BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Josef Neu, M.D. Professor of Pediatrics eRA COMMONS USER NAME NEUJOS EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION Wisconsin State Univ. Whitewater, WI University of Wisconsin, Madison, WI John Hopkins Hospital, Baltimore, MD Stanford University, Stanford, CA DEGREE (if applicable) B.S. M.D. Resident Fellow YEAR(s) 1971 1975 1975-78 1978-80 FIELD OF STUDY Medicine Pediatrics Neonatology A. Personal Statement I have been a clinician/scientist in the area of neonatal gastrointestinal development and nutrition for over 30 years. My focus over the past decade has been on intestinal mucosal immunology and the intestinal microbiome. I have recently been the PI of an NIH RO1 application designed to evaluate the intestinal microbial ecology prior to the development of NEC so that we might discover whether there is a microbial pathogen that may be related to the pathogenesis of this disease. This grant ended in the Fall of 2013, but we are in the process of accumulating and analyzing additional data that will lead to further characterization of the microbial ecology of the preterm infants’ intestine prior to the development of NEC. Once this data is analyzed we plan to submit an RO1 or R21 to evaluate whether the microbes we see associated with NEC may actually be causative agent by the use of cell culture, zebrafish and germ free mouse models. We have been able to collect longitudinal fecal samples from nearly 900 preterm infants from this study. In some of our recent work, we discovered that preterm infant meconium (the first stools after birth) contain significant microbial DNA, which goes against current dogma that this material is sterile. This is especially pertinent in that meconium reflects the in-utero and amniotic fluid environment because the fetus swallows large quantities of amniotic fluid. Further studies by our group showed that the microbial sequences in meconium strongly resemble sequences found in amniotic fluid of babies who delivered prematurely. We have thus developed the novel hypothesis that the microbes in meconium reflect the intrauterine milieu and will lead to important clues as to the causes of prematurity. Additional studies in our lab have shown that very preterm infant meconium also has a higher concentration of inflammatory markers, suggesting that the microbial milieu will initiate inflammation in the fetal gastrointestinal tract, thereby causing the fetal inflammatory response syndrome (FIRS), which is thought to be a major cause of preterm labor. We have recently submitted a PO1 application to continue with this work. Positions and Honors Positions and Employment: Professor, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 1993-present Director, Neonatology Fellowship Program Division of Neonatology, University of Florida Medical Center, Gainesville, FL Awards and other Professional Activities: AAP-Section for Perinatal Pediatrics - Young Investigator Award. 1982 and 1984 Sabbatical (6 months) at Univ. of Bern, Switzerland - worked with Dr. Michael Lentze on the intracellular processing of lactase in CaCO2 cells (1987) NIH Study Section: Member of Gastrointestinal Mucosal Pathobiology Study Section NIH Study Section: -SBIR-Special Emphasis Review Panel PHS 398/2590 (Rev. 09/04) Page 6 Biographical Sketch Format Page Ad hoc reviewer for HED study section Ad hoc reviewer for several additional study sections over the years Ad Hoc Reviewer: NIH; March of Dimes; United States Department of Agriculture; Action Charities. Editorial Board-Neo-Reviews, Journal of Nutrition, Journal of Parenteral and Enteral Nutrition, Neonatology, Nutrition Reviews. Associate Editor: NeoReviews, Journal of Nutrition, Yearbook of Neonatology and Perinatal Medicine, PLOS One. Reviewer for: Acta Paediatrica Scandinavia, American Journal of Clinical Nutrition, American Journal of Physiology, Biochimica Biophysica Acta, Biology of the Neonate, Clinical Pediatrics, Critical Care Medicine, Cytokine, Gastroenterology, Gut, Journal of Endocrinology, Journal of Nutrition, Journal of Pediatric, Endocrinology, Journal of Pediatric Gastroenterology & Nutrition, Journal of Pediatrics, Journal of Perinatology, Journal of Sports Medicine, New England Journal of Medicine, Pediatrics, Pediatric Research, Proceedings of the National Academy of Sciences, The Journal of Maternal and Fetal Medicine Previous Council member and Chairman of National Organization of Neonatal Program Training Directors. Pertinent Publications (since 2009): 1) Li N, Russell WM, Douglas-Escobar M, Hauser N, Lopez M, Neu J. Live and Heat-killed Lactobacillus Rhamnosus GG (LGG): Effects on Pro and Anti- Inflammatory Cyto/Chemokines in Gastrostomy-Fed Infant Rats. Pediatr Res. 2009 Apr 22. 2) Mshvildadze M, Neu J. The infant intestinal microbiome: Friend or foe? Early Hum Dev. 2010 Jan 28. 3) Sharma R, Young C, Neu J.Molecular modulation of intestinal epithelial barrier: contribution of microbiota. J Biomed Biotechnol. 2010;2010:305879 4) Neu J, Lorca G, Kingma SD, Triplett EW The intestinal microbiome: relationship to type 1 diabetes.Endocrinol Metab Clin North Am. 2010 Sep;39(3):563-71. 5) Li N, Russell WM, Douglas-Escobar M, Hauser N, Lopez M, Neu J. Live and Heat-killed Lactobacillus Rhamnosus GG (LGG): Effects on Pro and Anti- Inflammatory Cyto/Chemokines in Gastrostomy-Fed Infant Rats. Pediatr Res. 2009 Apr 22. 6) Mshvildadze, M. Neu, J. Shuster; J. Theriaque D. Li, N, Mai V. Intestinal Microbial Ecology in Premature Infants Using Non-Culture Based Techniques. Journal of Pediatrics 2009 Sep 25. 7) Li, N., Douglas-Escobar, M., Hatch, M., Atkinson, M., Schatz, D., Neu J. 'Butyrate and Type 1 Diabetes: Can We Fix the Intestinal Leak? Journal of Pediatric Gastroenterology and Nutrition: 2010 Oct;51(4):414 8) Valladares R, Sankar D, Li N, Williams E, Lai KK, Abdelgeliel AS, Gonzalez CF, Wasserfall CH, Larkin J, Schatz D, Atkinson MA, Triplett EW, Neu J, Lorca GL. Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.PLoS One. 2010 May 6;5(5):e10507. 9) Kenneth Lau, Patrick Benitez, Alexandria Ardissone, Tenisha D. Wilson, Erin L. Collins,Graciela Lorca, Nan Li†, Dhyana Sankar, Clive Wasserfall, Josef Neu, Mark A. Atkinson‡, Desmond Schatz†, Eric W. Triplett, and Joseph Larkin III*, Inhibition of Type 1 Diabetes Correlated to a Lactobacillus johnsonii N6.2 Mediated Th17 Bias1. J Immunol. 2011 Feb 11. 10) Neu, J. Walker, W.A. Necrotizing Enterocolitis: New England Journal of Medicine 2011 Jan 20;364(3):255-64. 11) Murgas Torrazza R, Neu J. The developing intestinal microbiome and its relationship to health and disease in the neonate. J Perinatol. 2011 Apr;31 Suppl 1:S29-34. 12) Neu J, Rushing J. Cesarean Versus Vaginal Delivery: Long-term Infant Outcomes and the Hygiene Hypothesis. Clin Perinatol. 2011 Jun;38(2):321-31 13) Li N, Quidgley MC, Kobeissy FH, Joseph J, Neu J. Microbial cell components induced tolerance to flagellin-stimulated inflammation through Toll-like receptor pathways in intestinal epithelial cells.Cytokine. 2012 Dec;60(3):806-11. 14) Douglas-Escobar M, Elliott E, Neu J.Effect of intestinal microbial ecology on the developing brain.JAMA Pediatr. 2013 Apr 1;167(4):374-9. 15) Murguía-Peniche T, Mihatsch WA, Zegarra J, Supapannachart S, Ding ZY, Neu J.Intestinal mucosal defense system, Part 2. Probiotics and prebiotics.J Pediatr. 2013 Mar;162(3 Suppl):S64-71. 16) Murgas Torrazza R, Li N, Young C, Kobeissy F, Chow M, Chen S, Mai V, Sharma R, Hudak M, Shuster J, Neu J.Pilot Study Using Proteomics to Identify Predictive Biomarkers of Necrotizing Enterocolitis from Buccal Swabs in Very Low Birth Weight Infants.Neonatology. 2013 Sep 12;104(3):234-242. 17) Ma, L., Li N., Liu X., Shaw L., LiCalzi.S., Grant, M., Neu J. Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice. Nutrition. 2012 Nov;28(11-12):1186-91. 18) Mai V, Torrazza RM, Ukhanova M, Wang X, Sun Y, Li N, Shuster J, Sharma R, Hudak ML, Neu J. Distortions in development of intestinal microbiota associated with late onset sepsis in preterm infants. PLoS One. 2013;8(1):e52876. doi: 10.1371/journal.pone.0052876. 19) Murgas Torrazza, R., Nan Li, Christopher Young, Firas Kobeissy, Marjorie Chow, Sixue Chen, Volker Mai, Renu Sharma, Mark Hudak, Jonathan Shuster and Josef Neu Biomarkers for Early Diagnosis and Prediction of Necrotizing Enterocolitis in Very Low Birth Weight Infants. Neonatology. 2013;104(3):234-42.. 20) Shuster, J.F., Neu J. A Pocock approach to sequential meta-analysis of clinical trials. Research Synthesis Methods. Res Synth Methods. 2013 Sep;4(3). 21) Torrazza RM, Neu J.The altered gut microbiome and necrotizing enterocolitis. Clinics in Perinatol. 2013 Mar;40(1):93-108. 22) F Neu J, Bradley CL, Ding ZY, Tucker HN, Berseth CL.Feeding the preterm infant: opportunities and challenges of bringing science to the bedside.J Pediatr. 2013 Mar;162(3 Suppl):S10123) INeu J, Mihatsch WA, Zegarra J, Supapannachart S, Ding ZY, Murguía-Peniche T. Intestinal mucosal defense system, Part 1. Consensus recommendations for immunonutrients. J Pediatr. 2013 Mar;162(3 Suppl):S56-63 24) Murguía-Peniche T, Mihatsch WA, Zegarra J, Supapannachart S, Ding ZY, Neu J. Intestinal mucosal defense system, Part 2. Probiotics and prebiotics. J Pediatr. 2013 Mar;162(3 Suppl):S64-71 25) Torrazza RM, Li N, Neu J.Decoding the enigma of necrotizing enterocolitis in premature infants. Pathophysiology. 2013 Dec 24. 26) Torrazza RM, Ukhanova M, Wang X, Sharma R, Hudak ML, Neu J, Mai V.Intestinal microbial ecology and environmental factors affecting necrotizing enterocolitis.PLoS One. 2013 Dec 30;8(12):e83304. 27) Cacho N, Neu J. Manipulation of the intestinal microbiome in newborn infants. Adv Nutr. 2014 Jan 1;5(1):114-8. doi: 10.3945/an.113.004820.PMID: 24425730 28) Ardissone AN, de la Cruz DM, Davis-Richardson AG, Rechcigl KT, Li N, Drew JC, MurgasTorrazza R, Sharma R, Hudak ML, Triplett EW, Neu J. Meconium microbiome analysis identifies bacteria correlated with premature birth. PLoS One. 2014 Mar 10;9(3):e90784. doi: 10.1371/journal.pone.0090784. eCollection 2014.PMID: 24614698 29) Neu J. The developing intestinal microbiome: probiotics and prebiotics. World Rev Nutr Diet. 2014;110:167-76. doi: 10.1159/000358465. Epub 2014 Apr 11.PMID: 24751628 30) Neu J. Necrotizing enterocolitis. World Rev Nutr Diet. 2014;110:253-63. doi: 10.1159/000358474. Epub 2014 Apr 11. PMID: 24751635. 31) Abrahamsson TR, Rautava S, Moore AM, Neu J, Sherman PM. The Time for a Confirmative Necrotizing Enterocolitis Probiotics Prevention Trial in the Extremely Low Birth Weight Infant in North America Is Now! J Pediatr. 2014 Jun 16. pii: S0022-3476(14)00431-4. doi: 10.1016/j.jpeds.2014.05.012. C. Research Support. Ongoing research projects pertinent to the proposed research. Research Support. I have had near continuous NIH funding for the past 15 years and have also been funded by industry, foundations, and Children’s Miracle Network. RECENTLY COMPLETED 1 R01HD059143 - 01 (Neu, PI) 12/01/2008 – 11/30/2013 NIH Intestinal Microecology, Inflammatory Markers and Necrotizing Enterocolitis The goal is to evaluate the pathogenesis on neonatal necrotizing enterocolitis using non-culture based techniques and inflammatory biomarkers. 1 R01 NR014019 (Neu, co-PI) 3/18/2013 – 1/31/2018 NIH NINR Routine Aspiration of Residual Gastric Contents in VLBW The goal of this study is to improve the nutritional and health status of premature, very low birth weight (VLBW) infants. Results have the potential to reduce short/long-term health complications and costs of lengthy hospital stays by improving nutritional status and decreasing complications. Results are also expected to (a) fill an important knowledge gap about safety and necessity of routine gastric residual measurements, and (b) influence protocols and practices regarding routine GR measurement in this vulnerable population. 011PH-007-423-2961 (Murgas, PI; Neu Mentor) 11/17/2011 – 11/16/2013 Gerber Foundation Effects of NOT measuring gastric residuals in very low birth weight babies Training grant as a mentor for a New Investigator. UF00100174 (Neu, PI) 6/13/2012 – 6/13/2014 Covidien Non-invasive monitoring for feeding intolerance The goal of this project is to (a) identify measurement characteristics of the gastrointestinal motility-related functions in the preterm infants using non-invasive monitoring technologies such as near infrared spectroscopy (NIRS), electrogastrography (EGG), and bowel sound monitoring; and (b) relate the monitoring technologies to currently used techniques such as gastric residual measurements and abdominal circumference. Josef Neu Dr. Josef Neu, MD, did his medical school training at the University of Wisconsin, was a pediatric resident at Johns Hopkins and a postdoctoral neonatology fellow at Stanford University. He came to the University of Florida as an associate professor in 1984 to continue his research in developmental gastroenterology and neonatal biochemical nutrition. In 1987 he pursued additional research training at the University of Bern (Switzerland) on basic mechanisms affecting intracellular processing of lactase in the intestinal epithelium. He is internationally recognized for his research in developmental gastroenterology and nutrition and has most recently focused his research efforts on the intestinal microbiome and mucosal immunology. He has been NIH RO-1 funded to study the developing microbiome in babies at risk for developing necrotizing enterocolitis. This involves a multicenter evaluation of intestinal microbiota using novel non-culture based technologies. He is also evaluating the effects of the fetal microbiome as it relates to prematurity. Dr Neu maintains an active interest in residency and fellowship training. He has served as director of the neonatology fellowship training program at UF since 1986 and on the Council for the Organization of Neonatal Training Program Directors (ONTPD). He has recently completed 2 years as National chairman of the ONTPD. He is on the editorial board of 7 journals, has served on numerous NIH study sections and is also active in international education; as a member of International Postgraduate Organization for Knowledge Transfer Research and Teaching Excellent Students (IPOKRaTES), he has organized seminars in neonatal gastroenterology and nutrition in Turkey, Italy, Poland, Georgia, Latvia, Slovenia, Israel, China, Portugal, Mexico , United Arab Emirates, and Brazil. He is currently Chairman of the Board of the IPOKRaTES Foundation. Dr. Neu has been involved in the mentorship of over 20 postdoctoral M.D. neonatology fellows, a pediatric gastroenterology fellow, approximately 15 visiting international scholars, 2 Ph.D. postdoctoral fellows, over 20 undergraduate independent study students (the majority of whom have gone on to medical, veterinary or graduate school in the sciences). He has also mentored 15 high school students in his laboratory.