Dr. Feng HeFeng (also known as Feng He) is now a tenured Senior Researcher focusing on immune ageing and experimental systems immunology in the Department of Infection and Immunity at the Luxembourg Institute of Health (LIH). From Mar. 2015 to Mar. 2020, HeFeng had led an independent junior research group in the Department of Infection and Immunity at the LIH. From Mar. 2020 to Dec. 2021, HeFeng had worked as a visiting scientist at Institute of Clinical Microbiology, University Hospital Essen, Germany. Following his return from Essen, from Mar. 2022 to Mar. 2025, HeFeng had worked as a tenure-track senior researcher in the Department of Infection and Immunity.

HeFeng accomplished his PhD (cumulative thesis) in biology at the Technical University of Braunschweig, Germany and the Helmholtz Centre for Infection Research (HZI) supervised by Prof. An-Ping Zeng. HeFeng then had received his early career training in infection and genetics in Prof. Klaus Schughart's group at HZI for two years. Afterwards, during his five-year term as a research associate at the University of Luxembourg in Prof. Rudi Balling’s lab and as a visiting researcher at the University of Cambridge and the Institute for Systems Biology, Seattle, HeFeng has initiated and developed his data-driven experimental immunology strategy, i.e., starting from the large-scale hypothesis-free unbiased screening followed by experimental validation of novel functions of key candidates and gene networks for various types of immune cells, especially T cells, from dynamic/time-series ‘Omics’ datasets.

Being the principal investigator (PI), HeFeng has been awarded several competitive grants through different external funding sources, either from Luxembourg National Research Fund (FNR) CORE programme (1X as PI, 1X as Co-PI and 1X as Co-Investigator), BRIDGES programme (1X as PI), individual AFR programme (2X as PI), bilateral AFR programme (1X as PI) or PRIDE DTU programme (3X as PI). HeFeng has also been supported twice by the Luxembourg Personalized Medicine Consortium (PMC) pump prime funds. Very recently, HeFeng has also been Co-Investigator of awarded competitive funds through the FNR CORE or ANR-FNR INTER programmes. Last but not least, HeFeng is the project partner of a large EU consortium that was recently selected via the highly-competitive EU Horizon Europe programme.

Theme 1: Immune Ageing/Immunoageing

The remarkable increase in life expectancy has been estimated to result in a global rise of elderly people worldwide. This will inevitably lead to an increase in the number of people suffering from complex non-communicable diseases and infectious diseases for which ageing is the major risk factor. The high prevalence of complex diseases among the elderly is at least partially caused by a decline in the protective functions of both the innate and adaptive immune system over time, a process we termed as 'immunoageing'. HeFeng and team seek to understand the underlying molecular and cellular mechanisms through which the immune functions decline. They discover that one key familial Parkinson’s disease (PD) gene (PARK7, encoding DJ-1) critically regulates the immunoageing process, not only in conventional T cell compartments (Zeng et al., EMBO Reports, 2022), but also in regulatory T cells using both rodent animal models and patients with DJ-1 deficiency (Danileviciute, et al., Nature Metabolism, 2022). Mechanistically, they reveal that DJ-1 regulates T cell homeostasis via modulating the activity of pyruvate dehydrogenase (PDH), the key gatekeeper enzyme of the tricarboxylic acid (TCA) cycle. Although the PDH enzyme activity is known to be tightly regulated by several PDH kinases and phosphatases, their findings add a new dimension to the regulation of the PDH complex and enable a better understanding of the PDH supercomplex system. Their discovery paves the way to make T cells “younger” when the people become older, which might have critical implementations in various ageing-associated diseases.

Beyond investigating rare genetic causes of PD cases, HeFeng and team further asked whether the observed DJ-1-deficiency mediated immunological dysregulation could be also applicable to a broader spectrum of PD, i.e., idiopathic PD (iPD). In another original work led by HeFeng (Capelle et al., Nature Communications, 2023), they found an enhanced cytotoxic immune milieu in early-to-mid stage iPD, with a much higher frequency of terminally-differentiated effector CD8 T (TEMRA) and enhanced cytotoxic pathways in CD8 TEMRA of PD patients. The frequency of CD8 TEMRA was negatively correlated with disease duration, suggesting a contribution to iPD pathogenesis.  As a natural extension, HeFeng and team are currently investigating the molecular mechanisms promoting or suppressing the differentiation of CD8 TEMRA and their implementation in PD pathogenesis via several external competitive funds.

Theme 2: Experimental Systems Immunology

In parallel to their efforts in basic immunology, based on their long-term interest in holistic research, HeFeng and team have led the establishment of a deep immunophenotyping systems-immunology pipeline at a single-cell level and successfully applied it to several non-communicable or infectious diseases, such as COVID-19 (Capelle et al., Cell Reports Medicine, 2022) or allergy (Pogorelov et al., Nature Communications, 2024). Those unbiased hypothesis-free approaches have led to several unexpected discoveries.

Selected Representative Publications (#, Corresponding author; Of note, before 10^th Jun 2021, “Feng He” or “Feng Q. He” rather than “Feng Q. Hefeng” was used in my publications)

1, Egle Danileviciute*, Ni Zeng*, Christophe M. Capelle, Nicole Paczia, Mark A. Gillespie, Henry Kurniawan, Mohaned Benzarti, Myriam P.Merz, Djalil Coowar, Sabrina Fritah, Daniela Maria Vogt Weisenhorn, Gemma Gomez Giro, Melanie Grusdat, Alexandre Baron, Coralie Guerin, Davide G. Franchina, Cathy Léonard, Olivia Domingues, Sylvie Delhalle, Wolfgang Wurst, Jonathan D. Turner, Jens Christian Schwamborn, Johannes Meiser, Rejko Krüger, Jeff Ranish, Dirk Brenner, Carole L. Linster, Rudi Balling, Markus Ollert, Feng Q. Hefeng#, PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during aging. Nature Metabolism, 2022, May 26, 4, 589-607                                    Access: https://www.nature.com/articles/s42255-022-00576-y.

2, Christophe M. Capelle, Séverine Ciré, Fanny Hedin, Maxime Hansen, Lukas Pavelka, Kamil Grzyb, Dimitrios Kyriakis, Oliver Hunewald, Maria Konstantinou, Dominique Revets, Vera Tslaf, Tainá M. Marques, Clarissa P. C. Gomes, Alexandre Baron, Olivia Domingues, Mario Gomez, Ni Zeng, Fay Betsou, Patrick May, Alexander Skupin, Antonio Cosma, Rudi Balling, Rejko Krüger, Markus Ollert#, Feng Q. Hefeng#, Early-to-mid stage idiopathic Parkinson’s disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females. Nature Communications (selected as Featured Article). 2023, Nov 20. 14:7461. Access: https:/www.nature.com/articles/s41467-023-43053-0.

3, Ni Zeng*, Christophe M Capelle*, Alexandre Baron, Takumi Kobayashi, Severine Cire, Vera Tslaf, Cathy Leonard, Djalil Coowar, Haruhiko Koseki, Astrid M Westendorf, Jan Buer, Dirk Brenner, Rejko Krüger, Rudi Balling, Markus Ollert, Feng Q. Hefeng#, DJ-1 depletion prevents immunoaging in T-cell compartments. EMBO Reports, 2022 Feb 3;e53302. Access: https://doi.org/10.15252/embr.202153302.

4, Dimitrii Pogorelov*, Sebastian Felix Nepomuk Bode*, Xin He*, Javier Ramiro-Garcia, Fanny Hedin, Wim Ammerlaan, Maria Konstantinou, Christophe M. Capelle, Ni Zeng, Aurélie Poli, Olivia Domingues, Guillem Montamat, Oliver Hunewald, Séverine Ciré, Alexandre Baron, Joseph Longworth, Agnieszka Demczuk, Murilo Luiz Bazon, Ingrid Casper, Ludger Klimek, Lorie Neuberger-Castillo, Dominique Revets, Lea Guyonnet, Sylvie Delhalle, Jacques Zimmer, Vladimir Benes, Françoise Codreanu-Morel, Christiane Lehners-Weber, Ilse Weets, Pinar Alper, Dirk Brenner, Jan Gutermuth, Coralie Guerin, Martine Morisset, François Hentges, Reinhard Schneider, Mohamed H. Shamji, Fay Betsou, Paul Wilmes, Enrico Glaab, Antonio Cosma, Jorge Goncalves, Feng Q. Hefeng#, Markus Ollert#, Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy. Nature Communications, 2024, Nov. 26, 15: 10266. Access: https://www.nature.com/articles/s41467-024-54684-2.

5, Christophe M. Capelle^*, Séverine Ciré^*, Olivia Domingues, Isabelle Ernens, Fanny Hedin, Aurélie Fischer, Chantal J. Snoeck, Wim Ammerlaan, Maria Konstantinou, Kamil Grzyb, Alexander Skupin, Cara L. Carty, Christiane Hilger, Georges Gilson, Aljosa Celebic, Paul Wilmes, Antonio Del Sol, Ian M. Kaplan, Fay Betsou, Tamir Abdelrahman, Antonio Cosma, Michel Vaillant, Guy Fagherazzi, Markus Ollert^#, Feng Q. Hefeng#, Combinatorial analysis reveals highly coordinated early-stage immune reactions that predict later antiviral immune responses in mild COVID-19 patients. Cell Reports Medicine, 2022, 3 (4):100600. Access: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(22)00117-3.

6, Christophe M. Capelle, Anna Chen, Ni Zeng, Alexandre Baron, Kamil Grzyb, Thais Arns, Alexander Skupin, Markus Ollert, Feng Q. Hefeng#, Stress hormone signaling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1. Immunology, 2022, 165 (4):428-444. Access: https://onlinelibrary.wiley.com/doi/full/10.1111/imm.13448.

7, Christophe M. Capelle, Ni Zeng, Egle Danileviciute, Sabrina Freitas Rodrigues, Markus Ollert, Rudi Balling, Feng Q. He#, Identification of VIMP as a gene inhibiting cytokine production in human CD4+ effector T cells. Cell Press iScience, 2021 Mar 9, 24(4): 102289.
Access: https://www.cell.com/iscience/fulltext/S2589-0042(21)00257-1.

8, Korneliusz Golebski, Janice A Layhadi, Umit Sahiner, Esther H Steveling-Klein, Madison M Lenormand, Rachael C Y Li, Suzanne M Bal, Balthasar A Heesters, Gemma Vilà-Nadal, Oliver Hunewald, Guillem Montamat, Feng Q. He, Markus Ollert, Oleksandra Fedina, Mongkol Lao-Araya, Susanne J H Vijverberg, Anke-Hilse Maitland-van der Zee, Cornelis M van Drunen, Wytske J Fokkens, Stephen R Durham, Hergen Spits, Mohamed H Shamji, Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response. Immunity, 2021 Feb 9, 54(2):291-307.e7. Access: https://www.sciencedirect.com/science/article/pii/S1074761320305410.

9, Sylvie Delhalle, Sebastian Bode, Rudi Balling, Markus Ollert, Feng He#, A Roadmap towards Personalized Immunology. Npj Systems Biology and Applications, 2018, 4:9. Access: https://www.nature.com/articles/s41540-017-0045-9.

10, Feng He, Hairong Chen, Michael Probst-Kepper, Robert Geffers, Serge Eifes, Antonio del Sol, Klaus Schughart, An-Ping Zeng and Rudi Balling, PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells. Molecular Systems Biology (EMBO Press), 2012, 8:624-643 (chosen as Featured Article). Access: https://www.embopress.org/doi/full/10.1038/msb.2012.56.

Current Postdoc fellows:

• Aristeidis Roubanis, PhD
• Zi Mei, MD, PhD

Alumni: PhD students or Postdoc fellows:

• Egle Danileviciute, PhD student
• Ni Zeng, PhD student
• Christophe M. Capelle, PhD student
• Sebastian Felix Nepomuk Bode, Postdoc