U.S. Department of Health and Human Services

Drug Response - A Tool for Understanding the Systems Biology of Type 2 Diabetes

4/21/2011 7:00 AM
4/22/2011 7:00 AM
 
No
(301) 822-9200
(800) 228-9290
​For scientific questions, contact:
Dr. Salvatore Sechi
Director, Proteomic Program
Director, Diabetes Systems Biology Program
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard Room 797
Bethesda, MD 20892-5460
Telephone: (301) 594-8814
Fax: (301) 480-3503
Email: sechi@nih.gov
 
For logistical information, contact:
Denise Hoffman, CMP
Deputy Director of Conferences
The Scientific Consulting Group, Inc.
656 Quince Orchard Road, Suite 210
Gaithersburg, MD 20878-1409
Tel: (301) 670-4990 x232
Fax: (301) 670-3815
E-mail: dhoffman@scgcorp.com
Bethesda
 
Bethesda North Marriott Hotel & Conference Center

Event Details

Meeting Objective:

Many recent advances in diabetes research have generated a body of knowledge indicating that diabetes is a heterogeneous disease with a complex genetic component. Environmental factors such as lifestyle and diet also play a major role in the development and progression of diabetes. Although diabetes is defined only by measuring glucose in the blood (or HbA1c as a surrogate), it is appare​nt that many factors can lead to hyperglycemia, and this single measurement does not accurately describe the cause(s) of the disease. In fact, several biological systems appear to be involved in the progression and development of type 2 diabetes, including several organs/tissues, hormones, as well as several intracellular molecular pathways. The limited understanding of the complexities of these systems and their interactions has been a major barrier in the development of optimal treatments in type 2 diabetes. A systems biology approach potentially could model these complex networks and thus help in characterizing key elements that affect the energy homeostasis. Within this new discipline, data sets obtained by the application of high-throughput technologies such as genomics, proteomics, and metabolomics are integrated to develop models that can be used to explain specific biological or physiological endpoints.

It may seem that at this stage of knowledge creating a model that can capture the complexity of the systems involved in the development of type 2 diabetes might be too difficult. As a result, within this workshop we would like to explore the possibility of focusing systems biology approaches on populations from clinical studies in which a specific agent (e.g., metaformin) is used as a single variable and the molecular profile, genes, and protein networks could be characterized before and after treatment.

More generally, within this workshop we intend to bring together experts in the areas of computational biology, clinical trials, proteomics, metabolomics, genomics, and physiology to identify how systems biology studies could be pursued in the context of diabetes.​​​​​​

Agenda

Thursday, April 21, 2011

7:30 a.m. - 8:00 a.m. Registration and Continental Breakfast
8:00 a.m. - 8:15 a.​m. Call To Order and Introduction
Salvatore Sechi, National​​ Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)  

Welcome
Gregory G. Germino, Deputy Director, NIDDK
8:15 a.m. - 9:00 a.m. Keynote Opening Lecture
A Multiscale Biology Approach for Linking the Molecular Biology of Disease to Clinical Medicine
Eric Schadt (PDF, 34KB), Pacific Biosciences

Session I:

The Clinical and Physiological Perspective

Chair:   William Knowler

9:00 a.m. - 9:25 a.m. Systems Biology and Type 2 Diabetes:  What Do We Hope to Learn?
William Knowler (PDF, 24KB), NIDDK, NIH
9:25 a.m. - 9:50 a.m. Fatty Liver:  A Marker of Looming Diabetes in Obese Youth
Sonia Caprio (PDF, 67KB), Yale University
9:50 a.m. - 10:15 a.m. Systems Biology Analysis of Metabolic Dysfunction:  Lessons From the Past and Future Directions
Richard Bergman (PDF, 63KB),  University of Southern California
10:15 a.m. - 10:30 a.m. Break
10:30 a.m. - 10:55 a.m. Inflammation in T2D:  Potential Pathophysiological Mediator and Pharmacological Target
Steven Shoelson (PDF, 45KB), Joslin Diabetes Center
10:55 a.m. - 11:20 a.m. Cellular Mechanisms of Insulin Resistance in Humans
Gerald I. Shulman (PDF, 23KB),  Yale University
11:20 a.m. - 11:45 a.m. Diabetes Drug Discovery and Development - Where are we now? What do we really need to be successful?
David Moller (PDF, 22KB),  Eli Lilly and Company

Session II:

Molecular Profiling - The State of the Art

Chair:   Robert Gerszten

11:45 a.m. - 12:10 p.m. Pharmacogenetics in Type 2 Diabetes
Jose Florez (PDF, 22KB),  Massachusetts General Hospital
12:10 p.m. - 1:15 p.m. Lunch
1:15 p.m. - 1:40 p.m. The Role of UCP3 in Exercise Metabolism Studied by Comprehensive Metabolomics
Olivier Fiehn (PDF, 25KB),  University of California, Davis
1:40 p.m. - 2:05 p.m. Metabolic Profiling for Understanding of Metabolic Disease Mechanisms and Progression
Christopher B. Newgard (PDF, 18KB),  Duke University
2:05 p.m. - 2:30 p.m. Large-scale Analysis of Metabolite-protein Interactions Reveals Novel Regulatory Mechanisms in Eucaryotes
Mike Snyder, Stanford University
2:30 p.m. - 2:55 p.m. Metabolite Profiles and the Risk of DM
Robert Gerszten (PDF, 17KB),  Massachusetts General Hospital
2:55 p.m. - 3:20 p.m. Imaging Mass Spectrometry:  New Views of Biology and Medicine
Richard Caprioli (PDF, 23KB),  Vanderbilt University
3:20 p.m. - 3:35 p.m. Break
3:35 p.m. - 4:00 p.m. Epigenetics, Imprinting and Metabolism
Anne Ferguson-Smith (PDF, 45KB), University of Cambridge (UK)

Session III:

The Animal Models of Diabetes

Chair:   C. Ronald Kahn

4:00 p.m. - 4:25 p.m. Defining Causal Factors in Diabetes Prone vs. Diabetes Resistant Mice Using a Systems Biology Approach
C. Ronald Kahn (PDF, 38KB),  Joslin Diabetes Center
4:25 p.m. - 4:50 p.m. Genetics of Diabetes in Mice:  New Pathways of Diabetes Susceptibility
Alan Attie (PDF, 15KB),  University of Wisconsin
4:50 p.m. - 5:15 p.m. MAP Kinases and the Metabolic Stress Response
Roger Davis (PDF, 105KB),  University of Massachusetts Medical School
5:15 p.m. - 5:40 p.m. Nonhuman Primates in Translational Metabolic Studies: Importance of Chronomics
Barbara Hansen (PDF, 18KB), University of South Florida
5:40 p.m. - 6:05 p.m. Profiling Obesity Phenotypes in Adipose Tissue
Dorothy D. Sears (PDF, 19KB), University of California, San Diego

Session IV:

Modeling a Complex Disease

Chair:   Albert-L�szl� Barabasi

6:05 p.m. - 6:30 p.m. Network Medicine:  From Cellular Networks to Human Diseases
Albert-Laszlo Barabasi (PDF, 41KB),  Northeastern University
6:30 p.m. Adjournment
Friday, April 22, 2011
7:30 a.m. - 8:00 a.m. Registration and Continental Breakfast

Session IV:

Modeling a Complex Disease (continued)

8:00 a.m. - 8:25 a.m. Systems Macro-Biology:  From Genes and Genomes to Network Signatures of Disease
Simon Kasif (PDF, 56KB),  Boston University
8:25 a.m. - 8:50 a.m. Systems Biology of Type 2 Diabetes:  The Road Ahead
Pierre DeMeyts (PDF, 22KB),  Novo-Nordisk
8:50 a.m. - 9:15 a.m.  Systems Pharmacology and Adverse Event Predictions
Ravi Iyengar (PDF, 44KB),  Mount Sinai School of Medicine
Discussion Panels​
9:15 a.m. - 10:30 a.m. (1-hour parallel discussions that specifically answer the questions posed for each of the above four sessions) Key Questions for "The Clinical and Physiological Perspective" Session:
Moderators: Peter Savage and William Knowler
  • What patient population and type of samples might be available for initiating systems biology studies?
  • Is the "drug treatment" concept a reasonable entry point for systems biology studies in humans, or are there better models that we could start with?
  • How should we apply systems biology approach for better understanding the meachanism of action of insulin sensitizers (e.g., metformin) in human?
  • How can we best use drug response and systems biology for understanding type 2 diabetes and potentially improve its treatment and diagnosis?
  • How should the NIDDK further promote the application of systems biology approaches?
Key Questions for the "Molecular Profiling - The State of the Art" Session:
Moderators: Olivier Blondel and Robert Gerszten
  • What samples are needed?
  • What data already are available?
  • What is the state of the art in molecular profiling?
  • How well can we apply high-throughput approaches to large cohorts?
  • What could be an ideal clinical study, and what type of samples could be analyzed?
  • Can we characterize the molecular phenotypes of different stages in diabetes pathogenesis?
  • How should we apply systems biology approach for better understanding the meachanism of action of insulin sensitizers (e.g., metformin) in human?
  • How can we best use drug response and systems biology for understanding type 2 diabetes and potentially improve its treatment and diagnosis?
  • How should the NIDDK further promote the application of systems biology approaches?
Key Questions for "The Animal Models of Diabetes" Session:
Moderators: Saul Malozowsky and C. Ronald Kahn
  • How have animal models contributed to advance this field, and what are their relevance to humans?
  • To what extent should we focus on animal models and on humans?
  • How should we apply systems biology approach for better understanding the meachanism of action of insulin sensitizers (e.g., metformin) in human?
  • How can we best use drug response and systems biology for understanding type 2 diabetes and potentially improve its treatment?
  • How should the NIDDK further promote the application of systems biology approaches?
 Key Questions for the "Modeling Complex Disease" Session:
Moderators: Salvatore Sechi and Albert-Laszlo Barabasi
  • To what extent has computational modeling been used successfully in complex diseases for describing molecular networks?
  • What type of data are needed and can be integrated for generating systems biology models of diabetes in humans?
  • How should we apply systems biology approach for better understanding the meachanism of action of insulin sensitizers (e.g., metformin) in human?
  • How can we best use drug response and systems biology for understanding type 2 diabetes and potentially improve its treatment and diagnosis?
  • How should the NIDDK further promote the application of systems biology approaches?
10:30 a.m. - 10:45 a.m. Break
10:45 a.m. - 11:30 a.m. Reports From Working Groups
(One speaker from each group - 10 minutes per speaker)
11:30 a.m. - 12:15 p.m. Keynote Closing Lecture
FDA:  A Perspective on Personalized Medicine
Janet Woodcock (PDF, 16KB), U.S. Food and Drug Administration (FDA)
12:15 p.m. Adjournment

Directions/Travel

ACCOMMODATIONS AND MEETING LOCATION

Bethesda North Marriott Hotel & Conference Center

Parking:  Complimentary

5701 Marinelli Road
Bethesda, MD 20852
Telephone:  (301) 822-9200 or (800) 228-9290
Web Site:  www.bethesdanorthmarriott.com 

A block of sleeping rooms has been reserved at the hotel for arrival on Wednesday, April 20, 2011, and departure on Friday, April 22, 2011. You may make reservations by calling the hotel at (800) 228-9290 or (301) 822-9200. Please indicate that you are booking a room under the group code name  Diabetes System Biology  to receive the group rate of $211. The room block will be in effect at the government rate until  Wednesday, March 23, 2011 . Any room reservations received after that date will be accepted on a space- and rate-availability basis. Please make your reservations as soon as possible.

GROUND TRANSPORTATION TO THE BETHESDA NORTH MARRIOTT HOTEL & CONFERENCE CENTER

DRIVING DIRECTIONS

From Baltimore/Washington International Thurgood Marshall Airport (BWI)
Take I-195 to Exit 4B (Route I-95 South). Take I-95 South toward Washington (20 miles) to I-495 West (Exit 27-Capital Beltway) toward Silver Spring. Follow I-495 West for 9 miles to Exit 34 (Bethesda/Wisconsin Avenue) toward Rockville. Continue on Route 355 North (Rockville Pike) for 3 miles. Turn left at the light onto Marinelli Road. The hotel is on the right.
 
From Washington Dulles International Airport
Take the Dulles Access Road to Exit 18 (I-495) to Maryland. Take Exit 36 (MD-187) toward Bethesda/Rockville. Bear left to take the ramp toward Rockville. Turn left onto Old Georgetown Road. Turn right onto Executive Boulevard. Turn left at the light onto Marinelli Road. The hotel is on the left.
 
From Ronald Reagan Washington National Airport
Take the George Washington Parkway North for 12 miles to the Capital Beltway (I-495) toward Maryland. Take Exit 36 (MD-187) toward Bethesda/Rockville. Bear left to take the ramp toward Rockville. Turn left onto Old Georgetown Road. Turn right onto Executive Boulevard. Turn left at the light onto Marinelli Road. The hotel is on the left.

METRORAIL INFORMATION

The Metro System is clean, reliable, and safe. It operates from 5:00 a.m. to 12:00 midnight Monday through Thursday; 5:00 a.m. to 3:00 a.m. on Fridays; 7:00 a.m. to 3:00 a.m. on Saturdays; and 7:00 a.m. to 12:00 midnight on Sundays. Each passenger must buy a fare card to travel in the system. Guides for purchasing fare cards are posted on the vending machines in each station. Each Metro car features a complete color-coded map. Station attendants on duty at each station can provide additional information on request. 
 
From Union Station or downtown Washington (main Metro lines into the city converge at Metro Center Station and Gallery Place Station), take the Metro Red Line toward Shady Grove (make sure that the train says "Shady Grove"). Exit at the White Flint Station. Take the escalator out of the station, go right to the corner, and cross Rockville Pike at the light; you are on Marinelli Road. The conference center is approximately 1 block further on your right. (Note: There is an underpass that goes under Rockville Pike that can be used rather than having to cross Rockville Pike.)

SHUTTLES

SuperShuttle offers service to most hotels from the major area airports: Ronald Reagan National, Washington Dulles International Airport (both are approximately $27 per person and $10 for each additional person), and Baltimore/Washington International Thurgood Marshall Airport (BWI) (approximately $40 per person and $11 for each additional person). The shuttles leave on an as-needed basis between the hours of 5:30 a.m. and 11:00 p.m. During other times, arrange for a shuttle by calling (800) 258-3826 from the airport, or visit the website at http://supershuttle.com.

TAXIS

The taxi fare is approximately $55 from Ronald Reagan Washington National Airport, approximately $65 from Washington Dulles International Airport, and approximately $75 from Baltimore/Washington International Thurgood Marshall Airport (BWI) . 

MARC TRAINS 

From BWI Airport, take the MARC train on the Penn Line to Union Station. Take the Metro Red Line toward Shady Grove (make sure that the train says "Shady Grove"). Exit at the White Flint Station. Take the escalator out of the station, go right to the corner, and cross Rockville Pike at the light; you are on Marinelli Road. The conference center is approximately 1 block further on your right. (Note: there is an underpass that goes under Rockville Pike that can be used rather than having to cross Rockville Pike.)

Minutes

​Minutes are currently unavailable.

Attendees

​​Attendees are currently unavailable.

Abstracts

PUBLICATIONS

Barabasi AL, et al.
Network medicine: a network-based approach to human disease.
Nat Rev Genet. 2011 Jan;12(1):56-68.


Berger SI, et al.
Network analyses in systems pharmacology.
Bioinformatics. 2009 Oct 1;25(19):2466-72. Epub 2009 Jul 30.


Berger SI, et al.
Systems pharmacology of arrhythmias.
Sci Signal. 2010 Apr 20;3(118):ra30.


Bergman RN. et al.
Orchestration of glucose homeostasis: from a small acorn to the California oak.
Diabetes. 2007 Jun;56(6):1489-501.


Charalambous M, et al.
Genomic imprinting, growth control and the allocation of nutritional resources: consequences for postnatal life.
Curr Opin Endocrinol Diabetes Obes. 2007 Feb;14(1):3-12.


Donath Marc Y., et al.
Type 2 diabetes as an inflammatory disease
Nat Rev Immunol. 2011 Feb;11(2):98-107. Epub 2011 Jan 14.


Ferguson-Smith AC, et al.
You are what your dad ate
Cell Metab. 2011 Feb 2;13(2):115-7.


Fiehn O, et al.
Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women.
PLoS One. 2010 Dec 10;5(12):e15234.


GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group; et al.
Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes.
Nat Genet. 2011 Feb;43(2):117-20. Epub 2010 Dec 26.


Goldfine AB, et al.
Biomarkers in fasting serum to estimate glucose tolerance, insulin sensitivity, and insulin secretion.,
Clin Chem. 2011 Feb;57(2):326-37. Epub 2010 Dec 13.


Goldfine AB, et al.
The Effects of Salsalate on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Trial
Ann Intern Med. 2010 Mar 16;152(6):346-57.


Hansen BC, et al.
Effects of aleglitazar, a balanced dual peroxisome proliferator-activated receptor α/γ agonist on glycemic and lipid parameters in a primate model of the metabolic syndrome.
Cardiovasc Diabetol. 2011 Jan 20;10:7.


Hivert MF, et al.
An Updated Genetic Score Based on 34 Confirmed Type 2 Diabetes Loci Is Associated With Diabetes Incidence and Regression to Normoglycemia in the Diabetes Prevention Program.
Diabetes. 2011 Mar 4. [Epub ahead of print]


Hsiao G, et al.
Multi-tissue, selective PPARγ modulation of insulin sensitivity and metabolic pathways in obese rats.
Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E164-74. Epub 2010 Oct 19.


Jablonski KA, et al.
Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program.
Diabetes. 2010 Oct;59(10):2672-81. Epub 2010 Aug 3.


Ji Y, et al.
Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics.
Clin Pharmacol Ther. 2011 Jan;89(1):97-104. Epub 2010 Nov


Kiselyov VV, et al.
Harmonic oscillator model of the insulin and IGF1 receptors' allosteric binding and activation.
Mol Syst Biol. 2009;5:243. Epub 2009 Feb 17.


Li X, et al.
Extensive in vivo metabolite-protein interactions revealed by large-scale systematic analyses.
Cell. 2010 Nov 12;143(4):639-50. Epub 2010 Oct 28.

Lorenzo C, et al.
Disposition index, glucose effectiveness, and conversion to type 2 diabetes: the Insulin Resistance Atherosclerosis Study (IRAS).
Diabetes Care. 2010 Sep;33(9):2098-103.


Ortmeyer HK, et al.
Insulin signaling and insulin sensitizing in muscle and liver of obese monkeys: peroxisome proliferator-activated receptor gamma agonist improves defective activation of atypical protein kinase C.
Antioxid Redox Signal. 2011 Jan 15;14(2):207-19. Epub 2010 Nov 23.


Reitman ML, et al.
Pharmacogenetics of metformin response: a step in the path toward personalized medicine.
J Clin Invest. 2007 May;117(5):1226-9.


Rigbolt KT, et al.
System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
Sci Signal. 2011 Mar 15;4(164):rs3.

Santoro N, et al.
A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents.
Hepatology. 2010 Oct;52(4):1281-90.


Sears DD, et al.
Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization.
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18745-50. Epub 2009 Oct 19.


Seeley EH, et al.
MALDI imaging mass spectrometry of human tissue: method challenges and clinical perspectives.
Trends Biotechnol. 2011 Mar;29(3):136-43. Epub 2011 Feb 2.

Shamekh R, et al.
Endogenous and diet-induced hypercholesterolemia in nonhuman primates: effects of age, adiposity, and diabetes on lipoprotein profiles.
Metabolism. 2011 Mar 2. [Epub ahead of print]


Tu Z, et al.
Integrating siRNA and protein-protein interaction data to identify an expanded insulin signaling network.
Genome Res. 2009 Jun;19(6):1057-67. Epub 2009 Mar 4.


Wang TJ,et al.
Metabolite profiles and the risk of developing diabetes.
Nat Med. 2011 Mar 20. [Epub ahead of print]


Wolkenhauer O, et al.
SysBioMed report: advancing systems biology for medical applications.
University of Rostock, Rostock, Germany. olaf.wolkenhauer@informatik.uni-rostock.de
IET Syst Biol. 2009 May;3(3):131-6.


Zhong H, et al.
Liver and adipose expression associated SNPs are enriched for association to type 2 diabetes.
PLoS Genet. 2010 May 6;6:e1000932.

Location

Line
  • 5701 Marinelli Road
  • MD 20892
Webinar

Contacts

Line
​For scientific questions, contact:
Dr. Salvatore Sechi
Director, Proteomic Program
Director, Diabetes Systems Biology Program
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard Room 797
Bethesda, MD 20892-5460
Telephone: (301) 594-8814
Fax: (301) 480-3503
Email: sechi@nih.gov
 
For logistical information, contact:
Denise Hoffman, CMP
Deputy Director of Conferences
The Scientific Consulting Group, Inc.
656 Quince Orchard Road, Suite 210
Gaithersburg, MD 20878-1409
Tel: (301) 670-4990 x232
Fax: (301) 670-3815
E-mail: dhoffman@scgcorp.com