Karl Deisseroth

Karl Deisseroth, MD PhD, D.H. Chen Professor, Departments of Bioengineering and of Psychiatry and Behavioral Sciences, 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. 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). Deisseroth lab has also developed advanced light-sheet and computational methodologies to collect and analyze new kinds of intact-system data. Also, a clinician in the psychiatry department, Dr. Deisseroth focuses on developing molecular and cellular tools to observe, perturb, and re-engineer brain circuits. He employs novel electromagnetic brain stimulation techniques in human patients for therapeutic purposes. 

Selected relevant publications (Stanford DRC Members in BOLD):

  1. Kim YS, Kato HE, Yamashita K, Ito S, Inoue K, Ramakrishnan C, Fenno LE, Evans KE, Paggi JM, Dror RO, Kandori H, Kobilka BK, Deisseroth K. Crystal structure of the natural anion-conducting channelrhodopsin GtACR1. Nature. 2018 Sep;561(7723):343-348. doi: 10.1038/s41586-018-0511-6. PMID: 30158696; PMCID: PMC6340299. 

  2. Wang X, Allen WE, Wright MA, Sylwestrak EL, Samusik N, Vesuna S, Evans K, Liu C, Ramakrishnan C, Liu J, Nolan GP, Bava FA, Deisseroth K. Three-dimensional intact-tissue sequencing of single-cell transcriptional states. Science. 2018 Jul 27;361(6400):eaat5691. doi: 10.1126/science.aat5691. PMID: 29930089; PMCID: PMC6339868. 

  3. Hsueh B, Burns VM, Pauerstein P, Holzem K, Ye L, Engberg K, Wang AC, Gu X, Chakravarthy H, Arda HE, Charville G, Vogel H, Efimov IR, Kim SK, Deisseroth K. 2017. Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease. Scientific Reports. 7(1): 5899. PMCID: PMC5675443.  

  4. Pauerstein PT, Tellez K, Willmarth KB, Park KM, Hsueh B, Efsun Arda H, Gu X, Aghajanian H, Deisseroth K, Epstein JA, Kim SK. A radial axis defined by semaphorin-to-neuropilin signaling controls pancreatic islet morphogenesis. Development. 2017 Oct 15;144(20):3744-3754. doi: 10.1242/dev.148684. PMID: 28893946; PMCID: PMC5675443.