Profiles

The UC Irvine Development, Health and Disease Research Program is a transdisciplinary effort to elucidate the nature and consequences of the interplay between biological, behavioral, social and environmental conditions during early human development (intrauterine and early postnatal life) on subsequent health outcomes over the lifespan, and on the propensity, or susceptibility, for developing one or more of the complex common disorders that collectively confer the major global burden of disease. Our approach, broadly informed and guided by an evolutionary-developmental perspective, seeks to address developmental processes underlying the transduction of signaling of short- and long-term energetic state-related parameters in the maternal environment (stress, nutrition) on outcomes related to fetal growth and maturation, birth phenotypes, and newborn, infant and child physical and mental health. Our studies focus on putative mechanisms involving maternal-placental-fetal endocrine, immune, vascular and genetic/epigenetic processes, including telomere, mitochondrial and stem cell biology.

Established in 2000, our program had been supported continuously since its inception by several major research grants from the National Institutes of Health (NIH) and other agencies. Our interdisciplinary team currently includes a total of 36 faculty investigators directly funded by our program (of which 14 are based at UC Irvine and 22 at other institutions), along with several additional collaborators. We have been conducting primarily prospective, longitudinal studies of human pregnancy and birth outcomes, with an initial focus on the effects of maternal-fetal stress and stress-related biological processes on prematurity-related birth outcomes. Our studies have expanded to include follow-up investigations of the longer-term effects of various prenatal stress and nutrition-related exposures on newborn, infant and child health outcomes, with an emphasis on newborn and infant phenotypes related to a) obesity, energy balance homeostasis, and metabolic function, and b) structural and functional brain development. Our on-going studies in population-based samples from diverse socioeconomic and racial/ethnic backgrounds utilize state-of-the-art ecological momentary assessment (EMA) approaches to characterize maternal states (psychosocial stress, social interactions), behaviors (diet, physical activity, sleep) and physiology (autonomic, endocrine and immune function) in real time and natural settings over the course of pregnancy. Assessments of newborn and infant outcomes related to body composition/ adiposity, metabolic function and energy expenditure in free-living conditions are performed serially across infancy using dual-emission x-ray absorptiometry imaging (DXA), measurement of glucose-insulin homeostasis, and quantification of traceable hydrogen (deuterium) and oxygen (18O) decay using doubly-labeled water (DLW), respectively. Characterizations of newborn and infant brain structure, connectivity and function are also performed serially across infancy using magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), resting state fMRI, and laboratory- and home-based neurocognitive, affective and behavioral assessment protocols, respectively. Study hypotheses address i) the role of maternal-placental-fetal endocrine, immune/ inflammatory and oxidative state-related processes across gestation as key mediators of fetal programming of birth, newborn and infant health outcomes, ii) the role of maternal and fetal gene–environment interactions, with a focus on genes and gene networks (including mitochondrial genetic variation) implicated in the regulation of key enzyme systems, steroid hormones and peptides associated with stress as well as fetal development, iii) the role of maternal exposure to childhood trauma on the structural and functional development of the fetal/newborn brain; iv) the role of maternal social disadvantage in programming fetal cellular aging-related processes, with a focus on telomere and mitochondrial biology; and v) the biological, behavioral and social determinants of the well-documented racial/ethnic disparities and the Hispanic acculturation paradox in reproductive and maternal-child health outcomes in the United States. In addition to our own studies our program has established formal, funded collaborations with several other investigators and DOHaD-related projects in the U.S., Canada, Europe and Australia.