U01 - Chung 1U01MH117072-01

Towards Integrated 3D Reconstruction of Whole Human Brains at Subcellular Resolution

A detailed understanding of the anatomical and molecular architectures of brain cells and their brain-wide organization is essential for interrogating human brain function and dysfunction. Extensive efforts have been made toward mapping brain cells through various lenses, which have established invaluable databases yielding new insights. However, integrative extraction of the multimodal properties of various cell-types brain-wide within the same brain, crucial to elucidating complex intercellular relationships, remains nearly impossible. We have developed high-throughput, cost-effective technology platforms to create a fully integrated three-dimensional (3D) human brain cell atlas by simultaneously mapping high-dimensional features (e.g., spatial, molecular, morphological, and microenvironment information) of all cells acquired from the same whole brain. The proposed work will establish the most comprehensive 3D human brain map to date, with unprecedented resolution and completeness. We envision that this atlas will facilitate the integration of a broad range of studies and allow the research community to interrogate human brain structure and function at multiple levels. 


Project Leadership

Kwanghun Chung, Ph.D. (Principal Investigator) 
Assistant Professor, Department of Chemical Engineering 
Institute for Medical Engineering and Science (IMES)
Picower Institute for Learning and Memory 
Massachusetts Institute of Technology 
https://www.chunglab.org/members/ 

 

Laura Brattain, Ph.D. (Co-investigator) 
Technical Staff, Lincoln Laboratory 
Massachusetts Institute of Technology 

 

Matthew P. Frosch, M.D., Ph.D. (Co-investigator) 
Lawrence J. Henderson Associate Professor of Pathology and Health Sciences & Technology, Harvard Medical School 
Director, Neuropathology Service, Massachusetts General Hospital 
Core Leader, Neuropathology Core, Massachusetts Alzheimer's Disease Research Center 
https://www.massgeneral.org/neurology/researcher_profiles/frosch_matthew.aspx 

 

H. Sebastian Seung, Ph.D. (Co-investigator) 
Evnin Professor in Neuroscience
Professor of Computer Science and the Princeton Neuroscience Institute
https://pni.princeton.edu/directory/h.-sebastian-seung 

 

Van Wedeen, M.D. (Co-investigator) 
Associate Professor in Radiology, Harvard Medical School
Assistant Neuroscientist, Massachusetts General Hospital
Director of Connectomics, Martinos Center
https://www.nmr.mgh.harvard.edu/user/5194 


Project Data Types

  • 3D fluorescent microscopy images mapping the distribution of 8-10 cell-type specific proteins in two whole human brain hemispheres.

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