june 22, 2009 transdisciplinary research on energetics and
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Transdisciplinary Researchon Energetics and Cancer
Division of Cancer Control and Population Sciences
Concept Renewal Presentation
June 22, 2009
2
Outline
• What we know.• What has TREC accomplished.• Where does TREC II go next?• Questions
Macro-Level
Societalandcultural
norms
Community and Organizational
Home/ Family
Individual
Agriculture andeconomic policies, foodsubsidies
Food Industry action (product, packaging, pricing)
Gov’t foodassistance
programs
Local health care services/coverage
Local public healthprograms,policies
Point-of-purchase information, promotions in restaurants, convenience/grocery stores
Access to healthy and unhealthy foods in schools
Media andpublic
educationcampaigns
Access to healthy foods in communities (grocery stores, fast food, farmers markets)
National healthcarepolicy Land use,
zoning, business incentives
Federal policies (dietary guidelines, food labeling)
Food advertising
and marketing
Psychosocial• food norms,
preferences• knowledge• attitudes • skills,supports• role models
Biological• age• gender• genes• physiology
Household environment and feeding practices, incl. portion size
Parent/child care provider training and education
Individualized health careinterventions
ExposuresPhysical
Diet Body Size Activity
Mechanisms Growth Factors
Insulin Resistance
Chronic inflammation
Steroid Hormones
Gene Variants
Biomarkers
Endpoints Carcinogenesis
IGF-1IGFBP-3
Insulin C-Peptide
HbA1c
IL-6 CRP TNF-
Estrogen Progesterone
SHBG
Proposed Mechanisms that Link Energy Balance and Carcinogenesis
(Gunter MJ et al. 2006)
Metabolic Syndrome & Obesity: Influence on
Cancer Cell Metabolism and Growth
Source: C. Thompson (Penn) NCI Executive Committee Retreat, 2009
↑ ATP
↓ ATPTranscription
Translation
Glucose – P
Pyruvate
CO2 + H2O
↓ ATP
↑ ATPTranscription
Translation
Glucose – P
Pyruvate
CO2 + H2O
Growth Signal
Fuel Signal
Glucose
Lactate
*BRFSS 2005 (30 min x 5d mod or 20 min x 3 d vig)** NHANES 2003-2004 (150 min/week)*** NHANES 2003-2004, 20-59 y (Troiano et al., 2008) 30 min x 5d mod or greater
Percentage of U.S. Adults Meeting Physical Activity Recommendations
49.9
3.8
57.846.4
3.2
42.5
0
20
40
60
80
100
BRFSS Self-Report* NHANES Self-Report** Accelerometer***
% m
eetin
g re
com
men
datio
n
Men Women
8
What Has TREC Accomplished?
Transdisciplinary Researchon Energetics and Cancer
Division of Cancer Control and Population Sciences
39th Regular Meeting of the Board of Scientific Advisors
March 2009
Diet-induced obesity:Gene - diet interactions
B6 on HFHSA/J on HFHSB6 on LFLS A/J on LFLS
0 25 50 75 100 125 1500
10
20
30
40
50
60
Age (days)
Bod
y W
eigh
t (gr
ams)
N ~ 25, Error Bars = 1 SD
Normaldiet
High fat, high sucroseor low fat, low sucrose
(HF = Whopper w/ cheese)
B6 is obese only with a HFHS diet
A/J is lean regardless of diet Hill-Baskin et al.,, 2009
Metabolic Syndrome, NASH, HCC
On High Fat, High Sucrose Diet: B6 A/J
Obesity
Hypertension
Insulin Resistance
Cardiovascular Disease Risk
XXXX
Genetics of disease
Genetics of health
J. Nadeau and E. Topol, Nat. Genet. 2006; Shao et al. PNAS; JHN in press.
XHepatocellular
carcinoma X
Non-alcoholicsteatohepatitis
Diet
Obesity
Physical Activity
Cells Animals Humans Populations
GrowthProliferationApoptosis
TumorgenesisTissue
Angiogenesis
Biomarkers of carcinogenesis
Outcomes
Models
Intermediate BiologyGlucose InflammationInsulin AdipokinesIGF
Exposures
The FHCRC Transdisciplinary Research on Energetics and Cancer Center
Glycemic Load (GL) Effects of Diet on Cancer Incidence
High GL
Low GL
15
Sleep Disturbance andMetabolic Effects
• Increased cortisol, insulin resistance• Inflammatory cytokines• Sympathetic nervous system over activity
– Vascular effects (hypertension)• Abnormalities in appetite regulatory
hormones– Decrease Leptin; Increase Ghrelin
Redline, 2009
16
TREC Midcourse Accomplishments
• Rate of Progress• Collaboration Ethos• Career Development (73 New Investigators)
• Developmental Projects (n=96)
• New NIH Grants (n=13)• Outreach
• Publications, Presentations, Workshops
TREC Expert Report, March 2009
17
Basic
•Hill-Baskin, A. E., Markiewski, M. M., Buchner, D. A., Shao, H., Desantis, D., Hsiao, G., et al. (2009). Diet-induced hepatocellular carcinoma in genetically-predisposed mice. Hum Mol Genet, 19, 19.
•Yan, M., Myung, S. J., Fink, S. P., Lawrence, E., Lutterbaugh, J., Yang, P., et al. (2009). 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors. Proc Natl Acad Sci U S A, 106(23), 9409-9413.
•Hu, H. H., & Nayak, K. S. (2008). Quantification of absolute fat mass using an adipose tissue reference signal model. J Magn Reson Imaging, 28(6), 1483-1491.
•Ochs-Balcom, H. M., Cicek, M. S., Thompson, C. L., Tucker, T. C., Elston, R. C., S, J. P., et al. (2008). Association of vitamin D receptor gene variants, adiposity and colon cancer. Carcinogenesis, 29(9), 1788-1793.
•Doerner, S. K., Croniger, C. M., Berger, N. A., & Nadeau, J. H. (in press). Testing the Contributions of Obesity, Diet and Metabolic Diseases on Cancer Susceptibility
in Congenic-Consomic Strains.
18
Translational
•McTiernan, A. (2008). Mechanisms linking physical activity with cancer. Nat Rev Cancer, 8(3), 205-211.
•Nock, N. L., Thompson, C. L., Tucker, T. C., Berger, N. A., & Li, L. (2008). Associations between obesity and changes in adult BMI over time and colon cancer risk. Obesity (Silver Spring), 16(5), 1099-1104.
•Stovitz, S. D., Pereira, M. A., Vazquez, G., Lytle, L. A., & Himes, J. H. (2008). The interaction of childhood height and childhood BMI in the prediction of young adult BMI. Obesity (Silver Spring), 16(10), 2336-2341.
•Ievers-Landis, C. E., & Redline, S. (2007). Pediatric sleep apnea: implications of the epidemic of childhood overweight. Am J Respir Crit Care Med, 175(5), 436-441.
•Thompson, H. J., Jiang, W., & Zhu, Z. (in press). Energetics and Cancer: Exploring A Road Less Traveled.
19
Behavioral
•Heinberg, L. J., Kutchman, E. M., Lawhun, S. A., Berger, N. A., Seabrook, R. C., Cuttler, L., et al. (2009). Parent Involvement Is Associated With Early Success in Obesity Treatment. Clin Pediatr (Phila), 1, 1.
•French, S. A., Shimotsu, S. T., Wall, M., & Gerlach, A. F. (2008). Capturing the spectrum of household food and beverage purchasing behavior: a review. J Am Diet Assoc, 108(12), 2051-2058.
•Fulkerson, J. A., Nelson, M. C., Lytle, L., Moe, S., Heitzler, C., & Pasch, K. E. (2008). The validation of a home food inventory. Int J Behav Nutr Phys Act, 5(55), 55.
•Davis, J. N., Tung, A., Chak, S. S., Ventura, E. E., Byrd-Williams, C. E,, Alexander, K. E., et al. (in press). Aerobic and strength training reduces adiposity in overweight Latina adolescents.
•Lytle, L. A., Pasch, K., & Farbaksh, K. (in press). The Relationship Between Sleep and Weight in a Sample of Adolescents.
NHLBI Childhood Obesity Prev &
Treat RFA
Trans-NIH Initiatives Related to Multilevel Obesity Research
Multilevel Methodology
Obesity Treatment
Obesity Prevention
Capacity Building
Observational & Basic Studies
NICHDMultilevel ObesityMethods
RFA;Policy PA
OBSSRSystems Methods Initiatives
NICHD Global
Multilevel Centers
RFA
2010 2011
NICHD/NIDDKSchool, Site-Specific, &
Primary Care Interventions
NCI TREC translational research
(adults / children); obesity and cancer outcomes; training
NICHD Training
Dev. Country
(PA)
NCIEconomics & Obesity; Built Environment
NCI Geo-context & Obesity
(PA)
Topic Area
2009
NIH Upcoming Initiatives
TREC 2 RFA
NIH Active Initiatives
NHLBI Behav
Interven-tion Ctr
RFA
NHLBI Trans-
Behavior Obesity
RFA
21
Where Does TREC Go Next?
TREC II
22
Recommendations – TREC II
• Elucidate underlying biological mechanisms of obesity and cancer, explore new biomarkers
• Explore potential for genetics/genomics to advance individualized treatment
• Expand translational research focus, particular emphasis on cancer survivors
• Strengthen use and integration of theoretical constructs
TREC Expert Report, March 2009
23
Recommendations – TREC II
• Establish Expert Consultants Committee• Establish virtual and technical cores • Expand career development • Continue developmental projects• Broaden network outside of TREC• Actively synthesize and disseminate
findings
TREC Expert Report, March 2009
24
Evaluation Plan
• Success establishing transdisciplinary collaborative research
• Success/impact of training • Quantity/quality of publications and impact• Level of utilization of shared resources• Success obtaining new funding• Long-term impact on policy and health
TREC Expert Report, March 2009
25
TREC II Renewal
• U54/U01 – Competitive Renewal
• $1.5 M/yr direct cost for 6 sites– Two new sites added
• Coordination Center - $1 M/yr direct cost for one award– External expert committee added
26
Acknowledgements
• Rachel Ballard-Barbash• Frank Perna• April Oh• David Berrigan• Audie Atienza• Ming Lei• Barbara Spalholz• Tanya Agurs-Collins• Julia Rowland• Yvonne Grant
• John Milner• Sharon Ross• Jo Anne Zujewski• Catherine Alfano• Nancy Potischman• Robin McKinnon• Heather Bowles• Emily Dowling• Colleen McBride• Mary O’Connell
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