Research Interests
Our research will tackle these open questions:
1) What are the epigenetic processes regulating stress and leading to depression and chronic pain risk?
2) What is the role of non-coding RNAs in regulating stress, depression, and chronic pain in both sexes?
3) How can we prevent, treat, or diagnose mood disorders by probing either central or peripheral ncRNAs?
Basic Research
How do non-coding RNAs contribute to the regulation of stress and pain?
Identify sex-specific non-coding RNAs with a role in stress and chronic pain
Women suffer from depression and chronic pain more frequently than men, yet the molecular mechanisms leading to this sex difference remain poorly understood. We will expand our research on the sex-specific role of non-coding RNAs in regulating stress, depression, and chronic pain. This will be done by both following up on current findings and systematically identifying additional novel targets.
To that end, we will be using advanced cell culture models, murine stress models, human post-mortem brain tissue and liquid biopsies, and advanced bioinformatics. We will determine a causal role for such RNAs utilizing a combination of brain-site and cell-type-specific genetic manipulation and stress and pain animal models and utilize advanced in vitro and biochemical assays to determine the mechanisms of action of specific target RNAs.
Translational Research
Developing novel ncRNA-based diagnostic and therapeutic tools for stress and pain disorders
Developing novel ncRNA-based diagnostic and therapeutic tools for mood disorders
Despite several decades of research, virtually all psychiatric conditions, including depression, are diagnosed solely based on behavioral abnormalities, with no biological endpoint used for diagnosis or treatment efficacy tracking. Our ambitious goal is to develop a biomarker tool based on signatures of circulating non-coding RNAs in depression and chronic pain.
Additionally, there is an urgent clinical need for novel therapeutic approaches for depression, as many patients show partial remission or no response to available antidepressants. A key challenge in developing novel therapeutic strategies for CNS disorders, particularly RNA-based ones, is delivering the active compound to the brain. We addressed this need by manipulating a circulating miRNA with a systemic administration of antisense oligonucleotides (ASOs). We will follow up on this research to Determine the mechanism by which manipulation of circulating ncRNAs alters and expand it to additional RNA targets.
Our Tool Kit
Molecular biology
Genome-wide and target genes analysis
RNA-seq, ChIRP -seq, Mass spectrometry, qPCR, molecular cloning, cell culture, IHC, FISH
Mouse models
Behavioral, molecular, and histological phenotyping
Stress models, behavioral analysis, stereotactic surgery, viral gene delivery, tissue and liquid biopsies
Bioinformatics
Making Sense of Omics Data- from patterns to targets
RNA-seq, ChIRP-seq, Mass Spec, gene ontology, pathways, upstream regulators, networks analysis