Harvard Catalyst Profiles

Contact, publication, and social network information about Harvard faculty and fellows.

Nicolas Da Silva, Ph.D.


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.

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

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.
Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  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 04 20; 169(3):510-522.e20. PMID: 28431249.
    Citations: 34     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 28     Fields:    Translation:AnimalsCells
  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.
    Citations: 7     Fields:    Translation:AnimalsCells
  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.
    Citations: 13     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 6     Fields:    Translation:AnimalsCells
  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.
    Citations: 18     Fields:    Translation:AnimalsCells
  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.
    Citations: 83     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 15     Fields:    Translation:AnimalsCells
  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.
    Citations: 32     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 15     Fields:    Translation:AnimalsCells
  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.
    Citations: 25     Fields:    Translation:AnimalsCells
  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.
    Citations: 24     Fields:    Translation:AnimalsCells
  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.
    Citations: 104     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 18     Fields:    Translation:AnimalsCells
  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.
    Citations: 15     Fields:    Translation:AnimalsCells
  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.
    Citations: 19     Fields:    Translation:AnimalsCells
  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.
    Citations: 42     Fields:    Translation:AnimalsCells
  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.
    Citations: 47     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 7     Fields:    Translation:AnimalsCells
  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.
    Citations: 22     Fields:    Translation:AnimalsCells
  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.
    Citations: 41     Fields:    Translation:AnimalsCells
  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.
    Citations: 33     Fields:    Translation:AnimalsCells
  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.
    Citations: 15     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 25     Fields:    Translation:HumansAnimalsCells
  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.
    Citations: 11     Fields:    Translation:Animals
  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.
    Citations: 16     Fields:    Translation:AnimalsCells
  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.
    Citations: 55     Fields:    Translation:Animals
  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.
    Citations: 40     Fields:    Translation:AnimalsCells
  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.
    Citations: 33     Fields:    Translation:Animals
  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.
    Citations: 97     Fields:    Translation:AnimalsCells
  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.
    Citations: 9     Fields:    Translation:HumansCells
  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.
    Citations: 16     Fields:    Translation:AnimalsCells
  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.
    Citations: 15     Fields:    Translation:HumansCells
  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.
    Citations: 7     Fields:    Translation:HumansCells
  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.
    Citations: 5     Fields:    Translation:HumansCells
  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.
    Citations: 3     Fields:    Translation:HumansCells
  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.
    Citations: 2     Fields:    Translation:HumansCells
  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.
    Citations: 1     Fields:    Translation:HumansCells
  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.
    Citations: 6     Fields:    Translation:HumansCells
  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.
    Citations: 7     Fields:    Translation:HumansCells
Local representatives can answer questions about the Profiles website or help with editing a profile or issues with profile data. For assistance with this profile: HMS/HSDM faculty should contact feedbackcatalyst.harvard.edu. For faculty or fellow appointment updates and changes, please ask your appointing department to contact HMS. For fellow personal and demographic information, contact HMS Human Resources at human_resourceshms.harvard.edu. For faculty personal and demographic information, contact HMS Office for Faculty Affairs at facappthms.harvard.edu.
Da Silva's Networks
Click the
buttons for more information and interactive visualizations!
Concepts (287)
Co-Authors (33)
Similar People (60)
Same Department 
Physical Neighbors
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.