Our research focus is to understand the molecular mechanisms of pain with emphasis on epigenetics. We are interested in pursuing various aspects of epigenetics such as DNA methylation, histone modifications and small noncoding RNAs called microRNAs (miRNAs).
Aberrant miRNA expression is a common feature in a variety of human diseases, thus providing avenues for the identification of biomarkers and new opportunities for the discovery and validation of novel therapeutic targets. Currently we are studying miRNA regulation and its utility as biomarkers in patients with complex regional pain syndrome (CRPS) a chronic neuropathic pain condition. We have identified several differentially expressed miRNAs, highlighting the potential utility of these miRNAs as biomarkers in grouping patients based on their disease etiology.
One mode of miRNAs transport in body fluids is via exosomes. Exosomes are small vesicles originating from the inward budding of the plasma membrane. They carry mRNAs and miRNAs to recipient cells with functional gene regulatory consequences via blood indicating a new mechanism of intercellular communication. Intercellular communication was thought to be limited to gap junctions or secreted signals such as hormones and neurotransmitters. Interestingly, a majority of differentially expressed miRNAs we identified in CRPS patients are present in exosomes. We are studying the role of these miRNAs in exosome-mediated signal transduction in pain.
We are also extending our studies to rodent models of pain since the patient population is heterogeneous in terms of genetics and prior treatments received. This will enable us to evaluate and confirm the feasibility of testing miRNA fingerprints after administering therapeutic agents and to develop rigorous translational approaches to predict utility for novel therapeutics and clinical response.
We are investigating alterations of key epigenetic regulators to understand the molecular changes underlying pain. A multi-pronged approach, combining next generation sequencing to characterize the epigenome with pharmacological and behavioral studies using rodent models of pain, is being pursued to elucidate the role of epigenetics in pain.
Current Lab members
Marguerite McDonald, Ph.D. (Post-Doctoral Researcher)
Melissa Manners (Graduate Student)
Botros Shenoda, M.D. (Graduate Student)
Christian Czmielewski (MMS Student)
Andrew Touati (Undergraduate Student, B.S./M.D. program)
Sabrina Douglas (Undergraduate Student, STAR Scholar)
Research supported by:
Rita Allen Foundation
Professional Enrichment and Growth Grant from Drexel University College of Medicine
Commonwealth Universal Research Enhancement (CURE) Grant