Hartmann Laboratory
Microenvironment-induced therapy resistance in leukemia and lymphomaScientific focus
Our research group focuses on the interface of tumor immunology and cell biology. We are specifically interested in how the tumor microenvironment promotes therapy resistance in leukemia and lymphoma, with an emphasis on the role of cell adhesion and integrin activation.
We use an assortment of advanced techniques including time-lapse and shear-flow microscopy, flow cytometry, immunofluorescence and confocal microscopy, combined with animal mouse models and adoptive transplant strategies.
Specifically, we focus on VLA-4 integrin (CD29/CD49d) activation in chronic lymphocytic leukemia (CLL) and other hematopoietic malignancies, such as acute myeloid leukemia (AML) and multiple myeloma (MM). The interaction between leukemic and stromal cells, mediated by VLA-4, provides critical survival and proliferation signals to tumor cells.
In CLL, VLA-4 integrin is activated via an inside-out mechanism in response to antigen or chemokine stimulation in secondary lymphoid organs, and involves several kinases. CD49d expression in CLL identifies a high-risk patient group due to its contribution to therapy resistance. In AML, CD44 plays a critical role in VLA-4 activation in the bone marrow, mediated by Src and other kinases.
Our lab is also interested in the role of the integrin adaptor protein Kindlin-3 in B-cells. Research from our lab has shown that Kindlin-3 is crucial for B-cell development, maturation, proliferation, and localization.
Join our team
Master thesis position
The group of Prof. Tanja Nicole Hartmann, PhD, Department of Internal Medicine I (Hematology, Oncology and Stem Cell Transplantation) at the University Medical Center Freiburg is looking for a
Master student, M. Sc. (m/f/d)
Team
Principal Investigator
Prof. Dr. rer. nat. Tanja Nicole Hartmann
+49 (0) 761 270 71511
tanja.hartmann@uniklinik-freiburg.de
Dr. rer. nat. Abhishek Pethe
Postdoctoral scientist
+49 (0) 761 270 71800
Danielle-Justine Danner
Technician, MD student
+49 (0) 761 270 71920
Julius Plomer
Master Student
LABORATORY ACTIVITIES
Summer 2023
Hartmann Lab retreat at the Kletterpark in Titisee
September 2024:
Congratulation to Driti Ashok for winning the Best Abstract Award of the 2024 CRIION Sympoium.
October 2023:
Congrats to Laura and Lixia for acceptance of their abstracts for oral presentation at the Annual Meeting of the American Society of Hematology!
Highlights of our new publication in JLB:
Kindlin-3 puts the brakes on B cell activation and differentiation.
Justement LB. J Leukoc Biol. 2022 Apr;111(4):741-743. doi: 10.1002/JLB.1CE1121-597R. Epub 2022 Feb 3.
Highlighting Editorial zu:
Härzschel A, Li L, Krenn PW, Szenes-Nagy E, Andrieux G, Bayer E, Pfeifer D, Polcik L, Denk U, Höpner JP, Karabatak E, Danner DJ, Tangermann S, Kenner L, Jumaa H, Greil R, Börries M, Ruppert R, Maity PC, Hartmann TN. J Leukoc Biol. 2022 Apr;111(4):745-758. doi: 10.1002/JLB.1HI0621-313R. Epub 2021 Dec 10.
New Frontiers Research Topic
Metabolism and Cell Adhesion in Cancer is a new article that will add to our continuing efforts to understand the intricate relationship between cell metabolism, oncogenesis and adhesion.
Full publication list see: https://pubmed.ncbi.nlm.nih.gov/?term=Hartmann%20TN&page=6
Selected publications of last two years:
- The VLA-4 integrin is constitutively active in circulating chronic lymphocytic leukemia cells via BCR autonomous signaling: a novel anchor-independent mechanism exploiting soluble blood-borne ligands.
Maity PC, Jumaa H, Hartmann TN, Zucchetto A, Gattei V. The VLA-4 integrin is constitutively active in circulating chronic lymphocytic leukemia cells via BCR autonomous signaling: a novel anchor-independent mechanism exploiting soluble blood-borne ligands. Leukemia. 2024 Aug 14 - Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma.
Keppler-Hafkemeyer A, Greil C, Wratil PR, Shoumariyeh K, Stern M, Hafkemeyer A, Ashok D, Hollaus A, Lupoli G, Priller A, Bischof ML, Ihorst G, Engelhardt M, Marks R, Finke J, Bertrand H, Dächert C, Muenchhoff M, Badell I, Emmerich F, Halder H, Spaeth PM, Knolle PA, Protzer U, von Bergwelt-Baildon M, Duyster J, Hartmann TN, Moosmann A, Keppler OT. Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma. Nat Cancer. 2023 Jan - Integrin Signaling Shaping BTK-Inhibitor Resistance.
Polcik L, Dannewitz Prosseda S, Pozzo F, Zucchetto A, Gattei V, Hartmann TN. Integrin Signaling Shaping BTK-Inhibitor Resistance. Cells. 2022 Jul 18 - Insights Into Bone Marrow Niche Stability: An Adhesion and Metabolism Route.
Ashok D, Polcik L, Dannewitz Prosseda S, Hartmann TN. Front Cell Dev Biol. 2022 - Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation.
Härzschel A, Li L, Krenn PW, Szenes-Nagy E, Andrieux G, Bayer E, Pfeifer D, Polcik L, Denk U, Höpner JP, Karabatak E, Danner DJ, Tangermann S, Kenner L, Jumaa H, Greil R, Börries M, Ruppert R, Maity PC, Hartmann TN. J Leukoc Biol. 2022 - CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor venetoclax by decreasing CXCL12-driven survival cues.
Yu X, Munoz-Sagredo L, Streule K, Muschong P, Bayer E, Walter RJ, Gutjahr JC, Greil R, Concha ML, Müller-Tidow C, Hartmann TN, Orian-Rousseau V. Blood. 2021 - CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity
Gutjahr JC, Bayer E, Yu X, Laufer JM, Höpner JP, Tesanovic S, Härzschel A, Auer G, Rieß T, Salmhofer A, Szenes E, Haslauer T, Durand-Onayli V, Ramspacher A, Pennisi SP, Artinger M, Zaborsky N, Chigaev A, Aberger F, Neureiter D, Pleyer L, Legler DF, Orian-Rousseau V, Greil R, Hartmann TN.
Haematologica. 2020 - VLA-4 Expression and Activation in B Cell Malignancies: Functional and Clinical Aspects
Härzschel A, Zucchetto A, Gattei V, Hartmann TN.
Int J Mol Sci. 2020 - TCL1 transgenic mice as a model for CD49d-high chronic lymphocytic leukemia
Szenes E, Härzschel A, Decker S, Tissino E, Pischeli J, Gutjahr JC, Kissel S, Pennisi S, Höpner JP, Egle A, Zaborsky N, Dierks C, Follo M, Chigaev A, Zucchetto A, Greil R, Gattei V, Hartmann TN.
Leukemia 2020 - CD49d promotes disease progression in chronic lymphocytic leukemia: new insights from CD49d bimodal expression
Tissino E, Pozzo F, Benedetti D, Caldana C, Bittolo T, Rossi FM, Bomben R, Nanni P, Chivilò H, Cattarossi I, Zaina E, Norris K, Polesel J, Gentile M, Tripepi G, Moia R, Santinelli E, Innocenti I, Olivieri J, D'Arena G, Laurenti L, Zaja F, Pozzato G, Chiarenza A, Di Raimondo F, Rossi D, Pepper C, Hartmann TN, Gaidano G, Del Poeta G, Gattei V, Zucchetto A.
Blood 2020