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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

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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 Metabonomics

    • 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





Bruker Daltonics Agilent-MicrOTOF Metabonomics

HPLC-Mass Spectrometer



Structural Genomics Metabonomics

Goal

“to make the three-dimensional structure of all proteins easily available from the knowledge of their corresponding DNA sequences”


Rutgers University Metabonomics

  • 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

10 Institutions

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


40 MetabonomicsPNNL / NESG NMR Structures in PSI-1

1XPN

1NY8

1EIJ

1JYG

1NYN

1Q48

1XJS

1EIW

1R57

PSI-2

Miami - 60 Protein Structures

1SQR

1JI8

1SUO

1JW3

1X9B

1PUL

1JSB

1XPW

1M94

1JJG

1RZW

1NY4

1SOU

1XMO

1JRM

1LV3

1NEI

1NE3

1L7Y

1NXI

1E01


Metabonomics Studies of Human Diseases Metabonomics

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

Cancer

Heart disease

Obesity

Gastrointestinal Disorders

Asthma and Allergy

Cincinnati Children’s Hospital:

Biliary atresia

Inflammatory bowel disease

Eosinophilic gastrointestinal disorders (EGID)

Liver transplant rejection

Kawasaki Disease

Solid brain tumors

Childhood Obesity

Rainbow Babies Children’s Hospital:

Brain tumors

Columbus Children’s Hospital:

Adolescent type I diabetes and vascular disease

Neonatal necrotizing enterocolitis

Genome Research Institute:

Childhood Obesity


Metabonomics Study of Human Pancreatic Cancer Diseases

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 Diseases

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 Diseases

Overlay of NMR Spectra of Urine

Disease Model

Control


Preliminary Study of A Mouse Model for Pancreatic Cancer Diseases

PLS-DA Scores Plot

disease

control


Preliminary Study of A Mouse Model for Pancreatic Cancer Diseases

The search for biomarkers for early detection

of human pancreatic cancer

PLS-DA - Loadings Plot


Distinguishing Ulcerative Colitis and Crohn Diseases’s Disease

Crohn’s Disease (CD)

  • 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

Ulcerative Colitis (UC)


Distinguishing Ulcerative Colitis and Crohn Diseases’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 Diseases’s Disease

Ted Denson, MD CCHMC

10 Crohn’s samples

10 Ulcerative Colitis samples

Preliminary discovery of misdiagnoses?


Kennedy Research Group at Miami University Diseases

Lindsey Aaron Miki Theresa Shuisong Keyang

Romick Goodpaster Watanabe Ramelot Ni Ding

Erik

Feldman

NESG:

Gaetano Montelione

Cheryl Arrowsmith

Thomas Szyperski

Aled Edwards

NESG Members

John Hunt

Funding:

National Institutes of Health

Battelle Memorial Institute

Department of Energy

Environmental Molecular Sciences Laboratory

Miami University

undergraduates

PNNL and WSU staff:

Garry

Buchko

Amy

Lindenberger

Adam

Ring

John Cort

Kate

McAteer

+ 6 more


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