Evgeny Kvon, PhD

Academic Distinctions

Hellman Fellowship Award (2025)
NIH Director’s New Innovator Award (2022)
NIH Pathway to Independence Award (2017)
Helen Hay Whitney Foundation Fellowship (2015)
Human Frontier Science Program Fellowship (2015)

Courses

BIO SCI 97: Genetics (4 units, Introduction to Genetics)
DEV BIO 210: Developmental Genetics and Genomics

Research

Specific non-coding regulatory DNA elements called enhancers regulate gene transcription during animal development. The Kvon lab investigates transcriptional regulation by enhancers using cutting-edge genomics, genome editing, and transgenic tools. We are particularly interested in studying the role of enhancers in development and evolution and how enhancer malfunction leads to congenital disease.

Transcriptional regulation plays a crucial role in animal development. Major regulators of gene expression are enhancers, non-coding DNA elements bound by transcription factors in a sequence-specific manner. Many developmental enhancers can activate their target genes over long genomic distances, sometimes exceeding hundreds of thousands of base pairs. How these distant enhancers activate genes specifically and precisely during development remains a central unresolved question in gene regulation. We use mouse embryonic development as a model system and combine genome-editing and genomics tools to understand how enhancers function in the 3D genome during mammalian development.

Many non-coding variants associated with congenital disorders are hypothesized to affect developmental enhancers. Determining which of these potentially pathogenic enhancer variants matter, and understanding how they disrupt gene regulatory networks to cause congenital disorders, is a major challenge. We use innovative mouse transgenesis and genomics tools to understand the molecular mechanisms by which pathogenic non-coding variants lead to congenital disorders.

Changes in gene regulatory networks are hypothesized to drive changes in body shape between animals, but identifying genomic loci associated with major morphological transitions in vertebrates has remained challenging. The mouse is a powerful model for studying evolutionary loci because we can introduce regulatory DNA sequences from different vertebrate species into the mouse genome and directly compare their activities. We use transgenic and genetically engineered mice to better understand the molecular basis of vertebrate evolution.

We use deep learning to crack the syntax of enhancers and design entirely synthetic, functional enhancers from scratch. These custom AI-built switches successfully targeted specific tissues, such as the heart, limbs, and brain, in mouse embryos. We aim to push this technology beyond whole tissues to achieve precision at cellular resolution. This could transform our understanding of developmental biology and open new frontiers for targeted gene therapies.

Selected Publications

• 1. Bower G, Kvon EZ†. (2026) Deep learning uncovers hidden power of low-affinity motifs. Cell Genomics.
• 2. Chen S, Loubiere V, Hollingsworth EW, Murakami K, Mandlburger N, Jacinto SH, Dizehchi A, Schreiber J, Kvon EZ, Stark A. (2026) Predictive design of tissue-specific mammalian enhancers that function in the mouse embryo. Nature Genetics. 58(9):2129–2133.
• 3. Hollingsworth EW, Chen Z, Chen CX, Jacinto SH, Liu TA, Kvon EZ†. Enhancer poising enables pathogenic gene activation by noncoding variants [Internet]. bioRxiv. 2025.
• 4. Bower G, Hollingsworth EW, Jacinto SH, Alcantara JA, Clock B, Cao K, Liu M, Dziulko A, Alcaina-Caro A, Xu Q, Skowronska-Krawczyk D, Lopez-Rios J, Dickel DE, Bardet AF, Pennacchio LA, Visel A, Kvon EZ†. Range extender mediates long-distance enhancer activity. Nature, 2025 Jul 2;1–9.
• 5. Hollingsworth EW, Liu TA, Alcantara JA, Chen CX, Jacinto SH, Kvon EZ†. (2025) Rapid and quantitative functional interrogation of human enhancer variant activity in live mice. Nature Communications, Jan 6;16(1):1–15.
• 6. Bower G, Kvon EZ†. (2025) Genetic factors mediating long-range enhancer–promoter communication in mammalian development. Current Opinion in Genetics & Development. Feb;90(102282):102282.
• 7. Chen Z, Snetkova V, Bower G, Jacinto S, Clock B, Dizehchi A, Barozzi I, Mannion BJ, Alcaina-Caro A, Lopez-Rios J, Dickel DE, Visel A, Pennacchio LA, Kvon EZ†. (2024) Increased enhancer–promoter interactions during developmental enhancer activation in mammals. Nature Genetics, Mar 20;1–11.
• 8. Kvon EZ*†, Waymack R, Elabd MG, Wunderlich Z*† (2021) Enhancer redundancy in development and disease. Nature Reviews Genetics, 53:521–8.

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