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Rosalyn Adam, PhD

PhD Adam
Urology Research
Hospital Title:
Director, Urology Research
Academic Title:
Associate Professor of Surgery, Harvard Medical School
Research Focus Area:
Hollow organ pathophysiologyUrologic cancersSmooth muscle biology
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Research Overview

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. 

About Rosalyn Adam

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

Key Publications

See a complete list of published work in my bibliography.


Publications powered by Harvard Catalyst Profiles
  1. Wise SS, Holmes AL, Liou L, Adam RM, Wise JP. Hexavalent chromium induces chromosome instability in human urothelial cells. Toxicol Appl Pharmacol. 2016 Apr 1; 296:54-60.
  2. Chung YG, Seth A, Doyle C, Franck D, Kim D, Cristofaro V, Benowitz LI, Tu DD, Estrada CR, Mauney JR, Sullivan MP, Adam RM. Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury. PLoS One. 2015; 10(11):e0141492.
  3. Adam RM, DeGraff DJ. 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.
  4. Vivante A, Kleppa MJ, Schulz J, Kohl S, Sharma A, Chen J, Shril S, Hwang DY, Weiss AC, Kaminski MM, Shukrun R, Kemper MJ, Lehnhardt A, Beetz R, Sanna-Cherchi S, Verbitsky M, Gharavi AG, Stuart HM, Feather SA, Goodship JA, Goodship TH, Woolf AS, Westra SJ, Doody DP, Bauer SB, Lee RS, Adam RM, Lu W, Reutter HM, Kehinde EO, Mancini EJ, Lifton RP, Tasic V, Lienkamp SS, Jüppner H, Kispert A, Hildebrandt F. Mutations in TBX18 Cause Dominant Urinary Tract Malformations via Transcriptional Dysregulation of Ureter Development. Am J Hum Genet. 2015 Aug 6; 97(2):291-301.
  5. Morley S, You S, Pollan S, Choi J, Zhou B, Hager MH, Steadman K, Spinelli C, Rajendran K, Gertych A, Kim J, Adam RM, Yang W, Krishnan R, Knudsen BS, Di Vizio D, Freeman MR. Regulation of microtubule dynamics by DIAPH3 influences amoeboid tumor cell mechanics and sensitivity to taxanes. Sci Rep. 2015; 5:12136.
  6. Preis L, Herlemann A, Adam RM, Dietz HG, Kappler R, Stehr M. 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.
  7. Mauney JR, Adam RM. Dynamic reciprocity in cell-scaffold interactions. Adv Drug Deliv Rev. 2015 Mar; 82-83:77-85.
  8. Tyagi P, Smith PP, Kuchel GA, de Groat WC, Birder LA, Chermansky CJ, Adam RM, Tse V, Chancellor MB, Yoshimura N. Pathophysiology and animal modeling of underactive bladder. Int Urol Nephrol. 2014 Sep; 46 Suppl 1:S11-21.
  9. Lin-Tsai O, Taylor JA, Clark PE, Adam RM, Wu XR, DeGraff DJ. 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.
  10. Yang W, Ramachandran A, You S, Jeong H, Morley S, Mulone MD, Logvinenko T, Kim J, Hwang D, Freeman MR, Adam RM. Integration of proteomic and transcriptomic profiles identifies a novel PDGF-MYC network in human smooth muscle cells. Cell Commun Signal. 2014; 12:44.
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  12. Chung YG, Algarrahi K, Franck D, Tu DD, Adam RM, Kaplan DL, Estrada CR, Mauney JR. 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.
  13. Chung YG, Tu D, Franck D, Gil ES, Algarrahi K, Adam RM, Kaplan DL, Estrada CR, Mauney JR. Acellular bi-layer silk fibroin scaffolds support tissue regeneration in a rabbit model of onlay urethroplasty. PLoS One. 2014; 9(3):e91592.
  14. Gandhi D, Molotkov A, Batourina E, Schneider K, Dan H, Reiley M, Laufer E, Metzger D, Liang F, Liao Y, Sun TT, Aronow B, Rosen R, Mauney J, Adam R, Rosselot C, Van Batavia J, McMahon A, McMahon J, Guo JJ, Mendelsohn C. Retinoid signaling in progenitors controls specification and regeneration of the urothelium. Dev Cell. 2013 Sep 16; 26(5):469-82.
  15. Tu DD, Chung YG, Gil ES, Seth A, Franck D, Cristofaro V, Sullivan MP, Di Vizio D, Gomez P, Adam RM, Kaplan DL, Estrada CR, Mauney JR. Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large animal model of augmentation cystoplasty. Biomaterials. 2013 Nov; 34(34):8681-9.
  16. Mukhopadhyay NK, Kim J, You S, Morello M, Hager MH, Huang WC, Ramachandran A, Yang J, Cinar B, Rubin MA, Adam RM, Oesterreich S, Di Vizio D, Freeman MR. 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.
  17. Ayala G, Morello M, Frolov A, You S, Li R, Rosati F, Bartolucci G, Danza G, Adam RM, Thompson TC, Lisanti MP, Freeman MR, Di Vizio D. 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.
  18. Allard MA, Adam R, Ruiz A, Vibert E, Paule B, Levi F, Sebagh M, Guettier C, Azoulay D, Castaing D. 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.
  19. Majumdar S, Gong EM, Di Vizio D, Dreyfuss J, Degraff DJ, Hager MH, Park PJ, Bellmunt J, Matusik RJ, Rosenberg JE, Adam RM. Loss of Sh3gl2/endophilin A1 is a common event in urothelial carcinoma that promotes malignant behavior. Neoplasia. 2013 Jul; 15(7):749-60.
  20. Seth A, Chung YG, Kim D, Ramachandran A, Cristofaro V, Gomez P, Tu D, Huang L, Benowitz LI, Di Vizio D, Sullivan MP, Adam RM. The impact of discrete modes of spinal cord injury on bladder muscle contractility. BMC Urol. 2013; 13:24.
  21. Seth A, Chung YG, Gil ES, Tu D, Franck D, Di Vizio D, Adam RM, Kaplan DL, Estrada CR, Mauney JR. The performance of silk scaffolds in a rat model of augmentation cystoplasty. Biomaterials. 2013 Jul; 34(20):4758-65.
  22. Franck D, Gil ES, Adam RM, Kaplan DL, Chung YG, Estrada CR, Mauney JR. 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.
  23. Ramachandran A, Gangopadhyay SS, Krishnan R, Ranpura SA, Rajendran K, Ram-Mohan S, Mulone M, Gong EM, Adam RM. JunB mediates basal- and TGFß1-induced smooth muscle cell contractility. PLoS One. 2013; 8(1):e53430.
  24. Di Vizio D, Morello M, Dudley AC, Schow PW, Adam RM, Morley S, Mulholland D, Rotinen M, Hager MH, Insabato L, Moses MA, Demichelis F, Lisanti MP, Wu H, Klagsbrun M, Bhowmick NA, Rubin MA, D'Souza-Schorey C, Freeman MR. 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.
  25. Wang Z, Cheng Z, Cristofaro V, Li J, Xiao X, Gomez P, Ge R, Gong E, Strle K, Sullivan MP, Adam RM, White MF, Olumi AF. Inhibition of TNF-a improves the bladder dysfunction that is associated with type 2 diabetes. Diabetes. 2012 Aug; 61(8):2134-45.
  26. Bielenberg DR, Seth A, Shimizu A, Pelton K, Cristofaro V, Ramachandran A, Zwaans BM, Chen C, Krishnan R, Seth M, Huang L, Takashima S, Klagsbrun M, Sullivan MP, Adam RM. Increased smooth muscle contractility in mice deficient for neuropilin 2. Am J Pathol. 2012 Aug; 181(2):548-59.
  27. Hager MH, Morley S, Bielenberg DR, Gao S, Morello M, Holcomb IN, Liu W, Mouneimne G, Demichelis F, Kim J, Solomon KR, Adam RM, Isaacs WB, Higgs HN, Vessella RL, Di Vizio D, Freeman MR. DIAPH3 governs the cellular transition to the amoeboid tumour phenotype. EMBO Mol Med. 2012 Aug; 4(8):743-60.
  28. Adam RM. On the (C)USP(2a) of new targets for bladder cancer therapy? Cell Cycle. 2012 Apr 1; 11(7):1270-1.
  29. Ramachandran A, Gong EM, Pelton K, Ranpura SA, Mulone M, Seth A, Gomez P, Adam RM. FosB regulates stretch-induced expression of extracellular matrix proteins in smooth muscle. Am J Pathol. 2011 Dec; 179(6):2977-89.
  30. DeGraff DJ, Cates JM, Mauney JR, Clark PE, Matusik RJ, Adam RM. When urothelial differentiation pathways go wrong: implications for bladder cancer development and progression. Urol Oncol. 2013 Aug; 31(6):802-11.
  31. Gomez P, Gil ES, Lovett ML, Rockwood DN, Di Vizio D, Kaplan DL, Adam RM, Estrada CR, Mauney JR. 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.
  32. Guo C, Sun Y, Zhou B, Adam RM, Li X, Pu WT, Morrow BE, Moon A, Li X. A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. J Clin Invest. 2011 Apr; 121(4):1585-95.
  33. Kim J, Ji M, DiDonato JA, Rackley RR, Kuang M, Sadhukhan PC, Mauney JR, Keay SK, Freeman MR, Liou LS, Adam RM. 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.
  34. Mauney JR, Cannon GM, Lovett ML, Gong EM, Di Vizio D, Gomez P, Kaplan DL, Adam RM, Estrada CR. Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation. Biomaterials. 2011 Jan; 32(3):808-18.
  35. Chen C, Krishnan R, Zhou E, Ramachandran A, Tambe D, Rajendran K, Adam RM, Deng L, Fredberg JJ. Fluidization and resolidification of the human bladder smooth muscle cell in response to transient stretch. PLoS One. 2010; 5(8):e12035.
  36. Mauney JR, Ramachandran A, Yu RN, Daley GQ, Adam RM, Estrada CR. All-trans retinoic acid directs urothelial specification of murine embryonic stem cells via GATA4/6 signaling mechanisms. PLoS One. 2010; 5(7):e11513.
  37. Adam RM. Histone deacetylase inhibitors and bladder cancer. J Urol. 2010 Jun; 183(6):2120-1.
  38. Ramachandran A, Ranpura SA, Gong EM, Mulone M, Cannon GM, Adam RM. 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.
  39. Adam R. Cell signaling in kidney cancer. J Urol. 2009 Dec; 182(6):2555-6.
  40. Di Vizio D, Kim J, Hager MH, Morello M, Yang W, Lafargue CJ, True LD, Rubin MA, Adam RM, Beroukhim R, Demichelis F, Freeman MR. Oncosome formation in prostate cancer: association with a region of frequent chromosomal deletion in metastatic disease. Cancer Res. 2009 Jul 1; 69(13):5601-9.
  41. Mukhopadhyay NK, Kim J, Cinar B, Ramachandran A, Hager MH, Di Vizio D, Adam RM, Rubin MA, Raychaudhuri P, De Benedetti A, Freeman MR. Heterogeneous nuclear ribonucleoprotein K is a novel regulator of androgen receptor translation. Cancer Res. 2009 Mar 15; 69(6):2210-8.
  42. Adam RM, Yang W, Di Vizio D, Mukhopadhyay NK, Steen H. Rapid preparation of nuclei-depleted detergent-resistant membrane fractions suitable for proteomics analysis. BMC Cell Biol. 2008; 9:30.
  43. Di Vizio D, Adam RM, Kim J, Kim R, Sotgia F, Williams T, Demichelis F, Solomon KR, Loda M, Rubin MA, Lisanti MP, Freeman MR. Caveolin-1 interacts with a lipid raft-associated population of fatty acid synthase. Cell Cycle. 2008 Jul 15; 7(14):2257-67.
  44. Cinar B, Fang PK, Lutchman M, Di Vizio D, Adam RM, Pavlova N, Rubin MA, Yelick PC, Freeman MR. The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1. EMBO J. 2007 Oct 31; 26(21):4523-34.
  45. Kanematsu A, Ramachandran A, Adam RM. GATA-6 mediates human bladder smooth muscle differentiation: involvement of a novel enhancer element in regulating alpha-smooth muscle actin gene expression. Am J Physiol Cell Physiol. 2007 Sep; 293(3):C1093-102.
  46. Adam RM, Mukhopadhyay NK, Kim J, Di Vizio D, Cinar B, Boucher K, Solomon KR, Freeman MR. Cholesterol sensitivity of endogenous and myristoylated Akt. Cancer Res. 2007 Jul 1; 67(13):6238-46.
  47. Mukhopadhyay NK, Cinar B, Mukhopadhyay L, Lutchman M, Ferdinand AS, Kim J, Chung LW, Adam RM, Ray SK, Leiter AB, Richie JP, Liu BC, Freeman MR. 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.
  48. Adam R. Cyclooxygenase-2 in transitional cell carcinoma--a legitimate target? J Urol. 2007 Mar; 177(3):818-9.
  49. Freeman MR, Cinar B, Kim J, Mukhopadhyay NK, Di Vizio D, Adam RM, Solomon KR. Transit of hormonal and EGF receptor-dependent signals through cholesterol-rich membranes. Steroids. 2007 Feb; 72(2):210-7.
  50. Estrada CR, Adam RM, Eaton SH, Bägli DJ, Freeman MR. Inhibition of EGFR signaling abrogates smooth muscle proliferation resulting from sustained distension of the urinary bladder. Lab Invest. 2006 Dec; 86(12):1293-302.
  51. Duque JL, Loughlin KR, Adam RM, Kantoff P, Mazzucchi E, Freeman MR. 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.
  52. Estrada CR, Salanga M, Bielenberg DR, Harrell WB, Zurakowski D, Zhu X, Palmer MR, Freeman MR, Adam RM. Behavioral profiling of human transitional cell carcinoma ex vivo. Cancer Res. 2006 Mar 15; 66(6):3078-86.
  53. MacLellan DL, Steen H, Adam RM, Garlick M, Zurakowski D, Gygi SP, Freeman MR, Solomon KR. 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.
  54. Nguyen HT, Hsieh MH, Gaborro A, Tinloy B, Phillips C, Adam RM. 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.
  55. Adam RM. Recent insights into the cell biology of bladder smooth muscle. Nephron Exp Nephrol. 2006; 102(1):e1-7.
  56. Kim J, Adam RM, Freeman MR. 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.
  57. Marcus K, Johnson M, Adam RM, O'Reilly MS, Donovan M, Atala A, Freeman MR, Soker S. 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.
  58. Zhuang L, Kim J, Adam RM, Solomon KR, Freeman MR. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest. 2005 Apr; 115(4):959-68.
  59. Kanematsu A, Yamamoto S, Iwai-Kanai E, Kanatani I, Imamura M, Adam RM, Tabata Y, Ogawa O. 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.
  60. Kim J, Lin J, Adam RM, Lamb C, Shively SB, Freeman MR. An oxidative stress mechanism mediates chelerythrine-induced heparin-binding EGF-like growth factor ectodomain shedding. J Cell Biochem. 2005 Jan 1; 94(1):39-49.
  61. Orsola A, Estrada CR, Nguyen HT, Retik AB, Freeman MR, Peters CA, Adam RM. 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.
  62. Stehr M, Estrada CR, Khoury J, Danciu TE, Sullivan MP, Peters CA, Solomon KR, Freeman MR, Adam RM. 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.
  63. Adam RM, Eaton SH, Estrada C, Nimgaonkar A, Shih SC, Smith LE, Kohane IS, Bägli D, Freeman MR. 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.
  64. Danciu TE, Gagari E, Adam RM, Damoulis PD, Freeman MR. Mechanical strain delivers anti-apoptotic and proliferative signals to gingival fibroblasts. J Dent Res. 2004 Aug; 83(8):596-601.
  65. Adam R. Rho-kinase inhibitors: potential therapeutics for benign prostate hyperplasia. J Urol. 2003 Dec; 170(6 Pt 1):2523-4.
  66. Kim J, Adam RM, Solomon KR, Freeman MR. Involvement of cholesterol-rich lipid rafts in interleukin-6-induced neuroendocrine differentiation of LNCaP prostate cancer cells. Endocrinology. 2004 Feb; 145(2):613-9.
  67. Adam RM, Roth JA, Cheng HL, Rice DC, Khoury J, Bauer SB, Peters CA, Freeman MR. 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.
  68. Stehr M, Adam RM, Khoury J, Zhuang L, Solomon KR, Peters CA, Freeman MR. 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.
  69. Danciu TE, Adam RM, Naruse K, Freeman MR, Hauschka PV. Calcium regulates the PI3K-Akt pathway in stretched osteoblasts. FEBS Lett. 2003 Feb 11; 536(1-3):193-7.
  70. Adam RM, Danciu T, McLellan DL, Borer JG, Lin J, Zurakowski D, Weinstein MH, Rajjayabun PH, Mellon JK, Freeman MR. 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.
  71. Adam RM, Kim J, Lin J, Orsola A, Zhuang L, Rice DC, Freeman MR. 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.
  72. Zhuang L, Peng JB, Tou L, Takanaga H, Adam RM, Hediger MA, Freeman MR. 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.
  73. Orsola A, Adam RM, Peters CA, Freeman MR. 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.
  74. Kim J, Adam RM, Freeman MR. 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 1; 62(5):1549-54.
  75. Adam RM, Orsola A, Freeman MR. 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.
  76. Peng JB, Zhuang L, Berger UV, Adam RM, Williams BJ, Brown EM, Hediger MA, Freeman MR. CaT1 expression correlates with tumor grade in prostate cancer. Biochem Biophys Res Commun. 2001 Apr 6; 282(3):729-34.
  77. Duque JL, Adam RM, Mullen JS, Lin J, Richie JP, Freeman MR. 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.
  78. Nguyen HT, Adam RM, Bride SH, Park JM, Peters CA, Freeman MR. Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells. Am J Physiol Cell Physiol. 2000 Oct; 279(4):C1155-67.
  79. Nguyen HT, Bride SH, Badawy AB, Adam RM, Lin J, Orsola A, Guthrie PD, Freeman MR, Peters CA. 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.
  80. Adam RM, Borer JG, Williams J, Eastham JA, Loughlin KR, Freeman MR. 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.
  81. Borer JG, Park JM, Atala A, Nguyen HT, Adam RM, Retik AB, Freeman MR. 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.
  82. Duque JL, Loughlin KR, Adam RM, Kantoff PW, Zurakowski D, Freeman MR. Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer. Urology. 1999 Sep; 54(3):523-7.
  83. Park JM, Adam RM, Peters CA, Guthrie PD, Sun Z, Klagsbrun M, Freeman MR. AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells. Am J Physiol. 1999 Aug; 277(2 Pt 1):C294-301.
  84. Nguyen HT, Park JM, Peters CA, Adam RM, Orsola A, Atala A, Freeman MR. 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.
  85. Lin J, Adam RM, Santiestevan E, Freeman MR. 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.
  86. Dethlefsen SM, Raab G, Moses MA, Adam RM, Klagsbrun M, Freeman MR. 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 1; 69(2):143-53.
  87. Freeman MR, Paul S, Kaefer M, Ishikawa M, Adam RM, Renshaw AA, Elenius K, Klagsbrun M. 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 1; 68(3):328-38.
  88. Freeman MR, Yoo JJ, Raab G, Soker S, Adam RM, Schneck FX, Renshaw AA, Klagsbrun M, Atala A. 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 1; 99(5):1028-36.
  89. Adam RM, Chamberlin SG, Davies DE. Induction of anchorage-independent growth by amphiregulin. Growth Factors. 1996; 13(3-4):193-203.
  90. Adam R, Drummond DR, Solic N, Holt SJ, Sharma RP, Chamberlin SG, Davies DE. Modulation of the receptor binding affinity of amphiregulin by modification of its carboxyl terminal tail. Biochim Biophys Acta. 1995 Apr 6; 1266(1):83-90.
  91. Adam R, Schmidt C, Di Paolo M, Tulusan AH. [Long-term follow-up of patients with borderline tumors of the ovaries]. Gynakol Rundsch. 1990; 30 Suppl 1:48-50.
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