For more information please visit: https://www.dkfz.de/en/gmp-t-zell-therapie/JC-CanImm.html

 

SAVE THE DATE

SAVE THE DATE: This year (2021)  no IMMUNORETREAT at Rothenfels Casle

Next Years IMMUNORETREAT ?

Immunoretreat 2019 - Three days of exciting immunology on beautiful Rothenfels Castle

From 13-15 of May 2019, FSD scientists gathered at the Castle of Rothenfels for our annual retreat.

Many thanks to Thorsten Feyerabend for the fantastic organization!

© T. Feyerabend

GRADUATES AND ALUMNI

© dkfz.de

Lasse Neukirch defended his PhD thesis entitled "Evaluation of antigen-displaying adeno-associated virus-like particles (AAVLPs) as future candidates for personalized cancer vaccination" on the 17th of June 2021.


In his thesis, L. Neukirch tested a novel vaccination strategy to induce CD8+ T cell responses by displaying antigen peptides on the capsid of adeno-associated virus-like particles (AAVLPs). 
Vaccination of mice induced CD8+ T cell responses against the displayed antigen that were long-term protective in a B16F10 melanoma model. Generation of these CD8+ T cell responses was promoted by the presence of T helper epitopes in the AAVLP capsid, indicating a distinct advantage of the AAVLP strategy. Vaccination with neoepitope-displaying particles lead to a reduced tumor growth of B16F10 melanomas, which was not achieved by a corresponding peptide vaccination.


Highlights
- AAVLP vaccines induce long-lasting CD8+ T cell responses against displayed antigens
- CD8+ T cell responses are promoted by T helper epitopes in the AAVLP capsid
- AAVLP-display of neoepitopes reduced tumor growth more efficiently than peptide vaccination

Congratulations on this great work!

© dkfz.de

Kevin Bode defended his PhD thesis entitled "Molecular analysis of annexin receptor-induced immunosuppression in autoimmunity and tumor growth" on the 13th of March 2020.

In his thesis and in a paper published in Cell Reports, K.Bode and colleagues identify Dectin-1 on dendritic cells as a novel receptor for apoptotic cell-bound annexins, responsible for induction of peripheral immune tolerance. Tolerogenic signaling depends on selective SYK-phosphorylation and production of reactive oxygen species via NADPH oxidase-2. Dectin-1-deficient mice generate stronger immune responses against apoptotic cells and develop autoimmunity.

Highlights
-  Dectin-1 is a tolerogenic receptor for annexins on the surface of apoptotic cells

- Annexin-binding to Dectin-1 induces selective SYK-phosphorylation

- SYK-dependent ROS-production via NOX-2 is critical for tolerogenic signaling

- Dectin-1 deficiency causes autoimmunity

Congratulations Dr. Bode!

FSP-D PhD Graduates - 2019

Congratulations to Dr. Sicong Ma, who defended his PhD thesis entitled "Metabolic synchronization of effector and regulatory T cell responses" in October 2019!

Thesis Abstract: Our study revealed that SPTLC2 underpins the adaptive protective immunity by translating extracellular stimuli into intracellular anabolic signals and reducing the cellular stress in maintaining metabolic reprogramming sustainability. In addition, SPTLC2 is required to maintain the suppressive activity of Treg cells to keep the immune tolerance and restrict the anti-tumor responses. Collectively, we address that the SPTLC2-mediated sphingolipid de novo synthetic pathway synchronizes metabolic reprogramming and the immune reaction of regulatory and effector T cells in infection and cancer.

On the 10th of September 2019, Stefanie Dünnbier defended her doctoral thesis entitled "The role of Thioredoxin-interacting protein in T cell receptor signalling".

Abstract: T cell receptor (TCR) engagement and subsequent signalling are a prerequisite to initiate a T cell immune response. This study examined the role of Thioredoxin-interacting protein (TXNIP) in TCR signalling and shows that TXNIP acts as transcriptional inhibitor. Hence, TXNIP might be considered as a potential therapeutic target to shape T cell responses e.g. in autoimmune or tumour diseases.

Congratulations on this excellent work!

On the 10th of Mai 2019, Csilla Kongsaysak-Lengyel defended her PhD. The title of her thesis is "Importance of Notch1 PEST domain mutations in T-cell acute lymphoblastic leukemia".

Abstract: My PhD work was focusing on the characteristic frameshift mutations of the Notch1 PEST domain, leading to the expression of a truncated, hyperactive Notch1 protein. These mutations are found with very high frequencies in human T-ALL, and also in our spontaneous T-ALL mouse model. To investigate the importance of such frameshift mutations in leukemia pathogenesis, we developed a modified Notch1 allele, where frameshift mutations are non-functional. Interestingly, mice bearing such a modified Notch1 allele overcome frameshift disability by specifically acquiring direct STOP mutations leading to a truncated PEST domain. Overall, our results reveal an enormous selection pressure for mutations leading to a hyperactive Notch signaling in T-ALL pathogenesis.

Congratulations Dr. Kongsaysak-Lengyel!

On the 29th of April 2019, Ann-Kathrin Fanti defended her PhD thesis entitled "Fate Mapping of Hematopoietic Stem Cell Activity under Challenges".

Abstract: In my PhD project I investigated the regulation of the hematopoietic system, and in particular HSC, under stress conditions. To enable HSC fate mapping, I employed a Cre knock-in reporter mouse and performed time-resolved analysis of hematopoietic compartment sizes and label propagation. Our findings show that the activation of HSC, in terms of differentiation, depends strongly on the nature of the challenge, giving important insights on the hematopoietic response to severe insults such as sepsis and irradiation.

Congratulations on this great work!

LATEST PUBLICATIONS

Gross-Cohen M, Yanku Y, Kessler O, Barash U, Boyango I, Cid-Arregui A, Neufeld G, Ilan N, Vlodavsky I

Heparanase 2 (Hpa2) attenuates tumor growth by inducing Sox2 expression.

Matrix Biology, Volume 99, May 2021, Pages 58-71

https://doi.org/10.1016/j.matbio.2021.05.001

 

Poorebrahim M, Mohammadkhani, N, Mahmoudi, R, Gohlizadeh, Fakhr, E and Cid-Arregui, A.

TCR-like CARs and TCR-CARs targeting neoepitopes: an emerging potential.

Cancer Gene Ther 28, pages 581–589 (2021),

https://doi.org/10.1038/s41417-021-00307-7

 

Zeelen, J, van Straaten, M, Verdi, J, Hempelmann, A, Hashemi, H, Perez,K, Jeffrey, PD, Hälg, S, Wiedemar, N, Mäser, P, Papavasiliou, FN, Stebbins CE

Structure of trypanosome coat protein VSGsur and function in suramin resistance

Nature Microbiology volume 6, pages392–400(2021)

https://doi.org/10.1038/s41564-020-00844-1 

Poorebrahim M, Melief J, Pico de Coaña Y, L Wickström S, Cid-Arregui A, Kiessling R.

Counteracting CAR T cell dysfunction

Oncogene 40, 421–435 (2021).

https://doi.org/10.1038/s41388-020-01501-x

Fakhr, E, Modic, Z and Cid-Arregui, A.

Recent developments in immunotherapy of cancers caused by human papillomaviruses.

Immunology 2020.

https://doi.org/10.1111/imm.13285

Wu J, Weisshaar N, Hotz-Wagenblatt A, Madi A, Ma S, Mieg A, Hering M, Mohr K, Schlimbach T, Borgers H, Cui G

Skeletal muscle antagonizes antiviral CD8+ T cell exhaustion.

Science Advances (2020) 6:eaba3458

https://doi.org/10.1126/sciadv.aba3458

Murugan R, Scally SW, Costa G, Mustafa G, Thai E, Decker T, Bosch A, Prieto K, Levashina EA, Julien J-P & Wardemann H

Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs

Nat Med (2020)

https://doi.org/10.1038/s41591-020-0881-9

Aslan K, Turco V, Blobner J, Sonner JK, Liuzzi AR, Núñez NG, De Feo D, Kickingereder P, Fischer M, Green E, Sadik A, Friedrich M, Sanghvi K, Kilian M, Cichon F, Wolf L, Jähne K, von Landenberg A, Bunse L, Sahm F, Schrimpf D, Meyer J, Alexander A, Brugnara G, Röth R, Pfleiderer K, Niesler B, von Deimling A, Opitz C, Breckwoldt MO, Heiland S, Bendszus M, Wick W, Becher B & Platten M

Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas

Nat Commun 11, 931 (2020).

https://doi.org/10.1038/s41467-020-14642-0

Bode K, Bujupi F, Link C, Hein T, Zimmermann S, Peiris D, Jaquet V, Lepenies B, Weyd H and Krammer PH

Dectin-1 binding to annexins on apoptotic cells induces peripheral immune tolerance via NADPH oxidase-2

Cell Reports. Volume 29, Dec 2019, Pages 4435-4446.e9

https://doi.org/10.1016/j.celrep.2019.11.086

Buchauer L, Wardemann H

Calculating germinal centre reactions

Current Opinion in Systems Biology (Dec 2019)

https://doi.org/10.1016/j.coisb.2019.10.004

Dorshkind K, Höfer T, Montecino-Rodriguez E, Pioli PD, Rodewald HR

Do haematopoietic stem cells age?

Nature Reviews Immunology (Nov 2019); PMID 31740804

Julien JP, Wardemann H.
Antibodies against Plasmodium falciparum malaria at the molecular level
Nature Reviews Immunology (Aug. 2019); PMID 31462718

Sonner JK, Keil M, Falk-Paulsen M, Mishra N, Rehman A, Kramer M, Deumelandt K, Röwe J, Sanghvi K, Wolf L, von Landenberg A, Wolff H, Bharti R, Oezen I, Lanz TV, Wanke F, Tang Y, Brandao I, Mohapatra SR, Epping L, Grill A, Röth R, Niesler B, Meuth SG, Opitz CA, Okun JG, Reinhardt C, Kurschus FC, Wick W, Bode HB, Rosenstiel P, Platten M
Dietary Tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology
Nature Communications (Oct 2019); PMID: 31653831

Do you have a new publication that you would like others to know about? Please contact us at fsp-d@dkfz-heidelberg.de

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