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Marten Hoeksema

Gene regulation in macrophages

Hoeksema Lab

Marten Hoeksema, PhD


Biosketch

Dr. Marten Hoeksema is a Group Leader and Assistant Professor at the department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam. He obtained his PhD at the University of Amsterdam on the epigenetic regulation of macrophage function in 2016. After which, he did his post-doctoral training at the University of California, San Diego (UCSD) with Prof. Chris Glass. During this time, he led the labs efforts to study enhancer activation in mouse macrophages from different genetic strains to study the effects of genetic variants on enhancer activation. In 2021, he moved back to Amsterdam UMC, where he focusses on the transcriptional regulation of macrophages in health and disease. 


The Hoeksema lab studies how macrophage enhancers function: which transcriptional regulators activate enhancers when macrophages are exposed to disease-associated signals, what genetic variants affect enhancer activity and how does this in turn result in differential gene expression?

This research is currently funded through an ERC Starting Grant, by the European Commission (Marie Skłodowska-Curie Fellowship) and by the Netherlands Organisation for Health Research and Development (ZonMW).

Hoeksema Lab

Marten Hoeksema, PhD


Biosketch

Dr. Marten Hoeksema is a Group Leader and Assistant Professor at the department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam. He obtained his PhD at the University of Amsterdam on the epigenetic regulation of macrophage function in 2016. After which, he did his post-doctoral training at the University of California, San Diego (UCSD) with Prof. Chris Glass. During this time, he led the labs efforts to study enhancer activation in mouse macrophages from different genetic strains to study the effects of genetic variants on enhancer activation. In 2021, he moved back to Amsterdam UMC, where he focusses on the transcriptional regulation of macrophages in health and disease. 


The Hoeksema lab studies how macrophage enhancers function: which transcriptional regulators activate enhancers when macrophages are exposed to disease-associated signals, what genetic variants affect enhancer activity and how does this in turn result in differential gene expression?


This research is currently funded through an ERC Starting Grant, by the European Commission (Marie Skłodowska-Curie Fellowship) and by the Netherlands Organisation for Health Research and Development (ZonMW).

Medical Biochemistry

News

Bertus Kemp Stipendium for Marten Hoeksema

By duda-wsm • November 6, 2024
Marten Hoeksema received a Bertus Kemp Stipendium from the " Genootschap ter bevordering van Natuur-, Genees- en Heelkunde ". The aim is to study kinase activity differences in macrophages activated with various cytokines. The grant will be used for this research as well as a work visit to the lab of collaborator dr. Emiel van der Vorst at the university of Aachen.

PhD defense Sanne Lith

By duda-wsm • October 16, 2024
Congratulations to Dr. Sanne Lith on successfully defending her PhD thesis last Friday! Wishing Sanne all the best in her next chapter!
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Hoeksema Lab

Research

EGR1 and EGR2 regulate opposite inflammatory pathways in macrophages

Macrophages play important roles in many aspects of immunity and therefore contribute to a diverse range of human inflammatory diseases. The expression of macrophage genes is tightly controlled by regulatory DNA elements, such as enhancers. When macrophages are exposed to external stimuli, specific transcription factors affect enhancer activity, thereby impacting macrophage function in health and disease.


I found that the anti-inflammatory cytokine IL-4 activates the transcription factor EGR2 leading to specific IL-4-induced enhancer and gene activation in macrophages. I surprisingly noticed that EGR1, while binding highly similar DNA motifs as EGR2, actually regulates pro-inflammatory gene and enhancer activity when macrophages are exposed to pro-inflammatory stimuli, indicating opposite effects of EGR1 and EGR2. By targeting transcriptional regulators, macrophages can be skewed to disease-favorable phenotypes. I am investigating and targeting EGR1 and EGR2 in pro- and anti-inflammatory macrophage phenotypes in vitro and in disease.


This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie SkÅ‚odowska-Curie grant agreement No 895411. 

Cytokine signaling in macrophages: beyond JAK-STAT

Dysregulated macrophage function underlies many inflammatory diseases. Cytokines, small secreted signaling molecules with immune-modulatory functions, shape the macrophage’s phenotype, thereby affecting disease states. Puzzlingly, many cytokines with opposing functions, utilize highly similar JAK-STAT signaling cascades, leaving it unclear how cytokine-specific responses can occur. 


By studying macrophage enhancer responses, we will reveal novel, cytokine-specific TFs, which will aid in developing better tailored intervention strategies. 


Funded by the European Union (ERC, CytoMAC, 101076170). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.

Hoeksema Lab

The Team

Marten Hoeksema

Principal Investigator

Mees Botman

Research Technician

Ricky Siebeler

PhD Student

Alexandra Drakaki

PhD Student

Josje Huisman

PhD Student

Thirza Lapré

PhD Student

You?

Let us know if interested!

??

MSc Student

Alumni


Mees Botman (2023-24, BSc student)

Max Lange (2023-24, technician)

Guillem Buesa Maes (2023, MSc student)

Dixie Bakker (2022, MSc student)

Hoeksema Lab

Job opportunities


We are looking for a new PhD student right now (see the jobs/internships tab) and again in mid 2025!


Contact me below for information:

Hoeksema Lab

Internships

If you are looking for a future internship, you can always contact me below for information:

Marten Hoeksema

Publications

Recent peer-reviewed publications:


• Lund SJ, Del Rosario PGB, Honda A, Caoili KJ, Hoeksema MA, Nizet V, Patras KA, Prince LS.Sialic Acid-Siglec-E Interactions Regulate the Response of Neonatal Macrophages to Group B Streptococcus. Immunohorizons. 2024 May 1;8(5):384-396. doi: 10.4049/immunohorizons.2300076.


• Reilly NA, Sonnet F, Dekkers KF, Kwekkeboom JC, Sinke L, Hilt S, Suleiman HM, Hoeksema MA, Mei H, van Zwet EW, Everts B, Ioan-Facsinay A, Jukema JW, Heijmans BT.  Oleic acid triggers metabolic rewiring of T cells poising them for T helper 9 differentiation. iScience. 2024 Mar 12;27(4):109496. doi: 10.1016/j.isci.2024.109496. eCollection 2024 Apr 19.


• van Os BW, Vos WG, Bosmans LA, van Tiel CM, Toom MD, Beckers L, Admiraal M, Hoeksema MA, de Winther MP, Lutgens E. CD40L modulates CD4+ T cell activation through receptor for activated C kinase 1.Eur J Immunol. 2023 Sep 8:e2350520. doi: 10.1002/eji.202350520. 


• Czimmerer Z, Patsalos A, Hoeksema MA. Editorial: Transcriptional regulation of macrophage function. Front Immunol. 2023 Nov 2;14:1321064.


• Siebeler R, de Winther MPJ, Hoeksema MA. The regulatory landscape of macrophage interferon signaling in inflammation. J Allergy Clin Immunol. 2023 Aug;152(2):326-337. doi: 10.1016/j.jaci.2023.04.022. Epub 2023 Jun 3.


• van Wouw SAE, van den Berg M, El Ouraoui M, Meurs A, Kingma J, Ottenhoff R, Loix M, Hoeksema MA, Prange K, Pasterkamp G, Hendriks JJA, Bogie JFJ, van Klinken JB, Vaz FM, Jongejan A, de Winther MPJ, Zelcer N. Sterol-regulated transmembrane protein TMEM86a couples LXR signaling to regulation of lysoplasmalogens in macrophages. J Lipid Res. 2023 Feb;64(2):100325. doi: 10.1016/j.jlr.2022.100325.


• Czimmerer Z, Halasz L, Daniel B, Varga Z, Bene K, Domokos A, Hoeksema M, Shen Z, Berger WK, Cseh T, Jambrovics K, Kolostyak Z, Fenyvesi F, Varadi J, Poliska S, Hajas G, Szatmari I, Glass CK, Bacsi A, Nagy L. The epigenetic state of IL-4-polarized macrophages enables inflammatory cistromic expansion and extended synergistic response to TLR ligands. Immunity. 2022 Nov 8;55(11):2006-2026.e6. doi: 10.1016/j.immuni.2022.10.004. 


• Breuss MW, Yang X, Schlachetzki JCM, Antaki D, Lana AJ, Xu X, Chung C, Chai G, Stanley V, Song Q, Newmeyer TF, Nguyen A, O'Brien S, Hoeksema MA, Cao B, Nott A, McEvoy-Venneri J, Pasillas MP, Barton ST, Copeland BR, Nahas S, Van Der Kraan L, Ding Y; NIMH Brain Somatic Mosaicism Network, Glass CK, Gleeson JG. Somatic mosaicism reveals clonal distributions of neocortical development. Nature. 2022 Apr;604(7907):689-696. 


• Honda A, Hoeksema MA, Sakai M, Lund SJ, Lakhdari O, Butcher LD, Rambaldo TC, Sekiya NM, Nasamran CA, Fisch KM, Sajti E, Glass CK, Prince LS. The Lung Microenvironment Instructs Gene Transcription in Neonatal and Adult Alveolar Macrophages. J Immunol. 2022 Apr 15;208(8):1947-1959. doi: 10.4049


• Willemsen L, Chen HJ, van Roomen CPAA, Griffith GR, Siebeler R, Neele AE, Kroon J, Hoeksema MA*, de Winther MPJ*. Monocyte and Macrophage Lipid Accumulation Results in Down-Regulated Type-I Interferon Responses. Front Cardiovasc Med. 2022 Feb 10;9:829877. *shared senior author


• Hoeksema MA, Shen Z, Holtman IR, Zheng A, Spann NJ, Cobo I, Gymrek M, Glass CK. Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4. Sci Adv. 2021 Jun 16;7(25):eabf9808.


• Shen Z, Li RZ, Prohaska TA, Hoeksema MA, Spann NJ, Tao J, Fonseca GJ, Le T, Stolze LK, Sakai M, Romanoski CE, Glass CK. Systematic analysis of naturally occurring insertions and deletions that alter transcription factor spacing identifies tolerant and sensitive transcription factor pairs. Elife. 2022 Jan 20;11:e70878.


• Weiss R, Spahn P, Chiang A, Liu Q, Li J, Hamill K, Rother S, Clausen T, Hoeksema MA, Timm B, Godula K, Glass CK, Tor Y, Gordts P, Lewis N, Esko J. Genome-wide screens uncover KDM2B as a modifier of protein binding to heparan sulfate. Nat. Chem. Biol. 2021 Jun;17(6):684-692.


• Neele AE, Chen HJ, Gijbels MJJ, van der Velden S, Hoeksema MA, Boshuizen MCS, Van den Bossche J, Tool AT, Matlung HL, van den Berg TK, Lutgens E, de Winther MPJ. Myeloid Ezh2 Deficiency Limits Atherosclerosis Development. Front Immunol. 2021 Jan 26;11:594603.


• Shen Z, Hoeksema MA, Ouyang Z, Benner C, Glass CK. MAGGIE: leveraging genetic variation to identify DNA sequence motifs mediating transcription factor binding and function. Bioinformatics. 2020 Jul 1;36(Suppl_1):i84-i92.
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