How do the tens of trillions of cells in our body develop highly specialized functions, and how do they degenerate as we age? How do complex biological functions arise from the physical properties (3D structure) and chemical composition (DNA sequence and epigenetics) of our genome? To find answers, Longzhi Tan focused on an emerging molecular mechanism: 3D genome architecture.
As a biophysicist by training, Tan has 13 years of interdisciplinary research experience. As an undergraduate student in Physics at MIT, he achieved the first experimental demonstration of a decline in reversible evolution over genomic distance, and reconstructed the origin and spread of a crucial mutation in the human EDAR gene and measured its phenotypes in modern populations.
As a PhD student in Systems Biology at Harvard, Tan developed several of the most sensitive and accurate methods in single-cell genomics and their computational algorithms. For example, Dip-C resolved the first 3D structure of the human genome, tackling a longstanding problem dating back to the 1880s. LIANTI was the first method to amplify a genome linearly, enabling genome-wide observation of DNA replication and UV-induced mutations. META-CS revealed artifact-free somatic mutations in single human cells.
As a postdoctoral scholar in Bioengineering at Stanford, Tan obtained the first 3D genome structure of a single brain cell and developed multi-omic algorithms, uncovering an unprecedented transformation of both transcriptome and 3D genome in the brain after birth.
Tan firmly believes that solving the biophysics of our genome will lead to unprecedented insights into both fundamental biology and disease treatment. In 2022, he started his independent lab as an Assistant Professor in Neurobiology at Stanford. The lab will build the next generation of single-cell multi-omic toolkits that span the fields of genomics, neuroscience, biochemistry, and computer science to measure and control single-cell 3D genome architecture in our brain. His interdisciplinary work will build “the AlphaFold for 3D genome” to better understand and better engineer the human genome, and to develop 3D genome–based treatment for developmental and degenerative disorders.