Evgeny Kvon, Ph.D.
University of California, Irvine
4311 McGaugh Hall
Irvine, CA 92697
Evgeny obtained his Ph.D. from the University of Vienna and IMP where he worked on mapping the regulatory landscape of the Drosophila genome. He continued his training at Berkeley lab where he investigated the molecular basis of vertebrate evolution and human congenital disorders. Evgeny is currently an Assistant Professor in the Departments of Developmental and Cell Biology and Ecology and Evolutionary Biology.
During animal development, a complex multicellular organism is formed from a single cell – the fertilized egg. This process is regulated through differential gene expression. Specific non-coding DNA elements called enhancers regulate gene transcription during animal development. The Kvon lab uses a combination of novel genomics tools, genome editing, and mouse developmental biology techniques to understand transcriptional regulation by enhancers in the context of mammalian development, evolution, and human congenital disorders.
I. Transcriptional regulation in development
The regulation of transcription plays a crucial role in animal development. It is orchestrated by enhancers, non-coding DNA elements that are bound by multiple transcription factors in a sequence-specific manner. A typical enhancer activates the expression of its target gene, often over long genomic distances, which in turn specifies the fate of different cell types during development. We will use mouse embryo development as a model system and a combination of novel genome editing and genomics tools to understand how enhancers work in the 3D genome in the context of mammalian development.
II. Transcriptional regulation in congenital disorders
Many human variants associated with congenital disorders are hypothesized to affect developmental enhancers. Determining which of these potentially pathogenic enhancer variants are important and understanding the etiology of the enhancer malfunction is a major challenge. We will use novel mouse transgenesis tools that are based on CRISPR/Cas9 and single-cell RNA sequencing to assess the effect of human variants on enhancer activity in vivo and to understand the mechanism by which they disrupt target gene expression that eventually leads to congenital limb malformations.
III. Transcriptional regulation in vertebrate evolution
Changes in gene regulatory networks are hypothesized to be a primary driver of changes in body shape between different animals, but identifying genomic loci associated with major morphological transitions in vertebrates has remained challenging. The mouse is a powerful model for studying evolution loci because regulatory DNA sequences from different vertebrate species can be introduced into the mouse genome, and their activities can be directly compared with each other. We are interested in using mice to further develop novel genome manipulation tools to better understand the molecular basis of vertebrate evolution.
1. Kvon, E.Z., Zhu, Y., Novak, C.S., …21 authors…, Visel A., Dickel, D.E., Pennacchio, L.A. (2020) Comprehensive in vivo interrogation reveals phenotypic impact of human enhancer variants. Cell, 180(6):1262–1271. PMID 32169219
2. Kvon, E.Z., Kamneva, O., Melo, U.S., …12 authors…, Rubin, E.M., Dickel, D.E., Pennacchio, L.A., Visel A. (2016). Progressive loss of function in a limb enhancer during snake evolution. Cell, 167(3):633-642. PMID 27768887
3. Kvon, E.Z. (2015). Using transgenic reporter assays to functionally characterize enhancers in animals. Genomics, 106(3):185-92. PMID 26072435
4. Kvon, E.Z., Kazmar, T., Stampfel, G., Yáñez-Cuna, J.O., Pagani M., Schernhuber K., Dickson, B.J., Stark, A. (2014). Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature, 512(7512):91-5. PMID 24896182
5. Yáñez-Cuna, J.O.*, Kvon, E.Z.*, Stark, A. (2013). Deciphering the transcriptional cis-regulatory code. Trends in Genetics, 29(1):11-22. PMID 23102583
6. Kvon, E.Z.*, Stampfel, G.*, Yáñez-Cuna, J.O., Dickson, B.J., Stark, A. (2012). HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature. Genes & Development, 26(9):908-13. PMID 22499593
For the full list of publications, please see PubMed