Britta Will, Ph.D.

Mechanisms of stem cell aging and transformation

Hematopoietic stem cells (HSC) maintain blood formation throughout our lifetime. Balancing stem cell regeneration and differentiation commitment to produce mature blood cells is quintessential for a healthy hematopoietic system. Dysregulation of such HSC fate determination processes can lead to loss of immune function, bone marrow failure, and malignant transformation during aging. Up to date, very little is known about the molecular events driving age-related HSC changes and how they contribute to disease. Understanding age-associated molecular alterations will not only uncover fundamental mechanisms guiding function of HSC, but may also allow for therapeutic intervention to "rejuvenate" aged hematopoietic systems and possibly even prevent age-associated hematopoietic diseases.

Our mission is to clarify the central mechanisms establishing and guarding sustained hematopoietic stem cell function, particular those that drive leukemogenesis, if disrupted.

We develop innovative genetic mouse models, use ex vivo and in vivo primary mouse and human stem cell assay systems, exploit lentiviral gene transfer, and apply state-of-the-art molecular biology and next generation sequencing techniques.

Research pipeline I | Molecular determinants of adult stem cells.

Research pipeline II | Therapeutically actionable safeguards in cancer stem cells.

Research pipeline III | New stem cell-directed therapies.

Gao X*, Carpenter RS, Boulais PE, Zhang D, Marlein CR, Li H, Smith M, Chung DJ, Maryanovich M, Will B*, Steidl U* and Frenette PS. [* co-corresponding authors]
Regulation of the mobilizable hematopoietic stem cell pool by c-Kit-mediated trogocytosis
Science 2024
PubMed PMID: 39116219

Kao YR, Chen J, Kumari R, Ng A, Zintiridou A, Tatiparthy M, Ma Y, Aivalioti MM, Moulik D, Sundaravel S, Sun D, Reisz JA, Grimm J, Martinez-Lopez N, Stransky S, Sidoli S, Steidl U, Singh R, D'Alessandro A, Will B.
An iron rheostat controls hematopoietic stem cell fate
Cell Stem Cell 2024
PubMed PMID: 38402617

Okoye-Okafor UC, Javarappa KK, Tsallos D, Saad J, Yang D, Zhang C, Benard L, Thiruthuvanathan VJ, Cole S, Ruiz S, Tatiparthy M, Choudhary G, DeFronzo S, Bartholdy BA, Pallaud C, Ramos PM, Shastri A, Verma A, Heckman CA, Will B.
Megakaryopoiesis impairment through acute innate immune signaling activation by azacitidine
Journal of Experimental Medicine 2022
Pubmed PMID: 36053753

Aivalioti MM, Bartholdy BA, Pradhan K, Bhagat TD, Zintiridou A, Jeong JJ, Thiruthuvanathan VJ, Pujato M, Paranjpe A, Zhang C, Levine RL, Viny AD, Wickrema A, Verma A, Will B.
PU.1-Dependent Enhancer Inhibition Separates Tet2-Deficient Hematopoiesis from Malignant Transformation
Blood Cancer Discovery 2022
PubMed PMID: 35820129

Dong S, Wang Q, Kao YR, Diaz A, Tasset I, Kaushik S, Thiruthuvanathan V, Zintiridou A, Nieves E, Dzieciatkowska M, Reisz JA, Gavathiotis E, D'Alessandro A, Will B* and Cuervo AM*. [* co-corresponding authors]
Chaperone-mediated autophagy sustains haematopoietic stem-cell function.
Nature 2021
PubMed PMID: 33442062

Kao YR, Chen J, Narayanagari SR, Todorova TI, Aivalioti M, Ferreira M, Ramos-Marques P, Pallaud C, Mantzaris I, Shastri A, Bussel JB, Verma A, Steidl U, Will B.
Thrombopoietin receptor-independent stimulation of hematopoietic stem cells by eltrombopag
Science Translational Medicine 2018
PubMed PMID: 30209246

Will B*, Vogler TO, Narayanagari S, Bartholdy B, Todorova TI, da Silva Ferreira M, Chen J, Yu Y, Mayer J, Barreyro L, Carvajal L, Neriah DB, Roth M, van Oers J, Schaetzlein S, McMahon C, Edelmann W, Verma A, Steidl U*. [* co-corresponding authors]
Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia
Nature Medicine 2015
PubMed PMID: 26343801

A complete list of our publications can be found at NCBI or Google Scholar.