Simon Gregory

Overview:

My principal area of research involves elucidating the molecular mechanisms underlying multi-factorial diseases. My lab is primarily interested identifying the complex genetic factors that give rise to multiple sclerosis (MS) and autism. We are using targeted approaches to identify differential methylation of the oxytocin receptor gene (OXTR) in individuals with autism, and applying these data to an NICHD funded ACE award, SOARS-B, to assess long term use of oxytocin nasal spray to improve social reciprocity in 300 children with autism, and for which we are developing e/genetic and transcriptomic predictors of response and effects of long term drug exposure.

My MS laboratory at Duke University is using cell signaling and immune cell flow sorting to establish the role of IL7R signaling in the development of MS; we are exploring the use of high sensitivity assays to develop a trajectory of disease development in progressive MS; we are exploring the use of endogenous oxysterols to trigger remyelination of white matter injury in MS; and establishing the immune expression and receptor profile of MS patients who do or do not respond to drug treatment.

I am PI of the MURDOCK-MS collection, a cross sectional MS cohort of ~1000 MS patients that will provide the basis for genetic, genomic and metabolomic biomarker identification of MS disease development and progression. I am Director of the Duke Center for Research in Autoimmunity and MS within the Duke Department of Neurology, and also Director of the Molecular Genomics Core at the DMPI in which we are applying a panoply of single cell approaches to basic and translation research.

Positions:

Professor in Neurology

Neurology, MS & Neuroimmunology
School of Medicine

Research Professor in Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Member of Duke Molecular Physiology Institute

Duke Molecular Physiology Institute
School of Medicine

Education:

B.A.Sc. 1990

RMIT University (Australia)

Ph.D. 2003

Open University, Milton Keynes (United Kingdom)

Grants:

High-Resolution CGH Characterization of Brain Tumors

Administered By
Duke Molecular Physiology Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Linkage and candidate gene analysis in non-syndromic Chiari type I

Administered By
Duke Molecular Physiology Institute
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Social Relationship Qualities as Predictors of Health & Aging from Adolescence thru Midlife

Administered By
Psychology and Neuroscience
Role
Co Investigator
Start Date
End Date

Characterizing the (epi)genetics of oxytocin response in clinical and animal models

Administered By
Duke Molecular Physiology Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Specific and Pervasive Symptoms in Adults with Multiple Sclerosis Using the MURDOCK-MS Dataset: A Secondary Analysis

Administered By
School of Nursing
Awarded By
National Institutes of Health
Role
Significant Contributor
Start Date
End Date

Publications:

Author Correction: Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Authors
Baht, GS; Bareja, A; Lee, DE; Rao, RR; Huang, R; Huebner, JL; Bartlett, DB; Hart, CR; Gibson, JR; Lanza, IR; Kraus, VB; Gregory, SG; Spiegelman, BM; White, JP
MLA Citation
Baht, Gurpreet S., et al. “Author Correction: Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.Nat Metab, vol. 2, no. 8, Aug. 2020, p. 794. Pubmed, doi:10.1038/s42255-020-0257-y.
URI
https://scholars.duke.edu/individual/pub1451819
PMID
32694832
Source
pubmed
Published In
Nature Metabolism
Volume
2
Published Date
Start Page
794
DOI
10.1038/s42255-020-0257-y

Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis.

We elucidated the molecular cross-talk between cartilage and synovium in osteoarthritis, the most widespread arthritis in the world, using the powerful tool of single-cell RNA-sequencing. Multiple cell types were identified based on profiling of 10,640 synoviocytes and 26,192 chondrocytes: 12 distinct synovial cell types and 7 distinct articular chondrocyte phenotypes from matched tissues. Intact cartilage was enriched for homeostatic and hypertrophic chondrocytes, while damaged cartilage was enriched for prefibro- and fibro-, regulatory, reparative and prehypertrophic chondrocytes. A total of 61 cytokines and growth factors were predicted to regulate the 7 chondrocyte cell phenotypes. Based on production by > 1% of cells, 55% of the cytokines were produced by synovial cells (39% exclusive to synoviocytes and not expressed by chondrocytes) and their presence in osteoarthritic synovial fluid confirmed. The synoviocytes producing IL-1beta (a classic pathogenic cytokine in osteoarthritis), mainly inflammatory macrophages and dendritic cells, were characterized by co-expression of surface proteins corresponding to HLA-DQA1, HLA-DQA2, OLR1 or TLR2. Strategies to deplete these pathogenic intra-articular cell subpopulations could be a therapeutic option for human osteoarthritis.
Authors
Chou, C-H; Jain, V; Gibson, J; Attarian, DE; Haraden, CA; Yohn, CB; Laberge, R-M; Gregory, S; Kraus, VB
MLA Citation
Chou, Ching-Heng, et al. “Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis.Sci Rep, vol. 10, no. 1, July 2020, p. 10868. Pubmed, doi:10.1038/s41598-020-67730-y.
URI
https://scholars.duke.edu/individual/pub1450701
PMID
32616761
Source
pubmed
Published In
Scientific Reports
Volume
10
Published Date
Start Page
10868
DOI
10.1038/s41598-020-67730-y

Finishing the euchromatic sequence of the human genome.

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers approximately 99% of the euchromatic genome and is accurate to an error rate of approximately 1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human genome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead.
Authors
International Human Genome Sequencing Consortium,
MLA Citation
International Human Genome Sequencing Consortium, Sean D. “Finishing the euchromatic sequence of the human genome.Nature, vol. 431, no. 7011, Oct. 2004, pp. 931–45. Pubmed, doi:10.1038/nature03001.
URI
https://scholars.duke.edu/individual/pub1435768
PMID
15496913
Source
pubmed
Published In
Nature
Volume
431
Published Date
Start Page
931
End Page
945
DOI
10.1038/nature03001

Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements.

Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker of platelet function, in two cohorts following a non-ST elevation acute coronary syndrome (NSTE-ACS) event. First, non-targeted microRNA concentrations and PR were compared in a case (N = 77) control (N = 76) cohort within the larger TRILOGY-ACS trial. MicroRNA significant in this analysis plus CVD-associated microRNAs from the literature were then quantified by targeted rt-PCR in the complete TRILOGY-ACS cohort (N = 878) and compared with matched PR samples. Finally, microRNA significant in the non-targeted & targeted analyses were verified in an independent post NSTE-ACS cohort (N = 96). From the non-targeted analysis, 14 microRNAs were associated with PR (Fold Change: 0.91-1.27, p-value: 0.004-0.05). From the targeted analysis, five microRNAs were associated with PR (Beta: -0.09-0.22, p-value: 0.004-0.05). Of the 19 significant microRNAs, three, miR-15b-5p, miR-93 and miR-126, were consistently associated with PR in the TRILOGY-ACS and independent Singapore post-ACS cohorts, suggesting the measurement of circulating microRNA concentrations may report on dynamic changes in platelet biology following a cardiovascular ischemic event.
Authors
Becker, KC; Kwee, LC; Neely, ML; Grass, E; Jakubowski, JA; Fox, KAA; White, HD; Gregory, SG; Gurbel, PA; Carvalho, LDP; Becker, RC; Magnus Ohman, E; Roe, MT; Shah, SH; Chan, MY
MLA Citation
Becker, Kristian C., et al. “Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements.Sci Rep, vol. 10, no. 1, Apr. 2020, p. 6169. Pubmed, doi:10.1038/s41598-020-63263-6.
URI
https://scholars.duke.edu/individual/pub1436676
PMID
32277149
Source
pubmed
Published In
Scientific Reports
Volume
10
Published Date
Start Page
6169
DOI
10.1038/s41598-020-63263-6

Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.

The immune system plays a multifunctional role throughout the regenerative process, regulating both pro-/anti-inflammatory phases and progenitor cell function. In the present study, we identify the myokine/cytokine Meteorin-like (Metrnl) as a critical regulator of muscle regeneration. Mice genetically lacking Metrnl have impaired muscle regeneration associated with a reduction in immune cell infiltration and an inability to transition towards an anti-inflammatory phenotype. Isochronic parabiosis, joining wild-type and whole-body Metrnl knock-out (KO) mice, returns Metrnl expression in the injured muscle and improves muscle repair, providing supportive evidence for Metrnl secretion from infiltrating immune cells. Macrophage-specific Metrnl KO mice are also deficient in muscle repair. During muscle regeneration, Metrnl works, in part, through Stat3 activation in macrophages, resulting in differentiation to an anti-inflammatory phenotype. With regard to myogenesis, Metrnl induces macrophage-dependent insulin-like growth factor 1 production, which has a direct effect on primary muscle satellite cell proliferation. Perturbations in this pathway inhibit efficacy of Metrnl in the regenerative process. Together, these studies identify Metrnl as an important regulator of muscle regeneration and a potential therapeutic target to enhance tissue repair.
Authors
Baht, GS; Bareja, A; Lee, DE; Rao, RR; Huang, R; Huebner, JL; Bartlett, DB; Hart, CR; Gibson, JR; Lanza, IR; Kraus, VB; Gregory, SG; Spiegelman, BM; White, JP
MLA Citation
Baht, Gurpreet S., et al. “Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.Nat Metab, vol. 2, no. 3, Mar. 2020, pp. 278–89. Pubmed, doi:10.1038/s42255-020-0184-y.
URI
https://scholars.duke.edu/individual/pub1435974
PMID
32694780
Source
pubmed
Published In
Nature Metabolism
Volume
2
Published Date
Start Page
278
End Page
289
DOI
10.1038/s42255-020-0184-y