Linlin Wang

Title: Professor, Doctoral Supervisor

Position: Deputy Director, Institute of Reproductive and Child Health, Peking University; Deputy Director, Key Laboratory of Reproductive Health and Child Health, National Health Commission

E-mail: linlinwang@pku.edu.cn

Address: Xueyuan Road 38, Haidian District, Beijing, China

Personal profile

08/2018 – Present	Professor: Institute of Reproductive and Child Health, School of Public Health, Peking University, Beijing, P. R. China
08/2012~ 07/2018	Associate Professor: Institute of Reproductive and Child Health, School of Public Health, Peking University, Beijing, P. R. China
07/2012 ~ 08/2012	Visiting Scholar: University of Texas at Austin, USA
04/2009 ~ 07/2012	Lecturer: Institute of Reproductive and Child Health, Department of Epidemiology and Health Statistics, School of Public Health, Peking University, Beijing, P. R. China
07/2010 ~ 08/2010	Visiting Scholar: Centers for Disease Control and Prevention, USA
02/2010 ~ 03/2010	Visiting Scholar: Texas A&M Health Science Center, USA
08/2005 ~ 03/2009	Ph.D. Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, P. R. China

My research primarily focuses on the etiology and mechanisms of reproductive health and birth defects. I am committed to elucidating the patterns of occurrence and development in reproductive health issues, providing novel scientific evidence for the causes and mechanisms of significant birth defects, and offering scientific support for population-based prevention strategies. I have directed numerous national and provincial projects, including major topics under the National Social Science Fund, the National Key R&D Program of China, the National Natural Science Foundation of China, and the Beijing Natural Science Foundation. As the first author or corresponding author, I have published over 80 scholarly articles in prestigious journals such as Environmental Science Technology, Journal of Hazardous Materials, Clinical Epigenetics, Human Genetics, and Epidemiology, with more than 60 of these being SCI-indexed papers. I have co-authored eight monographs in both English and Chinese and have been granted multiple patents for inventions, two of which have been commercialized. I also teach graduate courses on "Epidemiology and Precision Medicine" and undergraduate courses on "Precision Nutrition". I serve as a project evaluation expert for the Ministry of Science and Technology, expert for the panel review of the National Natural Science Foundation of China's General, Youth, and Regional Science Fund projects, and as a senior talent evaluation expert for the National Health Commission's Talent Exchange Service Center. Additionally, I hold positions such as expert in the Standardization Technical Committee of the China Reproductive Health Industry Association, Vice Chair and Secretary-General of the Health Management Committee of the China Medical Education Association, Standing Committee member of the Teratology Committee of the Chinese Environmental Mutagen Society, and Standing Committee member of the Birth Defects Prevention and Molecular Genetics Branch of the Chinese Maternal and Child Health Association. My contributions have been recognized with several awards, including the Beijing Science and Technology Award, the Ministry of Education's Research Achievements Award, the Chinese Medical Association Science and Technology Award, the Chinese Preventive Medicine Science and Technology Award, nominations for the U.S. CDC's Charles C. Shepard Science Awards, and the Shenzhen Science and Technology Award for Patents.

Main research directions

Molecular Epidemiology, Reproductive Health Epidemiology, Precision Nutrition

Representative scientific research projects

(1) National Key R&D Program of China, the Ministry of Science and Technology of the People’s Republic of China: Genetic and Risk Factor Interaction Mechanisms in Developmental Behavioral Disorders and the Establishment of an Early Warning System, Project No. 2022YFC2705205, Principal Investigator, December 2022 - November 2025, Ongoing.

(2) Major Project of the National Social Science Fund of China: Prevention Strategies and Application Research of Developmental Disabilities in the Context of Population Aging, Project No. 21&ZD187, Principal Investigator (Responsible for Subproject 1), December 2021 - November 2024, Ongoing.

(3) National Key R&D Program of China, the Ministry of Science and Technology of the People’s Republic of China: Systematic Identification of Pathogenic Mutations in Major Birth Defects, Project No. 2021YFC2701101, Key Researcher, December 2021 - November 2024, Ongoing.

(4) National Natural Science Foundation of China, General Program, Study on the Relationship Between Somatic Mutations in Fetal Central Nervous Tissue and Neural Tube Defects, Project No. 81773441, Principal Investigator, January 2018 - December 2021, Completed.

(5) National Natural Science Foundation of China, General Program, Association of rare variants and aberrant DNA methylation in PCP pathway with anencephaly, Project No. 81472987, Principal Investigator, January 2015 - December 2018, Completed.

(6) Collaborative Project: Impact of Prenatal Folate Metabolism on Maternal and Child Health, Principal Investigator, December 2021 - December 2025, Ongoing.

(7) Collaborative Project: Research on Breast Milk Components Based on Birth Cohorts, Principal Investigator, January 2020 - March 2025, Completed.

(8) National Natural Science Foundation of China, Youth Fund, Study on the Association between autoantibodies to folate receptors and the risk of neural tube defects, Project No. 81202215, Principal Investigator, January 2013 - December 2015, Completed.

(9) Ministry of Education, Research Fund for the Doctoral Program of Higher Education of China, Antoantibodies to folate receptor in pregnant mothers or fetus and folate levels, Project No. 20100001120132, Principal Investigator, January 2010 - December 2013, Completed.

(10) Beijing Natural Science Foundation, General Program, Aberrant DNA methylation of homeobox genes and neural tube defects, Project No. 7162094, Principal Investigator, January 2016 - June 2018, 180,000 RMB, Completed.

10 Representative papers

(1) Li S, Wang C, Yang C, Chen Y, Cheng Q, Liu J, Zhang Y, Jin L, Li Z, Ren A, Wang L*. Prenatal exposure to poly/perfluoroalkyl substances and risk for congenital heart disease in offspring. Journal of Hazardous Materials, 2024,469:134008.

(2) Zhu H, Cheng Q, Liu J, Jin L, Li Z, Ren A, Wang L*. Associations among bisphenol A, its analogs, and chlorinated derivatives in placenta and risk for neural tube defects: A case-control study, Science of The Total Environment, 2023, 900:165586.

(3) Liu L, Guo Q, Cui M, Liu J, Yang C, Li X, Liu P*, Wang L*. Impact of maternal nutrition during early pregnancy and diet during lactation on lactoferrin in mature breast milk. Nutrition, 2022, 93, 111500.

(4) Chen Y, Liu L, Ni W, Jin L, Li Z, Ren A, Wang L*. Association between selected alkaline earth elements concentrations in umbilical cord and risk for cleft lip with or without cleft palate. Science of the Total Environment, 2021,750:141735.

(5) Tian T, Lei Y, Chen Y, Karki M, Jin L, Finnell RH, Wang L*, Ren A*. Somatic mutations in planar cell polarity genes in neural tissue from human fetuses with neural tube defects. Human Genetics, 2020,139(10):1299-1314.

(6) Guo Y, Liu L, Ni W, Pan Y, Chen Y, Xie Q, Liu Y, Jin L, Li Z, Ren A, Wang L*. Uranium concentration in umbilical cord may increase the risk for orofacial clefts. Environmental Research, 2020, 182, 109103.

(7) Lin S, Ren A*, Wang L*, Santos C, Huang Y, Jin L, Li Z, Greene NDE. Aberrant methylation of Pax3 gene and neural tube defects in association with exposure to polycyclic aromatic hydrocarbons. Clin Epigenetics 2019;11(1):13.

(8) Ni W, Yang W, Jin L, Liu J, Li Z, Wang B, Wang L*, Ren A. Levels of polycyclic aromatic hydrocarbons in umbilical cord and risk of orofacial clefts, Science of the Total Environment, 2019, 678: 123-132.

(9) Ni W, Yang W, Yu J, Li Z, Jin L, Liu J, Zhang Y, Wang L*, Ren A. Umbilical Cord Concentrations of Selected Heavy Metals and Risk for Orofacial Clefts. Environmental Science & Technology, 2018,52(18):10787-10795.

(10) Wang L, Li Z*, Jin L, Li K, Yuan Y, Fu Y, Zhang Y, Ye R, Ren A*. Indoor air pollution and neural tube defects: effect modification by maternal genes. Epidemiology 2014;25(5):658-65.

Note：*Corresponding author

Main research progress

Reproductive health and birth defects significantly influence the quality of the population in China. Crucial factors such as early-life environmental exposures and nutritional status play vital roles in determining reproductive health outcomes, as well as the growth and development of children and their health across the lifespan. My research team is engaged in the study titled "Identifying Early-Life Adverse Environmental Exposures and Exploring Pathogenic Molecular Mechanisms." We focus on reproductive health outcomes such as birth defects and child growth, paying special attention to individual and combined exposures to persistent organic pollutants, metals, pesticides, emerging contaminants, and the nutritional components of breast milk. Utilizing epidemiological research combined with in vivo and in vitro disease phenotype models, we investigate the causal relationships between these risk factors and adverse reproductive outcomes. We have elucidated the roles of somatic mutations, biallelic gene mutations, epigenetic modifications, oxidative stress, and apoptosis in the disease processes. Additionally, employing various analytical techniques, we have systematically described traditional and emerging nutritional components in breast milk, analyzing their variations across different lactation stages and assessing the relationship between these components and infant growth and development. Our findings provide a scientific basis for public health policy-making and precise disease prevention, identifying specific intervention targets. We also focus on precision nutrition in breastfeeding, where in-depth analysis of breast milk components aids in optimizing breastfeeding policies and improving maternal and infant health. Typical work includes:

1. Identifying new risk factors for birth defects through integrated population and basic research, and clarifying the impact of adverse environmental exposures in early life on reproductive outcomes

The etiology of adverse reproductive outcomes such as birth defects is complex, and there are numerous challenges in identifying their causative risk factors and mechanisms of action. Our team has used a combination of population studies and basic research to focus on prenatal environmental factors such as exposure to pollutants and prenatal lifestyle habits affecting the risk of birth defects. We have uncovered new risk factors for birth defects by testing for multiple persistent organic pollutants, emerging environmental contaminants in maternal serum, placental, and umbilical cord tissues. We found that early-life exposure to polycyclic aromatic hydrocarbons, organochlorine pesticides, antibiotics, and bisphenol A are associated with increased risks of congenital heart defects and neural tube defects in offspring. We have established the relationship between exposure to metals and the risk of birth defects, revealing that high prenatal levels of rare earth elements, alkaline earth elements like magnesium, calcium, strontium, barium, and trace elements like manganese, selenium, and zinc are risk factors for neural tube defects, while higher cobalt levels in the placenta and umbilical cord are associated with reduced risk. Other adverse prenatal environmental exposures, such as indoor air pollution, passive smoking, tea drinking, and consumption of pickled vegetables, have also been associated to birth defects. These results have been published in esteemed journals such as Proc Natl Acad Sci USA, Environmental Science & Technology, Journal of Hazardous Materials, and Science of the Total Environment.

2. Developing in vivo and in vitro models for adverse reproductive health outcomes, and analyzing the mechanisms of genetic, epigenetic and environmental factors in poor reproductive health outcomes from the "population-animal-cell" level

The complex mechanisms through which environment, genetics, and gene-environment interactions trigger adverse reproductive outcomes require further clarification. Moreover, the roles of somatic mutations and biallelic gene mutations in these outcomes are urgently needing research. We have successfully constructed in vivo and in vitro models for disease phenotypes of adverse reproductive outcomes caused by environmental pollutants, using whole-animal toxicological exposure and genetic engineering modeling, as well as chemical induction and genetic intervention at the cellular and organoid levels. These models have confirmed potential pathogenic environmental factors identified in population studies, using DNA/RNA/protein analyses, CRISPR/Cas9, and other molecular biology and genetic editing techniques, integrated with multi-omics data. We have pioneered the idea that somatic mutations and biallelic gene mutations are new molecular genetic mechanisms for neural tube defects, with related research published in leading journals like Proc Natl Acad Sci USA, Human Molecular Genetics, Human Genetics, Epigenetics, and Clinical Epigenetics.

3. Focusing on precision nutrition in breastfeeding and systematically depicting the compositional content of breast milk at different stages of lactation, conducting functional studies on emerging breast milk components, and carrying out a series of studies on the factors influencing breast milk composition

Breast milk is a critical nutritional source in early life, with its composition influenced by factors such as the mother's ethnicity and health, showing regional and ethnic diversity. This diversity demands a refined and personalized approach to meeting infants' nutritional needs, and there is an urgent need to establish a breastmilk composition database for the Chinese population and carry out functional research. Our team has systematically described the distribution and trends of traditional and emerging nutritional components in breast milk across different lactation stages using various detection techniques. We have conducted functional studies on these emerging components, quantitatively assessing the relationship between precise nutrition in breast milk and infant growth and development, providing new scientific evidence for functional studies of breast milk components. Additionally, we have conducted epidemiological studies on factors affecting breast milk components, exploring the relationships between maternal prenatal nutrition and metabolic status, dietary conditions during lactation, and the bioactive components of breast milk. These studies have been published in international nutrition journals (Nutrition. 2022, 93:111500; Br J Nutr. 2023, 130(9):1537-1547).

Future work

We plan to conduct a large-scale prospective birth cohort study to collect a variety of biological samples during critical windows of fetal growth and development and birth defects. This study will focus on the effects and mechanisms of emerging environmental pollutants on reproductive health, given the recent surge of such pollutants. Additionally, we aim to continue and deepen our investigation into the impact of breast milk components and characteristics on infant growth and development. We intend to use machine learning and artificial intelligence technologies to further explore the factors influencing high-dimensional breast milk components. The key scientific questions to be addressed are as follows:

（1） Can exposure to emerging environmental pollutants during early life affect specific reproductive health outcomes and birth defects? If so, what are the pathogenic molecular mechanisms involved?

（2） Which biomarkers can be used to characterize exposure to new pollutants during early life?

（3） How can artificial intelligence and machine learning technologies, combined with high-dimensional data analysis of breast milk components and their characteristics, be used to predict the impact of breast milk on infant growth and development and identify key influencing factors?