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:

PRE-TEENS EXPOSED PRENATALLY TO MATERNAL OBESITY EXHIBIT PERSISTENT DNA METHYLATION CHANGES THAT ASSOCIATE WITH METABOLIC ABNORMALITIES, INCLUDING HIGH LIVER FAT

Authors
Moylan, CA; Jima, D; Mavis, A; Diehl, AM; Bashir, M; Hyun, J; Du, K; Abdelmalek, MF; Murphy, SK; Hoyo, C
URI
https://scholars.duke.edu/individual/pub1559938
Source
wos-lite
Published In
Hepatology (Baltimore, Md.)
Volume
76
Published Date
Start Page
S1522
End Page
S1523

AHRR METHYLATION MEDIATES THE EFFECTS OF MATERNAL SMOKING ON LIVER FAT CONTENT AND METABOLIC HEALTH IN CHILDREN

Authors
Chandramouli, SA; Brown, N; Wang, Y; Vidal, A; Marchesoni, J; Abdelmalek, MF; Mavis, A; Jima, D; Murphy, SK; Hoyo, C; Moylan, CA
MLA Citation
Chandramouli, Shivram Ayyappan, et al. “AHRR METHYLATION MEDIATES THE EFFECTS OF MATERNAL SMOKING ON LIVER FAT CONTENT AND METABOLIC HEALTH IN CHILDREN.” Hepatology, vol. 76, 2022, pp. S1531–32.
URI
https://scholars.duke.edu/individual/pub1560038
Source
wos-lite
Published In
Hepatology (Baltimore, Md.)
Volume
76
Published Date
Start Page
S1531
End Page
S1532

Maternal exposure to perfluorobutane sulfonate (PFBS) during pregnancy: evidence of adverse maternal and fetoplacental effects in New Zealand White (NZW) rabbits.

Perfluorobutanesulfonic acid (PFBS) is a replacement for perfluorooctanesulfonic acid (PFOS) that is increasingly detected in drinking water and human serum. Higher PFBS exposure is associated with risk for preeclampsia, the leading cause of maternal and infant morbidity and mortality in the United States. This study investigated relevant maternal and fetal health outcomes after gestational exposure to PFBS in a New Zealand White rabbit model. Nulliparous female rabbits were supplied drinking water containing 0 mg/L (control), 10mg/L (low) or 100mg/L (high) PFBS. Maternal blood pressure, body weights, liver and kidney weights and histopathology, clinical chemistry panels, and thyroid hormone levels were evaluated. Fetal endpoints evaluated at necropsy included viability, body weights, crown rump length, and liver and kidney histopathology, while placenta endpoints included weight, morphology, histopathology, and full transcriptome RNA sequencing. PFBS-high dose dams exhibited significant changes in blood pressure markers, seen through increased pulse pressure and renal resistive index measures, as well as kidney histopathological changes. Fetuses from these dams showed decreased crown-rump length. Statistical analysis of placental weight via a mixed model statistical approach identified a significant interaction term between PFBS high dose and fetal sex, suggesting a sex-specific effect on placental weight. RNA sequencing identified the dysregulation of angiotensin (AGT) in PFBS high dose placentas. These results suggest that PFBS exposure during gestation leads to adverse maternal outcomes, such as renal injury and hypertension, and fetal outcomes, including decreased growth parameters and adverse placenta function. These outcomes raise concerns about pregnant women's exposure to PFBS and pregnancy outcomes.
Authors
Crute, CE; Landon, CD; Garner, A; Hall, SM; Everitt, JI; Zhang, S; Blake, B; Olofsson, D; Chen, H; Stapleton, HM; Murphy, SK; Feng, L
MLA Citation
URI
https://scholars.duke.edu/individual/pub1558814
PMID
36453863
Source
pubmed
Published In
Toxicological Sciences
Published Date
DOI
10.1093/toxsci/kfac126

Maternal diet disrupts the placenta-brain axis in a sex-specific manner.

High maternal weight is associated with detrimental outcomes in offspring, including increased susceptibility to neurological disorders such as anxiety, depression and communicative disorders. Despite widespread acknowledgement of sex biases in the development of these disorders, few studies have investigated potential sex-biased mechanisms underlying disorder susceptibility. Here, we show that a maternal high-fat diet causes endotoxin accumulation in fetal tissue, and subsequent perinatal inflammation contributes to sex-specific behavioural outcomes in offspring. In male offspring exposed to a maternal high-fat diet, increased macrophage Toll-like receptor 4 signalling results in excess microglial phagocytosis of serotonin (5-HT) neurons in the developing dorsal raphe nucleus, decreasing 5-HT bioavailability in the fetal and adult brains. Bulk sequencing from a large cohort of matched first-trimester human samples reveals sex-specific transcriptome-wide changes in placental and brain tissue in response to maternal triglyceride accumulation (a proxy for dietary fat content). Further, fetal brain 5-HT levels decrease as placental triglycerides increase in male mice and male human samples. These findings uncover a microglia-dependent mechanism through which maternal diet can impact offspring susceptibility for neuropsychiatric disorder development in a sex-specific manner.
Authors
Ceasrine, AM; Devlin, BA; Bolton, JL; Green, LA; Jo, YC; Huynh, C; Patrick, B; Washington, K; Sanchez, CL; Joo, F; Campos-Salazar, AB; Lockshin, ER; Kuhn, C; Murphy, SK; Simmons, LA; Bilbo, SD
MLA Citation
Ceasrine, Alexis M., et al. “Maternal diet disrupts the placenta-brain axis in a sex-specific manner.Nat Metab, vol. 4, no. 12, Dec. 2022, pp. 1732–45. Pubmed, doi:10.1038/s42255-022-00693-8.
URI
https://scholars.duke.edu/individual/pub1557328
PMID
36443520
Source
pubmed
Published In
Nature Metabolism
Volume
4
Published Date
Start Page
1732
End Page
1745
DOI
10.1038/s42255-022-00693-8

Paternal factors in neurodevelopmental toxicology: THC exposure of male rats causes long-lasting neurobehavioral effects in their offspring.

The potential health risks of cannabis are of growing concern, including effects on reproduction and development. Extensive research has investigated risks associated with maternal exposure to THC during gestation and its impacts on the development of offspring, but little research has been done regarding paternal THC exposure effects prior to conception. We have previously found that paternal THC exposure in rats causes changes in sperm methylation. In an initial study we also showed that a 12-day paternal THC exposure prior to conception alters locomotor activity and impairs cognitive function of their offspring. This study investigated the cross-generational effects of chronic paternal THC exposure in rats (0, 2, or 4 mg/kg/day SC for 28 days) prior to mating with drug naïve females. The offspring of THC-exposed male rats had significant alterations in locomotor activity and cognitive function. Specifically, during adolescence there was significant locomotor hyperactivity in the offspring of males exposed to 2 mg/kg/day of THC. During the novel object recognition task, the controls maintained their relative preference for the novel object across the duration of the ten-min session while the rats whose fathers received THC (2 mg/kg/day) showed a significantly greater drop-off in interest in the novel object during the second half of the session. Learning in the radial-arm maze was significantly delayed in the offspring of males exposed to 4 mg/kg/day of THC. This study shows that premating chronic paternal THC exposure at multiple dose regimens can cause long-lasting detrimental behavioral effects in their offspring, including abnormal locomotor activity and impaired cognitive function. Future studies should investigate the underlying mechanisms driving these aberrant developmental outcomes and seek to identify possible treatments of alleviation in the presence of paternal THC exposure.
Authors
Holloway, ZR; Hawkey, AB; Pippin, E; White, H; Wells, C; Kenou, B; Rezvani, AH; Murphy, SK; Levin, ED
MLA Citation
Holloway, Zade R., et al. “Paternal factors in neurodevelopmental toxicology: THC exposure of male rats causes long-lasting neurobehavioral effects in their offspring.Neurotoxicology, vol. 78, May 2020, pp. 57–63. Pubmed, doi:10.1016/j.neuro.2020.01.009.
URI
https://scholars.duke.edu/individual/pub1432126
PMID
32045580
Source
pubmed
Published In
Neurotoxicology
Volume
78
Published Date
Start Page
57
End Page
63
DOI
10.1016/j.neuro.2020.01.009

Research Areas:

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