Research Groups

Cellular immunotherapy – especially chimeric antigen receptor (CAR) T cells – has revolutionized cancer therapy in recent years. However, many challenges still remain to harness the full potential of therapeutic T cells for patients suffering from malignant diseases. In our newly established lab, a closely integrated group of researchers is working on understanding and manipulating the mechanisms of CAR T cell killing. We are driven by the ultimate common goal of contributing to the next generation of cellular therapies for our patients.

Specifically, our group works on two main projects, addressing major unsolved challenges in the field:

i) CAR T cells need to discriminate between healthy and malignant tissue, to precisely eliminate cancer cells from the body without causing harmful side effects. To address this, we are exploring a novel anti-cancer target in the CAR T cell format.

ii) Once the CAR T cells successfully identify cancerous target cells, it has to perform its anti-cancer function and kill tumor cells, which in turn can resist this attack by several mechanisms. Understanding and manipulating this T cell-target cell dynamic is the second goal of our lab.

To tackle those challenges, we develop and use in vitro and in vivo tools and are benefitting from being situated in the highly collaborative Biocenter Innsbruck at the Institute of Molecular Biochemistry. Jan Müller is a hematologist, who is employed at the Department of Hematology and Oncology at the Medical University Innsbruck. This allows for close and fruitful collaborations with clinicians and researchers of the MUI. It is this synergy of scientific and clinical expertise that puts us in an optimal position to carry out our highly ambitious research projects. We are currently looking for motivated individuals at all levels of their scientific career with a passion for cellular immunotherapy to join our young research group.

Contact: jan.mueller@i-med.ac.at

Volta L, Myburgh R, Hofstetter M, Koch C, Kiefer JD, Gobbi C, Manfredi F, Zimmermann K, Kaufmann P, Fazio S, Pellegrino C, Russkamp NF, Villars D, Matasci M, Maurer M, Mueller J, Schneiter F, Büschl P, Harrer N, Mock J, Balabanov S, Nombela-Arrieta C, Schroeder T, Neri D, Manz MG. A single-chain variable fragment-based bispecific T-cell activating antibody against CD117 enables T-cell mediated lysis of acute myeloid leukemia and hematopoietic stem and progenitor cells. HemaSphere. 2024 Nov 19;8(11):e70055.

Spencer Chapman M, Wilk CM, Boettcher S, Mitchell E, Dawson K, Williams N, Mueller J, Kovtonyuk L, Jung H, Caiado F, Roberts K, O’Neill L, Kent DG, Green AR, Nangalia J, Manz MG, Campbell PJ. Clonal dynamics after allogeneic haematopoietic cell transplantation. Nature 2024 Oct 30.

Volta L, Myburgh R, Pellegrino C, Koch C, Maurer M, Manfredi F, Hofstetter M, Kaiser A, Schneiter F, Mueller J, Buehler MM, De Luca R, Favalli N, Magnani CF, Schroeder T, Neri D, Manz MG. Efficient combinatorial adaptor-mediated targeting of acute myeloid leukemia with CAR T-cells. Leukemia. 2024 Dec;38(12):2598-2613.

Mueller J, Schimmer RR, Koch C, Schneiter F, Fullin J, Lysenko V, Pellegrino C, Klemm N, Russkamp N, Myburgh R, Volta L, Theocharides AP, Kurppa KJ, Ebert BL, Schroeder T, Manz MG, Boettcher S. Targeting the mevalonate or Wnt pathways to overcome CAR T-cell resistance in TP53-mutant AML cells. EMBO Mol Med. 2024 Mar;16(3):445-474.

Schimmer RR, Kovtonyuk LV, Klemm N, Fullin J, Stolz SM, Mueller J, Caiado F, Kurppa KJ, Ebert BL, Manz MG, Boettcher S. TP53 mutations confer resistance to hypomethylating agents and BCL-2 inhibition in myeloid neoplasms. Blood Adv. 2022 Jun 14;6(11):3201-3206.

Mueller J, Szep G, Nemethova M, De Vries I, Lieber AD, Winkler C, Kruse K, Small JV, Schmeiser C, Keren K, Hauschild R, Sixt M. (2017) Load-adaptation of lamellipodial actin networks. Cell. 2017 Sep 21;171(1):188-200.e16.

Leithner A*, Eichner A*, Mueller J, Reversat A, Brown M, Schwarz J, Merrin J, de Gorter DJ, Schur F, Bayerl J, de Vries I, Wieser S, Hauschild R, Lai FP, Moser M, Kerjaschki D, Rottner K, Small JV, Stradal TE, Sixt M. (2016) Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nat Cell Biol. 2016 Nov;18(11):1253-1259. *equal contribution.

Mueller J, Pfanzelter J, Winkler C, Narita A, Le Clainche C, Nemethova M, Carlier MF, Maeda Y, Welch MD, Ohkawa T, Schmeiser C, Resch GP, Small JV. (2014) Electron tomography and simulation of baculovirus actin comet tails support a tethered filament model of pathogen propulsion. PLoS Biol. 2014 Jan;12(1):e1001765.