Max Planck Research Group Jachimowicz

Mechanisms of DNA Repair

Cells possess sophisticated mechanisms to detect and repair DNA damage. A network of DNA repair pathways safeguards genome integrity and limits the consequences of endogenous and exogenous genotoxic stress. Defects in these repair mechanisms lead to genome instability, a central driver of ageing and cancer. The importance of genome stability for organismal health is particularly evident in inherited genome instability syndromes. These syndromes are frequently associated with features of premature ageing and age-related diseases, including an increased susceptibility to cancer with a higher incidence of solid tumors and lymphomas.

Our research aims to uncover the mechanistic links between genome stability, ageing, and cancer. To address these questions, we integrate molecular biology, genetics, cancer biology, and translational approaches within an interdisciplinary research program. Using patient cohorts, primary patient material, and advanced mouse models, we investigate how defective DNA repair reshapes cellular signaling networks and influences ageing- and cancer-associated processes. A particular focus of our work lies in lymphoma, whose development and evolution are closely linked to alterations in genome maintenance pathways. Through the analysis of human samples and genetically engineered mouse models, we study how oncogenic signaling pathways interact with DNA repair mechanisms and how tumors exploit these processes to promote growth and survival.

Ultimately, we aim to identify therapeutically actionable pathways and exploit specific vulnerabilities that arise from defective DNA repair or tumor-specific signaling networks. Our long-term vision is to establish a deeper mechanistic understanding of genome stability that enables the development of precise therapeutic strategies.

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Selected publications 

UBQLN1-Mediated Repression of Homologous Recombination is an Actionable Target for Cancer Therapy
Huetzen M.A., Leidecker O., Hopff A.-S., Gajarská P.V., Pandrea M.-T., Camarillo R., Dominguez-Perez M.C., Goergens J., Graef C.M., Bröckelmann P.J., Stüdle A.S.T., Wirtz J., van Weert E., Kruessmann A., Patwardhan N., Müller L., Ghosh S., Reese M., Tröder S., Torres Fernandez L., Murray H., Chong K.K., Klein S., Basquin J., Beleggia F., Mesaros A., Wunderlich F.T., Panier S., Quaas A., Shiloh Y., Hoon D.S.B., Hucho T., Brägelmann J., Peifer M., Aydin H., Pehlivan D., Lupski J.R., Buettner R., Thelen M., Huertas P., Marschall T., Borkhardt A., Cartolano M., Hoppe T., Bustos M.A., Isensee J., Wieczorek D., Reinhardt H.C., Jachimowicz R.D.
(2026) Cell Press

Targeting a Glutamic Acid in PDEdelta with Fluoromethyl-Aryl Electrophiles Impairs K-Ras Signaling
Zhang R., Huetzen M.A., Binici A., Martin-Gago P., Gasper R., Rudashevskaya E., Liu J., Nagaraju C., Reckzeh E.S., Stüdle A.S.T., Hopff A.S., Mesaros A., Unger A., Thelen M., Janning P., Reinhardt H.C., Ziegler S., Jachimowicz R.D., Waldmann H.
(2026) J Med Chem. 2026;69(2):964–981.

Establishment and characterization of a CCND1-rearranged non-mantle cell lymphoma cell line and patient-derived xenograft model
Graf C.M., Reese M., Vicente-Luque A., Monig N., Bruzeau C., Nadeu F., Latacz M., Bihler J., Meinel J., Cartolano M., Peifer M., Bea S., Campo E., Thelen M., Brockelmann P.J., Jachimowicz R.D.
(2026) Leukemia. 2026;40(3):666–670.

Generation of faithful autochthonous mouse models of Mantle Cell Lymphoma
Moenig N., Broeckelmann P., Graef C.M., Bruzeau C., Reese M., Knittel G., Reinhardt H.C., Thelen M., Jachimowicz R.D.
(2025) Blood. 2025;146(Suppl 1):1757–1757.

UBQLN4 Represses Homologous Recombination and Is Overexpressed in Aggressive Tumors
Jachimowicz R.D., Beleggia F., Isensee J., Velpula B.B., Goergens J., Bustos M.A., Doll M.A., Shenoy A., Checa-Rodriguez C., Wiederstein J.L., Baranes-Bachar K., Bartenhagen C., Hertwig F., Teper N., Nishi T., Schmitt A., Distelmaier F., Ludecke H.J., Albrecht B., Kruger M., Schumacher B., Geiger T., Hoon D.S.B., Huertas P., Fischer M., Hucho T., Peifer M., Ziv Y., Reinhardt H.C., Wieczorek D., Shiloh Y.
(2019) Cell. 2019;176(3):505–519.e522.