RESEARCH

Integrated Multi-Omics Platform for Perinatal Exercise Genomics

The Perinatal Exercise Genomics Lab. employs an integrated multi-omics framework to define how maternal exercise during pregnancy reprograms molecular pathways in the placenta and fetal tissues. The lab leverages the Oxford Nanopore MinION platform as a core technology to perform RNA-seq for comprehensive transcriptomic profiling, methylation-seq to resolve epigenetic regulatory landscapes, and mtDNA-seq to interrogate mitochondrial genome stability, heteroplasmy, and structural variation. This long-read-based approach enables unified analysis of nuclear and mitochondrial genomic regulation within a single platform, allowing the lab to capture exercise-induced molecular remodeling across developmental contexts and to uncover fundamental mechanisms linking maternal physiological cues to fetal metabolic programming. 

Project 1-1. Uncovering the molecular mechanisms underlying maternal impact on placental development and function.

Project 1-1 is focusing on the roles of placenta in mediating the effects of maternal exercise on fetal development, which is based on our finding that maternal exercise induces changes in placental development and secretion of placental hormones. We discovered that apelin is one of exercise-induced cytokines, and its expression is regulated by maternal environment concomitant with exercise adaptation during pregnancy. Our preliminary data show that AMP-activated protein kinase (AMPK) is up-regulated in the placenta by maternal exercise (ME), which stimulates placental secretion of apelin. We suggested that apelin could be the potential therapeutic target gene to improve placental function and, thus, fetal development.

Project 1-2. Developing human iPSC-derived extracellular vesicle therapy for rescuing maternal obesity-induced feto-placental defects.

Maternal obesity disrupts placental mitochondrial function, contributing to pregnancy complications and long-term metabolic disease in offspring. This project develops a cell-free therapeutic strategy using extracellular vesicles (EVs) derived from human iPSCs primed with the exercise-mimetic exerkine [Pyr1]apelin-13. The central goal is to restore placental mitochondrial DNA stability and function during obese pregnancy. By combining stem cell biology, mitochondrial regulation, and pregnancy models, this work establishes a translational foundation for EV-based placental therapeutics. 

 Fig. 1. Schematic diagram for establishing research directions.

Project 2-1. Exploring epigenetic regulation of fetal development due to maternal exercise during pregnancy.

The mammals have two types of fat cells: brown and white adipocytes. Brown fat is thermogenic and has strong protective effects against obesity and metabolic diseases. Recently, we found that maternal exercise enhances fetal brown adipose tissue development, which has lasting beneficial effects on offspring metabolic health, but the underlying mechanisms remain to be established. Because brown and white adipocytes are derived from a group of progenitors which are descendants from fetal development, we are very interested in exploring the developmental sources of brown and white adipocytes, focusing on the lineage commitment of embryonic progenitor cells as affected by ME and placenta-induced hormones. 

Beside adipose tissue, muscle development is another topic very interesting to us. The fetal stage is critical for skeletal muscle development, with all fibers formed during pregnancy. We found that maternal exercise enhances cardio and muscle endurance capacities, which is correlated with  peroxisome proliferator-activated receptor g coactivator 1a (PGC-1a) activation. We further found that the DNA methylation was reduced in the PGC-1a promoter, which likely mediates the persistent improvement in offspring muscle function. However, mechanisms leading to epigenetic changes in the PGC-1a promoter during fetal development remains to be established. 

Project 2-2. Longitudinal imaging of maternal exercise and exerkine effects on offspring metabolism

Exercise is increasingly being seen as an effective form of therapy against many diseases. Maternal exercise, especially during pregnancy, has long-lasting effects on childhood wellbeing. Part of these beneficial effects come from the secretion of exercise-induced hormones called exerkines. While research into exercise and exerkines as medicines continue to grow, methods to longitudinally quantify exercise efficacy remain to be elucidated. This research builds tools and methods to track exercise efficacy using metabolic imaging. We hypothesize that exercise in mice will result in activation of brown adipose tissue (BAT). This metabolic activation can be detected using hyperpolarized magnetic resonance imaging (HP-MRI).

Project 3. Testing our novel discoveries for developing therapeutic intervention of pregnant women.

While cell culture and mouse studies ideally fit for identifying mechanisms, in order for these studies to generate clinical impacts, we conduct clinical studies of ME. Following novel discovery, we recruit pregnant women to undergo ME, and analyze changes in maternal and neonatal outcomes. These studies have the potential to define novel biologic molecules for reducing obesity, type 2 diabetes and other metabolic diseases.