Susan Murphy

Overview:

Ovarian and cervical cancer epigenetics, imprinted genes in ovarian and cervical cancers, identification of methylation biomarkers of disease, ovarian cancer stem cells, chemotherapeutic response in ovarian cancer, tumor dormancy, the influence of the in utero environment on DNA methylation and risk of disease.

Positions:

Associate Professor in Obstetrics and Gynecology

Obstetrics and Gynecology, Reproductive Sciences
School of Medicine

Chief, Division of Reproductive Sciences in the Department of Obstetrics and Gynecology

Obstetrics and Gynecology, Reproductive Sciences
School of Medicine

Associate Professor in the Division of Environmental Science and Policy

Environmental Sciences and Policy
Nicholas School of the Environment

Associate Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.A. 1992

University of North Carolina at Charlotte

Ph.D. 1998

Wake Forest University

Grants:

Disparities in cervical cancer precursors and deregulation of imprinted genes

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Triggering human anti-tumor stringent response to target recurrent ovarian cancer

Administered By
Molecular Genetics and Microbiology
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Gene Regulation in Recurrent Ovarian Cancers

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
Role
Principal Investigator
Start Date
End Date

Immune regulated amino acid pathways in Alzheimer's Disease

Administered By
Neurology, Behavioral Neurology
Awarded By
National Institutes of Health
Role
Collaborating Investigator
Start Date
End Date

Functional Genomic Screens of Tumor Recurrence in Ovarian Cancer

Administered By
Molecular Genetics and Microbiology
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Publications:

Associations between imprinted gene differentially methylated regions, appetitive traits and body mass index in children.

BACKGROUND: Knowledge regarding genetic influences on eating behaviours is expanding; yet less is known regarding contributions of epigenetic variation to appetitive traits and body mass index (BMI) in children. OBJECTIVE: The purpose of this study was to explore relationships between methylation at differentially methylated regions (DMRs) of imprinted genes (insulin-like growth factor 2/H19 and Delta-like, Drosophila, homolog 1/maternally expressed gene 3) using DNA extracted from umbilical cord blood leucocytes, two genetically influenced appetitive traits (food responsiveness and satiety responsiveness) and BMI. METHODS: Data were obtained from participants (N = 317; mean age = 3.6 years; SD = 1.8 years) from the Newborn Epigenetic STudy. Conditional process models were implemented to investigate the associations between DMRs of imprinted genes and BMI, and test whether this association was mediated by appetitive traits and birthweight and moderated by sex. RESULTS: Appetitive traits and birthweight did not mediate the relationship between methylation at DMRs. Increased insulin-like growth factor 2 DMR methylation was associated with higher satiety responsiveness. Higher satiety responsiveness was associated with lower BMI. Associations between methylation at DMRs, appetitive traits and BMI differed by sex. CONCLUSIONS: This is one of the first studies to demonstrate associations between epigenetic variation established prior to birth with appetitive traits and BMI in children, providing support for the need to uncover genetic and epigenetic mechanisms for appetitive traits predisposing some individuals to obesity.
Authors
Do, EK; Zucker, NL; Huang, ZY; Schechter, JC; Kollins, SH; Maguire, RL; Murphy, SK; Hoyo, C; Fuemmeler, BF
MLA Citation
Do, E. K., et al. “Associations between imprinted gene differentially methylated regions, appetitive traits and body mass index in children..” Pediatr Obes, vol. 14, no. 2, Feb. 2019. Pubmed, doi:10.1111/ijpo.12454.
URI
https://scholars.duke.edu/individual/pub1350630
PMID
30231188
Source
pubmed
Published In
Pediatr Obes
Volume
14
Published Date
Start Page
e12454
DOI
10.1111/ijpo.12454

Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes.

Background: Maternal diet during pregnancy has been shown to influence the child neuro-developmental outcomes. Studies examining effects of dietary patterns on offspring behavior are sparse. Objective: Determine if maternal adherence to a Mediterranean diet is associated with child behavioral outcomes assessed early in life, and to evaluate the role of differentially methylated regions (DMRs) regulating genomically imprinted genes in these associations. Methods: Among 325 mother/infant pairs, we used regression models to evaluate the association between tertiles of maternal periconceptional Mediterranean diet adherence (MDA) scores derived from a Food Frequency Questionnaire, and social and emotional scores derived from the Infant Toddler Social and Emotional Assessment (ITSEA) questionnaire in the second year of life. Methylation of nine genomically imprinted genes was measured to determine if MDA was associated with CpG methylation. Results: Child depression was inversely associated with maternal MDA (Bonferroni-corrected p = 0.041). While controlling for false-discovery, compared to offspring of women with the lowest MDA tertile, those with MDA scores in middle and high MDA tertiles had decreased odds for atypical behaviors [OR (95% CI) = 0.40 (0.20, 0.78) for middle and 0.40 (0.17, 0.92) for highest tertile], for maladaptive behaviors [0.37 (0.18, 0.72) for middle tertile and 0.42 (0.18, 0.95) for highest tertile] and for an index of autism spectrum disorder behaviors [0.46 (0.23, 0.90) for middle and 0.35 (0.15, 0.80) for highest tertile]. Offspring of women with the highest MDA tertile were less likely to exhibit depressive [OR = 0.28 (0.12, 0.64)] and anxiety [0.42 (0.18, 0.97)] behaviors and increased odds of social relatedness [2.31 (1.04, 5.19)] behaviors when compared to low MDA mothers. Some associations varied by sex. Perinatal MDA score was associated with methylation differences for imprinted control regions of PEG10/SGCE [females: Beta (95% CI) = 1.66 (0.52, 2.80) - Bonferroni-corrected p = 0.048; males: -0.56 (-1.13, -0.00)], as well as both MEG3 and IGF2 in males [0.97 (0.00, 1.94)] and -0.92 (-1.65, -0.19) respectively. Conclusion: In this ethnically diverse cohort, maternal adherence to a Mediterranean diet in early pregnancy was associated with favorable neurobehavioral outcomes in early childhood and with sex-dependent methylation differences of MEG3, IGF2, and SGCE/PEG10 DMRs.
Authors
House, JS; Mendez, M; Maguire, RL; Gonzalez-Nahm, S; Huang, Z; Daniels, J; Murphy, SK; Fuemmeler, BF; Wright, FA; Hoyo, C
MLA Citation
House, John S., et al. “Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes..” Frontiers in Cell and Developmental Biology, vol. 6, Jan. 2018. Epmc, doi:10.3389/fcell.2018.00107.
URI
https://scholars.duke.edu/individual/pub1353323
PMID
30246009
Source
epmc
Published In
Frontiers in Cell and Developmental Biology
Volume
6
Published Date
Start Page
107
DOI
10.3389/fcell.2018.00107

Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States.

During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes.
Authors
Hoffman, K; Butt, CM; Webster, TF; Preston, EV; Hammel, SC; Makey, C; Lorenzo, AM; Cooper, EM; Carignan, C; Meeker, JD; Hauser, R; Soubry, A; Murphy, SK; Price, TM; Hoyo, C; Mendelsohn, E; Congleton, J; Daniels, JL; Stapleton, HM
MLA Citation
Hoffman, Kate, et al. “Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States..” Environ Sci Technol Lett, vol. 4, no. 3, Mar. 2017, pp. 112–18. Pubmed, doi:10.1021/acs.estlett.6b00475.
URI
https://scholars.duke.edu/individual/pub1243614
PMID
28317001
Source
pubmed
Published In
Environmental Science & Technology Letters
Volume
4
Published Date
Start Page
112
End Page
118
DOI
10.1021/acs.estlett.6b00475

DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis.

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.
Authors
Joubert, BR; Felix, JF; Yousefi, P; Bakulski, KM; Just, AC; Breton, C; Reese, SE; Markunas, CA; Richmond, RC; Xu, C-J; Küpers, LK; Oh, SS; Hoyo, C; Gruzieva, O; Söderhäll, C; Salas, LA; Baïz, N; Zhang, H; Lepeule, J; Ruiz, C; Ligthart, S; Wang, T; Taylor, JA; Duijts, L; Sharp, GC; Jankipersadsing, SA; Nilsen, RM; Vaez, A; Fallin, MD; Hu, D; Litonjua, AA; Fuemmeler, BF; Huen, K; Kere, J; Kull, I; Munthe-Kaas, MC; Gehring, U; Bustamante, M; Saurel-Coubizolles, MJ; Quraishi, BM; Ren, J; Tost, J; Gonzalez, JR; Peters, MJ; Håberg, SE; Xu, Z; van Meurs, JB; Gaunt, TR; Kerkhof, M; Corpeleijn, E; Feinberg, AP; Eng, C; Baccarelli, AA; Benjamin Neelon, SE; Bradman, A; Merid, SK; Bergström, A; Herceg, Z; Hernandez-Vargas, H; Brunekreef, B; Pinart, M; Heude, B; Ewart, S; Yao, J; Lemonnier, N; Franco, OH; Wu, MC; Hofman, A; McArdle, W; Van der Vlies, P; Falahi, F; Gillman, MW; Barcellos, LF; Kumar, A; Wickman, M; Guerra, S; Charles, M-A; Holloway, J; Auffray, C; Tiemeier, HW; Smith, GD; Postma, D; Hivert, M-F; Eskenazi, B; Vrijheid, M; Arshad, H; Antó, JM; Dehghan, A; Karmaus, W; Annesi-Maesano, I; Sunyer, J; Ghantous, A; Pershagen, G; Holland, N; Murphy, SK; DeMeo, DL; Burchard, EG; Ladd-Acosta, C; Snieder, H; Nystad, W; Koppelman, GH; Relton, CL; Jaddoe, VWV; Wilcox, A; Melén, E; London, SJ
MLA Citation
Joubert, Bonnie R., et al. “DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis..” Am J Hum Genet, vol. 98, no. 4, Apr. 2016, pp. 680–96. Pubmed, doi:10.1016/j.ajhg.2016.02.019.
URI
https://scholars.duke.edu/individual/pub1127530
PMID
27040690
Source
pubmed
Published In
Am J Hum Genet
Volume
98
Published Date
Start Page
680
End Page
696
DOI
10.1016/j.ajhg.2016.02.019

Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease.

Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome. We discovered that alterations in a network of coexpressed cholesterol metabolism genes are a signature feature of obesity and inflammatory stress. This network included 11 BMI-associated genes related to sterol uptake (↑LDLR, ↓MYLIP), synthesis (↑SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (↓ABCA1, ABCG1), producing a molecular profile expected to increase intracellular cholesterol. Importantly, these alterations were associated with T2D and coronary artery calcium (CAC), independent from cardiometabolic factors, including serum lipid profiles. This network mediated the associations between obesity and T2D/CAC. Several genes in the network harbored C-phosphorus-G dinucleotides (e.g., ABCG1/cg06500161), which overlapped Encyclopedia of DNA Elements (ENCODE)-annotated regulatory regions and had methylation profiles that mediated the associations between BMI/inflammation and expression of their cognate genes. Taken together with several lines of previous experimental evidence, these data suggest that alterations of the cholesterol metabolism gene network represent a molecular link between obesity/inflammation and T2D/CAC.
Authors
Ding, J; Reynolds, LM; Zeller, T; Müller, C; Lohman, K; Nicklas, BJ; Kritchevsky, SB; Huang, Z; de la Fuente, A; Soranzo, N; Settlage, RE; Chuang, C-C; Howard, T; Xu, N; Goodarzi, MO; Chen, Y-DI; Rotter, JI; Siscovick, DS; Parks, JS; Murphy, S; Jacobs, DR; Post, W; Tracy, RP; Wild, PS; Blankenberg, S; Hoeschele, I; Herrington, D; McCall, CE; Liu, Y
MLA Citation
Ding, Jingzhong, et al. “Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease..” Diabetes, vol. 64, no. 10, Oct. 2015, pp. 3464–74. Pubmed, doi:10.2337/db14-1314.
URI
https://scholars.duke.edu/individual/pub1079411
PMID
26153245
Source
pubmed
Published In
Diabetes
Volume
64
Published Date
Start Page
3464
End Page
3474
DOI
10.2337/db14-1314

Research Areas:

Cancer
Cancer cells--Growth
Epigenetics
Genomic Imprinting