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Vaishali R Moulton, PH.D., M.D.

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Mentoring
Available: 09/01/18, Expires: 08/31/19

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multifactorial etiopathogenesis that primarily afflicts women in the childbearing years. Hormones especially estrogen are implicated in the pathogenesis of disease, however the precise molecular events regulated by estrogen in immune cells are not well understood. T cells play a key role in SLE pathogenesis and display abnormalities in gene expression and function. We previously identified a novel role for the multifunctional protein serine arginine rich splicing factor 1 (SRSF1) in T cell gene regulation and function. We have shown that SRSF1 promotes IL-2 production in normal T cells, and its overexpression into SLE T cells rescues IL-2 production. SRSF1 expression is decreased in SLE T cells, and associates with severe disease activity. These results suggest that the deficiency of SRSF1 is an important molecular defect in immune-mediated disease. However, not much is known about the regulation of SRSF1 in T cells, and if or how hormones/estrogen may contribute to its expression. The student will be involved in the project to determine mechanisms of transcriptional and post-transcriptional gene regulation of SRSF1 in response to estrogen in human T cells and cell lines. Techniques will involve cell culture, transfections, RT-PCR, western blotting, reporter-luciferase assays and flow cytometry. Prior basic research lab experience is preferred.


Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01AR068974 (MOULTON, VAISHALI) Sep 1, 2016 - Aug 31, 2021
    NIH/NIAMS
    Role of splicing factor SRSF1 in T cell function and autoimmunity
    Role: Principal Investigator
  2. K01AR060781 (MOULTON, VAISHALI) May 1, 2012 - Apr 30, 2017
    NIH/NIAMS
    Role and regulation of the splicing factor ASF/SF2 in human T lymphocyte physiolo
    Role: Principal Investigator
  3. Postdoctoral fellowship award (MOULTON, VAISHALI) Jul 1, 2008 - Jun 30, 2011
    Arthritis Foundation
    Post transcriptional regulation of human T cell receptor zeta chain
    Role: Principal Investigator

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Moulton VR. Sex Hormones in Acquired Immunity and Autoimmune Disease. Front Immunol. 2018; 9:2279. PMID: 30337927.
    View in: PubMed
  2. Li H, Tsokos MG, Bickerton S, Sharabi A, Li Y, Moulton VR, Kong P, Fahmy TM, Tsokos GC. Precision DNA demethylation ameliorates disease in lupus-prone mice. JCI Insight. 2018 Aug 23; 3(16). PMID: 30135300.
    View in: PubMed
  3. Katsuyama E, Yan M, Watanabe KS, Narazaki M, Matsushima S, Yamamura Y, Hiramatsu S, Ohashi K, Watanabe H, Katsuyama T, Zeggar S, Yoshida N, Moulton VR, Tsokos GC, Sada KE, Wada J. Correction: Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells. J Immunol. 2018 Aug 01; 201(3):1104. PMID: 29941662.
    View in: PubMed
  4. Kono M, Kurita T, Yasuda S, Kono M, Fujieda Y, Bohgaki T, Katsuyama T, Tsokos GC, Moulton VR, Atsumi T. Decreased Expression of Serine/Arginine-Rich Splicing Factor 1 in T Cells From Patients With Active Systemic Lupus Erythematosus Accounts for Reduced Expression of RasGRP1 and DNA Methyltransferase 1. Arthritis Rheumatol. 2018 Jun 14. PMID: 29905030.
    View in: PubMed
  5. Katsuyama T, Tsokos GC, Moulton VR. Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus. Front Immunol. 2018; 9:1088. PMID: 29868033.
    View in: PubMed
  6. Suárez-Fueyo A, Bradley SJ, Katsuyama T, Solomon S, Katsuyama E, Kyttaris VC, Moulton VR, Tsokos GC. Downregulation of CD3? in NK Cells from Systemic Lupus Erythematosus Patients Confers a Proinflammatory Phenotype. J Immunol. 2018 May 01; 200(9):3077-3086. PMID: 29602774.
    View in: PubMed
  7. Moulton VR, Suarez-Fueyo A, Meidan E, Li H, Mizui M, Tsokos GC. Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective. Trends Mol Med. 2017 07; 23(7):615-635. PMID: 28623084.
    View in: PubMed
  8. Katsuyama E, Yan M, Watanabe KS, Matsushima S, Yamamura Y, Hiramatsu S, Ohashi K, Watanabe H, Katsuyama T, Zeggar S, Yoshida N, Moulton VR, Tsokos GC, Sada KE, Wada J. Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells. J Immunol. 2017 06 01; 198(11):4268-4276. PMID: 28438897.
    View in: PubMed
  9. Katsuyama E, Yan M, Watanabe KS, Matsushima S, Yamamura Y, Hiramatsu S, Ohashi K, Watanabe H, Katsuyama T, Zeggar S, Yoshida N, Moulton VR, Tsokos GC, Sada K, Wada J. Downregulation of miR-200a-3p, Targeting CtBP2, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus–Derived T Cells. J. Immunol. 2017 10.4049/jimmunol.1601705. 2017.
  10. Moulton VR, Gillooly AR, Perl MA, Markopoulou A, Tsokos GC. Serine Arginine-Rich Splicing Factor 1 (SRSF1) Contributes to the Transcriptional Activation of CD3? in Human T Cells. PLoS One. 2015; 10(7):e0131073. PMID: 26134847; PMCID: PMC4489909.
  11. Moulton VR, Tsokos GC. T cell signaling abnormalities contribute to aberrant immune cell function and autoimmunity. J Clin Invest. 2015 Jun; 125(6):2220-7. PMID: 25961450; PMCID: PMC4497749.
  12. Moulton VR, Gillooly AR, Tsokos GC. Ubiquitination regulates expression of the serine/arginine-rich splicing factor 1 (SRSF1) in normal and systemic lupus erythematosus (SLE) T cells. J Biol Chem. 2014 Feb 14; 289(7):4126-34. PMID: 24368769; PMCID: PMC3924278.
  13. Moulton VR, Grammatikos AP, Fitzgerald LM, Tsokos GC. Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription. Proc Natl Acad Sci U S A. 2013 Jan 29; 110(5):1845-50. PMID: 23319613; PMCID: PMC3562779.
  14. Moulton VR, Holcomb DR, Zajdel MC, Tsokos GC. Estrogen upregulates cyclic AMP response element modulator a expression and downregulates interleukin-2 production by human T lymphocytes. Mol Med. 2012 May 09; 18:370-8. PMID: 22281835.
    View in: PubMed
  15. Moulton VR, Tsokos GC. Why do women get lupus? Clin Immunol. 2012 Jul; 144(1):53-6. PMID: 22659035.
    View in: PubMed
  16. Moulton VR, Lo MS, Tsokos GC. Methods and protocols to study T cell signaling abnormalities in human systemic lupus erythematosus. Methods Mol Biol. 2012; 900:25-60. PMID: 22933064.
    View in: PubMed
  17. Moulton VR, Tsokos GC. Abnormalities of T cell signaling in systemic lupus erythematosus. Arthritis Res Ther. 2011 Mar 17; 13(2):207. PMID: 21457530; PMCID: PMC3132009.
  18. Moulton VR, Tsokos GC. Alternative splicing factor/splicing factor 2 regulates the expression of the zeta subunit of the human T cell receptor-associated CD3 complex. J Biol Chem. 2010 Apr 23; 285(17):12490-6. PMID: 20118245; PMCID: PMC2857141.
  19. Shi T, Moulton VR, Lapchak PH, Deng GM, Dalle Lucca JJ, Tsokos GC. Ischemia-mediated aggregation of the actin cytoskeleton is one of the major initial events resulting in ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 2009 Feb; 296(2):G339-47. PMID: 19095765.
    View in: PubMed
  20. Moulton VR, Kyttaris VC, Juang YT, Chowdhury B, Tsokos GC. The RNA-stabilizing protein HuR regulates the expression of zeta chain of the human T cell receptor-associated CD3 complex. J Biol Chem. 2008 Jul 18; 283(29):20037-44. PMID: 18505733; PMCID: PMC2459291.
  21. Moulton VR, Bushar ND, Leeser DB, Patke DS, Farber DL. Divergent generation of heterogeneous memory CD4 T cells. J Immunol. 2006 Jul 15; 177(2):869-76. PMID: 16818741.
    View in: PubMed
  22. Moulton VR, Farber DL. Committed to memory: lineage choices for activated T cells. Trends Immunol. 2006 Jun; 27(6):261-7. PMID: 16684621.
    View in: PubMed
  23. Bingaman AW, Patke DS, Mane VR, Ahmadzadeh M, Ndejembi M, Bartlett ST, Farber DL. Novel phenotypes and migratory properties distinguish memory CD4 T cell subsets in lymphoid and lung tissue. Eur J Immunol. 2005 Nov; 35(11):3173-86. PMID: 16220537.
    View in: PubMed
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Funded by the NIH/NCATS Clinical and Translational Science Award (CTSA) program, grant number UL1TR001102, and through institutional support from Harvard University, Harvard Medical School, Harvard T.H. Chan School of Public Health, Beth Israel Deaconess Medical Center, Boston Children's Hospital, Brigham and Women's Hospital, Massachusetts General Hospital and the Dana Farber Cancer Institute.