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University of Colorado Denver

University of Colorado Denver
 

Jacob E. Friedman, Ph.D.

Faculty Profile


 

Professor

Department of Pediatrics, Biochemistry & Molecular Genetics

University of Colorado Denver

 

Genetic and environmental programming of obesity

Grants: 1) NIH R01 DK078590 Mechanisms for Fetal Hepatic Programming in the Non-Human Primate                                      

               2) NIH R01 DK059767 Regulation of Glucose Homeostasis by C/EBPb                      

               3) NIH R01 (Barbour) DK077630 Regulation of Maternal Fuel Supply and Neonatal Adiposity   

               4) NIH R01 (Dabelea) DK076648 Exploring the Fuel-Mediated Programming of Neonatal Growth

               5) NIH P30- DK048520 Clinical Nutrition Research Unit (CNRU) –Metabolic Core 

                                            

Description of Research


As a basic scientist interested in Maternal-Fetal Metabolism and obesity, I have spent the past 13 years investigating the causes and consequences of Gestational Diabetes Mellitus (GDM) and the impact on the fetus.  In addition, I have a ten year history of research in the basic molecular mechanisms for control of hepatic glucose output. This involved developing novel animal models (transgenic mice, Non-Human Primate) together with invasive clinical investigation of human pregnancy utilizing skeletal muscle and adipose tissue biopsies obtained from obese GDM women with post-partum follow-up.

    

     We are testing the hypothesis that changes in maternal diet, particularly saturated fatty acids are the driving force for obesity-linked infant adiposity in humans, transgenic mice, and in a non-human primate model whereby exposure to a High Fat diet programs the metabolic systems in the developing fetus and offspring.

 

     We are also investigating the role of the transcription factor CCAAT/Enhancer Binding Protein on systems that control fuel metabolism including appetite, lipogenesis, and inflammation.  Mice lacking C/EBPb are resistant to dietary and genetic forms of obesity. The long-term goal of these studies is to characterize the metabolic and gene regulatory effects of C/EBPb, particularly with regard to regulation of body weight, and to identify the regulatory mechanisms underlying these effects in tissue-specific gene knockout mice. 

 

 

1-2 Most Significant Publications

1)      Barbour LA, McCurdy CE, Knotts TA, Shao J, Kirwan J, Catalano P, and Friedman JE.  Cellular mechanisms for insulin resistance in human pregnancy and gestational diabetes, Diabetes Care, 30 Suppl 2:S112-9, 2007.

2)      McCurdy CE, Bishop J, Williams SM, Smith MS, Friedman JE+, and Grove KL+ (2009). Maternal high fat diet triggers lipotoxicity in the fetal liver of the nonhuman primate Journal of Clinical Investigation 119(2):323-35. +Co-Senior Authors.

 

Primary Focus Area (if part of the obesity initiative)

·         Maternal Origins of Obesity

 

Secondary Focus Areas (if part of the obesity initiative)

·         Obesity Cell Biology

·         Obesity Pathophysiology-Basic Mechanisms

 

Access to Specialized Populations

·         Clinical large scale (>1000) pregnant women and their offspring suitable for genetic and epigenetic analysis.

·         Non-human primates suitable for invasive studies of maternal-fetal metabolism.

 

Benefit of CNRU

The major benefit of the CNRU for me has been the clearinghouse of all things obesity, and potential collaboration opportunities with other clinical investigators. While I interact with junior investigators through the pilot project program and through the core laboratories, my ability to serve as a mentor is enhanced by these activities.  As director of the metabolic core lab, CNRU resources have allowed us to expand our services into newer metabolic areas such as inflammation, PCR, and rodent body composition.  I have also worked on Proteomic analysis with the Mass-Spec Core lab.

CNRU Cores Used

Metabolic, Mass Spectrometry

 

CNRU Collaborations

Eckel, Barbour, Wang, Klemm, McCurdy, Brown, Rozance, Hay, Jonsher, Rahman
University of Colorado Denver

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