Nikolas Herold

About me

Before Sidney Farber introduced chemotherapy to treat childhood cancer at the end of the 1940s, paediatric cancers have been – with the exception of a small subset of patients that could be cured by radical surgery only – considered universally lethal, and any treatment had been considered unethical experiments prolonging the patients’ suffering. However, empirical combinations of several cytotoxic drugs have led to an overall cure rate of childhood cancer of 85%. Nevertheless, 15% of paediatric cancer patients still succumb to their disease despite heavy combination therapies, and the death toll for adult cancer patients (e.g. 70% for acute myeloid leukaemia in adults vs less than 30% in children) is far higher. As of today, one understands surprisingly little about how combined drugs exert their synergistic effects on a cellular and molecular level. My research sets out to understand why certain combinations of chemotherapies work for some, but not all patients with the same diagnosis. The overarching hypothesis that drives my research is that genetic factors exist that determine the extent of cellular and clinical drug synergy of two or more drugs (combination chemotherapy). Identification of these factors will not only allow to establish predictive biomarkers for combination chemotherapies, but also constitute the starting point for the development of drugs targeting cellular factors that block synergy of combination treatments. Alternatively, existing drugs might be combined in a different schedule that circumvents these cellular factors. 

Research description

Aetiology of Langerhans Cell Histiocytosis (LCH)

Translational Paediatric Oncology

Chemoresistance

Nucleotide metabolism

HIV infection and inflammation

 

Publikationer (urval)

Targeting SAMHD1 with hydroxyurea in first-line cytarabine-based therapy of newly diagnosed acute myeloid leukaemia: Results from the HEAT-AML trial. Jädersten M, Lilienthal I, Tsesmetzis N, Lourda M, Bengtzén S, Bohlin A, Arnroth C, Erkers T, Seashore-Ludlow B, Giraud G, Barkhordar GS, Tao S, Fogelstrand L, Saft L, Östling P, Schinazi RF, Kim B, Schaller T, Juliusson G, Deneberg S, Lehmann S, Rassidakis GZ, Höglund M, Henter JI, Herold N J Intern Med 2022 Aug;():

A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma-LuDO-N. Sundquist F, Georgantzi K, Jarvis KB, Brok J, Koskenvuo M, Rascon J, van Noesel M, Grybäck P, Nilsson J, Braat A, Sundin M, Wessman S, Herold N, Hjorth L, Kogner P, Granberg D, Gaze M, Stenman J Front Pediatr 2022 ;10():836230

Sting Is Commonly and Differentially Expressed in T- and Nk-Cell but Not B-Cell Non-Hodgkin Lymphomas. Xagoraris I, Farrajota Neves da Silva P, Kokaraki G, Stathopoulou K, Wahlin B, Österborg A, Herold N, Ng SB, Medeiros LJ, Drakos E, Sander B, Rassidakis GZ Cancers (Basel) 2022 Feb;14(5):

Clinical and biological impact of SAMHD1 expression in mantle cell lymphoma. Merrien M, Wasik AM, Ljung E, Morsy MHA, de Matos Rodrigues J, Carlsten M, Rassidakis GZ, Christensson B, Kolstad A, Jerkeman M, Ek S, Herold N, Wahlin BE, Sander B Virchows Arch 2022 Mar;480(3):655-666

Response to mitogen-activated protein kinase inhibition of neurodegeneration in Langerhans cell histiocytosis monitored by cerebrospinal fluid neurofilament light as a biomarker: a pilot study. Henter JI, Kvedaraite E, Martín Muñoz D, Cheng Munthe-Kaas M, Zeller B, Nystad TA, Björklund C, Donnér I, Lourda M, Zetterberg H, Blennow K, Herold N, Gavhed D, von Bahr Greenwood T Br J Haematol 2022 01;196(1):248-254

Heterogeneities in Cell Cycle Checkpoint Activation Following Doxorubicin Treatment Reveal Targetable Vulnerabilities in TP53 Mutated Ultra High-Risk Neuroblastoma Cell Lines. Ödborn Jönsson L, Sahi M, Lopez-Lorenzo X, Keller FL, Kostopoulou ON, Herold N, Ährlund-Richter L, Shirazi Fard S Int J Mol Sci 2021 Apr;22(7):

Expression of the novel tumour suppressor sterile alpha motif and HD domain-containing protein 1 is an independent adverse prognostic factor in classical Hodgkin lymphoma. Xagoraris I, Vassilakopoulos TP, Drakos E, Angelopoulou MK, Panitsas F, Herold N, Medeiros LJ, Giakoumis X, Pangalis GA, Rassidakis GZ Br J Haematol 2021 Feb;():

Effects of PI3K and FGFR inhibitors alone and in combination, and with/without cytostatics in childhood neuroblastoma cell lines. Holzhauser S, Lukoseviciute M, Papachristofi C, Vasilopoulou C, Herold N, Wickström M, Kostopoulou ON, Dalianis T Int J Oncol 2021 Jan;():

Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies. Lilienthal I, Herold N Int J Mol Sci 2020 Sep;21(18)

Pharmacological strategies to overcome treatment resistance in acute myeloid leukemia: increasing leukemic drug exposure by targeting the resistance factor SAMHD1 and the toxicity factor Top2β. Herold N Expert Opin Drug Discov 2020 Aug;():1-5

Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy. Rudd SG, Tsesmetzis N, Sanjiv K, Paulin CB, Sandhow L, Kutzner J, et al EMBO Mol Med 2020 Jan;():e10419

Evidence for SAMHD1 Tumor Suppressor Functions in Acute Myeloid Leukemia. Schaller T, Herold N Acta Haematol. 2019 Jul;():1-2

Overexpression of the Interferon-Inducible Isoform 4 of NCOA7 Dissects the Entry Route of Enveloped Viruses and Demonstrates that HIV Enters Cells via Fusion at the Plasma Membrane. Herold N Viruses 2019 01;11(2):

Low-level expression of SAMHD1 in acute myeloid leukemia (AML) blasts correlates with improved outcome upon consolidation chemotherapy with high-dose cytarabine-based regimens. Rassidakis GZ, Herold N, Myrberg IH, Tsesmetzis N, Rudd SG, Henter JI, et al Blood Cancer J 2018 10;8(11):98

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):

Effects of Inner Nuclear Membrane Proteins SUN1/UNC-84A and SUN2/UNC-84B on the Early Steps of HIV-1 Infection. Schaller T, Bulli L, Pollpeter D, Betancor G, Kutzner J, Apolonia L, et al J. Virol. 2017 10;91(19):

With me or against me: Tumor suppressor and drug resistance activities of SAMHD1. Herold N, Rudd SG, Sanjiv K, Kutzner J, Myrberg IH, Paulin CBJ, et al Exp. Hematol. 2017 08;52():32-39

SAMHD1 protects cancer cells from various nucleoside-based antimetabolites. Herold N, Rudd SG, Sanjiv K, Kutzner J, Bladh J, Paulin CBJ, et al Cell Cycle 2017 Jun;16(11):1029-1038

Improved Local Control by Extensive Surgery in High-Risk Neuroblastoma May Be Dependent on Adjuvant Radiotherapy. Stenman J, Herold N, Svensson PJ, Kogner P J. Clin. Oncol. 2017 06;35(17):1965-1966

SAMHD1 is a barrier to antimetabolite-based cancer therapies. Rudd SG, Schaller T, Herold N Mol Cell Oncol 2017 ;4(2):e1287554

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, et al Nat. Med. 2017 Feb;23(2):256-263

Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors. Bulli L, Apolonia L, Kutzner J, Pollpeter D, Goujon C, Herold N, et al J. Virol. 2016 08;90(16):7469-7480

The Early Bird Catches the Worm--Can Evolution Teach us Lessons in Fighting HIV? Schaller T, Herold N Curr. HIV Res. 2016 ;14(3):183-210

HIV-1 entry in SupT1-R5, CEM-ss, and primary CD4+ T cells occurs at the plasma membrane and does not require endocytosis. Herold N, Anders-Ößwein M, Glass B, Eckhardt M, Müller B, Kräusslich HG J. Virol. 2014 Dec;88(24):13956-70

Teaching portfolio

Main supervisor PhD (Nikolaos Tsesmetzis)

Co-supervisor PhD (Hajar Ali Mohammed Ba Omar, Fredrik Sundquist, Maria Alpman Sjöborg)

Main supervisor Medical Degree Project (Aliyya Haciyeva, Julia Bladh)

PhD course organiser Translational Paediatric Oncology in the Era of Immunotherapy and Omics (http://kiwas.ki.se/katalog/katalog/kurs/2706, http://kiwas.ki.se/katalog/katalog/kurs/3217)

Education

Docentur (KI), 2021

Medical degree (Heidelberg, Germany, 2012)

Medical license (Sweden), 2015

Doctoral degree (Heidelberg, Germany), 2015

Academic honours, awards and prizes

Research Prize Jeanssons Foundations (http://jeanssonsstiftelser.se/nikolas-herold/)

Tranlational prize of the Swedish Medical Association (https://www.sls.se/om-oss/aktuellt/publicerat/2019/translationella-forskningspriset-2019)

NOPHO-prize 2016, Stockholm, Sweden