PROJECT SUMMARY/ABSTRACT
This K01 Career Development Award proposes a multidisciplinary 4-year training program to provide the
candidate, Dr. Yeyi Zhu, with the experience and resources necessary to launch a successful career as an
independent investigator to elucidate early origins of obesity and related comorbidities. The childhood obesity
epidemic remains an urgent public health priority. Early prevention is critical to stemming the tide of obesity.
Yet, our ability to identify promising prevention targets has been impeded by the difficulty in measuring the
holistic metabolic status by conventional tools. Several human studies, including from Dr. Zhu's previous work,
indicate that individual exposures including dietary factors in pregnancy may program obesity risk in later life.
However, the underlying metabolic pathways are elusive. To fill this important knowledge gap, Dr. Zhu will use
a novel holistic framework that leverages both targeted and untargeted metabolomics approach, the state-of-
the-art electronic health records (EHR) data, and bioinformatics analytics to investigate the mechanisms by
which the in-utero environment may infer risk of fetal growth extremes [small for gestational age (SGA) or large
for gestational age (LGA)] and altered infant growth trajectories and excess adiposity (weight-for-length or body-
mass-index-for-age z-score =85th percentile). This application takes advantage of the Pregnancy Environment
and Lifestyle Study within Kaiser Permanente Northern California, with unique, robust resources of fasting
serum specimens collection in early to mid-pregnancy, anthropometric measurements, multi-domain survey
data (e.g., diet, physical activity, psychosocial assessments), and EHR data throughout the gestation and
offspring infancy. The specific aims, to be examined in a sample of 150 LGA, 150 SGA, and 150 appropriate
for gestational age births, are to: examine the associations between candidate (branch-chain amino acids,
myo-inositol, trimethylamine N-oxide, acylcarnitines, and fatty acids) and untargeted metabolites in early to
mid-pregnancy with fetal growth extremes (Aim 1) and infant growth trajectories and excess adiposity from 0-2
years (Aim 2), and explore metabolomic signatures for dietary factors in utero (Aim 3). Study findings may
elucidate the underlying metabolic pathways and potential upstream preventive targets related to modifiable in-
utero exposures, such as maternal dietary factors, to mitigate childhood obesity. Dr. Zhu is well suited to
perform this research: 1) she has a solid foundation in epidemiology, nutrition, and biostatistics; 2) this K01 will
significantly broaden her repertoire of advanced training in metabolomics, bioinformatics, and related biological
interpretation; and 3) she has leveraged a carefully coordinated set of resources including a multidisciplinary
mentorship committee, coursework, and applied learning closely aligned with the training objectives and
specific aims. This K01 is essential to advance her long-term career objective of becoming an independent
investigator with expertise in omics and bioinformatics to study early origins of cardiometabolic disease, with
the ultimate goal to inform individualized care for upstream prevention of obesity and its comorbidities.