Professional Education

  • Doctor of Philosophy, Unlisted School (2021)
  • PhD, University of Luxembourg, Biology (Immunology) (2021)

Stanford Advisors

All Publications

  • PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during ageing. Nature metabolism Danileviciute, E., Zeng, N., Capelle, C. M., Paczia, N., Gillespie, M. A., Kurniawan, H., Benzarti, M., Merz, M. P., Coowar, D., Fritah, S., Vogt Weisenhorn, D. M., Gomez Giro, G., Grusdat, M., Baron, A., Guerin, C., Franchina, D. G., Leonard, C., Domingues, O., Delhalle, S., Wurst, W., Turner, J. D., Schwamborn, J. C., Meiser, J., Kruger, R., Ranish, J., Brenner, D., Linster, C. L., Balling, R., Ollert, M., Hefeng, F. Q. 2022; 4 (5): 589-607


    Pyruvate dehydrogenase (PDH) is the gatekeeper enzyme of the tricarboxylic acid (TCA) cycle. Here we show that the deglycase DJ-1 (encoded by PARK7, a key familial Parkinson's disease gene) is a pacemaker regulating PDH activity in CD4+ regulatory T cells (Treg cells). DJ-1 binds to PDHE1-beta (PDHB), inhibiting phosphorylation of PDHE1-alpha (PDHA), thus promoting PDH activity and oxidative phosphorylation (OXPHOS). Park7 (Dj-1) deletion impairs Treg survival starting in young mice and reduces Treg homeostatic proliferation and cellularity only in aged mice. This leads to increased severity in aged mice during the remission of experimental autoimmune encephalomyelitis (EAE). Dj-1 deletion also compromises differentiation of inducible Treg cells especially in aged mice, and the impairment occurs via regulation of PDHB. These findings provide unforeseen insight into the complicated regulatory machinery of the PDH complex. As Treg homeostasis is dysregulated in many complex diseases, the DJ-1-PDHB axis represents a potential target to maintain or re-establish Treg homeostasis.

    View details for DOI 10.1038/s42255-022-00576-y

    View details for PubMedID 35618940

  • Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells NATURE COMMUNICATIONS Franchina, D. G., Kurniawan, H., Grusdat, M., Binsfeld, C., Guerra, L., Bonetti, L., Soriano-Baguet, L., Ewen, A., Kobayashi, T., Farinelle, S., Minafra, A., Vandamme, N., Carpentier, A., Borgmann, F. K., Jager, C., Chen, Y., Kleinewietfeld, M., Vasiliou, V., Mittelbronn, M., Hiller, K., Lang, P. A., Brenner, D. 2022; 13 (1): 1789


    The metabolic principles underlying the differences between follicular and marginal zone B cells (FoB and MZB, respectively) are not well understood. Here we show, by studying mice with B cell-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), that glutathione synthesis affects homeostasis and differentiation of MZB to a larger extent than FoB, while glutathione-dependent redox control contributes to the metabolic dependencies of FoB. Specifically, Gclc ablation in FoB induces metabolic features of wild-type MZB such as increased ATP levels, glucose metabolism, mTOR activation, and protein synthesis. Furthermore, Gclc-deficient FoB have a block in the mitochondrial electron transport chain (ETC) due to diminished complex I and II activity and thereby accumulate the tricarboxylic acid cycle metabolite succinate. Finally, Gclc deficiency hampers FoB activation and antibody responses in vitro and in vivo, and induces susceptibility to viral infections. Our results thus suggest that Gclc is required to ensure the development of MZB, the mitochondrial ETC integrity in FoB, and the efficacy of antiviral humoral immunity.

    View details for DOI 10.1038/s41467-022-29426-x

    View details for Web of Science ID 000778265300019

    View details for PubMedID 35379825

    View details for PubMedCentralID PMC8980022

  • MondoA drives malignancy in B-ALL through enhanced adaptation to metabolic stress. Blood Sipol, A., Hameister, E., Xue, B., Hofstetter, J., Barenboim, M., Ollinger, R., Jain, G., Prexler, C., Rubio, R. A., Baldauf, M. C., Franchina, D. G., Petry, A., Schmah, J., Thiel, U., Gorlach, A., Cario, G., Brenner, D., Richter, G. H., Grunewald, T. G., Rad, R., Wolf, E., Ruland, J., Sorensen, P. H., Burdach, S. E. 2022; 139 (8): 1184-1197


    Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired antimetabolic stress responses to maintain homeostasis and survival. One mechanism to achieve this is reprogramming gene expression in a metabolism-dependent manner. MondoA (also known as Myc-associated factor X-like protein X-interacting protein [MLXIP]), a member of the MYC interactome, has been described as an example of such a metabolic sensor. However, the role of MondoA in malignancy is not fully understood and the underlying mechanism in metabolic responses remains elusive. By assessing patient data sets, we found that MondoA overexpression is associated with worse survival in pediatric common acute lymphoblastic leukemia (ALL; B-precursor ALL [B-ALL]). Using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and RNA-interference approaches, we observed that MondoA depletion reduces the transformational capacity of B-ALL cells in vitro and dramatically inhibits malignant potential in an in vivo mouse model. Interestingly, reduced expression of MondoA in patient data sets correlated with enrichment in metabolic pathways. The loss of MondoA correlated with increased tricarboxylic acid cycle activity. Mechanistically, MondoA senses metabolic stress in B-ALL cells by restricting oxidative phosphorylation through reduced pyruvate dehydrogenase activity. Glutamine starvation conditions greatly enhance this effect and highlight the inability to mitigate metabolic stress upon loss of MondoA in B-ALL. Our findings give novel insight into the function of MondoA in pediatric B-ALL and support the notion that MondoA inhibition in this entity offers a therapeutic opportunity and should be further explored.

    View details for DOI 10.1182/blood.2020007932

    View details for PubMedID 33908607