Aliye Uc, MD
Research Profile

Research Interests.
Basic and Translational Research. Our laboratory focuses on the Cystic Fibrosis-related pancreatic disease. We study the pathogenesis of exocrine and endocrine pancreatic disease using the porcine and ferret models of CF. We have shown that the destruction of CF pancreas involves an immune-mediated mechanism that starts in utero. We are developing safe and efficient techniques to transfer genes to the pancreas as a potential treatment for CF pancreatic disease. We employ histopathology, immunohistochemistry, immunofluorescence, ELISA, immunoblotting, flow cytometry, RT-PCR and real-time qRT-PCR, inductively coupled plasma-mass spectroscopy (ICP-MS), laser capture microscopy-mass spectroscopy (LCM-MS), pancreatic fluid analysis and duct microperfusion techniques. Given the fact that nearly half of infants diagnosed at birth by CF newborn screening are pancreatic sufficient, we expect that the insight gained from our studies will lead to early interventions and preservation of the pancreatic function in children. Our long-term goal is to prevent pancreatic disease progression in CF patients by developing innovative therapies based on a mechanistic understanding of the disease process.

Clinical Research. Dr. Uc is the President to INSPPIRE (International Study Group of Pediatric Pancreatitis: In search for a cure). This multicenter study group was formed to address important questions such as the epidemiology, natural history and genotype-phenotype correlations in pediatric pancreatitis. Pancreatitis is a poorly understood problem in pediatrics for which there are no clear diagnostic guidelines or therapeutic alternatives. The constitution of INSPPIRE represents the first initiative to create a multi-center approach to systematically characterize pancreatitis in children. We are developing a database and sample repository of children with acute recurrent and chronic pancreatitis to understand the epidemiology, etiologies, natural history and disease outcomes. We anticipate that the results of our work will be crucial in paving a path towards therapies and management standards for children with pancreatitis. Our long-term goal is to develop novel, effective therapies to prevent the progression to acute recurrent and chronic pancreatitis in children.

Lab Members.
Michelle Griffin (RAIII),
Marwa Abu-El-Haija (post-doc), Maisam Abu-El-Haija (post-doc fellow), Elizabeth Buchanan (undergraduate student), Jasmine Grindeland (undergraduate student)

Model System.
Pig and ferret model of cystic fibrosis, pancreatic ductal epithelial cell cultures

Recent Publications

1. Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ, Rogan MP, Pezzulo AA, Karp PH, Itani OA, Kabel AC, Wohlford-Lenane CL, Davis GJ, Smith TL, Samuel M, Wax D, Murphy CN, Rieke A, Whitworth K, Uc A, Starner TD, Brogden KA, Shilyansky J, McCray PB, Zabner J, Prather RS and Welsh MJ. Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn Piglets. Science 321(5897):1837-41, 2008.
2. Uc, A, McDonagh AF, Stokes JB. Metabolism of heme in Caco-2 cells. Exp Physiol. 95:296-303, 2010.
3. Stoltz DA, Meyerholz DK, Pezzulo AA, Ramachandran S, Rogan MP, Davis GJ, Hanfland RA, Wohlford-Lenane C, Dohrn CL, Bartlett JA, Nelson GA IV, Chang EH, Taft PJ, Ludwig PS, Estin M, Hornick EE, Launspach JL, Samuel M, Rokhlina T, Karp PH, Ostedgaard LS, Uc A, Starner TD, Horswill AR, Brogden KA, Prather RS, Richter SS, Shilyansky J, McCray PG Jr, Zabner J, Welsh MJ. Cystic Fibrosis Pigs Develop Lung Disease and Exhibit Defective Bacterial Eradication at Birth. Science Translational Medicine. 2010:2;29ra31.
4. Ostedgaard LS, Meyerholz DK, Chen JH, Pezzulo AA, Karp PH, Rokhlina T, Ernst SE, Hanfland RA, Reznikov L, Ludwig PS, Rogan MP, Davis GJ, Dohrn CL, Taft PJ, Rector MV, Hornick E, Nassar P, Samuel M, Richter SS, Uc A, Shilyansky J, Prather RS, McCray, Jr., PB, Zabner J, Welsh MJ, Stoltz DA. Low Levels of cftr Activity in CFTRDF508/DF508 Pigs Do Not Prevent the Gastrointestinal and Lung Disease of Cystic Fibrosis. Science Translational Medicine, 3:74ra24; 2011.
5. Uc, A. Chronic Pancreatitis in Children: Current Knowledge in Diagnosis and Treatment. Journal of Pediatric Sciences 2011:3(4); e98.
6. Uc A, Zhu X, Wagner BA, Buettner GR, Berg DJ. Heme Oxygenase-1 is Protective against Non-Steroidal Anti-inflammatory Drug-Induced Gastric Ulcers. Journal of Pediatric Gastroenterology and Nutrition, 2011 Aug 25. [Epub ahead of print]. PMID: 21873894.
7. Abu-El-Haija M, Sinkora M, Meyerholz DK, Welsh MJ, McCray, Jr., PB, Butler J, Uc A. An Activated Immune and Inflammatory Response Targets the Newborn Cystic Fibrosis Pig Pancreas. Pancreatology 2011:11(5);506-515.

E-mail: aliye-uc@uiowa.edu