Susan Murphy

Overview:

My research interests are largely centered around epigenetics and the role of epigenetic modifications in health and disease. My research projects include studies of gynecologic malignancies, including working on approaches to target ovarian cancer cells that survive chemotherapy and later give rise to recurrent disease.  I have ongoing collaborative projects in which we investigate the nature of the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD reflects the idea that our early environment plays an important part in shaping our risk of developing neurodevelopmental disorders or other chronic health problems. I am currently focused on preconception exposures in males with studies of the impact of cannabis use on the sperm epigenome and heritability of these effects. My lab is also working on the effects of in utero exposures, with our primary work revolving around the Newborn Epigenetics STudy (NEST), a mother-infant dyad cohort recruited from central North Carolina between 2005 and 2011 and whom we have followed since early pregnancy.

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 - 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
Awarded By
Gynecologic Cancer Foundation
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:

Developmental nicotine exposure and masculinization of the rat preoptic area.

Nicotine is a neuroteratogenic component of tobacco smoke, e-cigarettes, and other products and can exert sex-specific effects in the developing brain, likely mediated through sex hormones. Estradiol modulates expression of nicotinic acetylcholine receptors in rats, and plays critical roles in neurodevelopmental processes, including sexual differentiation of the brain. Here, we examined the effects of developmental nicotine exposure on the sexual differentiation of the preoptic area (POA), a brain region that normally displays robust structural sexual dimorphisms and controls adult mating behavior in rodents. Using a rat model of gestational exposure, developing pups were exposed to nicotine (2 mg/kg/day) via maternal osmotic minipump (subcutaneously, sc) throughout the critical window for brain sexual differentiation. At postnatal day (PND) 4, a subset of offspring was analyzed for epigenetic effects in the POA. At PND40, all offspring were gonadectomized, implanted with a testosterone-releasing capsule (sc), and assessed for male sexual behavior at PND60. Following sexual behavior assessment, the area of the sexually dimorphic nucleus of the POA (SDN-POA) was measured using immunofluorescent staining techniques. In adults, normal sex differences in male sexual behavior and in the SDN-POA area were eliminated in nicotine-treated animals. Using novel analytical approaches to evaluate overall masculinization of the adult POA, we identified significant masculinization of the nicotine-treated female POA. In neonates (PND4), nicotine exposure induced trending alterations in methylation-dependent masculinizing gene expression and DNA methylation levels at sexually-dimorphic differentially methylated regions, suggesting that developmental nicotine exposure is capable of triggering masculinization of the rat POA via epigenetic mechanisms.
Authors
Joglekar, R; Cauley, M; Lipsich, T; Corcoran, DL; Patisaul, HB; Levin, ED; Meyer, JN; McCarthy, MM; Murphy, SK
MLA Citation
Joglekar, Rashmi, et al. “Developmental nicotine exposure and masculinization of the rat preoptic area.Neurotoxicology, vol. 89, Mar. 2022, pp. 41–54. Pubmed, doi:10.1016/j.neuro.2022.01.005.
URI
https://scholars.duke.edu/individual/pub1505860
PMID
35026373
Source
pubmed
Published In
Neurotoxicology
Volume
89
Published Date
Start Page
41
End Page
54
DOI
10.1016/j.neuro.2022.01.005

Sex-specific DNA methylation and associations with in utero tobacco smoke exposure at nuclear-encoded mitochondrial genes

DNA methylation data (Illumina HumanMethylation450 BeadChip) specifically focused on nuclear-encoded mitochondrial genes in cord blood from 191 males and 190 females.
Authors
Murphy, S; King, D; Hoyo, C
MLA Citation
URI
https://scholars.duke.edu/individual/pub1518994
Source
manual
Published Date
DOI
10.7924/r44b36p48

Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children.

Non-Alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Epigenetic alterations, such as through DNA methylation (DNAm), may link adverse childhood exposures and fatty liver and provide non-invasive methods for identifying children at high risk for NAFLD and associated metabolic dysfunction. We investigated the association between differential DNAm and liver fat content (LFC) and liver injury in pre-adolescent children. Leveraging data from the Newborn Epigenetics Study (NEST), we enrolled 90    mother-child dyads and used linear regression to identify CpG sites and differentially methylated regions (DMRs) in peripheral blood associated with LFC and alanine aminotransferase (ALT) levels in 7-12yo children. DNAm was measured using Infinium HumanMethylationEPIC BeadChips (Illumina). LFC and fibrosis were quantified by magnetic resonance imaging proton density fat fraction and elastography. Median LFC was 1.4% (range, 0.3-13.4%) and MRE was 2.5 kPa (range, 1.5-3.6kPa). Three children had LFC ≥ 5%, while six (7.6%) met our definition of NAFLD (LFC ≥ 3.7%). All children with NAFLD were obese and five were Black. LFC was associated with 88 DMRs and 106 CpGs (FDR<5%). The top two CpGs, cg25474373 and cg07264203, mapped to or near RFTN2 and PRICKLE2 genes. These two CpG sites were also significantly associated with a NAFLD diagnosis. As higher LFC associates with an adverse cardiometabolic profile already in childhood, altered DNAm may identify these children early in disease course for targeted intervention. Larger, longitudinal studies are needed to validate these findings and determine mechanistic relevance.
Authors
Moylan, CA; Mavis, AM; Jima, D; Maguire, R; Bashir, M; Hyun, J; Cabezas, MN; Parish, A; Niedzwiecki, D; Diehl, AM; Murphy, SK; Abdelmalek, MF; Hoyo, C
MLA Citation
Moylan, Cynthia A., et al. “Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children.Epigenetics, Feb. 2022, pp. 1–16. Pubmed, doi:10.1080/15592294.2022.2039850.
URI
https://scholars.duke.edu/individual/pub1510607
PMID
35188871
Source
pubmed
Published In
Epigenetics : Official Journal of the Dna Methylation Society
Published Date
Start Page
1
End Page
16
DOI
10.1080/15592294.2022.2039850

Neighborhood Deprivation is Associated with Increased Risk of Prenatal Smoke Exposure.

Despite years of advisories against the behavior, smoking among pregnant women remains a persistent public health issue in the USA. Recent estimates suggest that 9.4% of women smoke before pregnancy and 7.1% during pregnancy in the USA. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy, including educational attainment, employment status, housing conditions, poverty, and racial demographics. However, most of these studies have relied upon self-reported measures of smoking, which are subject to reporting bias. To more accurately and objectively assess smoke exposure in mothers during pregnancy, we used Bayesian index models to estimate a neighborhood deprivation index (NDI) for block groups in Durham County, North Carolina, and its association with cotinine, a marker of smoke exposure, in pregnant mothers (n = 887 enrolled 2005-2011). Results showed a significant positive association between NDI and log cotinine (beta = 0.20, 95% credible interval = [0.11, 0.29]) after adjusting for individual covariates (e.g., race/ethnicity and education). The two most important variables in the NDI according to the estimated index weights were percent females without a high school degree and percent Black population. At the individual level, Hispanic and other race/ethnicity were associated with lowered cotinine compared with non-Hispanic Whites. Higher education levels were also associated with lowered cotinine. In summary, our findings provide stronger evidence that the socio-geographic variables of educational attainment and neighborhood racial composition are important factors for smoking and secondhand smoke exposure during pregnancy and can be used to target intervention efforts.
Authors
Wheeler, DC; Boyle, J; Barsell, DJ; Maguire, RL; Dahman, B; Murphy, SK; Hoyo, C; Zhang, J; Oliver, JA; McClernon, J; Fuemmeler, BF
MLA Citation
Wheeler, David C., et al. “Neighborhood Deprivation is Associated with Increased Risk of Prenatal Smoke Exposure.Prev Sci, Feb. 2022. Pubmed, doi:10.1007/s11121-022-01355-7.
URI
https://scholars.duke.edu/individual/pub1510793
PMID
35179695
Source
pubmed
Published In
Prev Sci
Published Date
DOI
10.1007/s11121-022-01355-7

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

BACKGROUND: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. METHODS: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268). RESULTS: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10-7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10-6) in older children and had methylation differences in the same direction. CONCLUSIONS: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.
Authors
Solomon, O; Huen, K; Yousefi, P; Küpers, LK; González, JR; Suderman, M; Reese, SE; Page, CM; Gruzieva, O; Rzehak, P; Gao, L; Bakulski, KM; Novoloaca, A; Allard, C; Pappa, I; Llambrich, M; Vives, M; Jima, DD; Kvist, T; Baccarelli, A; White, C; Rezwan, FI; Sharp, GC; Tindula, G; Bergström, A; Grote, V; Dou, JF; Isaevska, E; Magnus, MC; Corpeleijn, E; Perron, P; Jaddoe, VWV; Nohr, EA; Maitre, L; Foraster, M; Hoyo, C; Håberg, SE; Lahti, J; DeMeo, DL; Zhang, H; Karmaus, W; Kull, I; Koletzko, B; Feinberg, JI; Gagliardi, L; Bouchard, L; Ramlau-Hansen, CH; Tiemeier, H; Santorelli, G; Maguire, RL; Czamara, D; Litonjua, AA; Langhendries, J-P; Plusquin, M; Lepeule, J; Binder, EB; Verduci, E; Dwyer, T; Carracedo, Á; Ferre, N; Eskenazi, B; Kogevinas, M; Nawrot, TS; Munthe-Kaas, MC; Herceg, Z; Relton, C; Melén, E; Gruszfeld, D; Breton, C; Fallin, MD; Ghantous, A; Nystad, W; Heude, B; Snieder, H; Hivert, M-F; Felix, JF; Sørensen, TIA; Bustamante, M; Murphy, SK; Raikkönen, K; Oken, E; Holloway, JW; Arshad, SH; London, SJ; Holland, N
MLA Citation
Solomon, Olivia, et al. “Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.Mutat Res Rev Mutat Res, vol. 789, Jan. 2022, p. 108415. Pubmed, doi:10.1016/j.mrrev.2022.108415.
URI
https://scholars.duke.edu/individual/pub1515459
PMID
35690418
Source
pubmed
Published In
Mutat Res Rev Mutat Res
Volume
789
Published Date
Start Page
108415
DOI
10.1016/j.mrrev.2022.108415

Research Areas:

Cancer
Children and the environment
DNA Methylation
Effect of environment on
Epigenetics
Genomic Imprinting
Molecular Biology
Spermatogenesis
Spermatogonia