Photo of Rona S. Carroll,  PhD

Rona S. Carroll, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 278-0177
Fax: (617) 232-9029

Rona S. Carroll, PhD

Brigham And Women's Hospital


  • Assistant Professor, Medicine, Harvard Medical School


Research Abstract

The goal of our research is to understand how angiogenesis, and receptor mediated growth mechanisms contribute to nervous system neoplasia. Human malignant gliomas are among the most malignant and most intensely vascularized solid tumors. Tumor angiogenesis is believed to be mediated by soluble factors released from tumor cells which then act on endothelial cells in a paracrine manner. . Vascular endothelial growth factor (VEGF) is a prime regulator of normal and tumor angiogenesis as well as vasculogenesis. VEGF is expressed in glioma cells and its receptors (FLT-1 and KDR) are expressed in the same gliomas. We used a synthetic tyrosine phosphopeptide to raise an antibody that reports the phosphorylation state of tyrosine in the KDR receptor. Immunoblotting and immunostaining of this antibody shows that the KDR receptor is activated in human high grade astrocytomas (71%), but not low grade astrocytomas (0%).

Angiostatin and endostatin are two endogenous inhibitors of tumor-related angiogenesis by selective inhibition of endothelial cell growth. We have demonstrate that systemic administration of angiostatin efficiently suppresses malignant glioma growth in vivo. We are presently examining the effects of endostatin on glioma growth. The findings of the current study strongly support the hypothesis that the onset of angiogenesis is an important event during the disease progression of gliomas.


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  • Min L, Hodi FS, Giobbie-Hurder A, Ott PA, Luke JJ, Donahue H, Davis M, Carroll RS, Kaiser UB. Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study. Clin Cancer Res 2015; 21:749-55. PubMed
  • Thompson IR, Ciccone NA, Xu S, Zaytseva S, Carroll RS, Kaiser UB. GnRH Pulse Frequency-Dependent Stimulation of FSH硫 Transcription Is Mediated via Activation of PKA and CREB. Mol Endocrinol 2013; 27:606-18. PubMed
  • Jiang X, Xing H, Kim TM, Jung Y, Huang W, Yang HW, Song S, Park PJ, Carroll RS, Johnson MD. Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity. Stem Cells 2012; 30:1313-26. PubMed
  • Goutagny S, Yang HW, Zucman-Rossi J, Chan J, Dreyfuss JM, Park PJ, Black PM, Giovannini M, Carroll RS, Kalamarides M. Genomic profiling reveals alternative genetic pathways of meningioma malignant progression dependent on the underlying NF2 status. Clin Cancer Res 2010; 16:4155-64. PubMed
  • Lee YB, Polio S, Lee W, Dai G, Menon L, Carroll RS, Yoo SS. Bio-printing of collagen and VEGF-releasing fibrin gel scaffolds for neural stem cell culture. Exp Neurol 2010; 223:645-52. PubMed
  • Arai T, Benny O, Joki T, Menon LG, Machluf M, Abe T, Carroll RS, Black PM. Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes. Anticancer Res 2010; 30:1057-64. PubMed
  • Ciccone NA, Xu S, Lacza CT, Carroll RS, Kaiser UB. Frequency-dependent regulation of follicle-stimulating hormone beta by pulsatile gonadotropin-releasing hormone is mediated by functional antagonism of bZIP transcription factors. Mol Cell Biol 2010; 30:1028-40. PubMed
  • Schmidt NO, Ziu M, Cargioli T, Westphal M, Giese A, Black PM, Carroll RS. Inhibition of thromboxane synthase activity improves glioblastoma response to alkylation chemotherapy. Transl Oncol 2010; 3:43-9. PubMed
  • Yang HW, Menon LG, Black PM, Carroll RS, Johnson MD. SNAI2/Slug promotes growth and invasion in human gliomas. BMC Cancer 2010; 10:301. PubMed
  • Menon LG, Kelly K, Yang HW, Kim SK, Black PM, Carroll RS. Human bone marrow-derived mesenchymal stromal cells expressing S-TRAIL as a cellular delivery vehicle for human glioma therapy. Stem Cells 2009; 27:2320-30. PubMed
  • Lee DH, Ahn Y, Kim SU, Wang KC, Cho BK, Phi JH, Park IH, Black PM, Carroll RS, Lee J, Kim SK. Targeting rat brainstem glioma using human neural stem cells and human mesenchymal stem cells. Clin Cancer Res 2009; 15:4925-34. PubMed
  • Jeong KH,Gill JC,Nose V,Parlow AF,Carroll RS,Kaiser UB. Expression of a gonadotropin-releasing hormone receptor-simian virus 40 T antigen transgene has sex-specific effects on the reproductive axis. Endocrinology 2009; 150:3383-91. PubMed
  • Schmidt NO,Koeder D,Messing M,Mueller FJ,Aboody KS,Kim SU,Black PM,Carroll RS,Westphal M,Lamszus K. Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche. Brain Res 2009; 1268:24-37. PubMed
  • Benny O,Menon LG,Ariel G,Goren E,Kim SK,Stewman C,Black PM,Carroll RS,Machluf M. Local delivery of poly lactic-co-glycolic acid microspheres containing imatinib mesylate inhibits intracranial xenograft glioma growth. Clin Cancer Res 2009; 15:1222-31. PubMed
  • Benny O, Kim SK, Gvili K, Radzishevsky IS, Mor A, Verduzco L, Menon LG, Black PM, Machluf M, Carroll RS. In vivo fate and therapeutic efficacy of PF-4/CTF microspheres in an orthotopic human glioblastoma model. FASEB J 2007; 22:488-99. PubMed
  • Claus EB, Park PJ, Carroll R, Chan J, Black PM. Specific genes expressed in association with progesterone receptors in meningioma. Cancer Res 2008; 68:314-22. PubMed
  • Kalamarides M, Stemmer-Rachamimov AO, Takahashi M, Han ZY, Chareyre F, Niwa-Kawakita M, Black PM, Carroll RS, Giovannini M. Natural history of meningioma development in mice reveals: a synergy of Nf2 and p16(Ink4a) mutations. Brain Pathol 2007; 18:62-70. PubMed
  • Cao W, Mah K, Carroll RS, Slayden OD, Brenner RM. Progesterone withdrawal up-regulates fibronectin and integrins during menstruation and repair in the rhesus macaque endometrium. Hum Reprod 2007; 22:3223-31. PubMed
  • Tzika AA, Astrakas L, Cao H, Mintzopoulos D, Andronesi OC, Mindrinos M, Zhang J, Rahme LG, Blekas KD, Likas AC, Galatsanos NP, Carroll RS, Black PM. Combination of high-resolution magic angle spinning proton magnetic resonance spectroscopy and microscale genomics to type brain tumor biopsies. Int J Mol Med 2007; 20:199-208. PubMed
  • Ugur HC, Ramakrishna N, Bello L, Menon LG, Kim SK, Black PM, Carroll RS. Continuous intracranial administration of suberoylanilide hydroxamic acid (SAHA) inhibits tumor growth in an orthotopic glioma model. J Neurooncol 2007; 83:267-75. PubMed
  • Cargioli TG, Ugur HC, Ramakrishna N, Chan J, Black PM, Carroll RS. Establishment of an in vivo meningioma model with human telomerase reverse transcriptase. Neurosurgery 2007; 60:750-9; discussion 759-60. PubMed
  • Yu Y, Jiang X, Schoch BS, Carroll RS, Black PM, Johnson MD. Aberrant splicing of cyclin-dependent kinase-associated protein phosphatase KAP increases proliferation and migration in glioblastoma. Cancer Res 2007; 67:130-8. PubMed
  • Liu F, Park PJ, Lai W, Maher E, Chakravarti A, Durso L, Jiang X, Yu Y, Brosius A, Thomas M, Chin L, Brennan C, DePinho RA, Kohane I, Carroll RS, Black PM, Johnson MD. A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma. Cancer Res 2006; 66:10815-23. PubMed
  • Kim SK, Kim SU, Park IH, Bang JH, Aboody KS, Wang KC, Cho BK, Kim M, Menon LG, Black PM, Carroll RS. Human neural stem cells target experimental intracranial medulloblastoma and deliver a therapeutic gene leading to tumor regression. Clin Cancer Res 2006; 12:5550-6. PubMed
  • Ziu M, Schmidt NO, Cargioli TG, Aboody KS, Black PM, Carroll RS. Glioma-produced extracellular matrix influences brain tumor tropism of human neural stem cells. J Neurooncol 2006; 79:125-33. PubMed
  • Aboody KS, Najbauer J, Schmidt NO, Yang W, Wu JK, Zhuge Y, Przylecki W, Carroll R, Black PM, Perides G. Targeting of melanoma brain metastases using engineered neural stem/progenitor cells. Neuro-oncol 2006; 8:119-26. PubMed
  • Kim SK, Cargioli TG, Machluf M, Yang W, Sun Y, Al-Hashem R, Kim SU, Black PM, Carroll RS. PEX-producing human neural stem cells inhibit tumor growth in a mouse glioma model. Clin Cancer Res 2005; 11:5965-70. PubMed
  • Schmidt NO, Przylecki W, Yang W, Ziu M, Teng Y, Kim SU, Black PM, Aboody KS, Carroll RS. Brain tumor tropism of transplanted human neural stem cells is induced by vascular endothelial growth factor. Neoplasia 2005; 7:623-9. PubMed
  • Kirsch M, Weigel P, Pinzer T, Carroll RS, Black PM, Schackert HK, Schackert G. Therapy of hematogenous melanoma brain metastases with endostatin. Clin Cancer Res 2005; 11:1259-67. PubMed
  • Benny O, Duvshani-Eshet M, Cargioli T, Bello L, Bikfalvi A, Carroll RS, Machluf M. Continuous delivery of endogenous inhibitors from poly(lactic-co-glycolic acid) polymeric microspheres inhibits glioma tumor growth. Clin Cancer Res 2005; 11:768-76. PubMed
  • Schmidt KF, Ziu M, Schmidt NO, Vaghasia P, Cargioli TG, Doshi S, Albert MS, Black PM, Carroll RS, Sun Y. Volume reconstruction techniques improve the correlation between histological and in vivo tumor volume measurements in mouse models of human gliomas. J Neurooncol 2004; 68:207-15. PubMed
  • Schmidt NO, Ziu M, Carrabba G, Giussani C, Bello L, Sun Y, Schmidt K, Albert M, Black PM, Carroll RS. Antiangiogenic therapy by local intracerebral microinfusion improves treatment efficiency and survival in an orthotopic human glioblastoma model. Clin Cancer Res 2004; 10:1255-62. PubMed
  • Giussani C, Carrabba G, Pluderi M, Lucini V, Pannacci M, Caronzolo D, Costa F, Minotti M, Tomei G, Villani R, Carroll RS, Bikfalvi A, Bello L. Local intracerebral delivery of endogenous inhibitors by osmotic minipumps effectively suppresses glioma growth in vivo. Cancer Res 2003; 63:2499-505. PubMed
  • Bello L, Giussani C, Carrabba G, Pluderi M, Lucini V, Pannacci M, Caronzolo D, Tomei G, Villani R, Scaglione F, Carroll RS, Bikfalvi A. Suppression of malignant glioma recurrence in a newly developed animal model by endogenous inhibitors. Clin Cancer Res 2002; 8:3539-48. PubMed
  • Bello L, Lucini V, Carrabba G, Giussani C, Machluf M, Pluderi M, Nikas D, Zhang J, Tomei G, Villani RM, Carroll RS, Bikfalvi A, Black PM. Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2. Cancer Res 2001; 61:8730-6. PubMed
  • Bello L, Carrabba G, Giussani C, Lucini V, Cerutti F, Scaglione F, Landr. Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo. Cancer Res 2001; 61:7501-6. PubMed
  • Joki T, Machluf M, Atala A, Zhu J, Seyfried NT, Dunn IF, Abe T, Carroll RS, Black PM. Continuous release of endostatin from microencapsulated engineered cells for tumor therapy. Nat Biotechnol 2001; 19:35-9. PubMed
  • Joki T, Carroll RS, Dunn IF, Zhang J, Abe T, Black PM. Assessment of alterations in gene expression in recurrent malignant glioma after radiotherapy using complementary deoxyribonucleic acid microarrays. Neurosurgery 2001; 48:195-201; discussion 201-2. PubMed
  • Joki T, Heese O, Nikas DC, Bello L, Zhang J, Kraeft SK, Seyfried NT, Abe T, Chen LB, Carroll RS, Black PM. Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Cancer Res 2000; 60:4926-31. PubMed
  • Carroll RS, Zhang J, Bello L, Melnick MB, Maruyama T, McL Black P. KDR activation in astrocytic neoplasms. Cancer 1999; 86:1335-41. PubMed
  • Carroll RS, Zhang J, Black PM. Expression of estrogen receptors alpha and beta in human meningiomas. J Neurooncol 1999; 42:109-16. PubMed
  • Di Rocco F, Carroll RS, Zhang J, Black PM. Platelet-derived growth factor and its receptor expression in human oligodendrogliomas. Neurosurgery 1998; 42:341-6. PubMed
  • Shamah SM, Alberta JA, Giannobile WV, Guha A, Kwon YK, Carroll RS, Black PM, Stiles CD. Detection of activated platelet-derived growth factor receptors in human meningioma. Cancer Res 1997; 57:4141-7. PubMed
  • Carroll RS, Black PM, Zhang J, Kirsch M, Percec I, Lau N, Guha A. Expression and activation of epidermal growth factor receptors in meningiomas. J Neurosurg 1997; 87:315-23. PubMed
  • Carroll RS, Zhang JP, Black PM. Hormone receptors in vestibular schwannomas. Acta Neurochir (Wien) 1997; 139:188-92; discussion 193. PubMed
  • Carroll RS, Zhang J, Chauncey BW, Chantziara K, Frosch MP, Black PM. Apoptosis in astrocytic neoplasms. Acta Neurochir (Wien) 1997; 139:845-50. PubMed
  • Carroll RS, Schrell UM, Zhang J, Dashner K, Nomikos P, Fahlbusch R, Black PM. Dopamine D1, dopamine D2, and prolactin receptor messenger ribonucleic acid expression by the polymerase chain reaction in human meningiomas. Neurosurgery 1996; 38:367-75. PubMed
  • Carroll RS, Zhang J, Dashner K, Sar M, Black PM. Steroid hormone receptors in astrocytic neoplasms. Neurosurgery 1995; 37:496-503; discussion 503-4. PubMed
  • Carroll RS, Zhang J, Dashner K, Black PM. Progesterone and glucocorticoid receptor activation in meningiomas. Neurosurgery 1995; 37:92-7. PubMed
  • Guha A, Glowacka D, Carroll R, Dashner K, Black PM, Stiles CD. Expression of platelet derived growth factor and platelet derived growth factor receptor mRNA in a glioblastoma from a patient with Li-Fraumeni syndrome. J Neurol Neurosurg Psychiatry 1995; 58:711-4. PubMed
  • Carroll RS, Zhang J, Dashner K, Sar M, Wilson EM, Black PM. Androgen receptor expression in meningiomas. J Neurosurg 1995; 82:453-60. PubMed
  • Leon SP, Carroll RS, Dashner K, Glowacka D, Black PM. Messenger ribonucleic acid expression of platelet-derived growth factor subunits and receptors in pituitary adenomas. J Clin Endocrinol Metab 1994; 79:51-5. PubMed