Mark Ellisman 

Mark H. Ellisman, PhD 

Professor
University of California, San Diego

 

Contact Information

School of Medicine, BSB Rm 1000

Email: mhellisman@ucsd.edu
Phone: 858-534-2251
Fax: 858-534-7497

Mailing Address:
9500 Gilman Drive # 0608
La Jolla, CA 92093-0608


Dr. Ellisman is recognized nationally and internationally for his commanding role and pioneering spirit in the development of new technologies that enhance neurobiological and clinical research. Under his leadership of the Center for Research in Biological Systems (CRBS), four major cross-disciplinary initiatives continue to make innovative contributions to the neurosciences and the biomedical sciences at an extraordinary pace of productivity: The Biomedical Informatics Research Network (BIRN) builds infrastructure and technologies to enable large-scale biomedical data mining and refinement. The National Center for Microscopy and Imaging Research (NCMIR) specializes in developing technologies to improve understanding of biological structure and function relationships spanning dimensions from 5nm3 to 50µm3. The National Biomedical Computation Resource conducts, catalyzes, and advances biomedical research by harnessing, developing, and deploying forefront computational, information, and grid technologies. The Joint Center for Structural Genomics creates new technologies to drive high-throughput structure determination.

By the sheer magnitude and range of his creative energies, Dr. Ellisman continues to raise the bar on innovation, scope, and output of both individual and collaborative efforts in academic medicine. His academic stature and the broadly based, high esteem for his work are additionally underscored by his service as Chair of the Biotechnology Research Resources Principal Investigators Group of the NIH National Center for Research Resources and National Institute of Biomedical Imaging Bioengineering, and Chair of the National Meeting Program Committee.

Dr. Ellisman pursues several major research tracks in his overall neurobiological agenda, each of which takes his laboratory in new directions and circumscribes an area of seminal contribution to the neurosciences field. These areas of specialty include the following.

The first track concerns the cellular organization of the brain and the role of the astrocyte. The Ellisman Laboratory is known in the international neurobiological community for its paradigm-shifting work on astrocytes, the most prevalent glial cell type in the mammalian nervous system. Through investigation of the dynamics of myelinated nerves and the maturation of astrocyte "spongiform" morphology, Ellisman and his colleagues were the first to observe and document that these cells establish individual domains of activity, with limited overlap occurring between the extents of neighboring astrocytes, a finding that fundamentally redefines our understanding of the cell as a unique domain. As an outgrowth of this earlier work, the team has developed innovative techniques for identifying immature astrocytes and elucidating these cells' complete, well-preserved morphologies through a combination of immunolabeling for the astrocyte-specific markers glial fibrillary acidic protein and S100beta with intracellular dye labeling in fixed tissue slices. Monitoring the maturation process from the first two postnatal weeks, the team found a remarkable consistency in morphology by two weeks of age, with subsequent elaboration of spongiform processes resulting in the development of boundaries between neighboring astrocyte domains. These observations suggest that domain formation is largely the consequence of competition between astrocyte processes, similar to the well-studied competitive interactions between neuronal dendritic fields. Extending these insights further to cell damage and the quite limited regenerative capacity of the CNS, Ellisman and colleagues used the entorhinal cortex lesion model in mice to investigate the relationship between astrocyte activation (reactive gliosis), in particular, the hallmark features of hypertrophy of astrocytic processes and upregulation of intermediate filaments, and neurotrauma. They found that reactive astrocytes devoid of the intermediate filament proteins glial fibrillary acidic protein and vimentin showed only a limited hypertrophy of cell processes, suggesting that the upregulation is intermediate filament dependent. These are potentially breakthrough findings in revealing a novel role for intermediate filaments in astrocytes and implicating reactive astrocytes as potent inhibitors of neuroregeneration.

On a second track of research, neuroinformatics and multiscale databases, Dr. Ellisman's unique talent for establishing and facilitating creative and productive collaborations is especially evident as he and BIRN colleagues nationwide tackle the challenges of large-scale federation and integration of biomedical databases. His brand of leadership and collaborative dynamics has led to the creation of new infrastructures and thinking on how to meld information and assemble systems that allow scientists to navigate mega-databases, and how to make new knowledge discoverable. A prime case in point of this intermixing of imagination and information technology is the cell-centered database (CCDB) for multiscale structural and protein localization data from light and electron microscopy. Structured shared data repositories for molecular data in the form of web-accessible databases such as GenBank serve not only to organize and manage molecular data being created by researchers worldwide but also to provide the starting point for data mining operations designed to uncover interesting information present in the large amount of sequence and structural data. To realize the full impact of the genomic and proteomic studies of the last decade, similar neuroinformatic resources are needed for structural and biochemical complexity in biological systems beyond the molecular level, where proteins and macromolecular complexes are situated within their cellular and tissue environments. The CCDB is a first-its-kind cyberinfrastructure composed of 3D microscopic imaging data and designed for structural and protein localization information at scales ranging from large expanses of tissue to cellular microdomains with their associated macromolecular constituents. The collaborative work environment of the Ellisman lab yields first-rate technological inventions wrought from the needs of project implementation.

On a third track of research, instrument development and new technologies, Dr. Ellisman and colleagues have created a new electron microscope that allows unprecedented 3D imaging and accessibility for mesoscale neuroscientific data collection. Through their innovative technique and application of energy filtering, automated most-probable-loss tomography to intermediate voltage electron microscopy (IVEM), they have demonstrated that for thick, selectively stained biological specimens, this method produces a dramatic increase in resolution of the projections and the computed volumes versus standard unfiltered transmission electron microscopy (TEM) methods. The method effectively increases the usable thickness of selectively stained samples that can be imaged at a given accelerating voltage by dramatically improving resolution versus unfiltered TEM and increasing signal-to-noise versus zero-loss imaging, thereby expanding the utility of the IVEM to deliver information from within specimens up to 3 microns thick.

Utilizing technologies developed at NCMIR and advanced imaging and reconstruction methods, on a fourth track of research the Ellisman group continues to pursue new lines of inquiry regarding the structure and function of nerve amplifiers within the node of Ranvier. Through microphysiological simulations or models of the amplifying structures, the aim is to enhance understanding of the effects of aging and disease on transmission of pulses. The group has built high-resolution 3D structures of the node of Ranvier, including localization of specific macromolecules, to achieve a better understanding of the relationship between its structure and function and the macromolecular basis for impaired conduction in disease. Using serial section electron tomographic methods, they have constructed accurate 3D models of the nodal complex from mouse spinal roots with resolution better than 7.5nm. The team has also directly imaged the glial axonal junctions that serve to anchor the terminal loops of the myelin lamellae to the axolemma. The models provide accurate structural descriptions of the membrane compartments, external spaces, and formed structures, enabling more realistic simulations of the role of the node in modulation of impulse propagation than have been conducted on myelinated nerves previously.

On a fifth track, the Ellisman group has simulated a ganglion synapse that has two neurotransmitter receptors, to demonstrate ectopic activation. The collaborative dynamic that Dr. Ellisman has set in motion here unites Neurosciences with the Department of Biology and the Salk Institute, for study of ectopic neurotransmission with a novel model synapse that combines Monte Carlo simulations with high-resolution serial electron microscopic tomography. The group has found that simulated synaptic activity is consistent with experimental recordings of miniature excitatory postsynaptic currents only when ectopic transmission is included in the model, broadening the possibilities for mechanisms of neuronal communication.

In addition to his CRBS directorship, he serves as Director of the Laboratory for Neurocytology (a core electron microscopy facility for UCSD), the BIRN Coordinating Center, and NCMIR. Further, he is former chair of the Executive Committee of the San Diego Super Computer Center and former leader of the "Neuroscience Thrust" of the National Partnership for Advanced Computational Infrastructure, a large-scale collaborative effort among 50 universities nationwide led by UCSD.

His editorial activities include numerous first-tier specialty journals such as the Journal of Neurocytology and Journal of Neuroinformatics, and he is a much sought-after lecturer and consultant to governmental agencies and foundations, in the United States and worldwide. He was recently appointed to the Scientific Advisory Boards of the Max-Planck Institute for Medical Research in Heidelberg, Germany, and the UK e-Science Institute at Edinburgh, Scotland.

Year Award
2008 Appointed to the US Department of Energy, Los Alamos National Laboratory, and Bioscience, Biosecurity, and Cognitive Science Review Committee
US Department of Energy, Los Alamos National Laboratory, and Bioscience, Biosecurity, and Cognitive Science Review Committee
2007 Appointed to Senate/Administrative Committee UCSD
UCSD
2007 Appointed to Editorial Board
Journal of Electron Microscopy
2007 Appointed to Honorary Editorial Board of Bioinformatics and Biology
Bioinformatics and Biology
2007 Appointed to Editorial Board (3-year appointment, 3-years extended)
Journal of Structural Biology
2007 Appointed to Program Committee
2008 American Society for Cell Biology 48th Annual Meeting
2007 Appointed to External Scientific Advisory Board of the Research Imaging Steering Committee
University of Texas Health Science Center at San Antonio, San Antonio, TX
2006 Appointed as Extended Council Member
National Advisory Research Resources Council
2006 Appointed to National Science Foundation Advisory Committee for Cyberinfrastructure
National Science Foundation for Cyberinfrastructure
2005 Appointed to the Scientific Advisory Board
e-Science Institute, Edinburgh, Scotland
2005 Appointed to the Scientific Advisory Board
Institute of Molecular Biophysics, Maine
2005 Appointed to the Scientific Advisory Board
Life Sciences Society
2005 Appointed to the Advisory Board
Pacific Northwest National Laboratory, Richland, WA
2005 Appointed to CalIt2 UCSD Divisional Council (2-year appointment, 2-years extended)
CalIt2 UCSD Divisional Council
2004 Appointed to the Program Committee for the Biophysical Society 2004 National Meeting
Biophysical Society 2004 National Meeting
2004 Series Advisor
Cambridge University Press
2003 Appointed to the External Advisory Committee
National Research Resource for Advanced Biomedical Graphics and Simulation at the University of Utah
2003 Elected Chair
NIH National Center for Research Resources (NCRR) and National Institute of Biomedical Imaging Bioengineering (NBIB) Biotechnology Research Resources Principal Investigators Group
2003 Elected Chair
National Meeting Program Committee
2002 Appointed by the Secretary of Health to the National Institutes of Health, National Center for Research Resources, National Advisory Research Resources Council (5-year appointment)
National Institutes of Health, National Center for Research Resources, National Advisory Research Resources Council
2002 Appointed to the Department of Energy, Los Alamos National Laboratory, and Physics Division Review Committee
Department of Energy, Los Alamos National Laboratory, and Physics Division Review Committee
2001 Selected by UCSD Academic Senate to present the campus lecture in 2001-2002 as the outstanding UCSD Faculty Researcher in medical sciences
UCSD Academic Senate
2001 Charter Member
UCSD Institute of Molecular Medicine
2001 Appointed Member
UCSD Committee on Academic Information Technology
2001 Appointed to Internet 2 Life Sciences Leadership Team
Internet 2 Life Sciences
2001 Director
National Institute of Health Biomedical Informatics Research Network (BIRN)
2000 Apopinted to the Scientific Advisory Board
National Foundation for Functional Brain Imaging
2000 Appointed member of the Committee on Frontiers at the Interface between Computing and Biology
National Research Council/NAS, "Computer Science and Technology Board"
1999 Appointed to Applications Strategy Council of Internet 2
Applications Strategy Council of Internet 2
1999 Appointed to Editorial Board
Journal of Computer Assisted Microscopy
1999 Appointed Chair
SDSC Executive Committee
1999 Executive Committee/Governing Board
University of California, Life Sciences Informatic Program
1998 Appointed, National Research Council Group "On Being a Researcher in the Digital Age"
National Research Council Group "On Being a Researcher in the Digital Age"
1998 Appointed to NPACI Executive Committee
NPACI Executive Committee
1997 Creativity Award
National Science Foundation
1996 Appointed to Editorial Board
Journal of Histochemistry and Cytochemistry
1995 Appointed to Editorial Board
Journal of Biomedical Optics
1994 Appointed Member
NSF Metacenter Advisory Council on Computational Neuroscience
1994 Appointed to Editorial Board
Journal of the Microscopy Society of America
1993 Program Chair (two years)
The Microscopy Society of America
1993 Computer World Smithsonian Award
Computer Award
1992 Faculty Distinguished Lecturer
UCSD School of Medicine
1991 Founding Fellow of the American Institute for Medical and Biological Engineering
American Institute for Medical and Biological Engineering
1990 Apopinted to Editorial Board, NeuroImage
NeuroImage
1990 Appointed to Editorial Board, Synapse
Synapse
1989 Jacob Javits Neuroscience Investigator Award
Jacob Javits
1988 Apopinted as Commentator/Correspondent, Comments on Development Neurobiology
Comments on Developmental Neurobiology
1987 Award for Outstanding Teaching
UCSD Department of Neurosciences
1980 Selected for Alfred P. Sloan Research Fellowship
Alfred P. Sloan
1980 Appointed Associate Editor, Editorial Board, The Journal of Neurocytology
The Journal of Neurocytology
1976 Fellow
Muscular Dystrophy Association of America
1970 A.B. with Honors
University of California, Berkeley