Hi, I am Aleks, I was born in Bulgaria, a small country in Eastern Europe and I have always loved foreign languages and science (I do believe maths and languages go very well together!) My dream to become a scientist and my love of French language made me move to France for my secondary education. That's how I landed in Lille to study Biochemistry. During my internship in Prevarskaya's Lab I discovered a passion for ion channels thanks to my research on the role of TRP channels in prostate cancer under the supervision of Doctor Dimitra Gkika. After the completion of my Bachelors, I really wanted to dive into the world of molecular biology and development. I moved to Strasbourg to study Molecular and Developmental Biology. During my Masters there, I performed research at Doctor Sophie Jarriault's laboratory at the Institute for Genetics and Molecular and Cell Biology (IGBMC). My research focused on the gene regulatory network governing the direct reprogramming of an epithelial cell into a motor neuron in C.elegans. I became fascinated with the Worm, with neurons, neurodegeneration and regeneration. That is how I deciced to do a PhD on the Molecular Pathology of Amyotrophic Lateral Sclerosis (ALS) under the supervision of Professor Serge Lumbroso and Doctor Kevin Mouzat from the University Hospital of Nimes and Doctor Cedric Raoul from the Institute of Neurosciences of Montpellier. My major contribution to the field is the establishment of the first French platform for functional analysis of ALS genetic variants using simple animal models such as Zebrafish and C.elegans.
My love for ion channels, C. elegans and for the sensori-motor system and my ambition to perform cutting-edge interdisciplinary research led me to the Wormsense lab here at Stanford, where I joined as a postdoc in February 2022. My desire to help the clinics with more relevant animal models for diagnosis and for treatment of neurodegenerative disease crystalized in my postdoc research project on the molecular mechanisms of neurodegeneration in chemotherapy-induced peripheral neuropathy (CIPN). I am working together with Professor Miriam Goodman to unravel the complex role of MAP kinases in neurodegeneration of sensory endings and to find new therapeutic targets to treat or alleviate CIPN.
Honors & Awards
Travel Award, L'Institut SERVIER (2022)
Philippe Foundation Scholarship, Philippe Foundation Inc (2022)
Doctor of Philosophy, Montpellier University, France, Molecular Pathology of Amyotrophic Lateral Sclerosis (2021)
Master of Science, University of Strasbourg, France, Integrated molecular and cell biology (2017)
Bachelors of Science, University of Science and Technology Lille 1, Biochemistry (2015)
Miriam Goodman, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
I am part of the wormsense lab where we study the molecular and biophysical mechanisms endowing sensory neurons with the capacity to perceive mechanical and thermal stimuli. I study the mechanisms involved in the regulation of degeneration and regeneration of sensory endings. Using genetics, in vivo imaging, electrophysiology and behavioral assays in C.elegans I screen for small molecules that restore touch sensation following chemotherapy and I validate their therapeutic potential in mice.
Theme 4 In vivo experimental models.
Amyotrophic lateral sclerosis & frontotemporal degeneration
2019; 20 (sup1): 160-187
Background: In 90% of Amyotrophic Lateral Sclerosis (ALS) cases, the disease is sporadic, the remaining 10% being familial. Many genes have been associated with the disease. The use of next generation sequencing has allowed increasing the number of genes analysed in routine diagnostics. However, this increase raises the issue of genetic variants interpretation within a growing number of ALS-associated-genes. Variant classification is based on a combinatory analysis of multiple factors. Among them, functional analyses provide strong arguments on pathogenicity interpretation.Objectives: We developed a simple animal model, the Zebrafish, for the functional analysis of candidate variants pathogenicity identified by routine genetic testing.Methods: Transient overexpression of different ALS associated genetic variants has been performed by mRNA injection in 1-cell stage zebrafish eggs. Validation of protein overexpression has been done by western blot. Embryos mortality, developmental delay and morphological abnormalities have been assessed within the first two days of development. Cellular phenotype has been investigated by the analysis of axonal length of 2-days old larvae with confocal microscopy. Motor phenotype of 5-days old larvae has been explored by touched-evoked response assay.Results: The model has been validated by the analysis of well-described ALS mutations, SOD1-Gly93Ala and OPTN Glu478Gly. Overexpression of this mutated protein was shown to provoke a shortening of axons and a premature axonal branching, as well as an impairment of motor performances as expected. We did not observe these aberrations in SOD1-WT injected fishes. Two candidate variants observed in ALS-patients have been explored with our model: SOD1 NM_000454.4:c.400_402del, p.Glu134del and OPTN NM_021980.4:c.1475T > G, p. Leu492Arg. Overexpression of both variants induced morphological abnormalities and motor impairment, suggesting a pathogenic involvement of these variants in ALS-patients.Discussion and conclusions: We developed for the first time a simple animal model, the Zebrafish, useful for the functional analysis of variant pathogenicity in order to assist ALS molecular diagnosis. Our model has been used to assess the pathogenicity of SOD1 and OPTN candidate variants, allowing to improve genetic testing interpretation.
View details for DOI 10.1080/21678421.2019.1646992
View details for PubMedID 31702459
Regulation of Brain Cholesterol: What Role Do Liver X Receptors Play in Neurodegenerative Diseases?
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2019; 20 (16)
Liver X Receptors (LXR) alpha and beta are two members of nuclear receptor superfamily documented as endogenous cholesterol sensors. Following conversion of cholesterol in oxysterol, both LXR isoforms detect intracellular concentrations and act as transcription factors to promote expression of target genes. Among their numerous physiological roles, they act as central cholesterol-lowering factors. In the central nervous system (CNS), cholesterol has been shown to be an essential determinant of brain function, particularly as a major constituent of myelin and membranes. In the brain, LXRs act as cholesterol central regulators, and, beyond this metabolic function, LXRs have additional roles such as providing neuroprotective effects and lowering neuroinflammation. In many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and multiple sclerosis (MS), dysregulations of cholesterol and oxysterol have been reported. In this paper, we propose to focus on recent advances in the knowledge of the LXRs roles on brain cholesterol and oxysterol homeostasis, neuroinflammation, neuroprotection, and their putative involvement in neurodegenerative disorders. We will discuss their potential use as candidates for both molecular diagnosis and as promising pharmacological targets in the treatment of ALS, AD, or MS patients.
View details for DOI 10.3390/ijms20163858
View details for Web of Science ID 000484411100015
View details for PubMedID 31398791
View details for PubMedCentralID PMC6720493