- PROFESSOR | Environmental Medicine & Public Health
- PROFESSOR | Medicine, Hematology and Medical Oncology
- PROFESSOR | Oncological Sciences
- PROFESSOR | Pediatrics
Cancer, Cancer Genetics, Epigenetics, Gene Expressions, Genetics, Genomics, Molecular Epidemiology, Tumorigenesis
Multi-Disciplinary Training Areas
Cancer Biology [CAB], Genetics and Genomic Sciences [GGS]
BS, Beijing (Peking) University
MA, College of William and Mary
ScD, Massachusetts Institute of Technology
, Brigham and Women's Hospital
, Harvard School of Public Health
Visiting Scientist Award
International Agency for Reserch on Cancer (IARC/WHO)
American Cancer Society Research Award
American Cancer Society
AACR-Phone-Poulenc Rorer Young Investigator Award
American Association of Cancer Research
NCI Career Development Award
Arthur T. Ippen Travel Fellowship
Massachusetts Institute of Technology
Student Merit Award
Molecular and genetic epidemiology: genetic susceptibility; gene-environment interactions in human diseases
The focus of our molecular epidemiology laboratory is to understand complex interactions between environment and genome/epigenome in contribution to human diseases. We are performing functional epi/genetic analyses in population studies to elucidate disease mechanism and to identify/validate biomarkers for disease risk or prognosis. Such work is of great importance in identifying disease-causing exposure, clarifying disease etiology, designing prevention strategies through lifestyle modifications, and even assisting disease treatment and management.
We have three active research tracks in the lab:
(1) Environmental epi/genetics in breast cancer.
We have been working extensively to elucidate the effects of environment (endocrine disruptors) and lifestyle (dietary intake) on breast cancer via epigenetic mechanisms. We incorporate environmental measurements (questionnaire, biomarkers), genomic/epigenomic tools (gene expression, SNPs, methylation, and microRNAs), and bioinformatics into large epidemiologic studies. Given that cancer is considered a “developmental disease”, we are using a translational approach, combining animal and population studies, to systematically evaluate the role of endocrine disruptors (chemicals found ubiquitously in the environment) in breast cancer etiology during different stage (windows of susceptibility) of breast development.
(2) Environmental Epi/genetics in Reproductive Health and Child Development.
We use placenta as our model system. As an interface between maternal and fetal environment, placenta is the source of fetal nutrients and immune regulation as well as a barrier for environmental toxins; these effects are modulated by simultaneous production of many pregnancy related hormones, proteins and growth factors thereby fulfilling a critical role in proper intrauterine development. Thus placenta plays a vital role in productive health as well as fetal growth and neurodevelopment. We are actively studying the role of placental genome and epigenome, such as genomic imprinting, in birth outcomes and child neurodevelopment. We are also studying the environmental influences, such as maternal stress, nutrition and chemical exposure, on the placental epigenome. Utilizing resources of several birth cohorts, we are trying to build a comprehensive model to examine the inter-relationships among in utero environment, placental epigenome, and fetal growth and neurobehavioral outcomes.
(3) Developmental Origins of Human Diseases.
The Developmental Origins and Health and Disease (DOHaD) hypothesis posits that lifelong health is partially shaped by the environment experienced during early developmental period. We are investigating this hypothesis in two exposure - disease models. The first model is endocrine disruptors and breast cancer in which are conducting trans-disciplinary studies combining animal and human studies to systematically evaluate the role of endocrine disruptors in breast cancer etiology during different stage of breast development. The second focuses on adverse maternal environment during pregnancy (maternal stress, toxin exposure) and neurodevelopment of the children in which we are conducting genetic and epigenetic profiling of the placentas and cord bloods.
Chen J, Giovannucci E, Kelsey K, Rimm EB, Stampfer MJ, Colditz GA, Spiegelman DA, Willett WC, Hunter DJ. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Research 1996; 56: 4862-64.
Chen J, Stampfer MJ, Hough HL, Garcia-Closas ML, Willett WC, Hennekens CH, Kelsey KT, Hunter DJ. A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer. Cancer Res 1998 Aug 1; 58(15): 3307-11.
Chen J, Stampfer MJ, Ma J, Selhub J, Malinow MR, Hennekens CH, Hunter DJ. Influence of a methionine synthase (D919G) polymorphism on plasma homocysteine and folate levels and relation to risk of myocardial infarction. Atherosclerosis 2001 Feb 15; 154(3): 667-72.
Chen J, Germer S, Higuchi R, Berkowitz GS, Godbold JH, Wetmur JG. Kinetic polymerase chain reaction on pooled DNA: a high-throughput, high-efficiency alternative in genetic epidemiological studies. Cancer Epidemiol Biomarkers Prev 2002 Jan; 11(1): 131-6.
Chen J, Hunter DJ, Stampfer MJ, Kyte CJ, Chan WJ, Wetmur JG, Selhub JG, Ma JG. Polymorphism in the thymidylate synthase promoter enhancer region modifies the risk and survival of colorectal cancer. Cancer Epidemiol Biomarkers Prev 2003 Oct; 12(10): 958-62.
Chen J, Kumar M, Chan W, Berkowitz G, James GW. Increased influence of genetic variation on paraoxonase-1 enzymatic activity in neonates. Environ Health Perspect 2003; 111: 1403-09.
Chen J, Kyte C, Valcin M, Chan W, Wetmur JG, Selhub JG, Hunter DJ, Ma JJ. Polymorphisms in the one-carbon metabolic pathway, serum folate levels and colorectal cancer in a prospective study. Int J Cancer 2004; 110: 617-20.
Chen J, Kyte C, Chan W, Wetmur JG, Fuchs CS, Giovannucci E. Polymorphism in the thymidylate synthase promoter enhancer region and risk of colorectal adenomas. CancerEpidemiol Biomarkers Prev 2004 Dec; 13(12): 2247-50.
Chen J, Gammon MD, Chan W, Palomeque C, Wetmur JG, Kabat GC, Teitelbaum SL, Britton JA, Terry MB, Neuqut AI, Santella RM. One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer. Cancer Res 2005 Feb 15; 65(4): 1606-14.
Chen J, Chan W, Wallenstein S, Berkowitz G, Wetmur JG. Haplotype-phenotype relationships of paraoxonase-1. Cancer Epidemiol Biomarkers Prev 2005 Mar; 14(3): 731-4.
Demetriou CA, Chen J, Polidoro S, van Veldhoven K, Cuenin C, Campanella G, Brennan K, Clavel-Chapelon F, Dossus L, Kvaskoff M, Drogan D, Boeing H, Kaaks R, Risch A, Trichopoulos D, Lagiou P, Masala G, Sieri S, Tumino R, Panico S, Quirós JR, Sánchez Perez MJ, Amiano P, Huerta Castaño JM, Ardanaz E, Onland-Moret C, Peeters P, Khaw KT, Wareham N, Key TJ, Travis RC, Romieu I, Gallo V, Gunter M, Herceg Z, Kyriacou K, Riboli E, Flanagan JM, Vineis P. Methylome analysis and epigenetic changes associated with menarcheal age. PloS one 2013; 8(11).
Nomura Y, Lambertini L, Rialdi A, Lee M, Mystal EY, Grabie M, Manaster I, Huynh N, Finik J, Davey M, Davey K, Ly J, Stone J, Loudon H, Eglinton G, Hurd Y, Newcorn JH, Chen J. Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity. Reproductive sciences (Thousand Oaks, Calif.) 2014 Jan; 21(1).
Khankari NK, Bradshaw PT, McCullough LE, Teitelbaum SL, Steck SE, Fink BN, Xu X, Ahn J, Ambrosone CB, Crew KD, Terry MB, Neugut AI, Chen J, Santella RM, Gammon MD. Genetic variation in multiple biologic pathways, flavonoid intake, and breast cancer. Cancer causes & control : CCC 2014 Feb; 25(2).
Stueve TR, Wolff MS, Pajak A, Teitelbaum SL, Chen J. CYP19A1 promoter methylation in saliva associated with milestones of pubertal timing in urban girls. BMC pediatrics 2014 Mar; 14.
Kappil M, Chen J. Environmental exposures in utero and microRNA. Current opinion in pediatrics 2014 Apr; 26(2).
Torres-Sánchez L, López-Carrillo L, Blanco-Muñoz J, Chen J. Maternal dietary intake of folate, vitamin B12 and MTHFR 677C>T genotype: their impact on newborn's anthropometric parameters. Genes & nutrition 2014 Sep; 9(5).
Tao MH, Zhou J, Rialdi AP, Martinez R, Dabek J, Scelo G, Lissowska J, Chen J, Boffetta P. Indoor air pollution from solid fuels and peripheral blood DNA methylation: findings from a population study in Warsaw, Poland. Environmental research 2014 Oct; 134: 325-30.
Song Y, Liu C, Hui Y, Srivastava K, Zhou Z, Chen J, Miller RL, Finkelman FD, Li XM. Maternal allergy increases susceptibility to offspring allergy in association with TH2-biased epigenetic alterations in a mouse model of peanut allergy. The Journal of allergy and clinical immunology 2014 Dec; 134(6): 1339-45.
McCullough LE, Chen J, White AJ, Xu X, Cho YH, Bradshaw PT, Eng SM, Teitelbaum SL, Terry MB, Garbowski G, Neugut AI, Hibshoosh H, Santella RM, Gammon MD. Gene-Specific Promoter Methylation Status in Hormone-Receptor-Positive Breast Cancer Associates with Postmenopausal Body Size and Recreational Physical Activity. International journal of cancer and clinical research 2015; 2(1).
Kappil M, Lambertini L, Chen J. Environmental Influences on Genomic Imprinting. Current environmental health reports 2015 Jun; 2(2).
Teitelbaum SL, Li Q, Lambertini L, Belpoggi F, Manservisi F, Falcioni L, Bua L, Silva MJ, Ye X, Calafat AM, Chen J. Paired Serum and Urine Concentrations of Biomarkers of Diethyl Phthalate, Methyl Paraben, and Triclosan in Rats. Environmental health perspectives 2015 Jun;.
Manservisi F, Gopalakrishnan K, Tibaldi E, Hysi A, Iezzi M, Lambertini L, Teitelbaum S, Chen J, Belpoggi F. Effect of maternal exposure to endocrine disrupting chemicals on reproduction and mammary gland development in female Sprague-Dawley rats. Reproductive toxicology (Elmsford, N.Y.) 2015 Jul; 54.
Kappil MA, Green BB, Armstrong DA, Sharp AJ, Lambertini L, Marsit CJ, Chen J. Placental Expression Profile of Imprinted Genes Impacts Birth Weight. Epigenetics : official journal of the DNA Methylation Society 2015 Jul;.
Cho YH, McCullough LE, Gammon MD, Wu HC, Zhang YJ, Wang Q, Xu X, Teitelbaum SL, Neugut AI, Chen J, Santella RM. Promoter Hypermethylation in White Blood Cell DNA and Breast Cancer Risk. Journal of Cancer 2015 Jul; 6(9).
Li Q, Kappil MA, Li A, Dassanayake PS, Darrah TH, Friedman AE, Friedman M, Lambertini L, Landrigan P, Stodgell CJ, Xia Y, Nanes JA, Aagaard KM, Schadt EE, Murray JC, Clark EB, Dole N, Culhane J, Swanson J, Varner M, Moye J, Kasten C, Miller RK, Chen J. Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS). Epigenetics 2015 Aug;.
Lambertini L, Chen J, Nomura Y. Mitochondrial Gene Expression Profiles Are Associated with Maternal Psychosocial Stress in Pregnancy and Infant Temperament. PloS one 2015 Sep; 10(9).
Andersson NW, Li Q, Mills CW, Ly J, Nomura Y, Chen J. Influence of prenatal maternal stress on umbilical cord blood cytokine levels. Archives of women's mental health 2016 Feb;.
McCullough LE, Chen J, Cho YH, Khankari NK, Bradshaw PT, White AJ, Garbowski G, Teitelbaum SL, Terry MB, Neugut AI, Hibshoosh H, Santella RM, Gammon MD. DNA methylation modifies the association between obesity and survival after breast cancer diagnosis. Breast cancer research and treatment 2016 Feb; 156(1).
Kappil MA, Li Q, Li A, Dassanayake PS, Xia Y, Nanes JA, Landrigan PJ, Stodgell CJ, Aagaard KM, Schadt EE, Dole N, Varner M, Moye J, Kasten C, Miller RK, Ma Y, Chen J, Lambertini L. In utero exposures to environmental organic pollutants disrupt epigenetic marks linked to fetoplacental development. Environmental epigenetics 2016 Mar; 2(1).
Davis A, Tao MH, Chen J, Scelo G, Bencko V, Fabianova E, Foretova L, Janout V, Lissowska J, Mates D, Mates IN, Rudnai P, Zaridze D, Boffetta P. No association between global DNA methylation in peripheral blood and lung cancer risk in nonsmoking women: results from a multicenter study in Eastern and Central Europe. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 2016 Apr;.
Hu J, Raikhel V, Gopalakrishnan K, Fernandez-Hernandez H, Lambertini L, Manservisi F, Falcioni L, Bua L, Belpoggi F, L Teitelbaum S, Chen J. Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model. Microbiome 2016 Jun; 4(1).
Houten SM, Chen J, Belpoggi F, Manservisi F, Sánchez-Guijo A, Wudy SA, Teitelbaum SL. Changes in the Metabolome in Response to Low-Dose Exposure to Environmental Chemicals Used in Personal Care Products during Different Windows of Susceptibility. PloS one 2016 Jul; 11(7).
Gopalakrishnan K, Teitelbaum SL, Lambertini L, Wetmur J, Manservisi F, Falcioni L, Panzacchi S, Belpoggi F, Chen J. Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development. Environmental research 2017 Jan; 152.
McCullough LE, Chen J, Cho YH, Khankari NK, Bradshaw PT, White AJ, Teitelbaum SL, Terry MB, Neugut AI, Hibshoosh H, Santella RM, Gammon MD. Modification of the association between recreational physical activity and survival after breast cancer by promoter methylation in breast cancer-related genes. Breast cancer research : BCR 2017 Feb; 19(1).
Litzky JF, Deyssenroth MA, Everson TM, Armstrong DA, Lambertini L, Chen J, Marsit CJ. Placental imprinting variation associated with assisted reproductive technologies and subfertility. Epigenetics 2017 Jun;.
Everson TM, Kappil M, Hao K, Jackson BP, Punshon T, Karagas MR, Chen J, Marsit CJ. Maternal exposure to selenium and cadmium, fetal growth, and placental expression of steroidogenic and apoptotic genes. Environmental research 2017 Jun; 158.
Deyssenroth MA, Peng S, Hao K, Lambertini L, Marsit CJ, Chen J. Whole-transcriptome analysis delineates the human placenta gene network and its associations with fetal growth. BMC genomics 2017 Jul; 18(1).
Furlong MA, Herring A, Buckley JP, Goldman BD, Daniels JL, Engel LS, Wolff MS, Chen J, Wetmur J, Barr DB, Engel SM. Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes. Environmental research 2017 Jul; 158.
Petralia F, Aushev VN, Gopalakrishnan K, Kappil M, W Khin N, Chen J, Teitelbaum SL, Wang P. A new method to study the change of miRNA-mRNA interactions due to environmental exposures. Bioinformatics (Oxford, England) 2017 Jul; 33(14).
Peng S, Deyssenroth MA, Di Narzo AF, Lambertini L, Marsit CJ, Chen J, Hao K. Expression quantitative trait loci (eQTLs) in human placentas suggest developmental origins of complex diseases. Human molecular genetics 2017 Sep; 26(17).
Kingsley SL, Deyssenroth MA, Kelsey KT, Awad YA, Kloog I, Schwartz JD, Lambertini L, Chen J, Marsit CJ, Wellenius GA. Maternal residential air pollution and placental imprinted gene expression. Environment international 2017 Sep; 108.
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