The DFG approves the new research consortium SFB TRR221, which focusses on harnessing anti-leukemia mechanisms without the risk of adverse immune reactions.
The new DFG consortium focuses on the modulation of transplant-versus-host and transplant-against-leukemia immune reactions.
Allogeneic hematopoietic stem cell transplantation is the only curative treatment option for many patients with leukemia and lymphoma. Their effectiveness is based on the so-called graft-versus-leukemia (GvL) effect: The transplanted immune cells of the donor form a new functional immune system in the patient to fight the tumor cells. However, the effect is not sufficient in all patients to prevent the return of leukemia or lymphoma. Furthermore, there is often an undesirable effect in which the immune cells of the donor attack healthy tissue of the patient, termed graft-versus-host disease (GvHD). Within the first five years after transplant, approximately 60 percent of patients die as a result of GvHD or the return of the disease.
A newly formed research consortium investigates how desired GvL responses can be separated from unwanted GvH reactions. The German Research Foundation (DFG) will fund the new SFB Transregio TRR221 consortium on the “Modulation of transplant-versus-host and transplant-against-leukemia immune reactions after allogeneic hematopoietic stem cell transplantation.” Under the leadership of Prof. Wolfgang Herr, three Bavarian universities – Erlangen, Regensburg and Würzburg will investigate the immunological mechanisms of blood stem cell transplantation. The teams of our consortium will address the central problems and deficits of allogeneic hematopoietic stem cell transplantation. Consequently we aim to develop immunomodulatory strategies for the specific enhancement of the GvL effect and for the selective attenuation of GvHD. This collective gain of knowledge will result in new treatment concepts. These will be tested outside the DFG TRR221 in clinical studies with the aim of reducing the incidence of morbidity and mortality of allogenic blood stem cell transplantation by promoting the highly effective GvL immune response without associated GvHD. The consortium is planned to operate for 12 years. On November 24, 2017, after a thorough two-step evaluation process, the DFG approved funding for an initial phase of four years.
With a generous donation, the married couple Merete and Alexander Knauf of the international building materials company of the same name are stimulating a promising basic research project in the Beilhack lab. Based on an entirely new approach, the project aims to control potential life-threatening immune reactions between a stem cell transplant and the recipient’s body.
From left: Prof. Andreas Beilhack and Musga Qureischi from the Experimental Stem Cell Transplantation Research Laboratory, the patrons Merete and Alexander Knauf, and Prof. Alfred Forchel, President of the University of Würzburg. © Arnika Hansen (Uniklinikum Würzburg).
“My wife and I are regularly involved in projects in which we have the impression that we can really help to advance important improvements in our society with financial support,” says Alexander Knauf, managing partner of the globally active building materials company Knauf from Iphofen near the city of Würzburg. Not least because his wife Merete is a medical doctor herself, this subject area is also in their common funding focus. In search of a suitable project, the patrons recently turned to Prof. Alfred Forchel. The President of the University of Würzburg presented them with a range of current local projects. Among them, the married couple Knauf chose a project of Prof. Beilhack with the aim to develop an entirely new immunotherapy concept. “We are talking here of basic research, but extremely goal-oriented and with high translational potential,” emphasizes the scientist Musga Qureischi, who is actively pursuing this project in the Beilhack lab. According to the young scientist, the new strategy specifically targets improvements in stem cell therapy, but if it succeeds, the principle could well be applied to many autoimmune and inflammatory diseases.
Private donation helps to prove effectiveness
“The generous donation of the couple Knauf helps to skip a typical hurdle in the German research funding landscape,” said University President Forchel, explaining: “For the acquisition of public funds, projects such as this must scientifically prove a high probability of success. But to be able to prove this, considerable resources are required. Private sponsors can help close this gap, as a kind of start-up financing. “
If the project goes well, this proof can be achieved within the next two years, according to Prof. Beilhack.
An adhesion molecule on multiple myeloma cells correlates with patient outcome and proves as a promising new target for cancer therapy. Today, the respected journal Leukemia published our new research article on JAM-A by lead authors Antonio Solimando and Andreas Brandl.
Our new study revealed that JAM-A expression correlates significantly with disease outcome in multiple myeloma patients. Targeting of JAM-A impacts cardinal features of cancer, such as multiple myeloma cell survival, progression and metastasis.
Read more about this new research publication.
Solimando AG*, Brandl A*, Mattenheimer K, Graf C, Ritz M, Ruckdeschel A, Stühmer T, Mokhtari Z, Rudelius M, Dotterweich J, Bittrich M, Desanti V, Ebert R, Trerotoli P, Frassanito MA, Rosenwald A, Vacca A, Einsele H, Jakob F, Beilhack A. (2017). JAM-A as a prognostic factor and new therapeutic target in multiple myeloma. Leukemia (advance online publication 24 October 2017) doi: 10.1038/leu.2017.287
*These authors contributed equally to this work.
12th International Symposium of the Graduate School of Life Sciences
From October 11th and 12th 2017 the annual international research conference organized by PhD students for PhD students of the Würzburg Graduate School of Life Sciences took place in the Rudolf-Virchow-Center. And again, the success of the meeting was founded in a perfect blend of lectures by international leaders in their respective research fields and presentations of our local PhD students covering the broad spectrum of life sciences. This year, members of the Beilhack lab contributed seven poster presentations. Notably, among more than 100 presentations, MD student Maria Ranecky and PhD student Haroon Shaikh made it into final selection for the poster award. The highlight and finale of this year’s symposium was the very entertaining but thought provoking lecture of the science-cartoonist Jorge Cham.
The graduate college 3D Infect met for two days in Rothenburg ob der Tauber.
All the participating research teams of the DFG research training group 3D Infect joined for the second annual retreat. Graduate students and principal investigators of the graduate college actively participated to present and discuss the recent progress of the individual projects within the research training group. This vivid exchange and further input from visiting faculty, this year especially on pulmonary host-pathogen interactions, provided a fruitful basis to foster collaborations between the members of the RTG 3D Infect. One such collaborative project authored by the PhD student Sarah Schuster and members of the Engstler and Beilhack labs resulted already in a first joint-publication, which recently appeared in the distinguished journal eLife.
This year’s Workshop for Experimental Blood and Marrow Transplantation took place in Schweinfurt, a town on the river Main near Würzburg.
From September 19th to 20th, 2017 cellular immunotherapy, graft-versus-host disease and inflammation, tumor immunology and immune responses against infections were in the focus of 20 research lectures and seven poster presentations by young scientists from four different universities. This year’s meeting was hosted by the Beilhack lab. Three other active research groups joined from the Charité Berlin, and the Universities of Frankfurt and Freiburg. The Interdisciplinary Center for Clinical Research (IZKF) Würzburg generously supported this interdisciplinary young investigator meeting. Originally, this workshop had been inspired by the annual Stanford immunology retreats in Asilomar, California, which were always highlights for Robert Zeiser and Andreas Beilhack during their postdoctoral training at Stanford University. After returning to Europe the Zeiser and Beilhack labs initiated an annual two-day scientific workshop together with the young research labs of Evelyn Ullrich and Olaf Penack: Once a year these four research teams meet to discuss recent research progress and new perspectives in the field of hematopoietic cell transplantation and immunotherapy. Beside an intense scientific program there was also time for a brief visit to the Georg Schäfer Museum to enjoy Central European art from the 19th century. Already we are looking forward to our 10th workshop, which will be held near Frankfurt am Main in 2018.
A long-standing collaboration with Prof. Edgar Serfling that was initiated in the Transregio SFB TRR52 reseach consortium comes now to fruition. Today, these research findings are being published in the prestigious journal Nature Communications.
Cytotoxic T lymphocytes are effector CD8+ T cells that very efficiently eradicate infected and malignant cells. Our new research publication by Stefan Klein-Hessling and colleagues demonstrates that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activated cytotoxic T lymphocytes, which were deficient for Nfatc1, were also defective to organize their cytoskeleton and to recruit cytosolic organelles to immunological synapses. If CD8+ T cells lacked NFATc1, their cytotoxic potential against malignant multiple myeloma cells dramatically declined. Furthermore, mice with NFATc1-deficient T cells could not control Listeria infections.
Extensive transcriptome analysis revealed that NFATc1 controls multiple programs in cytotoxic T cells including the production of cytokines, chemokines and metabolic programs. This new comprehensive study highlights that NFATc1 is an important regulator of cytotoxic T lymphocyte effector functions.
Klein-Hessling S, Muhammad K, Pusch T, Klein M, Rudolf R, Flöter J, Qureischi M, Beilhack A, Vaeth M, Kummerow C, Backes C, Schoppmeyer R, Hahn U, Hoth M, Bopp T, Berberich-Siebelt F, Patra A, Avots A, Müller N, Schulze A, Serfling E. (2017). NFATc1 controls the cytotoxicity of CD8+ T cells at multiple levels. Nature Communications 8:511.
Tsetse flies transmit African trypanosomiasis, known as sleeping sickness that causes death months or years after infection. More than 70 million people in sub-Saharan Africa are at risk of this disease.
The cause of these devastating infections are the protozoa of the species Trypanosoma brucei, which is the research focus of the group of Prof. Markus Engstler at the Biocenter at Würzburg University. Thanks to the recently founded DFG graduate college “3D Infect” our research teams connected and studied the week-long journey of Trypanosoma brucei through the different microenvironments of the tsetse fly´s interior organs with advanced microscopy techniques. Dynamic high resolution microscopy revealed the enormous versatility of the incessantly swimming trypanosomes, which cross various barriers and confined surroundings. These rapidly adaptive processes concur with major changes of parasite cell architecture. The new findings by Sarah Schuster et al. about these highly adaptable host-pathogen interactions are now published in the distinguished journal eLIFE.
Schuster S, Krüger T, Subota I, Thusek S, Rotureau B, Beilhack A, Engstler M. (2017). Developmental adaptations of trypanosome motility to the tsetse fly host environments unravel a multifaceted in vivo microswimmer system. Elife. 6: e27656.
This year’s lab retreat took us 20km down the river Main from Frickenhausen to Würzburg City.
On a stunningly beautiful summer day and removed from the research benches our team reconnected for a canoe tour on the picturesque river Main, embedded between vineyards, old Franconian towns and famous wine villages. We enjoyed the nature of the river, refreshing water and good conversations before finally reaching our destination at Würzburg’s city beach – happy and – for some of us – sore muscles guaranteed.