“My ambition is to solve fundamental questions in macrophage biology. In doing so, I strive to push the flourishing field of immunometabolism towards clinical applications that promote health.”

Jan Van den Bossche is now Associate Professor at the Department of Molecular Cell Biology and Immunology at Amsterdam UMC. He leads the Translational Macrophage Immunometabolism group IMMUNOMETLAB. His young and enthusiastic team specializes in the immune/metabolic profiling and targeting of macrophages and other immune cells, particularly in the context of cancer and cardiometabolic disease.

TRAINING AND BACKGROUND

The internship with Prof. Jo Van Ginderachter during his Master in Bioscience Engineering (graduated cum laude in 2006 at Vrije Universiteit Brussel, Belgium) piqued Jan’s interest in macrophages. Understanding these fascinating immune cells is the common thread throughout his career.

During his PhD at the VIB Myeloid Cell Immunology Lab in Brussels, Jan defined the regulation and function of E-cadherin in macrophages during cancer, allergic asthma and infections (Blood, 2009; Blood, 2012; Scientific Reports, 2015). His discovery of polyamines as key regulators of macrophages was Jan’s first step into the wonderful world of macrophage metabolism in a time that immunometabolism was not invented yet (Journal of Leukocyte Biology, 2012). This work was funded by a personal FWO fellowship. Publishing 6 first-author articles and contributing to the identification and understanding of distinct subsets of tumor-associated myeloid cells as co-author (Blood, 2008; Cancer Research, 2010) allowed Jan to complete this PhD cum laude in 2011.

After a short stay at University of Tübingen (Germany) studying immune changes during exercise, Jan started as a postdoc in Prof. Menno de Winther’s group at Academic Medical Center of Amsterdam in 2012 to investigate the epigenetic regulation of macrophages during atherosclerosis.

A junior postdoc grant from Netherlands Heart foundation (€277.120; 2013) and an NWO VENI (€250.000; 2014) allowed Jan to hire a PhD (Jeroen Baardman, finalized 19/10/2019) and start an independent research line on macrophage immunometabolism. During this position as junior group leader, he supervised one technician and two additional PhDs as co-promotor (Annette Neele, finalized 19/01/2018; Rosario Luque-Martin, 7/10/2021).

Rosario was appointed on the EU-funded Epimac training network, which allowed intensive collaboration with GlaxoSmithKline. During this period, Jan also cooperated with ITALFARMACO and Seahorse/Agilent. The resulting publications and follow-up studies towards clinical applications were a great lesson on how interactions with pharmaceutical companies are both exciting and rewarding.

At the end of 2017 Jan moved to the VUmc side of Amsterdam UMC, where he entered a tenure track and became Principal Investigator of IMMUNOMETLAB at the Department of Molecular Cell Biology and Immunology. In 2022, the tenure track was successfully finalized and Jan obtained a tenured position. Since 2023, he is Associate Professort (UHC) in Immunometabolism

IMMUNOMETLAB RESEARCH

Jan Van den Bossche’s lab performs pioneering research on macrophage immunometabolism. The overall aim is to explain how metabolic reprogramming regulates macrophage subsets in different settings, focusing on cancer and cardiovascular disease. By unravelling key questions in macrophage immunometabolism, the ultimate goal is to demonstrate whether and how targeting macrophage metabolism can be used for future therapy. Current research topics include immunometabolites (succinate, itaconate and new-found ones), metabolic immune-cancer interactions, metabolic enzymes (including ACLY; ATP citrate lyase).

Over the past decade, Jan’s team established an immunometabolic profiling platform allowing the phenotypic, functional and metabolic characterization of macrophage and other immune subsets in a fast and cost-effective way

In-house techniques include extracellular flux analysis (Seahorse), metabolomics, Cytation multi-mode imaging plate reader, transcriptomics, and cytometry- and imaging-based single-cell metabolic profiling.

EXPERTISE & OPPORTUNITIES FOR COLLABORATION

We are always keen to collaborate with both academia and industry on topics related to immunometabolism, myeloid cell subsets and (chronic) inflammation in the context of distinct (Western) diseases. We are always seeking new strategies to modulate macrophage phenotypes, promote resolution of inflammation, dampen (chronic) inflammation.

Common interests include the impact of lifestyle factors (such as diet, physical activity, sleep,…) on immune function, metabolism, inflammation, susceptibility to infections, disease risk and overall human health. We explore immunometabolism as a common denominator in these processes and consider it as a bridge between environment and immune health.

Immune-metabolic profiling platform

We established a broad array of techniques to phenotypically, functionally and metabolically profile immune cell subsets in a semi-high-throughput manner. This allows us to efficiently screen the effect of small molecules and genetic interventions on macrophages in vitro. Key targets are then further tested in in vivo disease models and patient material.

GET IN CONTACT

E-mail: j.vandenbossche [@] amsterdamumc.nl

Twitter: @immunometlab & @immunometnet & @ScienceLab_MCBI

LinkedIn: linkedin.com/in/vandenbosschejan/

Department's homepage: immunologyamsterdam.org

Department's Instagram: instagram.com/sciencelab_mcbi/

Metabolic/epigenetic crosstalk in macrophages

In addition to their function in host defense, macrophages secure tissue homeostasis and dampen inflammatory responses. To carry out these seemingly contrasting functions, macrophages show high plasticity and adopt a spectrum of polarization states, including M1 and M2 cells. Editing macrophage (re)polarization is emerging as a new therapeutic approach. For example, reprogramming tumor-promoting ‘M2-like’ tumor-associated macrophages into anti-tumor ‘M1-like’ cells is being tested as a cancer treatment. Conversely, the treatment of chronic inflammatory diseases such as atherosclerosis will benefit from the repolarization of inflammatory into anti-inflammatory macrophages.

Both metabolic and epigenetic mechanisms are emerging as crucial controllers of macrophages. Our research aims to target macrophage metabolism (Jeroen Baardman) and epigenetics (Rosario Luque-Martin) to improve disease outcome. Moreover, we are tackling the fundamental question how epigenetics could serve as a bridge between macrophage metabolism and its phenotype.