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

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

Genetic and Epigenetic Markers of Progressive Nonalcoholic Fatty Liver Disease

Administered By
Medicine, Gastroenterology
Awarded By
American Association for the Study of Liver Diseases
Role
Mentor
Start Date
End Date

Epigenetics and the Development of Nonalcoholic Fatty Liver Disease

Administered By
Medicine, Gastroenterology
Awarded By
American College of Gastroenterology
Role
Mentor
Start Date
End Date

Publications:

Cell-Type Specific Changes in DNA Methylation of SNCA Intron 1 in Synucleinopathy Brains.

Parkinson's disease (PD) and dementia with Lewy body (DLB) are the most common synucleinopathies. SNCA gene is a major genetic risk factor for these diseases group, and dysregulation of its expression has been implicated in the genetic etiologies of several synucleinopathies. DNA methylation at CpG island (CGI) within SNCA intron 1 has been suggested as a regulatory mechanism of SNCA expression, and changes in methylation levels at this region were associated with PD and DLB. However, the role of DNA methylation in the regulation of SNCA expression in a cell-type specific manner and its contribution to the pathogenesis of PD and DLB remain poorly understood, and the data are conflicting. Here, we employed a bisulfite pyrosequencing technique to profile the DNA methylation across SNCA intron 1 CGI in PD and DLB compared to age- and sex-matched normal control subjects. We analyzed homogenates of bulk post-mortem frozen frontal cortex samples and a subset of neuronal and glia nuclei sorted by the fluorescence-activated nuclei sorting (FANS) method. Bulk brain tissues showed no significant difference in the overall DNA methylation across SNCA intron 1 CGI region between the neuropathological groups. Sorted neuronal nuclei from PD frontal cortex showed significant lower levels of DNA methylation at this region compared to normal controls, but no differences between DLB and control, while sorted glia nuclei exhibited trends of decreased overall DNA methylation in DLB only. In conclusion, our data suggested disease-dependent cell-type specific differential DNA methylation within SNCA intron 1 CGI. These changes may affect SNCA dysregulation that presumably mediates disease-specific risk. Our results can be translated into the development of the SNCA intron 1 CGI region as an attractive therapeutics target for gene therapy in patients who suffer from synucleinopathies due to SNCA dysregulation.
Authors
Gu, J; Barrera, J; Yun, Y; Murphy, SK; Beach, TG; Woltjer, RL; Serrano, GE; Kantor, B; Chiba-Falek, O
MLA Citation
Gu, Jeffrey, et al. “Cell-Type Specific Changes in DNA Methylation of SNCA Intron 1 in Synucleinopathy Brains.Front Neurosci, vol. 15, 2021, p. 652226. Pubmed, doi:10.3389/fnins.2021.652226.
URI
https://scholars.duke.edu/individual/pub1482773
PMID
33994928
Source
pubmed
Published In
Frontiers in Neuroscience
Volume
15
Published Date
Start Page
652226
DOI
10.3389/fnins.2021.652226

Periconceptional Maternal Diet Characterized by High Glycemic Loading Is Associated with Offspring Behavior in NEST.

Maternal periconceptional diets have known associations with proper offspring neurodevelopment. Mechanisms for such associations include improper energy/nutrient balances between mother and fetus, as well as altered offspring epigenetics during development due to maternal nutrient and inflammatory status. Using a comprehensive food frequency questionnaire and assessing offspring temperament with the Infant-Toddler Social and Emotional Assessment (n = 325, mean age = 13.9 months), we sought to test whether a maternal periconceptional diet characterized by high glycemic loading (MGL) would affect offspring temperament using adjusted ordinal regression. After limiting false discovery to 10%, offspring born to mothers in tertile 3 of glycemic loading (referent = tertile 1) were more likely to be in the next tertile of anxiety [OR (95% CI) = 4.51 (1.88-11.07)] and inhibition-related behaviors [OR (95% CI) = 3.42 (1.49-7.96)]. Male offspring were more likely to exhibit impulsive [OR (95% CI) = 5.55 (1.76-18.33)], anxiety [OR (95% CI) = 4.41 (1.33-15.30)], sleep dysregulation [OR (95% CI) = 4.14 (1.34-13.16)], empathy [6.68 (1.95-24.40)], and maladaptive behaviors [OR (95% CI) = 9.86 (2.81-37.18)], while females were more likely to exhibit increased anxiety-related behaviors [OR (95% CI) = 15.02 (3.14-84.27)]. These associations persisted when concurrently modeled with the maternal-Mediterranean dietary pattern. In a subset (n = 142), we also found MGL associated with increased mean methylation of the imprint control region of SGCE/PEG10. In conclusion, these findings highlight the importance of maternal dietary patterns on offspring neurodevelopment, offering avenues for prevention options for mothers.
Authors
Alick, CL; Maguire, RL; Murphy, SK; Fuemmeler, BF; Hoyo, C; House, JS
MLA Citation
Alick, Candice L., et al. “Periconceptional Maternal Diet Characterized by High Glycemic Loading Is Associated with Offspring Behavior in NEST.Nutrients, vol. 13, no. 9, Sept. 2021. Pubmed, doi:10.3390/nu13093180.
URI
https://scholars.duke.edu/individual/pub1497116
PMID
34579057
Source
pubmed
Published In
Nutrients
Volume
13
Published Date
DOI
10.3390/nu13093180

Direct comparisons of bisulfite pyrosequencing versus targeted bisulfite sequencing.

DNA methylation is an important epigenetic mechanism involved in proper genome function. Bisulfite pyrosequencing (PSQ) is a commonly used technique to quantify DNA methylation. Although very accurate, bisulfite pyrosequencing can be expensive and time consuming for large-scale quantitative DNA methylation analysis at the single nucleotide level. High throughput DNA methylation sequencing has the potential to address these limitations, but its comparability to other methylation detection methods has not been well studied. We compared QIAseq Targeted Methyl Panel technologies (QMS) and PSQ by analyzing four CpG sites within four genes involved in neurodevelopment. QMS and PSQ had an average 5.6% difference in the detected level of DNA methylation for the same four CpG sites. However, we observed a strong correlation in the levels of methylation across all four CpG sites between the two technologies. These findings demonstrate the comparability of QMS relative to PSQ in the ability to accurately quantify DNA methylation at specific CpG sites.
Authors
King, DE; Sparling, AC; Joglekar, R; Meyer, JN; Murphy, SK
MLA Citation
King, Dillon E., et al. “Direct comparisons of bisulfite pyrosequencing versus targeted bisulfite sequencing.Micropubl Biol, vol. 2021, 2021. Pubmed, doi:10.17912/micropub.biology.000444.
URI
https://scholars.duke.edu/individual/pub1494695
PMID
34423283
Source
pubmed
Published In
Micropublication Biology
Volume
2021
Published Date
DOI
10.17912/micropub.biology.000444

Corrigendum to "Paternal cannabis extract exposure in rats: Preconception timing effects on neurobehavioral effects in offspring" [Neurotoxicology 81 (2020) 180-188].

Authors
Holloway, Z; Hawkey, AB; Pippen, E; White, H; Katragadda, V; Kenou, B; Wells, C; Murphy, SK; Rezvani, AH; Levin, ED
MLA Citation
URI
https://scholars.duke.edu/individual/pub1496003
PMID
34483001
Source
pubmed
Published In
Neurotoxicology
Published Date
DOI
10.1016/j.neuro.2021.08.009

Refraining from use diminishes cannabis-associated epigenetic changes in human sperm.

Cannabis use alters sperm DNA methylation, but the potential reversibility of these changes is unknown. Semen samples from cannabis users and non-user controls were collected at baseline and again following a 77-day period of cannabis abstinence (one spermatogenic cycle). Users and controls did not significantly differ by demographics or semen analyses. Whole-genome bisulfite sequencing identified 163 CpG sites with significantly different DNA methylation in sperm between groups (P < 2.94 × 10-9). Genes associated with altered CpG sites were enriched with those involved in development, including cardiogenesis and neurodevelopment. Many of the differences in sperm DNA methylation between groups were diminished after cannabis abstinence. These results indicate that sustained cannabis abstinence significantly reduces the number of sperm showing cannabis-associated alterations at genes important for early development.
Authors
Schrott, R; Murphy, SK; Modliszewski, JL; King, DE; Hill, B; Itchon-Ramos, N; Raburn, D; Price, T; Levin, ED; Vandrey, R; Corcoran, DL; Kollins, SH; Mitchell, JT
MLA Citation
Schrott, Rose, et al. “Refraining from use diminishes cannabis-associated epigenetic changes in human sperm.Environ Epigenet, vol. 7, no. 1, 2021, p. dvab009. Pubmed, doi:10.1093/eep/dvab009.
URI
https://scholars.duke.edu/individual/pub1497117
PMID
34557312
Source
pubmed
Published In
Environmental Epigenetics
Volume
7
Published Date
Start Page
dvab009
DOI
10.1093/eep/dvab009

Research Areas:

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