I am trained in epigenetics in diverse contexts, from viral infections to epigenetic inheritance and cancer biology. I have developed innovative technical tools to address fundamental questions in these contexts, expanding from the level of epigenetic control to the level of transcriptional regulation of gene expression. In my postdoctoral work, I have addressed how the interplay between metabolism and epigenetics regulates cellular programs.
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Nuclear metabolism in the control of tumour hypoxia - KULeuven
Nuclear metabolism in the control of tumour hypoxia - KULeuven
Hypoxia induces both metabolic and epigenetic remodelling in cancer cells. Several biochemical reactions that require oxygen are directly inhibited, with consequences on DNA methylation profiles. For instance, TET enzymes are dioxygenases and their decreased activity controls the dynamics of DNA methylation in cancer cells during hypoxia. However, it remains to be determined how hypoxic-induced metabolic changes concertedly translate to the specific DNA methylation signatures observed. In this project, I am exploring how metabolism within the nucleus shapes the DNA methylome of hypoxic cancer cells.
Verdikt, R., Thienpont B. Epigenetic remodelling under hypoxia. Seminars in Cancer Biology, 2024 Jan:98:1-10. doi: 10.1016/j.semcancer.2023.10.005.
Glutamate metabolism in stem cell programs - UCLA and KULeuven
Glutamate metabolism in stem cell programs - UCLA and KULeuven
The interplay between epigenetic and metabolic mechanisms in the control of gene expression has been an active domain of research in a wide range of research fields. During pluripotency transitions, stem cells undergo extended epigenetic and metabolic remodelling. Yet, how these changes concertedly control developmental potential is still unclear. I have addressed these questions in my postdoctoral work at UCLA with glutamate metabolism and will continue working on these subjects at KULeuven.
Verdikt, R., Allard, P. Metabolo-epigenetics: The interplay of metabolism and epigenetics during early germ cells development. Biology of Reproduction Journal, 2021, ioab118:1-9.
Harnessing the relevance of stem cell models for reproductive toxicology - UCLA
Harnessing the relevance of stem cell models for reproductive toxicology - UCLA
Fetal germ cells are lowly-abundant and their scarcity prevents detailed molecular analyses. In vitro models for germ cell development, derived from mouse embryonic stem cells, can be accurately used to assess the impact of environmental stressors. I have explored the impact of THC, the main component of cannabis, arsenic, and aluminium on fetal germ cell development. This work is to be set in the larger context of transgenerational epigenetic inheritance, which postulates that environmental influences can be passed along generations through epigenetic memory in the germline.
Verdikt, R., Armstrong, A. A., Cheng, J., Hwang, Y. S., Clark, A. T., Yang, X., Allard, P, Metabolic memory of Δ9-tetrahydrocannabinol exposure in pluripotent stem cells and primordial germ cells-like cells. eLife, October 2023. doi:10.7554/eLife.88795.1.
Verdikt, R., Armstrong, A., Allard, P. Transgenerational inheritance and its modulation by environmental cues in Current Topics in Developmental Biology, Academic Press, 2022. doi: 10.1016/bs.ctdb.2022.10.002.
Characterizing the epigenetic interplay on the HIV-1 promoter during latency - ULB
Characterizing the epigenetic interplay on the HIV-1 promoter during latency - ULB
Epigenetic processes are key elements in the silencing of HIV-1 gene expression. Upon infection, HIV-1 DNA is integrated into the host genome and adopts a chromatin architecture. The control of HIV-1 chromatin, especially on the viral promoter situated in the 5’ Long Terminal Repeat (5’LTR), is crucial for the outcome of viral gene expression and viral infection cycles. In one specific form of infection, termed latent infection, the HIV-1 promoter is maintained in a repressive state through a multitude of epigenetic mechanisms. However, how these epigenetic mechanisms are controlled in a coordinated manner has not been well characterized. I have shown that the cellular factor UHRF1 is involved in the DNA methylation-mediated repression of latent HIV-1. UHRF1 does not possess any epigenetic activity per se but serves as an integrator and a hub of recruitment for a multitude of epigenetic factors. In particular, I showed that on the HIV-1 5’LTR, UHRF1 recruits DNA methyltransferases and histone methyltransferases to lock the viral promoter through the interplay of at least two epigenetic mechanisms.
Verdikt, R., Bendoumou, M., Bouchat, S., Nestola, L., Pasternak, A., Darcis, G., Avettand-Fenoel, V., Vanhulle, C., Aït-Ammar, A., Santangelo, M., Plant, E., Le Douce, V., Delacourt, N., Cicilionyte, A., Necsoi, C., Corazza, F., Pereira Bittencourt, C., Schwartz, C., Bizet, M., Fuks, F., Sáez-Cirión, A., Rouzioux, C., De Wit, S., Berkhout, B., Gautier, V., Rohr, O., Van Lint, C. Novel role of UHRF1 in the epigenetic repression of the latent HIV-1. EBioMedicine, 2022 May;79:103985.
Verdikt, R*., Lange U.*, Aït-Ammar, A. Van Lint, C. Epigenetic crosstalk in chronic infection with HIV-1. Seminars in Immunopathology, 2020; 42:2,187-200. * equal contribution.
Applying genome editing techniques to interrogate host-pathogen interactions - ULB and Leibniz Institute
Applying genome editing techniques to interrogate host-pathogen interactions - ULB and Leibniz Institute
The transcriptional landscape of exogenous retroviruses has been shown to be increasingly more complex than previously thought. Non-canonical transcription in the context of HIV-1 infection also implies the existence of fusion transcripts with cellular genes, with consequences on cellular functions. To better characterize the transcriptional activity of HIV-1, I have developed several tools based on CRISPR gene editing. These molecular tools have provided insights into the interplay between HIV-1 transcriptional profiles.
Hamann, M.V., Ehmele, P.*, Verdikt, R.*, Bialek-Waldmann, J., Virdi, S., Günther, T., Van Lint, C., Grundhoff, A., Hauber, J., Lange, U.C. Transcriptional behavior of the HIV-1 promoter in context of the BACH2 prominent proviral integration gene. Virus Research, 2020; 293:198260. * equal contribution.
Verdikt, R., Darcis, G., Aït-Ammar, A., Van Lint, C. Applications of CRISPR/Cas9 tools in deciphering the mechanisms of HIV-1 persistence. Current Opinions in Virology, 2019 Sep 7;38:63-69.
Understanding the molecular mechanisms of HIV-1 persistence in myeloid lineages - ULB
Understanding the molecular mechanisms of HIV-1 persistence in myeloid lineages - ULB
Whether infected cells from myeloid lineages contribute to the long-term persistence of HIV-1 in individuals is much discussed. I worked during my PhD on understanding what were the molecular mechanisms regulating HIV-1 gene expression specifically in these lineages. My host laboratory during my PhD is still actively working on this subject.
Van Lint, C., Hernalsteens, O., Verdikt, R., A., Saez-Cirion, A., Role of the pol gene enhancer in HIV-1 transcription and replication in myeloid infected cells. Journal of Virus Eradication, 2022. doi: 10.1016/j.jve.2022.100131.
Verdikt, R., Hernalsteens, O. Van Lint, C. Epigenetic Mechanisms of HIV-1 Persistence. Vaccines, 2021, 9(5)514.
Le Douce, V., Forouzanfard, F., Eilebrecht, S., Van Driessche, B., Ait-Ammar, A., Verdikt, R., Kurashige, Y., Marban, C., Gautier, V., Candolfi, E., Benecke, A., Van Lint, C., Rohr, O., & Schwartz, C. HIC1 controls cellular- and HIV-1- gene transcription via interactions with CTIP2 and HMGA1. Scientific Reports, 2016, 6, 4920. doi:10.1038/srep34920.
Fundamental-based development of new anti-HIV strategies - ULB
Fundamental-based development of new anti-HIV strategies - ULB
Beyond fundamental science, a better understanding of HIV-1 persistence mechanisms provides clues to developing novel therapeutic strategies for the millions of people infected worldwide.
Verdikt, R., Bendoumou, M., Bouchat, S., Nestola, L., Pasternak, A., Darcis, G., Avettand-Fenoel, V., Vanhulle, C., Aït-Ammar, A., Santangelo, M., Plant, E., Le Douce, V., Delacourt, N., Cicilionyte, A., Necsoi, C., Corazza, F., Pereira Bittencourt, C., Schwartz, C., Bizet, M., Fuks, F., Sáez-Cirión, A., Rouzioux, C., De Wit, S., Berkhout, B., Gautier, V., Rohr, O., Van Lint, C. Novel role of UHRF1 in the epigenetic repression of the latent HIV-1. EBioMedicine, 2022 May;79:103985.
Ait Ammar A., Kula-Pacurar A., Darcis G., Verdikt R., De Wit S., Gautier V., Mallon P., Marcello A., Rohr O., Van Lint C. Current status of LRAs facing the heterogeneity of HIV-1 cellular and tissue reservoirs. Front. Microbiol., 2019, 10:3060, 1-23.
Kula A., Delacourt N., Bouchat S., Darcis G., Avettand-Fenoël V., Verdikt R., Corazza F., Necsoi C., Vanhulle C., Bendoumou M., Burny A., De Wit S., Rouzioux C., Rohr O. & Van Lint, C. Heterogeneous HIV-1 reactivation patterns of disulfiram and combined disulfiram+romidepsin treatments. Journal of Acquired Immune Deficiency Syndromes, 2019 Apr 15;80(5):605-613.
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