{"id":2323,"date":"2018-09-01T00:00:00","date_gmt":"2018-09-01T04:00:00","guid":{"rendered":"https:\/\/www.med.unc.edu\/childrensresearch\/2018\/09\/september-2018-update\/"},"modified":"2019-07-30T17:32:34","modified_gmt":"2019-07-30T21:32:34","slug":"september-2018-update","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/childrensresearch\/2018\/09\/september-2018-update\/","title":{"rendered":"September 2018 Update"},"content":{"rendered":"

In addition to our regular CRI Activities Update, this month\u2019s Research Focus highlights the research and work of Haiyan FU, PhD, Research Associate Professor of Pediatrics in the division of Genetics and Metabolism.<\/em><\/p>\n

Activities Update<\/u>:<\/p>\n

We are excited to welcome James Hagood, MD to UNC! Dr. Hagood comes from Rady Children\u2019s in University of California San Diego. Here at UNC he will serve as the Director of the Center for Rare and Interstitial Lung Disease, UNC Marsico Lung Institute and Children\u2019s Research Institute. He is an expert in Childhood Interstitial Lung Disease, working on triggers\/regulators of alveolar development, response to lung injury, and development of fibrosis. In this capacity he examines the epigenetic regulation of airway remodeling and normal lung development. His goal is to not only arrest but reverse fibrosis, a process once thought to be irreversible. Please join us in giving Dr. Hagood a warm welcome!<\/p>\n

Our new chair, Dr. Davis, had the pleasure of presenting at the School of Medicine, Office of Research annual retreat. She highlighted our many pediatric research activities, and goals to continue to build strong programs in clinical, translational, and basic research.<\/p>\n

The CRI is excited to announce that we will be cosponsoring a symposium focused on research in children\u2019s environmental health with the Center for Environmental Health and Susceptibility at the Gillings School of Global Public Health. \u201cKids Matter! Research to Action in Children\u2019s Environmental Health\u201d will be held at the Sonja Hayes Stone Center for Black Culture and History on Friday, October 12, 2018 from 9:00am-4:30pm. The symposium will bring together scientists, clinicians, public health professionals and community advocates interested in emerging research in the field to stimulate scientific collaboration within and across disciplines. Details and registration information will be out soon.<\/p>\n

Reminder<\/u>: Haiyan Fu, PhD, will be presenting \u201cCross Blood-Brain Barrier Gene Delivery for Treating Neuropathic Lysosomal Storage Diseases\u201d at our next CRI luncheon seminar series. This event will be held on Tuesday, September 11 from 12:15-1:30pm in the Bioinformatics Auditorium (room 1131). Please mark your calendars. We look forward to seeing you there.<\/p>\n

Research Focus of the Month<\/u>:<\/p>\n

\n
\"\"<\/a>
Haiyan Fu, PhD<\/figcaption><\/figure><\/figure>\n

The Department of Pediatrics is also pleased to welcome Haiyan Fu, PhD, to the UNC School of Medicine. Dr. Fu comes from The Research Institute at Nationwide Children\u2019s Hospital, Center for Gene Therapy. She has a long-standing interest in the development of gene therapy to treat neuropathic mucopolysaccharidosis (MPS) disorders, and collaborates with Joseph Muenzer, MD, PhD, in this arena. There are 11 types of MPS, all of which are inherited disorders where the body\u2019s enzymes cannot break down glycosaminoglycans. This buildup can lead to neurological impairment, stunted growth, and multisystem manifestations. Physical symptoms of MPS are managed through bone marrow transplants and enzyme replacement therapy. However, neurological manifestations of the disease are difficult to ameliorate because current therapeutics cannot cross the blood-brain barrier (BBB). In developing experimental treatments for MPS, Dr. Fu\u2019s research has focused on strategies to overcome the BBB to deliver genes to the Central Nervous System. To this end, Dr. Fu\u2019s team has developed novel gene therapy products that target the root cause of the disease, using adeno-associated virus (AAV) vectors that can cross the BBB to replace the defective gene with a correct gene, treating both the neurological and somatic manifestations of several MPS diseases via a single systemic administration. In collaboration with Dr. Muenzer, their MPS gene therapy research projects have led to 3 IND approvals from the FDA for phase 1\/2 clinical trials of systemic AAV9 gene delivery in pediatric patients with MPS IIIA, MPS IIIB and MPS II.<\/p>\n

Dr. Fu also studies the pathology and pathophysiology of MPS disorders, in order to better understand the disease mechanisms and identify alternative therapeutic targets. In recent years, her research team has expanded efforts to overcome the major challenges in translation of AAV gene therapy to clinical application in humans. Her team has been exploring potential biomarkers, especially neuro-specific biomarkers of MPS disease progression, which could be used as surrogate outcome measures in clinical trials for MPS and possibly other lysosomal storage diseases. For effective translation of AAV gene therapy, the team has also been working on developing approaches for effective depletion of the pre-existing antibodies against AAV, which is widespread in humans. Ongoing efforts in Fu lab also include developing strategies facilitating cross-BBB gene and drug delivery for the treatment of the CNS neurological diseases.<\/p>\n

For further information:<\/p>\n

Fu H, Zaraspe K, Murakami N, Meadows AS, Pineda RJ, McCarty DM, Muenzer J (2018) Targeting the root cause by a systemic scAAV9-hIDS<\/em>gene delivery: functional correction and reversal of severe MPS II in mice. Mol Ther Methods Clin Dev. 2018 (in press)<\/p>\n

Fu, H, Meadows, AS, Pineda, RJ, Mohney, RP, Stirdivant, S, and McCarty. Serum global metabolomics profiling reveals profound metabolic impairments in patients with MPS IIIA and MPS IIIB. Metabolic brain disease. DOI: 10.1007\/s11011-017-0009-1 Metab Brain Dis.\u00a02017 Oct;32(5):1403-1415. doi: 10.1007\/s11011-017-0009-1. Epub 2017 Apr 5. PMID: 28382573<\/p>\n

Fu, H., et al. (2017). \u201cDifferential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy Children and Patients with Mucopolysaccharidosis III: Perspective for AAV-Mediated Gene Therapy.\u201d Hum Gene Ther Clin Dev 2017:28(4): 187-196.<\/p>\n

Velazquez VM, Meadows AS, Pineda RJ, Camboni M, McCarty DM, Fu H. Effective Depletion of Pre-existing anti-AAV Antibodies Requires Broad Immune Targeting. Mol Ther Clin Methods Dev.\u00a02017 Mar 17; 4: 159\u201316. PMID: 28345001.<\/p>\n

Fu H, Meadows AS, Ware T, Mohney RP,3 McCarty DM. Near complete correction of profound metabolomic impairments corresponding to functional benefit in MPS IIIB mice after IV rAAV9-hNAGLU gene delivery. Mol Ther. DIO: 10.1016\/j.ymthe.2016.12. Mol Ther.\u00a02017 Mar 1;25(3):792-802. doi: 10.1016\/j.ymthe.2016.12.025. Epub 2017 Jan 28. PMID: 28143737<\/p>\n

Fu, H., et al. \u201cFunctional correction of neurological and somatic disorders at later stages of disease in MPS IIIA mice by systemic scAAV9-hSGSH gene delivery.\u201d Mol Ther Methods Clin Dev 2016: 3: 16036.<\/p>\n

Duncan, F. J., et al. \u201cBroad functional correction of molecular impairments by systemic delivery of scAAVrh74-hSGSH gene delivery in MPS IIIA mice.\u201d Mol Ther 2015: 23(4): 638-647.<\/p>\n

Meadows, A. S., et al. (2015). \u201cA GLP-Compliant Toxicology and Biodistribution Study: Systemic Delivery of an rAAV9 Vector for the Treatment of Mucopolysaccharidosis IIIB.\u201d Hum Gene Ther Clin Dev 26(4): 228-242.<\/p>\n

Naughton, B. J., et al. (2015). \u201cBlood genome-wide transcriptional profiles reflect broad molecular impairments and strong blood-brain links in Alzheimer\u2019s disease.\u201d J Alzheimers Dis 2015: 43(1): 93-108.<\/p>\n

Fu, H., et al. (2011). \u201cCorrection of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 trans-blood-brain barrier gene delivery.\u201d Mol Ther 2011:19(6): 1025-1033.<\/p>\n","protected":false},"excerpt":{"rendered":"

In addition to our regular CRI Activities Update, this month\u2019s Research Focus highlights the research and work of Haiyan FU, PhD, Research Associate Professor of Pediatrics in the division of Genetics and Metabolism. Activities Update: We are excited to welcome James Hagood, MD to UNC! Dr. Hagood comes from Rady Children\u2019s in University of California … Read more<\/a><\/p>\n","protected":false},"author":79819,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[3],"tags":[],"class_list":["post-2323","post","type-post","status-publish","format-standard","hentry","category-news","odd"],"acf":[],"yoast_head":"\nSeptember 2018 Update - UNC Children's Research Institute<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/childrensresearch\/2018\/09\/september-2018-update\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"September 2018 Update - UNC Children's Research Institute\" \/>\n<meta property=\"og:description\" content=\"In addition to our regular CRI Activities Update, this month\u2019s Research Focus highlights the research and work of Haiyan FU, PhD, Research Associate Professor of Pediatrics in the division of Genetics and Metabolism. 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