Alexey Fedulov

Assistant Professor in the Department of Environmental Health

Department of Environmental Health

Department of Environmental Health

 

Dr. Fedulov’s research aims to discover epigenetic mechanisms of allergy, and, more broadly, to develop molecular instruments to manipulate epigenetic status of living cells.

In utero exposures to environmental particulates and maternal allergic asthma both lead to genome-wide epigenetic alterations in dendritic cells of the neonate; these dendritic cells acquire powerful and unique ability to skew immune responses towards pro-allergic Th2 type. This may explain how allergy originates in early life. The project focuses on the effect of environmental particle exposures on maternal and neonatal immunology. The studies involve investigation of genome-wide or targeted approaches to normalize the altered DNA methylation status in dendritic cells in order to prevent and/or abrogate pro-allergic skew in the immune system of “at risk” neonates, and to demonstrate causality of epigenetic changes in the allergy process.

Interest to epigenetic manipulations has sparked a separate area of research. Almost any cell in an organism includes all genes of that organism’s genome. The difference in structure and function of cells results from epigenetic silencing of ‘unnecessary genes’. By learning to de-repress specific genes we will be able to transform one cell type into another, we will be able to stimulate production of regulatory and defensive factors, we will learn to induce proliferation of non-dividing specialized cells, and broadly will be able to intervene anywhere enhancement of function of intrinsic genes is required. Removal of methylation marks in promoters and other key regulatory sequences is associated with increased gene transcription; therefore the projects aims to design sequence-specific DNA demethylation approach, which would allow selective re-activation of epigenetically silenced genes.

Laboratory methods include techniques of epigenetics, molecular biology, cell and molecular immunology, and airway physiology.