Brian D. Athey, Ph.D.

Associate Professor, Bioinformatics and Computational Biology
Departments of Psychiatry and Internal Medicine

Associate Director, UM Center for Computational Medicine and Biology (CCMB)

Director, Michigan Center for Biological Information (MCBI)

Director, Biomedical Informatics Program (BIP), Michigan Institute for Clinical and Health Research (MICHR)

Principal Investigator, NIH National Center for Integrative Biomedical Informatics
(NCIBI) The University of Michigan Medical School

Dr. Brian Athey received his Ph.D. in Cellular and Molecular Biology (Biophysics concentration) from the University of Michigan (1990), with a research focus in macromolecular structural biology. Dr. Athey is currently an Associate Professor of Biomedical Informatics in the University of Michigan Medical School Departments of Psychiatry and Internal Medicine; Brian is also an Associate Professor of Bioinformatics and Computational Biology in the UM Bioinformatics Graduate Program, and he is an active course master in the Program. In addition, he is founding Associate Director of the University of Michigan Center for Computational Medicine and Biology (ccmb.med.umich.edu), which has responsibility for the university-wide bioinformatics  graduate program, interdisciplinary pilot grant programs, and for providing access to computing and data infrastructures for “omics” and systems biology technology throughout CCMB and beyond to medical school and campus researchers.  Brian is the Principal Investigator of the NIH National Center for Integrative Biomedical Informatics (www.ncibi.org), only one of seven NIH National Centers for Biomedical Computing (NCBC), a centerpiece of the NIH Roadmap initiative.  He is also the Director of the funded Clinical and Translational Sciences Award (CTSA) Biomedical Informatics Program, housed in the Michigan Center for Clinical and Health Research (MICHR). He has responsibility to direct the U-M Health Informatics Research Organization (HIRO), the U-M wide health informatics faculty consortium, and oversight of the MICHR Clinical Research Informatics Core. Dr. Athey is co-chair of the national CTSA informatics consortia working group.

During his Ph.D. thesis research in the 1980s, Brian proposed the double helical crossed-linker model for the structure of chromatin, at that time controversial, but now thought to be the correct model for this critical macromolecular complex, and featured in many textbooks.  In the mid 1990s, Brian served as the Director of Biological Imaging Programs at the Environmental Research Institute of Michigan (ERIM; now part of General Dynamics). Dr. Athey is also a founding member of the Michigan Nanotechnology Institute for Medicine and Biology (www.nano.med.umich.edu). Brian was also a longtime collaborator and friend for the world famous and late Professor Emmett Leith, the inventor of off-axis holography. He and Leith invented and demonstrated an incoherent white light holographic microscope in 2001 with their student Kurt Mills and collaborator David Dilworth.  Brian is well known for his work with the National Library of Medicine (NLM) Visible Human Project where he has been a leader in establishing a nationwide Internet2 end-to-end test-bed demonstration project with NIH/NLM sponsorship in collaboration with Pittsburgh Supercomputing Center (vhp.med.umich.edu). The NLM VHP naturally lead to the establishment of the very successful DARPA Virtual Soldier Project (VHP) (www.virtualsoldier.net), a nationwide consortium of which he was the Principal Investigator, which builds from the VHP to extend it from basic human anatomy to physiological modeling, functional simulation and prediction after a traumatic injury.  Many of these projects are well known internationally.  Dr. Athey has published over 50 papers in the scientific literature, and has given well over 200 talks nationally, including several keynotes and plenary talks.  Brian was awarded  a Peace Fellowship of the Federation of American Scientists (FAS.org) in 2000, for his efforts in the 1990s to prevent biological warfare and terrorism. He is also a founding board member of Scientists and Engineers for America (www.sefora.org).

‘Integrative Biomedical Informatics’ and ‘Translational Bioinformatics’: This research thrust is leading to increased understanding of systems models and mechanisms of human health and disease, and will contribute to our understanding of the basis of ‘individualized medicine’. These new disciplines involve integration of diverse bioinformatics data-types and information bases into disease-specific models and networks, allowing a researcher to explore the systems properties and complexity of biological and biomedical systems. This relies heavily on computer and information sciences, biostatistics, and bioinformatics. Several very fruitful collaborations across campus and the nation are already developing because of this work, being demonstrated initially with collaborators in the genetic heterogeneity of T2 diabetes mellitus (M. Boehnke, L. Scott), T1 diabetes complications of the peripheral nerves and of nephrons (E. Feldman, M. Kretzler), prostate cancer progression and gene fusion events (A. Chinnaiyan, L. Hood), and bipolar spectral disorders (M. McInnis). Gil Omenn is my major collaborator in these “driving biological problem” (DBP) projects. This integrative approach should also considerably speed discovery and validation of new and unexpected co-morbidities indicating shared pathways and mechanisms.

This is a new research thrust for me, started in the last four years, and is already quite productive, leading to several significant team-science based grant and contract activities I lead. The major efforts are 1) the NIH National Center for Integrative Biomedical Informatics, NCIBI.org; and 2) the Biomedical Informatics Program of the UM Clinical and Translational Sciences Award (CTSA) in the Michigan Institute for Clinical and Health Research (MICHR).

Future clinical research application foci include studying the co-morbidity of depression(s) and bipolar spectral disorder(s) with other diseases, syndromes, and behaviors including: T2 diabetes, heart disease, cancer(s), cigarette smoking and drug abuse. My Co-I role as informatics lead in the NIH-NHLBI “Re-Engineering the Clinical Research Network” contract has helped to deliver a prototype IT/clinical informatics system called the “Honest Broker” to integrate diverse elements of clinical research records to study disease co-morbidities in a HIPAA compliant manner.
An overall goal of this thrust is to develop and test informatics intensive techniques to better stratify and classify disease phenotypes of human research participants, leveraging the electronic patient record, and integrating these phenotypic records with personalized molecular information. The UM Comprehensive Depression Center (UMCDC) will serve as a personalized medicine testbed. It is hoped this approach will allow for the diversity and variation of human health and disease to be better understood.

Computational Multiscale Modeling and Simulation of Macroscopic and Microscopic Biological Systems: This research thrust has two components: 1) A ‘macroscopic’ Human Systems Biology (HSB) modeling and simulation thrust, building from earlier work on the NIH Visible Human Project (Anatomy), and the DARPA Virtual Soldier Project (Physiology, Function, Pathology); and 2) A ‘Microscopic’ cellular systems approach to further understand the hierarchal nature of the structure, function, and dynamics of the eukaryotic chromatin fiber. These are both long-standing research interests, and both involve multiscale theory, ontological descriptions and machine learning for extension and linkage to other informational components, cutting-edge integrative biomedical informatics, and experimental verification.

For the macroscopic HSB thrust, future work will focus on integrating the nervous system into existing human systems models which have ignored the nervous system thus far (i.e. neither the Visible Human nor the Virtual Soldier have an integrated nervous system, central or peripheral). This work will take advantage of my background in advanced imaging and image processing. Additional aspects will involve modeling structural variation and uncertainty, and also the development of novel web portals to disseminate the work and build a world-wide community. This latter goal is already starting, in partnership with the Physiome project and the existing Visible Human collaboratory I started 10 years ago (http://vhp.med.umich.edu). The goal of this work is to create the scientific and technical basis for the next generation Visible Human Project.

For the microscopic chromatin work, a bioinformatics approach integrating the genomics, transcriptomics, proteomics, and cellular systems biology layers will help to provide models of “active” and “inactive” chromatin substrates. ChIP-chip data from public databases such as the ENCODE Project, and from bioinformatics-informed experiments, will be used to provide initial conditions for modeling nucleosomal placement and occupancy on the genomic sequence. A major theme will be to understand the topological aspects of chromatin in the nucleus (in situ), modeling connections to the nuclear matrix and scaffold elements (MARs and SARs), and using algorithms to model the torsional and structural changes implicated by sequence and connection-state to the matrix and/or scaffold. The major goal will be the continued development and testing of the multiscaler theory of chromatin “under tension” to understand chromatin fiber structure transcriptional regulatory network (TRN) complexes, the transition between interphase and metaphase states, and other biologically interesting dynamics. This work is being done in collaboration with mathematician Daniel Burns, and several well-known experimental collaborators. I was the co-discoverer of the crossed-linker model of chromatin structure (refs. 1, 2, 3). This work is now widely accepted, but not proven definitively. I will endeavor to prove the proposed structure definitively in the next 5-7 years. This model will provide the basis upon which to understand the underlying mechanisms of transcription and its regulation.

Athey BD, Smith MF, Rankert DA, Williams SP, Langmore JP (1990) The Diameters of Frozen-Hydrated Chromatin Fibers Increase with DNA Linker Length: Evidence in Support of Variable Diameter Models for Chromatin. Journal of Cell Biology 111:795-806. I was one of the co-discoverers of the Crossed-linker model for Chromatin. This is one of the key early references.

Dai, M, Wang P, Boyd AD, Kostov G, Athey BD, Jones EG, Bunney WE, Myers RM, Speed TP, Akil H, Watson SJ, Meng F (2005) Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Research 33(20):e175, pp. 1-9.

Kim YJ, Boyd AD, Athey BD, Patel JM (2005) “miBLAST: scalable evaluation of a batch of nucleotide sequence queries with BLAST.” Nucleic Acids Research 33(13):4335-44.

Wang P, Dai M, Xuan W, McEachin RC, Jackson AU, Scott LJ, Athey BD, Watson SJ, Meng F (2006) SNP Function Portal: A web database for exploring the function implication of SNP alleles. Bioinformatics Jul 15; 22(14):e523-529. PMID: 16873516.

Boyd AD, Hosner C, Hunscher DA, Athey BD, Clauw DJ, Green L (2007) An 'Honest Broker' Mechanism to Maintain Privacy for Patient Care and Academic Medical Research. International Journal of Medical Informatics 76(5-6):407-411, May-June 2007.

Jayapandian M, Chapman A, Tarcea VG, Yu C, Elkiss A, Ianni A, Liu B, Nandi A, Santos C, Andrews P, Athey BD, States D, Jagadish HV (2007) Michigan Molecular Interactions (MiMI): Putting the Jigsaw Puzzle Together. Nucleic Acids Research 2007, 35:D566-D571.

Xuan W, Dai M, Mirel B, Wilson J, Athey BD, Watson SJ, Meng F (2007) Pubviz: An Interactive Visual Search Interface for Medline. Proceedings of the Computational Systems Bioinformatics Conference (CSB2007) (in press).

Sarntivijai S, Ade A, Athey BD, States DJ, Lee AW (2007) Cell Line Ontology: A Bioinformatics Approach to Knowledge-Based Cell Culture Data Structure. Bioinformatics (accepted).

BAA-RM-04-23 (Clauw, Daniel) 10/01/04 – 10/01/07 0.60 calendar
National Institute of Health/NHLBI
Michigan Clinical Research Collaboratory: An Integrated Academic-Community Research Enterprise

The major goal of this contract is to develop an “Honest Broker” system which will allow for the interaction of several distinct domains of the translational research medical record.
Role: Co-I

The major goal is to establish an Internet-based collaboration medical education teaching capability as part of the NLM SII program.
2 R01 AI 37141 (Baker, James R. Jr.) 05/01/04 - 04/30/09 0.00 calendar
National Institutes of Health-NIAID
Apoptosis in Thyroiditis. Role: Co-I

The major goal of this effort is to provide bioinformatics support for Dr. Baker’s project.
1 U54 DA021519-01A1 (Athey, Brian D.) 09/25/05 - 08/31/10 4.20 calendar
National Institute of Health
National Center for Integrative Biomedical Informatics (NCIBI)

This is one of the seven NIH National Centers for Biomedical Computing (NCBC). Focus is biomedical informatics data integration and modeling, including advanced biomedical Information Retrieval (IR).
Role: PI

GR-238 (Athey, Brian D.) 01/01/2001 - 12/31/2006 0.00 calendar
Michigan Economic Development Corporation (MEDC)
“The Michigan Center for Biological Information (MCBI)”
The major goal of this project is to provide statewide bioinformatics and computational biology capabilities to the Michigan Core Technology Alliance infrastructure partners and institutions. Now working in no-cost extension.
Role: PI

W81XWH-04-2-0012 DOD-Army, Athey, B.D. (PI) 12/01/2003 - 09/31/2006
Defense Advanced Research Projects Agency/DSO
“Core development, integration and demonstration of the DARPA Virtual Soldier”.
This multi-institutional project prototypes and integrates anatomical and physiology modeling, medical informatics and computer simulations to create the next generation “Digital Human” framework; with military applications.
Role: PI, 12 subcontracting sites.

NO1-LM-0-3511 Athey, BD (PI) 11/22/1999 - 11/21/2004
NIH/NLM-National Library of Medicine
“Biomedical Applications of the Next Generation Internet (NGI): Next Generation Internet Implementation to Serve Visible Human Datasets: Phase II – Development of Testbeds”.
The major goal of this project was the creation of Internet2 Visible Human navigation and software capability.
Role: PI

MEDC #270 Athey, BD 10/01/2002 – 10/01/2004
Michigan Economic Development Corporation (MEDC)
DNA Software, Inc.
“Development of a comprehensive simulation-based computer software system environment for designing DNA-based microarrays”.
The major goal of this project is to provide design consideration for the development of the user interface of the microarray Designer Software System.
Role: PI

1 U54 RR023422-01 (Clauw, Daniel) 09/30/2007 – 09/29/2012
NIH / NCRR
Michigan Institute for Clinical and Health Research (MICHR)
Role: Director of the Biomedical Informatics Program, Co-Investigator

Burant, Charles (PI) 08/01/07-07/31/2012
National Institute of Health
“Using Systems Biology to Understand Islet Adaptation and Failure in Diabetes”

The goals of this application are to combine novel metabolomic analysis techniques with bioinformatics to identify the way in which pancreatic islet adapt to differences in nutrient mix and supply.
Role: Co-I

Personal Data

Director, Biomedical Imaging Program
Environmental Research Institute of Michigan; Ann Arbor, MI

Environmental Research Institute of Michigan; Ann Arbor, MI

2 R01 AI 37141 (Baker, James R. Jr.)                         05/01/04 - 04/30/09                   0.00 calendar
NIH / NIAID
Apoptosis in Thyroiditis. Role: Co-I

The major goal of this effort is to provide bioinformatics support for Dr. Baker’s project.
Role: Co-I

1 U54 DA021519-01A1 (Athey, Brian D.)                         09/25/05 - 08/31/10           4.20 calendar
NIH
National Center for Integrative Biomedical Informatics (NCIBI)

This is one of the seven NIH National Centers for Biomedical Computing (NCBC). Focus is biomedical informatics data integration and modeling, including advanced biomedical Information Retrieval (IR).
Role: PI

1 UL1 RR024986 (D. Clauw PI)                         9/17/07 – 5/31/12                          2.4 calendar mo
NIH / NCRR                                                                                                  
Michigan Institute for