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 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:

Epigenetic alterations in cytochrome P450 oxidoreductase (Por) in sperm of rats exposed to tetrahydrocannabinol (THC).

As marijuana legalization is increasing, research regarding possible long-term risks for users and their offspring is needed. Little data exists on effects of paternal tetrahydrocannabinol (THC) exposure prior to reproduction. This study determined if chronic THC exposure alters sperm DNA methylation (DNAm) and if such effects are intergenerationally transmitted. Adult male rats underwent oral gavage with THC or vehicle control. Differentially methylated (DM) loci in motile sperm were identified using reduced representation bisulfite sequencing (RRBS). Another cohort was injected with vehicle or THC, and sperm DNAm was analyzed. Finally, THC-exposed and control adult male rats were mated with THC-naïve females. DNAm levels of target genes in brain tissues of the offspring were determined by pyrosequencing. RRBS identified 2,940 DM CpGs mapping to 627 genes. Significant hypermethylation was confirmed (p < 0.05) following oral THC administration for cytochrome P450 oxidoreductase (Por), involved in toxin processing and disorders of sexual development. Por hypermethylation was not observed after THC injection or in the subsequent generation. These results support that THC alters DNAm in sperm and that route of exposure can have differential effects. Although we did not observe evidence of intergenerational transmission of the DNAm change, larger studies are required to definitively exclude this possibility.
Authors
Acharya, KS; Schrott, R; Grenier, C; Huang, Z; Holloway, Z; Hawkey, A; Levin, ED; Murphy, SK
MLA Citation
Acharya, Kelly S., et al. “Epigenetic alterations in cytochrome P450 oxidoreductase (Por) in sperm of rats exposed to tetrahydrocannabinol (THC).Sci Rep, vol. 10, no. 1, July 2020, p. 12251. Pubmed, doi:10.1038/s41598-020-69204-7.
URI
https://scholars.duke.edu/individual/pub1452644
PMID
32704063
Source
pubmed
Published In
Scientific Reports
Volume
10
Published Date
Start Page
12251
DOI
10.1038/s41598-020-69204-7

Cannabis use and the sperm epigenome: a budding concern?

The United States is swiftly moving toward increased legalization of medical and recreational cannabis. Currently considered the most commonly used illicit psychoactive drug, recreational cannabis is legal in 11 states and Washington, DC, and male use is an important and understudied concern. Questions remain, however, about the potential long-term consequences of this exposure and how cannabis might impact the epigenetic integrity of sperm in such a way that could influence the health and development of offspring. This review summarizes cannabis use and potency in the USA, provides a brief overview of DNA methylation as an epigenetic mechanism that is vulnerable in sperm to environmental exposures including cannabis, and summarizes studies that have examined the effects of parental exposure to cannabis or delta-9 tetrahydrocannabinol (THC, the main psychoactive component of cannabis) on the epigenetic profile of the gametes and behavior of offspring. These studies have demonstrated significant changes to the sperm DNA methylome following cannabis use in humans, and THC exposure in rats. Furthermore, the use of rodent models has shown methylation and behavioral changes in rats born to fathers exposed to THC or synthetic cannabinoids, or to parents who were both exposed to THC. These data substantiate an urgent need for additional studies assessing the effects of cannabis exposure on childhood health and development. This is especially true given the current growing state of cannabis use in the USA.
Authors
Schrott, R; Murphy, SK
MLA Citation
Schrott, Rose, and Susan K. Murphy. “Cannabis use and the sperm epigenome: a budding concern?Environ Epigenet, vol. 6, no. 1, Jan. 2020, p. dvaa002. Pubmed, doi:10.1093/eep/dvaa002.
URI
https://scholars.duke.edu/individual/pub1435846
PMID
32211199
Source
pubmed
Published In
Environmental Epigenetics
Volume
6
Published Date
Start Page
dvaa002
DOI
10.1093/eep/dvaa002

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

© The Author(s) 2019. Published by Oxford University Press. Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science.
Authors
Brown, P; Zhou, Y; Tan, AC; El-Esawi, MA; Liehr, T; Blanck, O; Gladue, DP; Almeida, GMF; Cernava, T; Sorzano, CO; Yeung, AWK; Engel, MS; Chandrasekaran, AR; Muth, T; Staege, MS; Daulatabad, SV; Widera, D; Zhang, J; Meule, A; Honjo, K; Pourret, O; Yin, CC; Zhang, Z; Cascella, M; Flegel, WA; Goodyear, CS; van Raaij, MJ; Bukowy-Bieryllo, Z; Campana, LG; Kurniawan, NA; Lalaouna, D; Hüttner, FJ; Ammerman, BA; Ehret, F; Cobine, PA; Tan, EC; Han, H; Xia, W; McCrum, C; Dings, RPM; Marinello, F; Nilsson, H; Nixon, B; Voskarides, K; Yang, L; Costa, VD; Bengtsson-Palme, J; Bradshaw, W; Grimm, DG; Kumar, N; Martis, E; Prieto, D; Sabnis, SC; Amer, SEDR; Liew, AWC; Perco, P; Rahimi, F; Riva, G; Zhang, C; Devkota, HP; Ogami, K; Basharat, Z; Fierz, W; Siebers, R; Tan, KH; Boehme, KA; Brenneisen, P; Brown, JAL; Dalrymple, BP; Harvey, DJ; Ng, G; Werten, S; Bleackley, M; Dai, Z; Dhariwal, R; Gelfer, Y; Hartmann, MD; Miotla, P; Tamaian, R; Govender, P; Gurney-Champion, OJ; Kauppila, JH; Zhang, X; Echeverría, N; Subhash, S; Sallmon, H; Tofani, M; Bae, T; Bosch, O; Cuív, PO; Danchin, A; Diouf, B; Eerola, T; Evangelou, E; Filipp, F; Klump, H; Kurgan, L; Smith, SS; Terrier, O; Tuttle, N
MLA Citation
Brown, P., et al. “Large expert-curated database for benchmarking document similarity detection in biomedical literature search.” Database, vol. 2019, Jan. 2019, pp. 1–67. Scopus, doi:10.1093/database/baz085.
URI
https://scholars.duke.edu/individual/pub1421171
Source
scopus
Published In
Database : the Journal of Biological Databases and Curation
Volume
2019
Published Date
Start Page
1
End Page
67
DOI
10.1093/database/baz085

S100A4 deficiency-induced aberrant gene expression during lens differentiation is epigenetically regulated through altered Histone 3 lysine methylation marking

Authors
Maddala, R; Murphy, SK; Rao, V
MLA Citation
Maddala, Rupalatha, et al. “S100A4 deficiency-induced aberrant gene expression during lens differentiation is epigenetically regulated through altered Histone 3 lysine methylation marking.” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.
URI
https://scholars.duke.edu/individual/pub1418694
Source
wos
Published In
Investigative Ophthalmology & Visual Science
Volume
60
Published Date

Associations between attention deficit hyperactivity disorder symptoms and eating behaviors in early childhood.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms have been linked with eating behaviors and obesity adolescence and young adulthood. Yet, little is known about whether these associations occur during early childhood and few studies have examined these associations prospectively. OBJECTIVES: To assess magnitude and direction of associations between childhood ADHD symptoms and eating behaviors. METHODS: Participants were from the Newborn Epigenetics Study (N = 470, M age = 4 years). Multivariable linear regression models were used to examine cross-sectional associations between ADHD symptoms and eating behaviors. Latent Change Score (LCS) modeling was performed to examine prospective association among a subset of children with available follow-up data. (N = 100, M age = 7 years). RESULTS: The cross-sectional results showed that attention problem (AP) and hyperactivity (HY) were positively associated with food responsiveness, emotional overeating, desire to drink, and slowness in eating. AP, but not HY, was inversely associated with enjoyment of food. Results of the LCS models revealed AP and HY were both positively associated with prospective changes in emotional overeating and satiety responsiveness. AP was further positively associated with prospective changes in food responsiveness. The reverse relationship predicting changes in ADHD symptoms from earlier assessments of eating behaviors was not significant. CONCLUSION: Results suggest a link between ADHD symptoms and obesity-related eating behaviors in early childhood, highlighting the need to address self-regulation and healthy eating behaviors in the prevention of childhood obesity.
Authors
Fuemmeler, BF; Sheng, Y; Schechter, JC; Do, E; Zucker, N; Majors, A; Maguire, R; Murphy, SK; Hoyo, C; Kollins, SH
MLA Citation
Fuemmeler, Bernard F., et al. “Associations between attention deficit hyperactivity disorder symptoms and eating behaviors in early childhood.Pediatr Obes, vol. 15, no. 7, July 2020, p. e12631. Pubmed, doi:10.1111/ijpo.12631.
URI
https://scholars.duke.edu/individual/pub1434076
PMID
32119190
Source
pubmed
Published In
Pediatr Obes
Volume
15
Published Date
Start Page
e12631
DOI
10.1111/ijpo.12631

Research Areas:

Cancer
DNA Methylation
Epigenetics
Genomic Imprinting