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Last Name

profileNicolas Da Silva, Ph.D.

TitleAssistant Professor of Medicine
InstitutionMassachusetts General Hospital
AddressMassachusetts General Hospital, CPZN 8218
Systems Biology / Nephrology / Membrane Biology
185 Cambridge St
Boston MA 02114
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When sperm leave the testis, they are not motile and they do no have the ability to interact with the oocyte. Sperm acquire these abilities during their passage through the epididymis, which is a long, narrow and convoluted tube located between the testis and the vas deferens. The epididymis is the primary site of sperm maturation and storage. Sperm maturation involves a sequence of finely tuned molecular and cellular events that remain relatively understudied, despite their critical importance in the establishment and maintenance of male fertility.

Fertility is a reflection of the overall health of an individual and can be influenced by most organ systems, in addition to the heavy impact of environmental and lifestyle factors. Our laboratory specifically focuses on the role of the immune system in the post-testicular environment. We have found that a dense and heterogeneous network of mononuclear phagocytes (dendritic cells and macrophages) populates the epididymis. These specialized immune cells are considered to be the sentinels and the scavengers of the immune system. While mononuclear phagocytes are widely studied in other mucosal systems, their functions in the reproductive tract are largely unknown. Using mouse models and state-of-the-art technologies available at CSB, we aim to provide a better understanding of the interplay between the immune system and the reproductive tract.

In the US, 1 in every 10 couples is unable to conceive a child and breaches in the immune system are heavily implicated. Advances in male reproductive immunology will, ultimately, help to better understand and treat male infertility.

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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.
R01HD069623     (DA SILVA, NICOLAS)Aug 12, 2011 - May 31, 2021
Role of epididymal macrophages and dendritic cells in male reproductive function
Role: Principal Investigator

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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. Hulsmans M, Clauss S, Xiao L, Aguirre AD, King KR, Hanley A, Hucker WJ, Wülfers EM, Seemann G, Courties G, Iwamoto Y, Sun Y, Savol AJ, Sager HB, Lavine KJ, Fishbein GA, Capen DE, Da Silva N, Miquerol L, Wakimoto H, Seidman CE, Seidman JG, Sadreyev RI, Naxerova K, Mitchell RN, Brown D, Libby P, Weissleder R, Swirski FK, Kohl P, Vinegoni C, Milan DJ, Ellinor PT, Nahrendorf M. Macrophages Facilitate Electrical Conduction in the Heart. Cell. 2017 Apr 20; 169(3):510-522.e20. PMID: 28431249.
    View in: PubMed
  2. Da Silva N, Barton CR. Macrophages and dendritic cells in the post-testicular environment. Cell Tissue Res. 2016 Jan; 363(1):97-104. PMID: 26337514; PMCID: PMC4703462 [Available on 01/01/17].
  3. Da Silva N, Smith TB. Exploring the role of mononuclear phagocytes in the epididymis. Asian J Androl. 2015 Jul-Aug; 17(4):591-6. PMID: 25966624; PMCID: PMC4492049.
  4. Dutta P, Hoyer FF, Grigoryeva LS, Sager HB, Leuschner F, Courties G, Borodovsky A, Novobrantseva T, Ruda VM, Fitzgerald K, Iwamoto Y, Wojtkiewicz G, Sun Y, Da Silva N, Libby P, Anderson DG, Swirski FK, Weissleder R, Nahrendorf M. Macrophages retain hematopoietic stem cells in the spleen via VCAM-1. J Exp Med. 2015 Apr 06; 212(4):497-512. PMID: 25800955; PMCID: PMC4387283.
  5. Kim B, Roy J, Shum WW, Da Silva N, Breton S. Role of testicular luminal factors on Basal cell elongation and proliferation in the mouse epididymis. Biol Reprod. 2015 Jan; 92(1):9. PMID: 25411392; PMCID: PMC4434934.
  6. Ruan YC, Wang Y, Da Silva N, Kim B, Diao RY, Hill E, Brown D, Chan HC, Breton S. CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation through the ZONAB pathway. J Cell Sci. 2014 Oct 15; 127(Pt 20):4396-408. PMID: 25107366; PMCID: PMC4197086.
  7. Smith TB, Cortez-Retamozo V, Grigoryeva LS, Hill E, Pittet MJ, Da Silva N. Mononuclear phagocytes rapidly clear apoptotic epithelial cells in the proximal epididymis. Andrology. 2014 Sep; 2(5):755-62. PMID: 25082073; PMCID: PMC4396827.
  8. Shum WW, Smith TB, Cortez-Retamozo V, Grigoryeva LS, Roy JW, Hill E, Pittet MJ, Breton S, Da Silva N. Epithelial basal cells are distinct from dendritic cells and macrophages in the mouse epididymis. Biol Reprod. 2014 May; 90(5):90. PMID: 24648397; PMCID: PMC4076373.
  9. Heidt T, Courties G, Dutta P, Sager HB, Sebas M, Iwamoto Y, Sun Y, Da Silva N, Panizzi P, van der Laan AM, van der Lahn AM, Swirski FK, Weissleder R, Nahrendorf M. Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction. Circ Res. 2014 Jul 07; 115(2):284-95. PMID: 24786973; PMCID: PMC4082439.
  10. Ruan YC, Shum WW, Belleannée C, Da Silva N, Breton S. ATP secretion in the male reproductive tract: essential role of CFTR. J Physiol. 2012 Sep 01; 590(17):4209-22. PMID: 22711960; PMCID: PMC3473280.
  11. Shum WW, Ruan YC, Da Silva N, Breton S. Establishment of cell-cell cross talk in the epididymis: control of luminal acidification. J Androl. 2011 Nov-Dec; 32(6):576-86. PMID: 21441423; PMCID: PMC3753098.
  12. Shum WW, Da Silva N, Belleannée C, McKee M, Brown D, Breton S. Regulation of V-ATPase recycling via a RhoA- and ROCKII-dependent pathway in epididymal clear cells. Am J Physiol Cell Physiol. 2011 Jul; 301(1):C31-43. PMID: 21411727; PMCID: PMC3129830.
  13. Da Silva N, Cortez-Retamozo V, Reinecker HC, Wildgruber M, Hill E, Brown D, Swirski FK, Pittet MJ, Breton S. A dense network of dendritic cells populates the murine epididymis. Reproduction. 2011 May; 141(5):653-63. PMID: 21310816; PMCID: PMC3657760.
  14. Bouley R, Lu HA, Nunes P, Da Silva N, McLaughlin M, Chen Y, Brown D. Calcitonin has a vasopressin-like effect on aquaporin-2 trafficking and urinary concentration. J Am Soc Nephrol. 2011 Jan; 22(1):59-72. PMID: 21071524; PMCID: PMC3014035.
  15. Miranda KC, Bond DT, McKee M, Skog J, Paunescu TG, Da Silva N, Brown D, Russo LM. Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease. Kidney Int. 2010 Jul; 78(2):191-9. PMID: 20428099; PMCID: PMC4451567.
  16. Da Silva N, Pisitkun T, Belleannée C, Miller LR, Nelson R, Knepper MA, Brown D, Breton S. Proteomic analysis of V-ATPase-rich cells harvested from the kidney and epididymis by fluorescence-activated cell sorting. Am J Physiol Cell Physiol. 2010 Jun; 298(6):C1326-42. PMID: 20181927; PMCID: PMC2889637.
  17. Xia Y, Babitt JL, Bouley R, Zhang Y, Da Silva N, Chen S, Zhuang Z, Samad TA, Brenner GJ, Anderson JL, Hong CC, Schneyer AL, Brown D, Lin HY. Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells. J Am Soc Nephrol. 2010 Apr; 21(4):666-77. PMID: 20167703; PMCID: PMC2844302.
  18. Belleannée C, Da Silva N, Shum WW, Brown D, Breton S. Role of purinergic signaling pathways in V-ATPase recruitment to apical membrane of acidifying epididymal clear cells. Am J Physiol Cell Physiol. 2010 Apr; 298(4):C817-30. PMID: 20071692; PMCID: PMC2853219.
  19. Shum WW, Da Silva N, Brown D, Breton S. Regulation of luminal acidification in the male reproductive tract via cell-cell crosstalk. J Exp Biol. 2009 Jun; 212(Pt 11):1753-61. PMID: 19448084; PMCID: PMC2683015.
  20. Shum WW, Da Silva N, McKee M, Smith PJ, Brown D, Breton S. Transepithelial projections from basal cells are luminal sensors in pseudostratified epithelia. Cell. 2008 Dec 12; 135(6):1108-17. PMID: 19070580; PMCID: PMC2646085.
  21. Belleannée C, Da Silva N, Shum WW, Marsolais M, Laprade R, Brown D, Breton S. Segmental expression of the bradykinin type 2 receptor in rat efferent ducts and epididymis and its role in the regulation of aquaporin 9. Biol Reprod. 2009 Jan; 80(1):134-43. PMID: 18829705; PMCID: PMC2804812.
  22. Pietrement C, Da Silva N, Silberstein C, James M, Marsolais M, Van Hoek A, Brown D, Pastor-Soler N, Ameen N, Laprade R, Ramesh V, Breton S. Role of NHERF1, cystic fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9. J Biol Chem. 2008 Feb 01; 283(5):2986-96. PMID: 18055461.
    View in: PubMed
  23. Paunescu TG, Da Silva N, Russo LM, McKee M, Lu HA, Breton S, Brown D. Association of soluble adenylyl cyclase with the V-ATPase in renal epithelial cells. Am J Physiol Renal Physiol. 2008 Jan; 294(1):F130-8. PMID: 17959750.
    View in: PubMed
  24. Paunescu TG, Russo LM, Da Silva N, Kovacikova J, Mohebbi N, Van Hoek AN, McKee M, Wagner CA, Breton S, Brown D. Compensatory membrane expression of the V-ATPase B2 subunit isoform in renal medullary intercalated cells of B1-deficient mice. Am J Physiol Renal Physiol. 2007 Dec; 293(6):F1915-26. PMID: 17898041.
    View in: PubMed
  25. Da Silva N, Shum WW, Breton S. Regulation of vacuolar proton pumping ATPase-dependent luminal acidification in the epididymis. Asian J Androl. 2007 Jul; 9(4):476-82. PMID: 17589784.
    View in: PubMed
  26. Da Silva N, Shum WW, El-Annan J, Paunescu TG, McKee M, Smith PJ, Brown D, Breton S. Relocalization of the V-ATPase B2 subunit to the apical membrane of epididymal clear cells of mice deficient in the B1 subunit. Am J Physiol Cell Physiol. 2007 Jul; 293(1):C199-210. PMID: 17392376.
    View in: PubMed
  27. Da Silva N, Piétrement C, Brown D, Breton S. Segmental and cellular expression of aquaporins in the male excurrent duct. Biochim Biophys Acta. 2006 Aug; 1758(8):1025-33. PMID: 16935257.
    View in: PubMed
  28. Da Silva N, Silberstein C, Beaulieu V, Piétrement C, Van Hoek AN, Brown D, Breton S. Postnatal expression of aquaporins in epithelial cells of the rat epididymis. Biol Reprod. 2006 Feb; 74(2):427-38. PMID: 16221990.
    View in: PubMed
  29. Pietrement C, Sun-Wada GH, Silva ND, McKee M, Marshansky V, Brown D, Futai M, Breton S. Distinct expression patterns of different subunit isoforms of the V-ATPase in the rat epididymis. Biol Reprod. 2006 Jan; 74(1):185-94. PMID: 16192400.
    View in: PubMed
  30. Beaulieu V, Da Silva N, Pastor-Soler N, Brown CR, Smith PJ, Brown D, Breton S. Modulation of the actin cytoskeleton via gelsolin regulates vacuolar H+-ATPase recycling. J Biol Chem. 2005 Mar 04; 280(9):8452-63. PMID: 15591047.
    View in: PubMed
  31. Paunescu TG, Da Silva N, Marshansky V, McKee M, Breton S, Brown D. Expression of the 56-kDa B2 subunit isoform of the vacuolar H(+)-ATPase in proton-secreting cells of the kidney and epididymis. Am J Physiol Cell Physiol. 2004 Jul; 287(1):C149-62. PMID: 15013950.
    View in: PubMed
  32. Pastor-Soler N, Beaulieu V, Litvin TN, Da Silva N, Chen Y, Brown D, Buck J, Levin LR, Breton S. Bicarbonate-regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling. J Biol Chem. 2003 Dec 05; 278(49):49523-9. PMID: 14512417; PMCID: PMC3652382.
  33. Nicolaou F, Teodoridis JM, Park H, Georgakis A, Farokhzad OC, Böttinger EP, Da Silva N, Rousselot P, Chomienne C, Ferenczi K, Arnaout MA, Shelley CS. CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras and junD. Blood. 2003 May 15; 101(10):4033-41. PMID: 12576324.
    View in: PubMed
  34. Isnard-Bagnis C, Da Silva N, Beaulieu V, Yu AS, Brown D, Breton S. Detection of ClC-3 and ClC-5 in epididymal epithelium: immunofluorescence and RT-PCR after LCM. Am J Physiol Cell Physiol. 2003 Jan; 284(1):C220-32. PMID: 12475763.
    View in: PubMed
  35. Da Silva N, Bharti A, Shelley CS. hnRNP-K and Pur(alpha) act together to repress the transcriptional activity of the CD43 gene promoter. Blood. 2002 Nov 15; 100(10):3536-44. PMID: 12411317.
    View in: PubMed
  36. Shelley CS, Da Silva N, Teodoridis JM. During U937 monocytic differentiation repression of the CD43 gene promoter is mediated by the single-stranded DNA binding protein Pur alpha. Br J Haematol. 2001 Oct; 115(1):159-66. PMID: 11722429.
    View in: PubMed
  37. Da Silva N, Meyer-Monard S, Menot ML, Parrado A, Lebel A, Balitrand N, Fenaux P, Micléa JM, Rousselot P, Degos L, Dombret H, Chomienne C. Functional G-CSF pathways in t(8;21) leukemic cells allow for differentiation induction and degradation of AML1-ETO. Hematol J. 2000; 1(5):316-28. PMID: 11920209.
    View in: PubMed
  38. Shelley CS, Da Silva N, Georgakis A, Chomienne C, Arnaout MA. Mapping of the human CD11c (ITGAX) and CD11d (ITGAD) genes demonstrates that they are arranged in tandem separated by no more than 11.5 kb. Genomics. 1998 Apr 15; 49(2):334-6. PMID: 9598326.
    View in: PubMed
  39. Touhami M, Fauvel-Lafève F, Da Silva N, Chomienne C, Legrand C. Induction of thrombospondin-1 by all-trans retinoic acid modulates growth and differentiation of HL-60 myeloid leukemia cells. Leukemia. 1997 Dec; 11(12):2137-42. PMID: 9447832.
    View in: PubMed
  40. Da Silva N, Meyer-Monard S, Menot ML, Degos L, Baruchel A, Dombret H, Chomienne C. G-CSF activates STAT pathways in Kasumi-1 myeloid leukemic cells with the t(8; 21) translocation: basis for potential therapeutic efficacy. Cytokines Cell Mol Ther. 1997 Jun; 3(2):75-80. PMID: 9287246.
    View in: PubMed
  41. Gruss HJ, DaSilva N, Hu ZB, Uphoff CC, Goodwin RG, Drexler HG. Expression and regulation of CD30 ligand and CD30 in human leukemia-lymphoma cell lines. Leukemia. 1994 Dec; 8(12):2083-94. PMID: 7528856.
    View in: PubMed
  42. DaSilva N, Hu ZB, Ma W, Rosnet O, Birnbaum D, Drexler HG. Expression of the FLT3 gene in human leukemia-lymphoma cell lines. Leukemia. 1994 May; 8(5):885-8. PMID: 8182945.
    View in: PubMed
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