Transcript Remote Instrumentation Access for the Ohio Consortium for Metabonomics Aaron Goodpaster and Michael A.

Remote Instrumentation Access for the Ohio Consortium for
Metabonomics
Aaron Goodpaster and Michael A. Kennedy
Miami University, Ohio
Department of Chemistry and Biochemistry
Bioscience Cluster Expansion Guidelines
Columbus, Ohio
April 4, 2008
The Eminent Scholar Laboratory
• Nuclear Magnetic Resonance Spectroscopy
• X-ray Crystallography
• HPLC-Mass Spectrometry
National Collaborative Project on Structural Genomics
•
The National Institutes of Health’s Protein Structure Initiative
Traditional Structural Biology Research
• Focus on Human Diseases - DNA Repair
• Metabolism in Exotic Bacteria
• Protein Crystallography Studies
A State-Wide Consortium for Metabonomics
•
The Ohio Consortium for Metabonomics Studies of Children’s Diseases
The Eminent Scholar NMR Facility
Miami University: Eminent Scholar Laboratory Renovation
600 MHz NMR at Miami University
Bruker Daltonics Agilent-MicrOTOF
HPLC-Mass Spectrometer
Bruker AXS MicroStar ProteumR Single Crystal Diffractometer
Structural Genomics
Goal
“to make the three-dimensional structure of all proteins
easily available from the knowledge of their corresponding
DNA sequences”
Rutgers University
• Guy Montelione - PI
•
•
Stephen Anderson
Swapna Gurla
Columbia University
•
Wayne Hendrickson - Co-PI
•
Peter Allen
•
J. Eric Gouaux
•
Barry Honig
•
John Hunt
•
Burkhardt Rost
•
Liang Tong
Ontario Cancer Institute
•
Cheryl Arrowsmith - Co-PI
University of Toronto
•
Aled Edwards Co-PI
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Igor Jurisica
Yale University
•
Mark Gerstein Co- PI
•
Lynn Regan
10 Institutions
Hauptmann-Woodward Medical Research Institute
•
George DeTitta - Co-PI
Miami University (Pacific Northwest National Laboratory - through June 2006)
•
Michael Kennedy - Co-PI
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John Cort
•
Theresa Ramelot
•
Keyang Ding
SUNY Buffalo
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Thomas Szyperski
Cornell University- Weill Medical College
•
Hao Wu
Mount Sinai School of Medicine
•
Ming-Ming Zhou
40 PNNL / NESG NMR Structures in PSI-1
1XPN
1NYN
1EIW
1Q48
1JYG
1XJS
1EIJ
1NY8
1R57
PSI-2
Miami - 60 Protein Structures
1SQR
1JI8
1SUO
1X9B
1PUL
1JW3
1JSB
1JJG
1E01
1XPW
1M94
1SOU
1L7Y
1LV3
1NXI
1RZW
1NEI
1XMO
1NE3
1NY4
1JRM
Metabonomics Studies of Human Diseases
at
850 MHz
Ohio Consortium for Metabonomics Studies
of
Children’s Diseases
Ohio Consortium for Metabonomics Studies of Children’s Diseases
20 collaborations
on metabonomics
studies of children’s
diseases
Metabonomics: Biomarker discovery for clinical diagnostics
Ohio Consortium for Metabonomics Studies of Children’s Diseases
Initially targeting five clinical problems
1.
2.
3.
4.
5.
Cancer
Heart disease
Obesity
Gastrointestinal Disorders
Asthma and Allergy
Cincinnati Children’s Hospital:
1. Biliary atresia
2. Inflammatory bowel disease
3. Eosinophilic gastrointestinal disorders (EGID)
4. Liver transplant rejection
5. Kawasaki Disease
6. Solid brain tumors
Rainbow Babies Children’s Hospital:
7. Childhood Obesity
1. Brain tumors
Columbus Children’s Hospital:
1. Adolescent type I diabetes and vascular disease
2. Neonatal necrotizing enterocolitis
Genome Research Institute:
1. Childhood Obesity
Metabonomics Study of Human Pancreatic Cancer
Pancreatic cancer is the fourth leading cause of cancer death the in the USA
More than 35,000 new diagnoses and deaths each year
Five year survival rate is less than 3%
When early detection is possible (<1 cm tumor), surgical resection has
~100% five year survival rate
Obviously, most cases of pancreatic cancer go undetected until too late
Urgent need for novel method for early detection of pancreatic cancer!
Preliminary Study of Two Mouse Models for Pancreatic Cancer
Collaboration with Dr. Gloria Su at Columbia University
1. A model for human pancreatic intraepithelial neoplasias (PanIN)
2. A model for human mucinous cystis neoplasias (MCN)
Preliminary Study of A Mouse Model for Pancreatic Cancer
Overlay of NMR Spectra of Urine
Disease Model
Control
Preliminary Study of A Mouse Model for Pancreatic Cancer
PLS-DA Scores Plot
disease
control
Preliminary Study of A Mouse Model for Pancreatic Cancer
The search for biomarkers for early detection
of human pancreatic cancer
PLS-DA - Loadings Plot
Distinguishing Ulcerative Colitis and Crohn’s Disease
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CD and UC
Crohn’s Disease (CD)
– Major types of chronic inflammatory bowel
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–
–
•
CD
–
–
–
•
disease (IBD)
Increased development of disease in developing
countries
Cause of disease is unknown (both genetic and
environmental factors)
Intestinal microflora plays a key role, those
with IBD have an altered gut microbiota
Can involve any part of the GI tract (mouth to
the anus)
Affects the entire bowel wall
26-199 cases per 100,000 people
UC
–
–
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Generally restricted to the colon
Affects only the mucosa (inner lining) of the
colon
37-246 cases per 100,000 people
Ulcerative Colitis (UC)
Distinguishing Ulcerative Colitis and Crohn’s Disease
100 Crohn’s samples - 40 UC samples - Ted Denson, MD CCHMC
Child serum - Crohn’s 850 MHz
Child serum - Crohn’s 600 MHz
Distinguishing Ulcerative Colitis and Crohn’s Disease
Ted Denson, MD CCHMC
10 Crohn’s samples
10 Ulcerative Colitis samples
Preliminary discovery of misdiagnoses?
Kennedy Research Group at Miami University
Erik
Feldman
Lindsey
Romick
NESG:
Gaetano Montelione
Cheryl Arrowsmith
Thomas Szyperski
Aled Edwards
NESG Members
John Hunt
Aaron
Goodpaster
Theresa
Ramelot
PNNL and WSU staff:
Funding:
National Institutes of Health
Battelle Memorial Institute
Department of Energy
Environmental Molecular Sciences
Laboratory
Miki
Watanabe
John Cort
Garry
Buchko
Kate
McAteer
Shuisong
Ni
Keyang
Ding
undergraduates
Amy
Lindenberger
Adam
Ring
+ 6 more