A common thread in my work is that I investigate the epigenetic control of gene expression within different contexts. 

I originally started working on epigenetic regulation within the context of host-pathogen interactions (specifically for HIV-1). I have developed innovative technical tools to address fundamental questions in this context, expanding from the level of epigenetic control to the level of transcriptional regulation of gene expression. In my postdoctoral work, I started to address how the interplay between metabolism and epigenetics regulates cellular programs.

Addressing the interplay between metabolism and epigenetics - UCLA and KULeuven

The interplay between epigenetic and metabolic mechanisms in the control of gene expression has been an active domain of research in recent years in a wide range of research fields. In reproductive toxicology, an open question is how toxicants impact developmental processes through changes in this metabolo-epigenetic control of gene expression. I have addressed these questions in my postdoctoral work at UCLA and will continue working on these subjects as I transition to KULeuven, in the context of tumour hypoxia. 

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. 

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. 

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.


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.

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.