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Related Research Units

Intellectual and Developmental Disabilities Research Center Research
Pathology Research

Research Overview

Our laboratory works to understand the pathological basis of Sudden Infant Death Syndrome (SIDS) and the means by which biological vulnerabilities intersect with environmental risk factors, putting infants at risk for sudden and unexpected death. We focus predominately on brain and brainstem mechanisms involved in homeostasis including serotonin, a neurotransmitter found by the laboratory to be abnormal in the brainstem of some SIDS infants. We have also reported evidence of hippocampal abnormalities in SIDS infants; abnormalities that we are pursuing with neuropathological and genetic approaches. New directions in our research include the potential role of peripheral and central inflammatory and biochemical mediators in the brainstem dysfunction in SIDS.

Parallel to our work in the brain, we are also working to identify biomarkers of SIDS risk. Most recently, we have reported elevated levels of serum serotonin in SIDS infants, a finding that suggests peripheral serotonin as one such biomarker.

Our laboratory works in close collaboration with clinicians developing translational approaches to Sudden and Unexpected Death in Pediatrics (SUDP) and molecular geneticists and physiologists studying animal models related to SIDS.

Research Background

Dr. Robin Haynes received her Ph.D. in Biochemistry from Wake Forest University Medical School where she trained in the mechanisms of oxidative stress and free radical injury. She joined the laboratory of Dr. Hannah Kinney as a post-doctoral fellow to investigate the role of oxidative stress in premature brain injury. She continued in the laboratory of Dr. Kinney as an Instructor to train in the areas of human brain development and neuropathology of Sudden Infant Death Syndrome (SIDS). Upon the retirement of Dr. Kinney, Dr. Haynes assumed the role of Principal Investigator of the laboratory and continues to focus her research on the pathology underlying SIDS.

 

Publications

  1. Histology-guided MRI segmentation of brainstem nuclei critical to consciousness. medRxiv. 2024 Oct 18. View Abstract
  2. Platelet Pathophysiology: Unexpected New Research Directions. Semin Thromb Hemost. 2024 Nov; 50(8):1187-1190. View Abstract
  3. Dysregulation of platelet serotonin, 14-3-3, and GPIX in sudden infant death syndrome. Sci Rep. 2024 05 15; 14(1):11092. View Abstract
  4. Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness. Sci Transl Med. 2024 May; 16(745):eadj4303. View Abstract
  5. Multiomic Analysis of Neuroinflammation and Occult Infection in Sudden Infant Death Syndrome. JAMA Neurol. 2024 Mar 01; 81(3):240-247. View Abstract
  6. Altered 5-HT2A/C receptor binding in the medulla oblongata in the sudden infant death syndrome (SIDS): Part II. Age-associated alterations in serotonin receptor binding profiles within medullary nuclei supporting cardiorespiratory homeostasis. J Neuropathol Exp Neurol. 2024 02 21; 83(3):144-160. View Abstract
  7. Sustaining wakefulness: Brainstem connectivity in human consciousness. bioRxiv. 2023 Jul 15. View Abstract
  8. Integration of imaging measurements at micro-, meso and macro-scale of the caudal medulla on a postmortem infant subject. Proc Int Soc Magn Reson Med Sci Meet Exhib Int Soc Magn Reson Med Sci Meet Exhib. 2023 Jun; 2023. View Abstract
  9. Altered 5-HT2A/C receptor binding in the medulla oblongata in the sudden infant death syndrome (SIDS): Part I. Tissue-based evidence for serotonin receptor signaling abnormalities in cardiorespiratory- and arousal-related circuits. J Neuropathol Exp Neurol. 2023 05 25; 82(6):467-482. View Abstract
  10. Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age. Adv Genet (Hoboken). 2023 Mar; 4(1):2200012. View Abstract
  11. Genetic Determinants of Sudden Unexpected Death in Pediatrics. Genet Med. 2022 04; 24(4):839-850. View Abstract
  12. Medullary Serotonergic Binding Deficits and Hippocampal Abnormalities in Sudden Infant Death Syndrome: One or Two Entities? Front Pediatr. 2021; 9:762017. View Abstract
  13. Association of Prenatal Exposure to Maternal Drinking and Smoking With the Risk of Stillbirth. JAMA Netw Open. 2021 08 02; 4(8):e2121726. View Abstract
  14. Airway basal stem cells generate distinct subpopulations of PNECs. Cell Rep. 2021 04 20; 35(3):109011. View Abstract
  15. Nicotinic Receptors in the Brainstem Ascending Arousal System in SIDS With Analysis of Pre-natal Exposures to Maternal Smoking and Alcohol in High-Risk Populations of the Safe Passage Study. Front Neurol. 2021; 12:636668. View Abstract
  16. The role of sodium channels in sudden unexpected death in pediatrics. Mol Genet Genomic Med. 2020 08; 8(8):e1309. View Abstract
  17. Editorial: New insights into the role of central serotonin in the maintenance of homeostasis, autonomic control, and sleep. Exp Neurol. 2020 06; 328:113263. View Abstract
  18. Concurrent prenatal drinking and smoking increases risk for SIDS: Safe Passage Study report. EClinicalMedicine. 2020 Feb; 19:100247. View Abstract
  19. Prenatal intermittent hypoxia sensitizes the laryngeal chemoreflex, blocks serotoninergic shortening of the reflex, and reduces 5-HT3 receptor binding in the NTS in anesthetized rat pups. Exp Neurol. 2020 04; 326:113166. View Abstract
  20. The Serotonin Brainstem Hypothesis for the Sudden Infant Death Syndrome. J Neuropathol Exp Neurol. 2019 09 01; 78(9):765-779. View Abstract
  21. Mutations in NRXN1 and NRXN2 in a patient with early-onset epileptic encephalopathy and respiratory depression. Cold Spring Harb Mol Case Stud. 2019 02; 5(1). View Abstract
  22. SCN1A variants associated with sudden infant death syndrome. Epilepsia. 2018 04; 59(4):e56-e62. View Abstract
  23. High serum serotonin in sudden infant death syndrome. Proc Natl Acad Sci U S A. 2017 07 18; 114(29):7695-7700. View Abstract
  24. The Lateral Temporal Lobe in Early Human Life. J Neuropathol Exp Neurol. 2017 Jun 01; 76(6):424-438. View Abstract
  25. Long-Term Neuropathological Changes Associated with Cerebral Palsy in a Nonhuman Primate Model of Hypoxic-Ischemic Encephalopathy. Dev Neurosci. 2017; 39(1-4):124-140. View Abstract
  26. Serotonin Receptors in the Medulla Oblongata of the Human Fetus and Infant: The Analytic Approach of the International Safe Passage Study. J Neuropathol Exp Neurol. 2016 Nov 01; 75(11):1048-1057. View Abstract
  27. Hippocampal Formation Maldevelopment and Sudden Unexpected Death across the Pediatric Age Spectrum. J Neuropathol Exp Neurol. 2016 Oct; 75(10):981-997. View Abstract
  28. A Century of Germinal Matrix Intraventricular Hemorrhage in Autopsied Premature Infants: A Historical Account. Pediatr Dev Pathol. 2016 Mar-Apr; 19(2):108-14. View Abstract
  29. Dentate gyrus abnormalities in sudden unexplained death in infants: morphological marker of underlying brain vulnerability. Acta Neuropathol. 2015 Jan; 129(1):65-80. View Abstract
  30. Magnetic resonance spectroscopy markers of axons and astrogliosis in relation to specific features of white matter injury in preterm infants. Neuroradiology. 2014 Sep; 56(9):771-9. View Abstract
  31. KCNQ1, KCNE2, and Na+-coupled solute transporters form reciprocally regulating complexes that affect neuronal excitability. Sci Signal. 2014 Mar 04; 7(315):ra22. View Abstract
  32. Serotonin metabolites in the cerebrospinal fluid in sudden infant death syndrome. J Neuropathol Exp Neurol. 2014 Feb; 73(2):115-22. View Abstract
  33. Neuropathologic studies of the encephalopathy of prematurity in the late preterm infant. Clin Perinatol. 2013 Dec; 40(4):707-22. View Abstract
  34. Development of brainstem 5-HT1A receptor-binding sites in serotonin-deficient mice. J Neurochem. 2013 Sep; 126(6):749-57. View Abstract
  35. Disconnection of the ascending arousal system in traumatic coma. J Neuropathol Exp Neurol. 2013 Jun; 72(6):505-23. View Abstract
  36. 12/15-lipoxygenase expression is increased in oligodendrocytes and microglia of periventricular leukomalacia. Dev Neurosci. 2013; 35(2-3):140-54. View Abstract
  37. Radial coherence of diffusion tractography in the cerebral white matter of the human fetus: neuroanatomic insights. Cereb Cortex. 2014 Mar; 24(3):579-92. View Abstract
  38. Mechanisms of perinatal brain injury. Neurol Res Int. 2012; 2012:157858. View Abstract
  39. Neuron deficit in the white matter and subplate in periventricular leukomalacia. Ann Neurol. 2012 Mar; 71(3):397-406. View Abstract
  40. Late development of the GABAergic system in the human cerebral cortex and white matter. J Neuropathol Exp Neurol. 2011 Oct; 70(10):841-58. View Abstract
  41. The serotonergic anatomy of the developing human medulla oblongata: implications for pediatric disorders of homeostasis. J Chem Neuroanat. 2011 Jul; 41(4):182-99. View Abstract
  42. Potential neuronal repair in cerebral white matter injury in the human neonate. Pediatr Res. 2011 Jan; 69(1):62-7. View Abstract
  43. The cerebral cortex overlying periventricular leukomalacia: analysis of pyramidal neurons. Brain Pathol. 2010 Jul; 20(4):803-14. View Abstract
  44. Novel neuropathologic findings in the Haddad syndrome. Acta Neuropathol. 2010 Feb; 119(2):261-9. View Abstract
  45. Nitrosative stress and inducible nitric oxide synthase expression in periventricular leukomalacia. Acta Neuropathol. 2009 Sep; 118(3):391-9. View Abstract
  46. Thalamic damage in periventricular leukomalacia: novel pathologic observations relevant to cognitive deficits in survivors of prematurity. Pediatr Res. 2009 May; 65(5):524-9. View Abstract
  47. Interleukin-6 and the serotonergic system of the medulla oblongata in the sudden infant death syndrome. Acta Neuropathol. 2009 Oct; 118(4):519-30. View Abstract
  48. Oxidative injury in the cerebral cortex and subplate neurons in periventricular leukomalacia. J Neuropathol Exp Neurol. 2008 Jul; 67(7):677-86. View Abstract
  49. Diffuse axonal injury in periventricular leukomalacia as determined by apoptotic marker fractin. Pediatr Res. 2008 Jun; 63(6):656-61. View Abstract
  50. Myelin abnormalities without oligodendrocyte loss in periventricular leukomalacia. Brain Pathol. 2008 Apr; 18(2):153-63. View Abstract
  51. TLR8: an innate immune receptor in brain, neurons and axons. Cell Cycle. 2007 Dec 01; 6(23):2859-68. View Abstract
  52. Is the late preterm infant more vulnerable to gray matter injury than the term infant? Clin Perinatol. 2006 Dec; 33(4):915-33; abstract x-xi. View Abstract
  53. Lipid peroxidation during human cerebral myelination. J Neuropathol Exp Neurol. 2006 Sep; 65(9):894-904. View Abstract
  54. Development of microglia in the cerebral white matter of the human fetus and infant. J Comp Neurol. 2006 Jul 10; 497(2):199-208. View Abstract
  55. Oxidative and nitrative injury in periventricular leukomalacia: a review. Brain Pathol. 2005 Jul; 15(3):225-33. View Abstract
  56. Axonal development in the cerebral white matter of the human fetus and infant. J Comp Neurol. 2005 Apr 04; 484(2):156-67. View Abstract
  57. Developmental lag in superoxide dismutases relative to other antioxidant enzymes in premyelinated human telencephalic white matter. J Neuropathol Exp Neurol. 2004 Sep; 63(9):990-9. View Abstract
  58. Interferon-gamma expression in periventricular leukomalacia in the human brain. Brain Pathol. 2004 Jul; 14(3):265-74. View Abstract
  59. Nitrosative and oxidative injury to premyelinating oligodendrocytes in periventricular leukomalacia. J Neuropathol Exp Neurol. 2003 May; 62(5):441-50. View Abstract
  60. Selective protection by stably transfected human ALDH3A1 (but not human ALDH1A1) against toxicity of aliphatic aldehydes in V79 cells. Chem Biol Interact. 2001 Jan 30; 130-132(1-3):261-73. View Abstract
  61. Structure-activity relationships for growth inhibition and induction of apoptosis by 4-hydroxy-2-nonenal in raw 264.7 cells. Mol Pharmacol. 2000 Oct; 58(4):788-94. View Abstract

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Phone: 617-919-4508
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