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Group Bovenschen
Group Bovenschen

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Granule-exocytosis by cytotoxic lymphocytes (CTLs/NK cells) constitutes the main pathway for eliminating tumor cells and virus-infected. In humans, cytotoxic granules contain five serine proteases called granzymes (GrA, B, H, K, and M) that induce cell death or block viral replication by cleaving specific intracellular substrates. These granzymes also exist in the blood circulation and extracellular microenvironment. My lab is interested in the physiological relevance and molecular mechanisms by which granzymes attack and manipulate tumor cells and virus-infected cells.

Research interests/topics

  • Antitumor effects of granzymes: granule-exocytosis by cytotoxic lymphocytes constitutes the main pathway for eliminating tumor cells. Granzymes can activate many pathways of cell death with unique morphological hallmarks that cooperate during cytotoxic lymphocyte cytotoxicity. This redundancy likely evolved to provide protection against tumor cells with diverse strategies to evade immune surveillance. Unlike GrA and GrB, little is known about the cell death mechanism of GrH, GrK, and GrM. In this project, we aim to determine the relevance and mechanisms of these granzymes and how tumors can evade from this cytotoxic immune response. Also the therapeutic potential thereof is investigated.
  • Antiviral effects of granzymes: human cytomegalovirus (HCMV) reactivation in immune-compromised patients can trigger devastating disease. Treatment of HCMV infection is an urgent clinical problem, limited by inefficacy, toxicity of antiviral drugs, and the ongoing appearance of drug-resistant viruses. Cytotoxic lymphocytes are crucial in anti-HCMV immunity via delivering a set of pro-apoptotic serine proteases called granzymes inside virus-infected cells. However, the physiological importance and molecular mechanisms of human granzymes in controlling HCMV remain enigmatic. My group recently demonstrated for the first time that human GrM efficiently inhibits HCMV replication in the absence of host cell death. This points to a previously unrecognized noncytotoxic mechanism by which our immune system can mediate direct anti-HCMV activity. In this project, we aim to uncover the antiviral effector activity of our immune system and use this to develop novel anti-HCMV therapeutic strategies.
  • Extracellular role of granzymes: granzymes also exist in the extracellular matrix and microenvironment, in which the roles of granzymes largely remain unknown. This project aims to uncover the extracellular roles of granzymes in infection, immunity, and cancer.
 

Research programs

Infection and Immunity
Cancer
 

Contact

Niels Bovenschen

Associate Professor | Senior Fellow of UU Center for Academic Teaching
Examiner Scientific Internships Medicine
Head Pathology Research Laboratory | Head CTI Core Facility Proteins

> Email
Phone T: +31 88 7553889 | M: +31 6 15425000

Related website

> Infection and Immunity

Location

Department of Pathology | Division Laboratories, Pharmacy and Biomedical Genetics
University Medical Center Utrecht | Utrecht University
Room G03.504 | Secretary room H04.313 | Heidelberglaan 100 | 3584 CX  UTRECHT | The Netherlands
 

Group members


Research technicians

Jan Meeldijk (core facility Proteins)
Roel Broekhuizen


PhD students

Liling Shan
Shuang Li
Azadeh Lotfalikhani


Master students

Ruben Strien
Marina Brand

Key publications

  1. Drost RH, Dictus WJAG, Prakken BJ, Bovenschen N. How a four-year-old boy connects healthcare, biomedical research and undergraduate education. Nat Biotechnol. 2019;37:1092-1095. View
  2. Bengsch B, Ohtani T, Khan O, Setty M, Manne S, O'Brien S, Gherardini PF, Herati RS, Huang AC, Chang KM, Newell EW, Bovenschen N, Pe'er D, Albelda SM, Wherry EJ. Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells. Immunity. 2018;48:1029-1045. View
  3. de Poot SA, van Erp EA, Meeldijk J, Broekhuizen R, Goldschmeding R, Olthof MC, Steeghs EM, and Bovenschen N. Bioluminescent reporters to monitor killer cell-mediated delivery of granzymes inside target cells. Blood. 2015;126:2893-2895. View
  4. Wensink AC, Kemp V, Fermie J, García Laorden MI, van der Poll T, Hack CE, and Bovenschen N. Granzyme K synergistically potentiates LPS-induced cytokine responses in human monocytes. Proc Natl Acad Sci USA. 2014;111:5974-5979. View
  5. de Poot SA, Lai KW, van der Wal L, Plasman K, Van Damme P, Porter AC, Gevaert K, and Bovenschen N. Granzyme M targets topoisomerase II alpha to trigger cell cycle arrest and caspase-dependent apoptosis. Cell Death Differ. 2014;21:416-426. View

Grants

  

  

 
 
> See all grants 

Prizes

 
2019

NWO Comenius Teaching Fellow, Member: KNAW Comenius Network (advisory board for Ministry of OCW)

2019

Utrecht University - Docent van het jaar 2019

2018

Faculty of medicine - Docent van het jaar 2018

2018

UMC Utrecht -  Distinguished Member: Harmen Tiddens Society

2017

Utrecht University - Teaching fellow

2017

Utrecht University - Best course of the year 2017 award (course Pathology, Biomedical Sciences, 3rd year)

2016

Utrecht University - UU Docent van het jaar 2016-2017

Nominated

2016

Utrecht University - Certificate CEUT educational leadership track

 

UMC News & Media

UMC news

28 Dec 2018 - Studenten zoeken de oorzaak van Micha’s ziekte

> Read (in Dutch)

19 Dec 2018 - Nieuwe vorm van immunotherapie tegen kanker

> Read (in Dutch)

15 Sep 2017 - Niels Bovenschen creëert synergie tussen onderwijs en onderzoek

> Read (in Dutch)

 

UMC Utrecht

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In the media

21 Aug 2018 - Zo maak je van een wetenschappelijke stage een succes - Arts in Spe nieuws

> Read (in Dutch)

12 Dec 2017 - Medulloblastomen bij kinderen zijn meesters in het omzeilen van het immuunsysteem - Stichting Koppie-Au Weblog

> Read (in Dutch)

3 Mar 2016 - Speld in een hooiberg bijdrage van Niels Bovenschen UMC - Stichting Koppie-Au Weblog

> Read (in Dutch)
 

Utrecht University

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Education & Courses

Examiner/Coordinator course Experimental Translational Medicine (15 ECTS)

Biomedical Sciences Bachelor (BMW) + Medicine (GNK), 2nd year course, 16 students, 10 week-course, Utrecht University

Examiner/Coordinator Scientific Research Internships Medicine

(GNK, master, 6th year, >300 students per year)

Examiner/Coordinator course Biomedical Research Lab (15 ECTS)

Biomedical Sciences Bachelor (BMW), 3rd year course, 16 students, 10 week-course, Utrecht University

Examiner/Coordinator course Pathology (3 ECTS)

Biomedical Sciences Master (BMS), 1st year course, max. 30 students, 10 week-course, Utrecht University

Examiner/Coordinator course Pathologie (7.5 ECTS)

Biomedical Sciences Bachelor (BMW), 3rd year course, 75 students, 10 week-course, Utrecht University

Coordinator Scientific Internships, Dept. of Pathology, UMC Utrecht