Draft:William Greenleaf: Difference between revisions

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American scientist

William J. Greenleaf (born December 24, 1979) is an American molecular biologist, biophysicist, and inventor who is a professor of genetics at the Stanford University School of Medicine. His research focuses on high-throughput sequencing and optical microscopy methods for studying gene regulation and chromatin structure. Greenleaf is a co-inventor of ATAC-seq, a widely-used epigenomic method developed by his lab.

Biography

Greenleaf grew up in Rochester, Minnesota. He attended Mayo High School and worked summers as a research assistant at the Mayo Clinic, winning 6th place in the 1998 Westinghouse Science Talent Search for his project on ultrasound-mediated gene transfection. He graduated cum laude with an A.B. in Physics from Harvard University in 2002, followed by a stint as a Gates Cambridge Scholar at Trinity College, University of Cambridge, from which he received a Dip. Comp. Sci. in 2003. Greenleaf then entered the Applied Physics Ph.D. program at Stanford University, where he joined the laboratory of Steven Block and was funded by the NSF GRFP.

Greenleaf was first or co-first author of publications in Nature, Science, and Cell resulting from his Ph.D. work on single-molecule biophysics, an achievement his advisor Block called a “perfect trifecta,” or “quadfecta” if one were to include Greenleaf’s additional co-first author publication in Physical Review Letters. He received his Ph.D. in Applied Physics from Stanford in January 2008. From 2008 to 2011, Greenleaf worked on methods development for massively parallel sequencing-by-synthesis as a postdoctoral fellow in X. Sunney Xie‘s lab at Harvard University. In 2011, Greenleaf returned to Stanford as an assistant professor in the Department of Genetics, establishing his own laboratory within the interdisciplinary Beckman Center for Molecular and Genetic Medicine.

Research

During his Ph.D., Greenleaf worked on single-molecule methods for measuring the forces involved in gene transcription and protein folding. With colleagues in the Block lab, he developed an optical trapping system that enabled ångström–resolution measurement of RNA polymerase (RNAP) “stepping” along DNA. Using this system, he developed a method for DNA sequencing based on the observation that, when the concentration of a given nucleotide base is limiting, RNAP pauses for longer amounts of time at sequence positions corresponding to that base.

Greenleaf’s lab at Stanford has focused on high-throughput sequencing and optical microscopy methods for studying gene regulation and chromatin structure. In 2013, Greenleaf’s lab, in collaboration with the lab of Howard Y. Chang, introduced ATAC-seq, a method for assaying chromatin accessibility genome-wide. ATAC-seq is based on principle that, in an in vitro transposition reaction, active (open) chromatin is strongly enriched relative to inactive chromatin for transposition by a hyperactive transposase. Additionally, the genomic positions of nucleosomes and bound transcription factors can be inferred from ATAC-seq based on localized “footprints” depleted for transposition relative to surrounding DNA. A multi-year collaboration between Greenleaf’s lab and the lab of Sergiu P. Pașca used ATAC-seq to study chromatin dynamics in human brain organoids.

Other work in Greenleaf’s lab has centered on single-molecule measurements of transcription factor binding, including by disassembling and repurposing Illumina sequencers. In 2024, Greenleaf’s lab published a study in the journal Nature describing the experimentally-driven development of thermodynamic and kinetic models to quantitatively predict transcription factor binding microstates and relate those microstates to gene expression.

Greenleaf was named a CZ Biohub investigator in 2017 and an Arc Institute innovation investigator in 2023. He was awarded the NIH Director’s Pioneer Award in 2023. Since 2024, Greenleaf has served as Director of the Stanford RNA Medicine Program (RAMP). ATAC-seq used for personalized medicine.
Greenleaf was a scientific co-founder of Epinomics, which was acquired by 10x Genomics in 2018. He has also served as scientific advisor to biotech companies specializing in high-throughput sequencing and precision medicine, including Guardant Health and Ultima Genomics.

References

External links

Category:Living people
Category:Stanford University School of Medicine faculty
Category:American geneticists