Sean Rudd's Group

The ultimate goal of our research is to provide cancer patients with better treatment options. We believe one way this can be achieved in a timely manner is by focusing research efforts upon commonly used chemotherapeutic agents. These therapies, which form standard-of-care for many cancers, typically kill tumour cells by targeting pan-essential pathways, principally metabolism of the DNA molecule or its nucleotide building blocks (deoxynucleoside triphosphates, dNTPs). In our research program we aim to define the molecular underpinnings of why some cancers respond to these therapies whilst others do not. This information can provide the basis for rational therapy improvements through the identification of biomarkers and therapeutic targets together with the design of mechanism-based drug combinations. We employ a multidisciplinary approach in our research – centred upon biochemical, biophysical, and cell-based methods – and use both hypothesis-driven and hypothesis-free approaches in our efforts to define and exploit the molecular mechanisms underpinning clinical efficacy of chemotherapeutic agents.

In addition, these same pathways which are targeted by commonly used cancer drugs – metabolism of the DNA molecule and its dNTP building blocks – are also fundamental to cancer biology. Key aspects of oncogenesis derive from the interplay of these metabolic pathways, and thus we also investigate this interplay at the molecular level and seek to use knowledge gained in a translationally productive manner.

For more information, please see our external site: www.seanruddlab.com 

Group members

Sean Rudd, Assistant Professor & Group Leader
Si Min Zhang, Postdoc
Miriam Yagüe-Capilla, Postdoc
Femke Hormann, Postdoc
Christopher Dirks, PhD student

Selected publications

Identification and evaluation of small-molecule inhibitors against the dNTPase SAMHD1 via a comprehensive screening funnel
ZhangSM, PaulinCBJ, Michel M, Marttila P, Yagüe-CapillaM, Bwanika HC, ShuH, Papagudi VenkatramR, WiitaE, Jemth AS, Almlöf I, Loseva O, Ortis F, Dirk C, Koolmeister T, Linde E, Lee S, Llona-Minguez S, Haraldsson M, Strömberg K, Homan EJ, Scobie M, Lundbäck T, Helleday T, Rudd SG
bioRxiv 2023

Targeting the DNA damage response and repair in cancer through nucleotide metabolism.
Helleday T, Rudd SG
Mol Oncol 2022 Nov;16(21):3792-3810

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1.
Yagüe-Capilla M, Rudd SG
J Vis Exp 2021 Apr;(170):

Drug synergy scoring using minimal dose response matrices.
Mäkelä P, Zhang SM, Rudd SG
BMC Res Notes 2021 Jan;14(1):27

Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy.
Rudd SG, Tsesmetzis N, Sanjiv K, Paulin CB, Sandhow L, Kutzner J, Hed Myrberg I, Bunten SS, Axelsson H, Zhang SM, Rasti A, Mäkelä P, Coggins SA, Tao S, Suman S, Branca RM, Mermelekas G, Wiita E, Lee S, Walfridsson J, Schinazi RF, Kim B, Lehtiö J, Rassidakis GZ, Pokrovskaja Tamm K, Warpman-Berglund U, Heyman M, Grandér D, Lehmann S, Lundbäck T, Qian H, Henter JI, Schaller T, Helleday T, Herold N
EMBO Mol Med 2020 Mar;12(3):e10419

Nucleobase and Nucleoside Analogues: Resistance and Re-Sensitisation at the Level of Pharmacokinetics, Pharmacodynamics and Metabolism.
Tsesmetzis N, Paulin CBJ, Rudd SG, Herold N
Cancers (Basel) 2018 Jul;10(7):

Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies.
Herold N, Rudd SG, Ljungblad L, Sanjiv K, Myrberg IH, Paulin CB, Heshmati Y, Hagenkort A, Kutzner J, Page BD, Calderón-Montaño JM, Loseva O, Jemth AS, Bulli L, Axelsson H, Tesi B, Valerie NC, Höglund A, Bladh J, Wiita E, Sundin M, Uhlin M, Rassidakis G, Heyman M, Tamm KP, Warpman-Berglund U, Walfridsson J, Lehmann S, Grandér D, Lundbäck T, Kogner P, Henter JI, Helleday T, Schaller T
Nat Med 2017 Feb;23(2):256-263

Funding

Our research is generously funded by:

• Swedish Research Council (starting grant in Medicine & Health)
• Swedish Cancer Foundation (Junior Investigator Award & Project grant)
• Swedish Childhood Cancer Fund (Project grant & Postdoc fellowship)
• Karolinska Institutet (Faculty-funded career position)