Research Summary
Frances Northington’s research focuses on mechanisms of neurodegeneration following neonatal hypoxic-ischemia (HI) brain injury. Dr. Northington’s research team has developed one of the first mouse models of the role of hypothermia treatment following neonatal HI. Along with Dr. Chavez-Valdez, they have published multiple papers on this model. Dr. Northington was the first to recognize the importance of programmed necrosis in neonatal HI and has now defined novel roles for the endoplasmic reticulum and proteasome system in this injury. Dr. Northington has just begun a collaboration with Sujatha Kannan (Department of Anesthesiology and Critical Care Medicine-Pediatrics) to investigate the potential of nanoparticle delivery of N-acetyl cysteine as a microglial targeted therapeutic to prevent the development of cerebral palsy. This dendrimer-drug combination is under review by the FDA for use in humans. Additionally she, along with her former fellow, Dr. Fang, have found important novel responses to treatments aimed at mitochondrial neuroprotection in the neonatal model. In collaboration with Jiangyang Zhang and Dan Wu, Dr. Northington is co-investigator on an NIH grant that investigates novel and advanced imaging analysis of neonatal brain injury. From this work has recently come the first direct evidence of nuclear and mitochondrial swelling detected by MRI/DTI. She also collaborates with Raul Chavez-Valdez in his interest in the role of HI in perturbation of brain neurotrophins following neonatal HI. Dr. Northington is pioneering work on the effect of early life injury in the setting of genetic susceptibility to Alzheimer’s disease with Lee Martin on a funded R21. With Lauren Jantzie, she is also introducing advanced metrics of cognition and executive function to the evaluation of hypoxic-ischemic brain injury in newborns. Finally, Dr. Northington’s work extends to the clinic where Allen Everett, Ernest Graham and she have done a decadelong collection of neonatal brain injury biomarkers. She is funded through the NIH with several R01s, an R21 and a U01 grant.
Clinical Trials
Preterm Erythropoietin Neuroprotection Trial
Selected Publications
Hayashi M, Poretti A, Gorra M, Farzin A, Graham EM, Huisman TA, Northington FJ. “Prenatal Cerebellar Hemorrhage: Fetal and Postnatal Neuroimaging Findings and Postnatal Outcome.” Pediatr Neurol. 2015 Jan 29. pii: S0887-8994(15)00041-7. doi: 10.1016/j.pediatrneurol.2015.01.011. [Epub ahead of print] PubMed PMID: 25724371.
Wu D, Martin LJ, Northington FJ, Zhang J. “Oscillating gradient diffusion MRI reveals unique microstructural information in normal and hypoxia-ischemia injured mouse brains.” Magn Reson Med. 2014 Nov;72(5):1366-74. doi: 10.1002/mrm.25441. Epub 2014 Aug 28. PubMed PMID: 25168861; PubMed Central PMCID: PMC4198437.
Kesavan K, Ezell T, Bierman A, Nunes AR, Northington FJ, Tankersley CG, Gauda EB. “Breathing and temperature control disrupted by morphine and stabilized by clonidine in neonatal rats.” Respir Physiol Neurobiol. 2014 Sep 15;201:93-100. doi: 10.1016/j.resp.2014.06.015. Epub 2014 Jul 5. PubMed PMID: 25008573.
Xu J, Qin Q, Wu D, Hua J, Song X, McMahon MT, Northington FJ, Zhang J, van Zijl PC, Pekar JJ. “Steady pulsed imaging and labeling scheme for noninvasive perfusion imaging.” Magn Reson Med. 2015 Mar 2. doi: 10.1002/mrm.25641. [Epub ahead of print] PubMed PMID: 25732958.