Melissa D Halpern
- Associate Professor, Pediatrics - (Research Scholar Track)
- Ph.D. Microbiology and Immunology
- University of Arizona, Tucson, Arizona, United States
- University of Arizona, Tucson, Arizona (2009 - Ongoing)
- University of Arizona (2004 - 2009)
- University of Arizona (2002 - 2004)
- University of Arizona (2000 - 2002)
- Oak Ridge National Laboratory (1996 - 2000)
- Duke University, Durham, North Carolina (1993 - 1995)
- University of North Carolina at Chapel Hill (1990 - 1993)
- University of Arizona (1989 - 1990)
- UBRP Outstanding Faculty Mentor
- Undergraduate Bio Research Program, Spring 2011 (Award Finalist)
- Imedex Research Award
- CCFA National Research Conference, Spring 2005
No activities entered.
Master's ReportBME 909 (Spring 2021)
Honors Independent StudyNSCS 399H (Fall 2020)
Honors Independent StudyPSIO 399H (Spring 2020)
ThesisBME 910 (Spring 2020)
Rsrch Meth Biomed EngrBME 597G (Fall 2019)
Independent StudyPSIO 399 (Spring 2019)
Independent StudyPSIO 399 (Fall 2018)
Directed ResearchPSIO 492 (Spring 2018)
Honors ThesisPSIO 498H (Spring 2018)
Directed ResearchPSIO 492 (Fall 2017)
Honors ThesisPSIO 498H (Fall 2017)
Independent StudyPSIO 399 (Spring 2017)
Honors Independent StudyPSIO 499H (Fall 2016)
Honors Independent StudyPSIO 399H (Spring 2016)
Honors ThesisPSIO 498H (Spring 2016)
Independent StudyPSIO 499 (Spring 2016)
- Halpern, M., Cherrington, N. J., Estrada, T. E., Frisk, H. A., Canet, M. J., Hardwick, R. N., Dvorak, B., Lux, K., & Halpern, M. D. (2013). The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in experimental necrotizing enterocolitis. American journal of physiology. Gastrointestinal and liver physiology, 304(1).More infoNecrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants and is characterized by an extensive hemorrhagic inflammatory necrosis of the distal ileum and proximal colon. We have previously shown that, during the development of experimental NEC, the liver plays an important role in regulating inflammation in the ileum, and accumulation of ileal bile acids (BA) along with dysregulation of ileal BA transporters contributes to ileal damage. Given these findings, we speculated that hepatic BA transporters would also be altered in experimental NEC. Using both rat and mouse models of NEC, levels of Cyp7a1, Cyp27a1, and the hepatic BA transporters Bsep, Ntcp, Oatp2, Oatp4, Mrp2, and Mrp3 were investigated. In addition, levels of hepatic BA transporters were also determined when the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-18, which are both elevated in NEC, are neutralized during disease development. Ntcp and Mrp2 were decreased in NEC, but elevated ileal BA levels were not responsible for these reductions. However, neutralization of TNF-α normalized Ntcp, whereas removal of IL-18 normalized Mrp2 levels. These data show that the hepatic transporters Ntcp and Mrp2 are downregulated, whereas Cyp27a1 is increased in rodent models of NEC. Furthermore, increased levels of TNF-α and IL-18 in experimental NEC may play a role in the regulation of Ntcp and Mrp2, respectively. These data suggest the gut-liver axis should be considered when therapeutic modalities for NEC are developed.
- Halpern, M., Gephart, S. M., McGrath, J. M., Effken, J. A., & Halpern, M. D. (2012). Necrotizing enterocolitis risk: state of the science. Advances in neonatal care : official journal of the National Association of Neonatal Nurses, 12(2).More infoNecrotizing enterocolitis (NEC) is the most common cause of gastrointestinal-related morbidity and mortality in the neonatal intensive care unit (NICU). Its onset is sudden and the smallest, most premature infants are the most vulnerable. Necrotizing enterocolitis is a costly disease, accounting for nearly 20% of NICU costs annually. Necrotizing enterocolitis survivors requiring surgery often stay in the NICU more than 90 days and are among those most likely to stay more than 6 months. Significant variations exist in the incidence across regions and units. Although the only consistent independent predictors for NEC remain prematurity and formula feeding, others exist that could increase risk when combined. Awareness of NEC risk factors and adopting practices to reduce NEC risk, including human milk feeding, the use of feeding guidelines, and probiotics, have been shown to reduce the incidence of NEC. The purpose of this review is to examine the state of the science on NEC risk factors and make recommendations for practice and research.
- Halpern, M., Martin, N. A., Mount Patrick, S. K., Estrada, T. E., Frisk, H. A., Rogan, D. T., Dvorak, B., & Halpern, M. D. (2011). Active transport of bile acids decreases mucin 2 in neonatal ileum: implications for development of necrotizing enterocolitis. PloS one, 6(12).More infoNecrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants, but its etiology remains unclear. We have previously shown that mucin 2 (Muc2) positive goblet cells are significantly decreased in NEC. We have also shown that ileal bile acids (BAs) are significantly increased during the development of this disease. Because BAs can affect mucins, we hypothesized that elevated ileal BAs contribute to decreased Muc2 in experimental NEC. The role of Muc2 in NEC was evaluated in Winnie +/+ mice, a strain that produces aberrant Muc2. Muc2 and trefoil factor 3 (Tff3) were assessed in neonatal rats subjected to the NEC protocol when bile acids were removed, and in ileal explants from newborn and older rats cultured with and without BAs. Further, the role of active transport of BAs was determined using neonatal rats given the apical sodium dependent bile acid transporter (Asbt) inhibitor SC-435 and in neonatal Asbt knockout mice subjected to the NEC protocol. Mice with aberrant Muc2 had significantly greater incidence and severity of NEC. Using both in vivo and ex vivo techniques, we determined that BAs decrease Muc2 positive cells in neonatal but not older ileum. However, Tff3 positive cells are not decreased by BAs. In addition, active transport of BAs is required for BAs to decrease Muc2 in immature ileum. These data show that functional Muc2 plays a critical role in the prevention of NEC and BAs can potentiate the decreased Muc2 in disease development. Further, BAs have a more profound effect on Muc2 in immature versus older ileum, which may explain at least in part why NEC occurs almost exclusively in premature infants.
- Halpern, M., Dvorak, B., Khailova, L., Clark, J. A., Hosseini, D. M., Arganbright, K. M., Reynolds, C. A., & Halpern, M. D. (2008). Comparison of epidermal growth factor and heparin-binding epidermal growth factor-like growth factor for prevention of experimental necrotizing enterocolitis. Journal of pediatric gastroenterology and nutrition, 47(1).More infoNecrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of prematurely born infants. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) have protective effects against intestinal injury. The aim of this study was to compare the effect of oral administration of HB-EGF, EGF, or both on the incidence of NEC in a neonatal rat model.