Developmental programming of diabetes and obesity from mother to infant in Human and Non-Human Primates.
The Microbiome role in Innate Immunity and Non-alcoholic Fatty Liver Disease (NAFLD).
Metabolic/genomic determinants of Umbilical-cord derived Mesenchymal Stem Cell fate in Infants of Obese Mothers.
Nutritional intervention and epigenetic signatures in mothers and their infants in the developing world.
We are currently focused on the causal mechanisms of maternal diet driving the transmission of obesity and diabetes risk during the first 1000 days of life in mouse, monkey, and human infants. I have 25 years of experience investigating the causes and consequences of diet, obesity and Gestational Diabetes Mellitus (GDM) on the development of fetal metabolic systems particularly the mechanisms driving Obesity and Non-Alcoholic Fatty Liver Disease (NAFLD). My lab was the first to describe prenatal fatty liver in non-human primate (NHP) offspring and in human infants born to obese mothers. We investigate the mechanisms by which maternal Western-style diet remodels the offspring macrophage (MΦ) in liver and bone marrow and dysbiotic microbiome leading to inflammation and obesity in the offspring. We are also investigating the how maternal obesity impacts the transcriptomic profile of infant mesenchymal stem cells -fetal progenitor cells of adipose and skeletal muscle, associated with longitudinal adiposity gain in childhood obesity. Our findings suggest that exposure to western style diet (WSD) has both immediate and long-term effects on offspring liver gene expression and fibrogenesis, hematopoietic stem cell (HSC) and liver Mϕ function that are not resolved despite switching to a healthy diet, setting the stage for development of chronic metabolic disease pathways in multiple organs across the lifespan. New research questions and methods relevant to how the microbiome, and pediatric and infant stem cell metabolism can be reprogrammed by nutrition in early life are underway in clinical and pre-clinical models of disease.
1. NIH R01 DK129656-01 (MPI: Friedman, Short,). “Understanding the metabolic pathology of pediatric obesity and NAFLD” $3,535,684, 01/01/2022-06/30/2027. 6th Percentile.
2. NIH-R01-DK128416-01 (Friedman, PI) “Maternal Obesity and Pediatric NAFLD: Fetal Origins and Long-term outcomes in Non-Human Primates” $1,821,034. 09/01/2021-08/31/2024.
3. NIH-R01-DK128187-01 (MPI, Friedman, Aagaard, Kievit) “Metformin in Pregnancy: Fetal Consequences & Long-term Offspring Outcomes in a NHP Model” $$8,447,463. 09/01/2021-08/31/2025.
4. NIH-R01DK117418-01 (MPI: Friedman, Jonscher) “Role of the macrophage in developmentally programmed NAFLD” $2,815,935. 07/01/2020-06/30/2024.
5. NIH-1UG3OD023248-03. (Dabelea DD, PI, Friedman, Co-I) “Environmental Influences on Child Health Outcomes (ECHO) –The Healthy Start Study” $13,987,541 9/1/16 – 8/31/23.
6. PRESBYTERIAN HEALTH FOUNDATION/HHDC Team Science Grant (Myers PI, Friedman co-PI) “Development of a Baboon Model of Western Diet and Maternal Obesity-Mechanisms for Fetal Epigenetic Programming of Behavior and Metabolism”. $300,000. 7/1/2020- 6/30/2023.
7. PRESBYTERIAN HEALTH FOUNDATION/HHDC Team Science Grant (Friedman PI): “Infant Gut microbial Species and Programming Innate Immunity” $300,000 - 7/1/2020- 6/30/2023.
8. PRESBYTERIAN HEALTH FOUNDATION/HHDC Team Science Grant (Friedman Co-I): “Pilot RCT Intervention Targeting Elevated Triglycerides with a Point-of-Care Meter and Omega-3 Fatty Acids to Normalize Triglycerides and Fetal Growth $300,000 - 7/1/2020- 6/30/2023.
1. NIH/ F30 DK122672 (Michael Nash (PI) “The impact of maternal western style diet on immune cell function and development of non-alcoholic fatty liver disease” 09/01/2020-08/31/2024 Jacob E. Friedman, Mentor.
Keleher MR, Erickson K, Katerina K, Yang IV, Dabelea DD, Friedman JE, Boyle KE, and Jansson T.
Associations between the activity of placental nutrient sensing pathways and neonatal and postnatal
metabolic health: The ECHO Healthy Start Cohort, International Journal of Obesity 44(11):2203-221,
2020. PMID: 32327723
141. Boyle KE, Magill-Collins MJ, Newsom SA, Janssen RC, and Friedman JE. Maternal fat-1 transgene protects
offspring from excess weight gain, oxidative stress, and reduced fatty acid oxidation in response to high-fat
diet. Nutrients;12(3):767, 2020 PMID: 32183350.
142. Campodonico-Burnett W, Hetrick B, Wesolowski SR, Schenk S Takahashi DL, Dean TA, Sullivan EL, Kievit,
P, Gannon M, Aagaard K, Friedman JE, and McCurdy CE. Maternal obesity and western-style diet impair
fetal and juvenile offspring skeletal muscle insulin-stimulated transport in Nonhuman Primates, Diabetes
69(7):1389-1400, 2020. PMID: 32354857.
143. Jonscher KR, Abrams JK, Friedman JE. Maternal diet alters trained immunity in the pathogenesis of pediatric
NAFLD. Journal of Cellular Immunology. 2020; 2(6): 315-325. PMID: 33081177.
144. Soderborg TK*, Carpenter C*, Janssen R, Weir TL, Ir D, Young BE, Krebs NF, Robertson CE, Hernandez T,
Barbour LA, Frank DN, Krohel M, and Friedman, JE. Gestational diabetes is uniquely associated with altered
early seeding of the infant gut microbiota. Frontiers in Endocrinology, 2020. Nov 27;11:603021, PMID: 33329403.
*These authors contributed equally.
145. Martin-Carli J, Trahan GD, Jones KL, Hirsch N, Rolloff KP, Dunn E, Friedman JE, Barbour LA, Hernandez TL,
MacLean PS Monks J, McManaman JL, and Rudolph MC. Single cell RNA sequencing of human milk derived
cells illuminates differentiation trajectory among mammary epithelial cells. Journal of Mammary Gland Biology
and Neoplasia, 2020 PMID: 33216249
146. Keleher MR, Erickson K, Smith HA, Kechris KJ, Yang IV, Dabelea D, Friedman JE, Boyle KE, and Janssen T.
Placental insulin/IGF-1 signaling and inflammation are associated with metabolic outcomes at 4-6 years of age:
The ECHO Healthy Start Cohort. Diabetes, 70(3):745-751 2021. PMID: 33414248.
147. Matye D, Wang H, Luo W, Sharp R, Chen C, Gu L, Jones K, Friedman JE, Ding WX, Li T. Combined
ASBT inhibitor and FGF15 treatment improves therapeutic efficacy in experimental non-alcoholic
steatohepatitis Cellular and Molecular Gastroenterology and Hepatology, 12(3):1001-1019, 2021.
148. Elsakr JM, Zha SK, Ricciardi V, Dean TA, Takahashi DL, Sullivan E, Wesolowski S, Carrie E. McCurdy CE,
Kievit P, Friedman JE, Aagaard KM, Digna R. Velez-Edwards DR, Gannon M. Western-style diet consumption
impairs maternal insulin sensitivity and glucose metabolism during pregnancy in a Japanese macaque model.
Scientific Reports, Jun 21;11(1):12977, 2021. PMID: 34155315.