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Remote Instrumentation Access for the Ohio Consortium for Metabonomics
Aaron Goodpaster and Michael A. Kennedy
Miami University, OhioDepartment of Chemistry and Biochemistry
Bioscience Cluster Expansion GuidelinesColumbus, 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
Goal
“to make the three-dimensional structure of all proteins easily available from the knowledge of their
corresponding DNA sequences”
Structural Genomics
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
• Igor Jurisica
Yale University
• Mark Gerstein Co- PI
• Lynn Regan
Hauptmann-Woodward Medical Research Institute
• George DeTitta - Co-PI
Miami University (Pacific Northwest National Laboratory - through June 2006)
• Michael Kennedy - Co-PI
• John Cort
• Theresa Ramelot
• Keyang Ding
SUNY Buffalo
• Thomas Szyperski
Cornell University- Weill Medical College
• Hao Wu
Mount Sinai School of Medicine
• Ming-Ming Zhou
10 Institutions
40 PNNL / NESG NMR Structures in PSI-1
1R57
1JJG
1EIJ
1JW3
1JRM
1EIW
1E011NEI
1Q48
1L7Y 1LV3
1NY4
1NY8
1NYN
1PUL
1RZW
1JI8
1NE3
1JSB
1SUO
1SOU1XPW
1XPN
1XMO
1M94
1NXI
1JYG1XJS
1SQR
1X9B
PSI-2Miami - 60 Protein Structures
Metabonomics Studies of Human Diseasesat
850 MHz
Ohio Consortium for Metabonomics Studies of
Children’s Diseases
Ohio Consortium for Metabonomics Studies of Children’s Diseases
Metabonomics: Biomarker discovery for clinical diagnostics
20 collaborations on metabonomicsstudies of children’sdiseases
Initially targeting five clinical problems1. Cancer2. Heart disease3. Obesity4. Gastrointestinal Disorders5. Asthma and Allergy
Columbus Children’s Hospital:1. Adolescent type I diabetes and vascular disease2. Neonatal necrotizing enterocolitis
Genome Research Institute:1. Childhood Obesity
Ohio Consortium for Metabonomics Studies of Children’s Diseases
Cincinnati Children’s Hospital:1. Biliary atresia2. Inflammatory bowel disease3. Eosinophilic gastrointestinal disorders (EGID)4. Liver transplant rejection5. Kawasaki Disease 6. Solid brain tumors7. Childhood Obesity
Rainbow Babies Children’s Hospital:1. Brain tumors
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
1. A model for human pancreatic intraepithelial neoplasias (PanIN)
2. A model for human mucinous cystis neoplasias (MCN)
Collaboration with Dr. Gloria Su at Columbia University
Preliminary Study of A Mouse Model for Pancreatic Cancer
Overlay of NMR Spectra of Urine
Disease ModelControl
Preliminary Study of A Mouse Model for Pancreatic Cancer
PLS-DA - Loadings Plot
The search for biomarkers for early detection of human pancreatic cancer
Distinguishing Ulcerative Colitis and Crohn’s Disease
• CD and UC – Major types of chronic inflammatory
bowel 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
• CD– 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– Generally restricted to the colon – Affects only the mucosa (inner lining) of
the colon– 37-246 cases per 100,000 people
Crohn’s Disease (CD)
Ulcerative Colitis (UC)
Distinguishing Ulcerative Colitis and Crohn’s Disease
Child serum - Crohn’s 850 MHz
Child serum - Crohn’s 600 MHz
100 Crohn’s samples - 40 UC samples - Ted Denson, MD CCHMC
Distinguishing Ulcerative Colitis and Crohn’s Disease
Preliminary discovery of misdiagnoses?
10 Crohn’s samples 10 Ulcerative Colitis samples
Ted Denson, MD CCHMC
NESG:Gaetano MontelioneCheryl ArrowsmithThomas SzyperskiAled EdwardsNESG MembersJohn Hunt
Funding:National Institutes of HealthBattelle Memorial InstituteDepartment of Energy Environmental Molecular Sciences LaboratoryMiami University
Lindsey Aaron Miki Theresa Shuisong KeyangRomick Goodpaster Watanabe Ramelot Ni Ding
Garry Buchko
John Cort
Kennedy Research Group at Miami University
PNNL and WSU staff:
Kate McAteer
Adam Ring
Amy Lindenberger
+ 6 more
ErikFeldman
undergraduates
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