Core - Histopathology

Langston, Claire

Abstract

This core laboratory will provide gross and microscopic pathology support for projects using model systems for the delivery of various vectors. Samples are expected to be received from mice, rats, cotton rats, baboons, sheep, xenografts, and ultimately CF patients. The core director is Dr. Claire Langston, an experienced pediatric pulmonary pathologist. Expertise in in situ hybridization will be provided by Dr. Avi Orr-Urtreger who has published extensively with this method. This core facility will be located in the Research Histology Laboratory at Texas Children's Hospital. Procedures to be performed will include tissue handling and preparation, gross and microscopic pathological analysis, and evaluation of expression of transfected genes. Routine pathological stains will be used and a semiquantitative scoring system for pathology in the respiratory tract will be utilized. Histochemical detection of beta-galactosidase and immunohistochemical detection of adenoviral proteins and beta- galactosidase will be performed. Immunohistochemical detection of human CFTR will be performed using a variety of antibodies and detection methods. In situ hybridization for detection of transfected genes will be performed using human cDNA probes for transfection into rodents and using probes for the 3' untranslated region of transcripts in the case of samples from baboon or human tissue.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Heart, Lung, and Blood Institute (NHLBI)
• Type: Research Program Projects (P01)
• Project #: 5P01HL051754-04
• Application #: 5214123
• Support Year: 4
• Fiscal Year: 1996

Publications

Sakuma, Tsutomu; Gu, Xiu; Wang, Zheng et al. (2006) Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine. Crit Care Med 34:676-81

Toietta, Gabriele; Mane, Viraj P; Norona, Wilma S et al. (2005) Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci U S A 102:3930-5

Pastore, Lucio; Belalcazar, L Maria; Oka, Kazuhiro et al. (2004) Helper-dependent adenoviral vector-mediated long-term expression of human apolipoprotein A-I reduces atherosclerosis in apo E-deficient mice. Gene 327:153-60

Morral, Nuria; O'Neal, Wanda K; Rice, Karen et al. (2002) Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons. Hum Gene Ther 13:143-54

Toietta, Gabriele; Pastore, Lucio; Cerullo, Vincenzo et al. (2002) Generation of helper-dependent adenoviral vectors by homologous recombination. Mol Ther 5:204-10

O'Neal, W K; Zhou, H; Morral, N et al. (2000) Toxicity associated with repeated administration of first-generation adenovirus vectors does not occur with a helper-dependent vector. Mol Med 6:179-95

Morral, N; O'Neal, W; Rice, K et al. (1999) Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons. Proc Natl Acad Sci U S A 96:12816-21

Lee, B; Dennis, J A; Healy, P J et al. (1999) Hepatocyte gene therapy in a large animal: a neonatal bovine model of citrullinemia. Proc Natl Acad Sci U S A 96:3981-6

O'Neal, W K; Zhou, H; Morral, N et al. (1998) Toxicological comparison of E2a-deleted and first-generation adenoviral vectors expressing alpha1-antitrypsin after systemic delivery. Hum Gene Ther 9:1587-98

Morral, N; Parks, R J; Zhou, H et al. (1998) High doses of a helper-dependent adenoviral vector yield supraphysiological levels of alpha1-antitrypsin with negligible toxicity. Hum Gene Ther 9:2709-16