Karl Deisseroth, MD PhD, D.H. Chen Professor of Bioengineering and Psychiatry, Stanford University School of Medicine; Investigator, Howard Hughes Medical Institute.
Research Description: Dr. Deisseroth is Professor of Bioengineering with a joint appointment in the Department of Psychiatry and Behavioral Sciences. His group is renowned for development and application of applied high-resolution tools for controlling (e.g. optogenetics) and observing (e.g. CLARITY, next-generation fiber photometry, next-generation light sheet microscopy) specific elements of intact biological systems. His group has developed and applied these and other tools for the study of physiology and behavior in health and disease, and supported researchers at Stanford and around the world by disseminating the reagents and techniques. These optical methodologies have greatly advanced the exchange of high-resolution information with intact tissue, including from adult mammalian brains and human pancreas. For example, CLARITY is a technique developed in his lab that transforms intact tissue into an optically transparent and permeable hydrogel-hybridized form, that can undergo immunostaining and high-resolution 3-D imaging without damage to the sample. This process allows for marking and visualization of long-range projections and subcellular structures, multiple rounds of molecular phenotyping, and is applicable to multiple tissue types and sizes with no disruption or thin sectioning required to visualize whole intact tissue samples. By clearing while preserving fine structural details, CLARITY provides a technique now in wide use, with many papers already published from other labs, for obtaining high-resolution information from complex systems while maintaining the global perspective necessary to understand system function. They have also developed advanced light-sheet and computational methodologies to collect and analyze these new kinds of intact-system data. With Seung Kim’s group, members of the Deisseroth lab have collaborated to use CLARITY and advanced microscopy and computational methods to delineate pancreas development in mouse and humans (Hsueh et al 2017).
Selected relevant publications (Stanford DRC Members in BOLD):
1. Kato H, Zhang F, Yizhar O, Ramakrishnan C, Nishizawa T, Hirata K, Ito J, Aita Y, Tsukazaki T, Hayashi S, Hegemann P, Maturana A, Ishitani R, *Deisseroth K & *Nureki O (2012). Crystal structure of the channelrhodopsin light-gated cation channel. Nature 482:369-74. *Co-corresponding senior authors.
2. Berndt A, Lee SY, Ramakrishnan C & Deisseroth K (2014). Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science 344:420-4.
3. Chung K, Wallace J, Kim S, Kalyanasundram S, Andalman A, Davidson T, Mirzabekov J, Zalocusky K, Mattis J, Bernstein H, Ramakrishnan C, Grosenick L, Gradinaru V & Deisseroth K (2013). Structural and molecular interrogation of intact biological systems. Nature 497:332-7.
4. Tomer R, Lovett-Barron M, Kauvar I, Andalman A, Burns V, Grosenick L, Broxton M, Yang S & Deisseroth K (2015). SPED light sheet microscopy: fast mapping of biological system structure and function. Cell 163:1796-806.
5. Hsueh B, Burns V, Pauerstein P, Holzem K, Ye L, Engberg K, Wang A-C, Gu X, Chakravarthy H, Arda E, Charville G, Vogel H, Efimov I, Kim SK and Deisseroth K. (2017). Pathways to clinical CLARITY: methodologies for transparent-volume quantitative analysis of irregular, soft, and heterogeneous tissues in development and disease. Submitted