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:

Opposing Epigenetic Signatures in Human Sperm by Intake of Fast Food Versus Healthy Food.

Animal experiments have demonstrated that diets high in fats create a harmful environment for developing sperm cells, contributing to impaired reproductive health and induced risk for chronic diseases in the next generation. Changes at the level of the epigenome have been suggested to underlie these observations. Human data are limited to verify this hypothesis. While we earlier demonstrated a link between male obesity and DNA methylation changes at imprinted genes in mature sperm cells and newborns, it is currently unknown if -or how- a paternal eating pattern (related to obesity) is related to indices for epigenetic inheritance. We here aim to examine a yet unexplored link between consumption of healthy (rich in vitamins and fibers) or unhealthy ("fast") foods and methylation at imprint regulatory regions in DNA of sperm. We obtained semen and data from 67 men, as part of a North Carolina-based study: The Influence of the Environment on Gametic Epigenetic Reprogramming (TIEGER) study. Dietary data included intake of fruits/nuts, vegetables/soups, whole grain bread, meat, seafood/fish, and fatty or processed food items. Multiple regression models were used to explore the association between dietary habits and clinical sperm parameters as well as DNA methylation levels, quantified using bisulfite pyrosequencing at 12 differentially methylated regions (DMRs) of the following imprinted genes: GRB10, IGF2, H19, MEG3, NDN, NNAT, PEG1/MEST, PEG3, PLAGL1, SNRPN, and SGCE/PEG10. After adjusting for age, obesity status and recruitment method, we found that Total Motile Count (TMC) was significantly higher if men consumed fruits/nuts (β=+6.9, SE=1.9, p=0.0005) and vegetables (β=+5.4, SE=1.9, p=0.006), whereas consumption of fries was associated with lower TMC (β=-20.2, SE=8.7, p=0.024). Semen volume was also higher if vegetables or fruits/nuts were frequently consumed (β=+0.06, SE=0.03, p=0.03). Similarly, our sperm epigenetic analyses showed opposing associations for healthy versus fast food items. Frequent consumption of fries was related to a higher chance of sperm being methylated at the MEG3-IG CpG4 site (OR=1.073, 95%CI: 1.035-1.112), and high consumption of vegetables was associated with a lower risk of DNA methylation at the NNAT CpG3 site (OR=0.941, 95%CI: 0.914-0.968). These results remained significant after adjusting for multiple testing. We conclude that dietary habits are linked to sperm epigenetic outcomes. If carried into the next generation paternal unhealthy dietary patterns may result in adverse metabolic conditions and increased risk for chronic diseases in offspring.
Authors
Soubry, A; Murphy, SK; Vansant, G; He, Y; Price, TM; Hoyo, C
MLA Citation
Soubry, Adelheid, et al. “Opposing Epigenetic Signatures in Human Sperm by Intake of Fast Food Versus Healthy Food.Front Endocrinol (Lausanne), vol. 12, 2021, p. 625204. Pubmed, doi:10.3389/fendo.2021.625204.
URI
https://scholars.duke.edu/individual/pub1481512
PMID
33967953
Source
pubmed
Published In
Frontiers in Endocrinology
Volume
12
Published Date
Start Page
625204
DOI
10.3389/fendo.2021.625204

Association of Maternal Prenatal Selenium Concentration and Preterm Birth: A Multi-Country Meta-Analysis

Authors
Monangi, N; Xu, H; Khanam, R; Khan, W; Deb, S; Pervin, J; Price, JT; Consortium, I-SS; Al Mahmud, A; Fan, Y-M; Thanh, LQ; Care, A; Landero, JA; Combs, GF; Belling, E; Chappell, J; Kong, F; Lacher, C; Ahmed, S; Chowdhury, NH; Rahman, S; Kabir, F; Dhingra, U; Dutta, A; Ali, SM; Aftab, F; Juma, MH; Rahman, M; Vwalika, B; Musonda, P; Ahmed, T; Islam, MM; Ashorn, U; Maleta, K; Hallman, M; Goodfellow, L; Gupta, JK; Alfirevic, A; Murphy, SK; Rand, L; Ryckman, KK; Murray, JC; Bahl, R; Litch, JA; Baruch-Gravett, C; Alfirevic, Z; Ashorn, P; Baqui, A; Hirst, JE; Hoyo, C; Jehan, F; Jelliffe-Pawlowski, L; Rahman, A; Roth, DE; Sazawal, S; Stringer, J; Zhang, G; Muglia, L
URI
https://scholars.duke.edu/individual/pub1470662
Source
ssrn

Replicated Umbilical Cord Blood DNA Methylation Loci Associated with Gestational Age at Birth

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>DNA methylation is highly sensitive to <jats:italic>in utero</jats:italic> perturbations and has an established role in both embryonic development and regulation of gene expression. The fetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behavior of individual genes.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>The aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for <jats:italic>cis</jats:italic> gene relationships in matched specimens.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450K BeadChip, was associated with GA for 2,372 CpG probes (5% false discovery rate) in both the Pregnancy, Race, Environment, Genes (PREG – Virginia Commonwealth University) and Newborn Epigenetic Study (NEST – Duke University) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. This assessment provides a strong evidence to support the importance of DNAm change throughout the gestational time period.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>These results converge on support for the role of variation in DNAm measures as an important genetic regulatory mechanism contributing to inter-individual differences in gestational age at birth. In particular, the pathways described are consistent with the well-known hypothesis of pathogen detection and response by the immune system to elicit premature labor as a consequence of unscheduled inflammation.</jats:p></jats:sec>
Authors
York, TP; Jackson-Cook, C; Moyer, S; Roberson-Nay, R; Murphy, SK; Fuemmeler, BF; Latendresse, SJ; Lapato, DM; Wolen, AR; Do, EK; Hoyo, C; Strauss, JF
MLA Citation
York, Timothy P., et al. Replicated Umbilical Cord Blood DNA Methylation Loci Associated with Gestational Age at Birth. Cold Spring Harbor Laboratory. Crossref, doi:10.1101/749135.
URI
https://scholars.duke.edu/individual/pub1474492
Source
crossref
DOI
10.1101/749135

Paternal cannabis extract exposure in rats: Preconception timing effects on neurodevelopmental behavior in offspring.

Maternal toxicant exposure during gestation can have deleterious effects on neurobehavioral development of the offspring. The potential risks engendered by paternal toxicant exposure prior to conception have been largely understudied. Recently, we found that chronic THC exposure prior to conception in male rats causes long-lasting behavioral impairment in their offspring. The current study examined the effects of chronic preconception exposure to cannabis smoke extract in Sprague-Dawley rats at two different phases in sperm development. One group received daily subcutaneous (sc) injections of THC in cannabis extract at 4 mg/kg/day for 28 days until three days prior to mating with untreated females (late exposure group). Another group received the same regimen except they underwent 56 days of drug abstinence prior to mating (early exposure group). These were compared with a control group treated with vehicle. The offspring underwent a battery of tests for behavioral function to assess motor, emotional and cognitive function. On the elevated plus maze test, the offspring of both paternal cannabis smoke extract (CSE) exposure groups had significantly more time on the open arms than control offspring, indicative of greater risk-taking behavior. No significant main effects of CSE exposure were seen on adolescent or adult locomotor activity in the figure-8 apparatus. In the novel object recognition test, there was a significantly greater drop-off in novel object preference across the session in the male, but not female offspring of the late exposure group. There was also a sex-selective effect of paternal CSE treatment in the 16-arm radial maze test of memory function. Female offspring of the late exposure group had significantly more working memory errors than control females in the first half of the 12-session training sequence. No significant effects were seen in the operant visual signal sustained detection test of attention. This study shows that there are long-lasting behavioral consequences of preconception CSE exposure through the paternal lineage in rats.
Authors
Holloway, ZR; Hawkey, AB; Torres, AK; Evans, J; Pippen, E; White, H; Katragadda, V; Kenou, B; Wells, C; Murphy, SK; Rezvani, AH; Levin, ED
MLA Citation
Holloway, Zade R., et al. “Paternal cannabis extract exposure in rats: Preconception timing effects on neurodevelopmental behavior in offspring.Neurotoxicology, vol. 81, Dec. 2020, pp. 180–88. Pubmed, doi:10.1016/j.neuro.2020.10.007.
URI
https://scholars.duke.edu/individual/pub1463131
PMID
33091435
Source
pubmed
Published In
Neurotoxicology
Volume
81
Published Date
Start Page
180
End Page
188
DOI
10.1016/j.neuro.2020.10.007

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.

BACKGROUND: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. METHODS: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. RESULTS: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10-7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10-4; adolescence Penrichment = 2.10 × 10-7). CONCLUSIONS: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.
Authors
Vehmeijer, FOL; Küpers, LK; Sharp, GC; Salas, LA; Lent, S; Jima, DD; Tindula, G; Reese, S; Qi, C; Gruzieva, O; Page, C; Rezwan, FI; Melton, PE; Nohr, E; Escaramís, G; Rzehak, P; Heiskala, A; Gong, T; Tuominen, ST; Gao, L; Ross, JP; Starling, AP; Holloway, JW; Yousefi, P; Aasvang, GM; Beilin, LJ; Bergström, A; Binder, E; Chatzi, L; Corpeleijn, E; Czamara, D; Eskenazi, B; Ewart, S; Ferre, N; Grote, V; Gruszfeld, D; Håberg, SE; Hoyo, C; Huen, K; Karlsson, R; Kull, I; Langhendries, J-P; Lepeule, J; Magnus, MC; Maguire, RL; Molloy, PL; Monnereau, C; Mori, TA; Oken, E; Räikkönen, K; Rifas-Shiman, S; Ruiz-Arenas, C; Sebert, S; Ullemar, V; Verduci, E; Vonk, JM; Xu, C-J; Yang, IV; Zhang, H; Zhang, W; Karmaus, W; Dabelea, D; Muhlhausler, BS; Breton, CV; Lahti, J; Almqvist, C; Jarvelin, M-R; Koletzko, B; Vrijheid, M; Sørensen, TIA; Huang, R-C; Arshad, SH; Nystad, W; Melén, E; Koppelman, GH; London, SJ; Holland, N; Bustamante, M; Murphy, SK; Hivert, M-F; Baccarelli, A; Relton, CL; Snieder, H; Jaddoe, VWV; Felix, JF
MLA Citation
Vehmeijer, Florianne O. L., et al. “DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.Genome Med, vol. 12, no. 1, Nov. 2020, p. 105. Pubmed, doi:10.1186/s13073-020-00810-w.
URI
https://scholars.duke.edu/individual/pub1466354
PMID
33239103
Source
pubmed
Published In
Genome Medicine
Volume
12
Published Date
Start Page
105
DOI
10.1186/s13073-020-00810-w

Research Areas:

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