I am a cell biologist and biochemist, with over 20 years experience in studies related to fundamental mechanisms of urologic disease. Research in my laboratory is focused on deciphering the molecular processes that regulate growth, differentiation and pathologic remodeling in the urinary tract, in both benign and malignant conditions, as outlined below.

  1. We have implicated neuropilin 2 (Nrp2) as a potential ‘druggable’ target for restoration of bladder muscle contractility in the setting of decompensated bladder function following outlet obstruction. Clinically, no effective treatment exists to increase contractility of the underactive bladder in patients. Using a mouse model of bladder outlet obstruction, genetic ablation of Nrp2 during the decompensation phase was associated with sustained contractility. Moreover, evaluation of human patients with obstruction revealed that those displaying compensated bladder function had lower expression of NRP2 in bladder tissue compared to obstructed patients in whom bladder function was decompensated, consistent with the findings from our mouse model. We are continuing to characterize candidate small molecule inhibitors of neuropilin 2 that could be used to inhibit function in the setting of obstruction to restore contractility. Funding for this project is pending (R01 DK104641-01A1).
  2. In a separate line of investigation, we have demonstrated that the purine nucleoside inosine exerts profound effects on bladder function following spinal cord injury. When tested in both prevention and intervention regimens in a rat model of spinal cord injury, chronic inosine treatment led to attenuation of neurogenic detrusor overactivity as assessed by cystometry. Evaluation of underlying mechanisms suggested that the primary impact of inosine on the bladder was neuroprotective, but that inosine also modulated sensory neurotransmission, at least in part by attenuating pathologic upregulation of TRPV1. These findings were published in November 2015. Ongoing studies are focused on the molecular mechanisms underlying the beneficial effect of inosine on overactivity.
  3. In 2014, we published the first integrated quantitative proteomics and transcriptomics analysis of bladder smooth muscle cells in Cell Communication and Signaling. This study validated previous work from our group implicating the AP-1 transcriptional complex as a regulator of smooth muscle cell growth and migration but also revealed MYC as a novel ‘master regulator’ of smooth muscle cell behavior. We have proceeded to determine the functional significance of the MYC-centric network in bladder smooth muscle, and have demonstrated that pharmacologic targeting of MYC with novel bromodomain inhibitors currently undergoing clinical evaluation, leads to attenuation of MYC network target genes and proteins, as well as inhibition of mitogen-stimulated proliferation of smooth muscle cells. The demonstration of AP-1 and MYC as putative therapeutic targets in conditions characterized by fibroproliferative expansion of hollow organs such as the bladder formed the basis of the competitive renewal of our R01 (DK077195), which was funded on the first submission in August 2015. Current studies are employing a small molecule inhibitor of AP-1 to mitigate pathologic remodeling in the bladder wall secondary to spinal cord injury.
  4. Bioinformatics analysis conducted in our group identified the gene Sh3gl2/endophilin A1 as highly enriched in urothelium. Subsequent validation demonstrated progressive loss of Sh3gl2 with bladder cancer progression in humans, and implicated Sh3gl2 as a novel regulator of kinase activity in urothelial carcinoma. Silencing of Sh3gl2 using RNA interference technology led to increased proliferation in vitro and as xenografts in vivo, and was associated with increased activation of the EGFR, Src-family kinases and STAT3. Ongoing studies are investigating the utility of Sh3gl2 as potential biomarker for sensitivity to EGFR- and MET-targeted kinase inhibitors in urothelial carcinoma. 

    These studies relate to the mechanisms underlying pathologic remodeling of the bladder wall under conditions of urinary tract obstruction. Their ultimate goal is to identify critical signaling nodes that could be targeted for therapeutic benefit.


Rosalyn Adam received her PhD from the University of Southampton in the UK. She completed a postdoctoral fellowship at Boston Children's Hospital.


Selected Publications

See a complete list of published work in my bibliography.





Publications powered by Harvard Catalyst Profiles

  1. Molecular mechanisms of esophageal epithelial regeneration following repair of surgical defects with acellular silk fibroin grafts. Sci Rep. 2021 Mar 29; 11(1):7086. View abstract
  2. A Single Cell Dissociation Approach for Molecular Analysis of Urinary Bladder in the Mouse Following Spinal Cord Injury. J Vis Exp. 2020 06 17; (160). View abstract
  3. Novel discoveries in urology: big data to microbiome - highlights of the society for basic urologic research 2019 annual meeting. Am J Clin Exp Urol. 2020; 8(2):73-75. View abstract
  4. Systems analysis of benign bladder disorders: insights from omics analysis. Am J Physiol Renal Physiol. 2020 04 01; 318(4):F901-F910. View abstract
  5. A multi-omics approach to understanding the field effect in bladder cancer. Transl Androl Urol. 2019 Dec; 8(6):775-778. View abstract
  6. MCL1 and DEDD Promote Urothelial Carcinoma Progression. Mol Cancer Res. 2019 06; 17(6):1294-1304. View abstract
  7. Concordant miRNA and mRNA expression profiles in humans and mice with bladder outlet obstruction. Am J Clin Exp Urol. 2018; 6(6):219-233. View abstract
  8. Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation. PLoS Biol. 2018 11; 16(11):e2006951. View abstract
  9. Immunology, Immunotherapy, and Translating Basic Science into the Clinic for Bladder Cancer. Bladder Cancer. 2018 Oct 29; 4(4):429-440. View abstract
  10. Inosine - a Multifunctional Treatment for Complications of Neurologic Injury. Cell Physiol Biochem. 2018; 49(6):2293-2303. View abstract
  11. Heparin-Binding Epidermal Growth Factor-Like Growth Factor as a Critical Mediator of Tissue Repair and Regeneration. Am J Pathol. 2018 11; 188(11):2446-2456. View abstract
  12. The role of the mucosa in modulation of evoked responses in the spinal cord injured rat bladder. Neurourol Urodyn. 2018 06; 37(5):1583-1593. View abstract
  13. Mode of Surgical Injury Influences the Source of Urothelial Progenitors during Bladder Defect Repair. Stem Cell Reports. 2017 12 12; 9(6):2005-2017. View abstract
  14. The Cytotoxicity and Genotoxicity of Particulate and Soluble Cobalt in Human Urothelial Cells. Biol Trace Elem Res. 2017 Nov; 180(1):48-55. View abstract
  15. Inosine attenuates spontaneous activity in the rat neurogenic bladder through an A2B pathway. Sci Rep. 2017 03 15; 7:44416. View abstract
  16. MYC Mediates Large Oncosome-Induced Fibroblast Reprogramming in Prostate Cancer. Cancer Res. 2017 05 01; 77(9):2306-2317. View abstract
  17. Deletion of neuropilin 2 enhances detrusor contractility following bladder outlet obstruction. JCI Insight. 2017 02 09; 2(3):e90617. View abstract
  18. Inflammation and Lymphedema Are Exacerbated and Prolonged by Neuropilin 2 Deficiency. Am J Pathol. 2016 11; 186(11):2803-2812. View abstract
  19. Hexavalent chromium induces chromosome instability in human urothelial cells. Toxicol Appl Pharmacol. 2016 Apr 01; 296:54-60. View abstract
  20. Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury. PLoS One. 2015; 10(11):e0141492. View abstract
  21. Molecular mechanisms of squamous differentiation in urothelial cell carcinoma: a paradigm for molecular subtyping of urothelial cell carcinoma of the bladder. Urol Oncol. 2015 Oct; 33(10):444-50. View abstract
  22. Mutations in TBX18 Cause Dominant Urinary Tract Malformations via Transcriptional Dysregulation of Ureter Development. Am J Hum Genet. 2015 Aug 06; 97(2):291-301. View abstract
  23. Regulation of microtubule dynamics by DIAPH3 influences amoeboid tumor cell mechanics and sensitivity to taxanes. Sci Rep. 2015 Jul 16; 5:12136. View abstract
  24. Platelet Derived Growth Factor Has a Role in Pressure Induced Bladder Smooth Muscle Cell Hyperplasia and Acts in a Paracrine Way. J Urol. 2015 Dec; 194(6):1797-805. View abstract
  25. Dynamic reciprocity in cell-scaffold interactions. Adv Drug Deliv Rev. 2015 Mar; 82-83:77-85. View abstract
  26. Pathophysiology and animal modeling of underactive bladder. Int Urol Nephrol. 2014 Sep; 46 Suppl 1:S11-21. View abstract
  27. Progress made in the use of animal models for the study of high-risk, nonmuscle invasive bladder cancer. Curr Opin Urol. 2014 Sep; 24(5):512-6. View abstract
  28. Integration of proteomic and transcriptomic profiles identifies a novel PDGF-MYC network in human smooth muscle cells. Cell Commun Signal. 2014 Aug 01; 12:44. View abstract
  29. The use of bi-layer silk fibroin scaffolds and small intestinal submucosa matrices to support bladder tissue regeneration in a rat model of spinal cord injury. Biomaterials. 2014 Aug; 35(26):7452-9. View abstract
  30. Acellular bi-layer silk fibroin scaffolds support tissue regeneration in a rabbit model of onlay urethroplasty. PLoS One. 2014; 9(3):e91592. View abstract
  31. Retinoid signaling in progenitors controls specification and regeneration of the urothelium. Dev Cell. 2013 Sep 16; 26(5):469-482. View abstract
  32. Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large animal model of augmentation cystoplasty. Biomaterials. 2013 Nov; 34(34):8681-9. View abstract
  33. Scaffold attachment factor B1 regulates the androgen receptor in concert with the growth inhibitory kinase MST1 and the methyltransferase EZH2. Oncogene. 2014 Jun 19; 33(25):3235-45. View abstract
  34. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression. J Pathol. 2013 Sep; 231(1):77-87. View abstract
  35. Is unexpected peritoneal carcinomatosis still a contraindication for resection of colorectal liver metastases? Combined resection of colorectal liver metastases with peritoneal deposits discovered intra-operatively. Eur J Surg Oncol. 2013 Sep; 39(9):981-7. View abstract
  36. Loss of Sh3gl2/endophilin A1 is a common event in urothelial carcinoma that promotes malignant behavior. Neoplasia. 2013 Jul; 15(7):749-60. View abstract
  37. The impact of discrete modes of spinal cord injury on bladder muscle contractility. BMC Urol. 2013 May 13; 13:24. View abstract
  38. The performance of silk scaffolds in a rat model of augmentation cystoplasty. Biomaterials. 2013 Jul; 34(20):4758-65. View abstract
  39. Evaluation of silk biomaterials in combination with extracellular matrix coatings for bladder tissue engineering with primary and pluripotent cells. PLoS One. 2013; 8(2):e56237. View abstract
  40. JunB mediates basal- and TGFß1-induced smooth muscle cell contractility. PLoS One. 2013; 8(1):e53430. View abstract
  41. Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. Am J Pathol. 2012 Nov; 181(5):1573-84. View abstract
  42. Inhibition of TNF-a improves the bladder dysfunction that is associated with type 2 diabetes. Diabetes. 2012 Aug; 61(8):2134-45. View abstract
  43. Increased smooth muscle contractility in mice deficient for neuropilin 2. Am J Pathol. 2012 Aug; 181(2):548-59. View abstract
  44. DIAPH3 governs the cellular transition to the amoeboid tumour phenotype. EMBO Mol Med. 2012 Aug; 4(8):743-60. View abstract
  45. On the (C)USP(2a) of new targets for bladder cancer therapy? . 2012 Apr 01; 11(7):1270-1. View abstract
  46. FosB regulates stretch-induced expression of extracellular matrix proteins in smooth muscle. Am J Pathol. 2011 Dec; 179(6):2977-89. View abstract
  47. When urothelial differentiation pathways go wrong: implications for bladder cancer development and progression. Urol Oncol. 2013 Aug; 31(6):802-11. View abstract
  48. The effect of manipulation of silk scaffold fabrication parameters on matrix performance in a murine model of bladder augmentation. Biomaterials. 2011 Oct; 32(30):7562-70. View abstract
  49. A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. J Clin Invest. 2011 Apr; 121(4):1585-95. View abstract
  50. An hTERT-immortalized human urothelial cell line that responds to anti-proliferative factor. In Vitro Cell Dev Biol Anim. 2011 Jan; 47(1):2-9. View abstract
  51. Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation. Biomaterials. 2011 Jan; 32(3):808-18. View abstract
  52. Fluidization and resolidification of the human bladder smooth muscle cell in response to transient stretch. PLoS One. 2010 Aug 06; 5(8):e12035. View abstract
  53. All-trans retinoic acid directs urothelial specification of murine embryonic stem cells via GATA4/6 signaling mechanisms. PLoS One. 2010 Jul 13; 5(7):e11513. View abstract
  54. Histone deacetylase inhibitors and bladder cancer. J Urol. 2010 Jun; 183(6):2120-1. View abstract
  55. An Akt- and Fra-1-dependent pathway mediates platelet-derived growth factor-induced expression of thrombomodulin, a novel regulator of smooth muscle cell migration. Am J Pathol. 2010 Jul; 177(1):119-31. View abstract
  56. Cell signaling in kidney cancer. J Urol. 2009 Dec; 182(6):2555-6. View abstract
  57. Oncosome formation in prostate cancer: association with a region of frequent chromosomal deletion in metastatic disease. Cancer Res. 2009 Jul 01; 69(13):5601-9. View abstract
  58. Heterogeneous nuclear ribonucleoprotein K is a novel regulator of androgen receptor translation. Cancer Res. 2009 Mar 15; 69(6):2210-8. View abstract
  59. Rapid preparation of nuclei-depleted detergent-resistant membrane fractions suitable for proteomics analysis. BMC Cell Biol. 2008 Jun 05; 9:30. View abstract
  60. Caveolin-1 interacts with a lipid raft-associated population of fatty acid synthase. . 2008 Jul 15; 7(14):2257-67. View abstract
  61. The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1. EMBO J. 2007 Oct 31; 26(21):4523-34. View abstract
  62. GATA-6 mediates human bladder smooth muscle differentiation: involvement of a novel enhancer element in regulating alpha-smooth muscle actin gene expression. . 2007 Sep; 293(3):C1093-102. View abstract
  63. Cholesterol sensitivity of endogenous and myristoylated Akt. Cancer Res. 2007 Jul 01; 67(13):6238-46. View abstract
  64. The zinc finger protein ras-responsive element binding protein-1 is a coregulator of the androgen receptor: implications for the role of the Ras pathway in enhancing androgenic signaling in prostate cancer. Mol Endocrinol. 2007 Sep; 21(9):2056-70. View abstract
  65. Cyclooxygenase-2 in transitional cell carcinoma--a legitimate target? J Urol. 2007 Mar; 177(3):818-9. View abstract
  66. Transit of hormonal and EGF receptor-dependent signals through cholesterol-rich membranes. Steroids. 2007 Feb; 72(2):210-7. View abstract
  67. Inhibition of EGFR signaling abrogates smooth muscle proliferation resulting from sustained distension of the urinary bladder. Lab Invest. 2006 Dec; 86(12):1293-302. View abstract
  68. Measurement of plasma levels of vascular endothelial growth factor in prostate cancer patients: relationship with clinical stage, Gleason score, prostate volume, and serum prostate-specific antigen. Clinics (Sao Paulo). 2006 Oct; 61(5):401-8. View abstract
  69. Effective salvage therapy of liver-only colorectal cancer metastases with chronomodulated irinotecan-fluorouracil-oxaliplatin via hepatic artery infusion. J Clin Oncol. 2006 Jun 20; 24(18_suppl):3585. View abstract
  70. Behavioral profiling of human transitional cell carcinoma ex vivo. Cancer Res. 2006 Mar 15; 66(6):3078-86. View abstract
  71. A quantitative proteomic analysis of growth factor-induced compositional changes in lipid rafts of human smooth muscle cells. Proteomics. 2005 Dec; 5(18):4733-42. View abstract
  72. JNK/SAPK and p38 SAPK-2 mediate mechanical stretch-induced apoptosis via caspase-3 and -9 in NRK-52E renal epithelial cells. Nephron Exp Nephrol. 2006; 102(2):e49-61. View abstract
  73. Recent insights into the cell biology of bladder smooth muscle. Nephron Exp Nephrol. 2006; 102(1):e1-7. View abstract
  74. Trafficking of nuclear heparin-binding epidermal growth factor-like growth factor into an epidermal growth factor receptor-dependent autocrine loop in response to oxidative stress. Cancer Res. 2005 Sep 15; 65(18):8242-9. View abstract
  75. Tumor cell-associated neuropilin-1 and vascular endothelial growth factor expression as determinants of tumor growth in neuroblastoma. Neuropathology. 2005 Sep; 25(3):178-87. View abstract
  76. Three-drug chronotherapy via hepatic artery as salvage treatment for patients with liver-only metastases from colorectal cancer. J Clin Oncol. 2005 Jun; 23(16_suppl):3616. View abstract
  77. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest. 2005 Apr; 115(4):959-68. View abstract
  78. Induction of smooth muscle cell-like phenotype in marrow-derived cells among regenerating urinary bladder smooth muscle cells. Am J Pathol. 2005 Feb; 166(2):565-73. View abstract
  79. An oxidative stress mechanism mediates chelerythrine-induced heparin-binding EGF-like growth factor ectodomain shedding. J Cell Biochem. 2005 Jan 01; 94(1):39-49. View abstract
  80. Growth and stretch response of human exstrophy bladder smooth muscle cells: molecular evidence of normal intrinsic function. BJU Int. 2005 Jan; 95(1):144-8. View abstract
  81. Caveolae are negative regulators of transforming growth factor-beta1 signaling in ureteral smooth muscle cells. J Urol. 2004 Dec; 172(6 Pt 1):2451-5. View abstract
  82. Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells. Physiol Genomics. 2004 Dec 15; 20(1):36-44. View abstract
  83. Mechanical strain delivers anti-apoptotic and proliferative signals to gingival fibroblasts. J Dent Res. 2004 Aug; 83(8):596-601. View abstract
  84. Rho-kinase inhibitors: potential therapeutics for benign prostate hyperplasia. J Urol. 2003 Dec; 170(6 Pt 1):2523-4. View abstract
  85. Involvement of cholesterol-rich lipid rafts in interleukin-6-induced neuroendocrine differentiation of LNCaP prostate cancer cells. Endocrinology. 2004 Feb; 145(2):613-9. View abstract
  86. Signaling through PI3K/Akt mediates stretch and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells. J Urol. 2003 Jun; 169(6):2388-93. View abstract
  87. Platelet derived growth factor-BB is a potent mitogen for rat ureteral and human bladder smooth muscle cells: dependence on lipid rafts for cell signaling. J Urol. 2003 Mar; 169(3):1165-70. View abstract
  88. Calcium regulates the PI3K-Akt pathway in stretched osteoblasts. FEBS Lett. 2003 Feb 11; 536(1-3):193-7. View abstract
  89. A nuclear form of the heparin-binding epidermal growth factor-like growth factor precursor is a feature of aggressive transitional cell carcinoma. Cancer Res. 2003 Jan 15; 63(2):484-90. View abstract
  90. Heparin-binding epidermal growth factor-like growth factor stimulates androgen-independent prostate tumor growth and antagonizes androgen receptor function. Endocrinology. 2002 Dec; 143(12):4599-608. View abstract
  91. Calcium-selective ion channel, CaT1, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies. Lab Invest. 2002 Dec; 82(12):1755-64. View abstract
  92. The decision to undergo DNA or protein synthesis is determined by the degree of mechanical deformation in human bladder muscle cells. Urology. 2002 May; 59(5):779-83. View abstract
  93. Activation of the Erk mitogen-activated protein kinase pathway stimulates neuroendocrine differentiation in LNCaP cells independently of cell cycle withdrawal and STAT3 phosphorylation. Cancer Res. 2002 Mar 01; 62(5):1549-54. View abstract
  94. A novel method for implantation of LNCaP prostate tumor cells under the renal capsule. In Vitro Cell Dev Biol Anim. 2001 Jun; 37(6):360-2. View abstract
  95. CaT1 expression correlates with tumor grade in prostate cancer. Biochem Biophys Res Commun. 2001 Apr 06; 282(3):729-34. View abstract
  96. Heparin-binding epidermal growth factor-like growth factor is an autocrine mediator of human prostate stromal cell growth in vitro. J Urol. 2001 Jan; 165(1):284-8. View abstract
  97. Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells. . 2000 Oct; 279(4):C1155-67. View abstract
  98. Heparin-binding EGF-like growth factor is up-regulated in the obstructed kidney in a cell- and region-specific manner and acts to inhibit apoptosis. Am J Pathol. 2000 Mar; 156(3):889-98. View abstract
  99. Amphiregulin is coordinately expressed with heparin-binding epidermal growth factor-like growth factor in the interstitial smooth muscle of the human prostate. Endocrinology. 1999 Dec; 140(12):5866-75. View abstract
  100. Amphiregulin Is Coordinately Expressed with Heparin-Binding Epidermal Growth Factor-Like Growth Factor in the Interstitial Smooth Muscle of the Human Prostate1. Endocrinology. 1999 Dec 01; 140(12):5866-5875. View abstract
  101. Heparin-binding EGF-like growth factor expression increases selectively in bladder smooth muscle in response to lower urinary tract obstruction. Lab Invest. 1999 Nov; 79(11):1335-45. View abstract
  102. Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer. Urology. 1999 Sep; 54(3):523-7. View abstract
  103. AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells. Am J Physiol. 1999 08; 277(2):C294-301. View abstract
  104. Cell-specific activation of the HB-EGF and ErbB1 genes by stretch in primary human bladder cells. In Vitro Cell Dev Biol Anim. 1999 Jul-Aug; 35(7):371-5. View abstract
  105. The phosphatidylinositol 3'-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells. Cancer Res. 1999 Jun 15; 59(12):2891-7. View abstract
  106. Extracellular calcium influx stimulates metalloproteinase cleavage and secretion of heparin-binding EGF-like growth factor independently of protein kinase C. J Cell Biochem. 1998 May 01; 69(2):143-53. View abstract
  107. Heparin-binding EGF-like growth factor in the human prostate: synthesis predominantly by interstitial and vascular smooth muscle cells and action as a carcinoma cell mitogen. J Cell Biochem. 1998 Mar 01; 68(3):328-38. View abstract
  108. Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder. J Clin Invest. 1997 Mar 01; 99(5):1028-36. View abstract
  109. Induction of anchorage-independent growth by amphiregulin. Growth Factors. 1996; 13(3-4):193-203. View abstract
  110. Modulation of the receptor binding affinity of amphiregulin by modification of its carboxyl terminal tail. Biochim Biophys Acta. 1995 Apr 06; 1266(1):83-90. View abstract
  111. [Long-term follow-up of patients with borderline tumors of the ovaries]. Gynakol Rundsch. 1990; 30 Suppl 1:48-50. View abstract