DF/HCC Program Affiliation

Neuro-Oncology

Research Abstract

My laboratory has a primary interest in understanding what regulates the growth of medulloblastomas, the most common malignant brain tumors of childhood. Medulloblastomas arise by oncogenic transformation of cerebellar granule cells. Several years ago, we discovered that the tumors express neurotrophins and their receptors, and that the expression of the neurotrophin-3 receptor, TrkC, is correlated with clinical outcome. Patients with tumors expressing high levels of trkC have a more favorable outcome than those with low expression. Our results now indicate that TrkC is more than a prognostic marker. Medulloblastomas undergo apoptosis when grown in vitro in the presence of neurotrophin-3 and apoptosis is highly correlated with TrkC expression in tumor biopsy samples. Moreover, medulloblastomas that have been induced to express TrkC grow more slowly as xenografts in nude mice. Since the majority of medulloblastomas also express the TrkC ligand, we have proposed that tumors with high TrkC expression have a better prognosis because the receptors induce cell death.

Ultimately, we aim to use our understanding of growth regulation in the central and peripheral nervous system to devise new therapies based on molecular mechanisms that underlie disease states. For example, experiments are being planned to test whether neurotrophin-3 can be used as a therapy for medulloblastomas, that may be less toxic than the traditional therapies of radiation and chemotherapy.

Publications

• Ullrich NJ, Robertson R, Kinnamon DD, Scott RM, Kieran MW, Turner CD, Chi SN, Goumnerova L, Proctor M, Tarbell NJ, Marcus KJ, Pomeroy SL.Moyamoya following cranial irradiation for primary brain tumors in children.Neurology 2007 Mar 20;68(12):932-8.
  17372129
• Lo KC, Rossi MR, Burkhardt T, Pomeroy SL, Cowell JK.Overlay analysis of the oligonucleotide array gene expression profiles and copy number abnormalities as determined by array comparative genomic hybridization in medulloblastomas.Genes Chromosomes Cancer
  17044047
• Ullrich NJ, Pomeroy SL.Molecular genetics of pediatric central nervous system tumors.Curr Oncol Rep 2006 Nov;8(6):423-9.
  17040620
• De Bortoli M, Castellino RC, Lu XY, Deyo J, Sturla LM, Adesina AM, Perlaky L, Pomeroy SL, Lau CC, Man TK, Rao PH, Kim JY.Medulloblastoma outcome is adversely associated with overexpression of EEF1D, RPL30, and RPS20 on the long arm of chromosome 8.BMC Can
  16968546
• Ullrich NJ, Marcus K, Pomeroy SL, Turner CD, Zimmerman M, Lehmann LE, Scott RM, Goumnerova L, Gillan E, Kieran MW, Chi SN.Transverse Myelitis After Therapy For Primitive Neuroectodermal Tumors.Pediatr Neurol 2006 Aug;35(2):122-125.
  16876009
• Pomeroy SL.Neural development and the ontogeny of central nervous system tumors.Neuron Glia Biol 2004 May;1(2):127-133.
  16520827
• Waber DP, Pomeroy SL, Chiverton AM, Kieran MW, Scott RM, Goumnerova LC, Rivkin MJ.Everyday cognitive function after craniopharyngioma in childhood.Pediatr Neurol 2006 Jan;34(1):13-9.
  16376272
• Isakoff MS, Sansam CG, Tamayo P, Subramanian A, Evans JA, Fillmore CM, Wang X, Biegel JA, Pomeroy SL, Mesirov JP, Roberts CW.Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformati
  16301525
• Kho AT, Zhao Q, Cai Z, Butte AJ, Kim JY, Pomeroy SL, Rowitch DH, Kohane IS.Conserved mechanisms across development and tumorigenesis revealed by a mouse development perspective of human cancers.Genes Dev 2004 Mar 15;18(6):629-40.
  15075291
• Kim JY, Nelson AL, Algon SA, Graves O, Sturla LM, Goumnerova LC, Rowitch DH, Segal RA, Pomeroy SL.Medulloblastoma tumorigenesis diverges from cerebellar granule cell differentiation in patched heterozygous mice.Dev Biol 2003 Nov 1;263(1):50-66.
  14568546
• Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP,
  11807556