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Related Research Units

Intellectual and Developmental Disabilities Research Center Research
Pathology Research
Lehtinen Laboratory Research
F.M. Kirby Neurobiology Center

Research Background

Maria Lehtinen received her Ph.D. in Neurobiology from Harvard University, where she trained with Azad Bonni on signaling mechanisms that regulate neuronal survival and death. She joined Anna-Elina Lehesjoki’s lab for her first postdoc at the University of Helsinki where she investigated the role of redox homeostasis in progressive myoclonus epilepsy. She then carried out a second postdoc with Christopher A. Walsh at Children’s Hospital where she discovered that secreted factors in the cerebrospinal fluid (CSF) play an active role in instructing the development of the mammalian cerebral cortex. The Lehtinen lab carries out basic and translational research on CSF-based signaling. She has been supported by the NIH, NSF, Ellison/AFAR, and the Sigrid Juselius Foundation, and is currently an Alfred P. Sloan Research Fellow.

 

Publications

  1. Choroid Plexus Pathophysiology. Annu Rev Pathol. 2025 Jan; 20(1):193-220. View Abstract
  2. Choroid Plexus as a Mediator of CNS Inflammation in Multiple Sclerosis. Mult Scler. 2024 Dec; 30(5_suppl):19-23. View Abstract
  3. Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain. Nat Neurosci. 2024 Nov; 27(11):2115-2129. View Abstract
  4. Profiling metabolome of mouse embryonic cerebrospinal fluid following maternal immune activation. J Biol Chem. 2024 Oct; 300(10):107749. View Abstract
  5. The choroid plexus synergizes with immune cells during neuroinflammation. Cell. 2024 Sep 05; 187(18):4946-4963.e17. View Abstract
  6. BioLuminescent OptoGenetics in the choroid plexus: integrated opto- and chemogenetic control in vivo. Neurophotonics. 2024 Apr; 11(2):024210. View Abstract
  7. Mechanistic patterns and clinical implications of oncogenic tyrosine kinase fusions in human cancers. Nat Commun. 2024 Jun 14; 15(1):5110. View Abstract
  8. Antibodies expand the scope of angiotensin receptor pharmacology. Nat Chem Biol. 2024 Dec; 20(12):1577-1585. View Abstract
  9. WNT signalling control by KDM5C during development affects cognition. Nature. 2024 Mar; 627(8004):594-603. View Abstract
  10. Optimized Mass Spectrometry Detection of Thyroid Hormones and Polar Metabolites in Rodent Cerebrospinal Fluid. Metabolites. 2024 Jan 23; 14(2). View Abstract
  11. Mechanistic patterns and clinical implications of oncogenic tyrosine kinase fusions in human cancers. Res Sq. 2024 Jan 17. View Abstract
  12. A choroid plexus apocrine secretion mechanism shapes CSF proteome and embryonic brain development. bioRxiv. 2024 Jan 16. View Abstract
  13. Metabolomics of Mouse Embryonic CSF Following Maternal Immune Activation. bioRxiv. 2023 Dec 24. View Abstract
  14. Optimized Mass Spectrometry Detection of Thyroid Hormones and Polar Metabolites in Rodent Cerebrospinal Fluid. bioRxiv. 2023 Dec 08. View Abstract
  15. SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation. Fluids Barriers CNS. 2023 Dec 05; 20(1):89. View Abstract
  16. Antibodies Expand the Scope of Angiotensin Receptor Pharmacology. bioRxiv. 2023 Aug 24. View Abstract
  17. A collaboration between immune cells and the choroid plexus epithelium in brain inflammation. bioRxiv. 2023 Aug 08. View Abstract
  18. Snapshot: Choroid plexus brain barrier. Cell. 2023 08 03; 186(16):3522-3522.e1. View Abstract
  19. SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation. bioRxiv. 2023 Aug 03. View Abstract
  20. LRP1 mediates leptin transport by coupling with the short-form leptin receptor in the choroid plexus. bioRxiv. 2023 Jul 03. View Abstract
  21. Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution. Nat Commun. 2023 06 22; 14(1):3720. View Abstract
  22. Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1. Fluids Barriers CNS. 2023 Jun 16; 20(1):45. View Abstract
  23. Choroid plexus-targeted NKCC1 overexpression to treat post-hemorrhagic hydrocephalus. Neuron. 2023 05 17; 111(10):1591-1608.e4. View Abstract
  24. Outcomes of the 2019 hydrocephalus association workshop, "Driving common pathways: extending insights from posthemorrhagic hydrocephalus". Fluids Barriers CNS. 2023 Jan 13; 20(1):4. View Abstract
  25. In utero intracerebroventricular delivery of adeno-associated viral vectors to target mouse choroid plexus and cerebrospinal fluid. STAR Protoc. 2023 03 17; 4(1):101975. View Abstract
  26. The choroid plexus: a missing link in our understanding of brain development and function. Physiol Rev. 2023 01 01; 103(1):919-956. View Abstract
  27. Choroid plexus-CSF-targeted antioxidant therapy protects the brain from toxicity of cancer chemotherapy. Neuron. 2022 10 19; 110(20):3288-3301.e8. View Abstract
  28. Experimental approaches for manipulating choroid plexus epithelial cells. Fluids Barriers CNS. 2022 May 26; 19(1):36. View Abstract
  29. Young cerebrospinal fluid improves memory in old mice. Nature. 2022 05; 605(7910):428-429. View Abstract
  30. Disruption of GMNC-MCIDAS multiciliogenesis program is critical in choroid plexus carcinoma development. Cell Death Differ. 2022 08; 29(8):1596-1610. View Abstract
  31. Correction: MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus. Development. 2022 02 01; 149(3). View Abstract
  32. Mitochondria in Early Forebrain Development: From Neurulation to Mid-Corticogenesis. Front Cell Dev Biol. 2021; 9:780207. View Abstract
  33. Macrophages on the margin: choroid plexus immune responses. Trends Neurosci. 2021 11; 44(11):864-875. View Abstract
  34. MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus. Development. 2021 05 15; 148(10). View Abstract
  35. A cellular and spatial map of the choroid plexus across brain ventricles and ages. Cell. 2021 05 27; 184(11):3056-3074.e21. View Abstract
  36. Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development. Nat Commun. 2021 01 19; 12(1):447. View Abstract
  37. Inflammation of the Embryonic Choroid Plexus Barrier following Maternal Immune Activation. Dev Cell. 2020 12 07; 55(5):617-628.e6. View Abstract
  38. Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface. Neuron. 2020 11 25; 108(4):623-639.e10. View Abstract
  39. Choroid Plexus Organoids: Harnessing CSF Gatekeepers for Brain Therapeutics. Cell Stem Cell. 2020 08 06; 27(2):191-192. View Abstract
  40. Cerebrospinal Fluid Magnetic Resonance Imaging: Improving Early Diagnosis of Autism and Other Neurodevelopmental Conditions. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 07; 5(7):635-637. View Abstract
  41. Emergence and Developmental Roles of the Cerebrospinal Fluid System. Dev Cell. 2020 02 10; 52(3):261-275. View Abstract
  42. A concerted metabolic shift in early forebrain alters the CSF proteome and depends on MYC downregulation for mitochondrial maturation. Development. 2019 10 24; 146(20). View Abstract
  43. Spatiotemporal Gradient of Cortical Neuron Death Contributes to Microcephaly in Knock-In Mouse Model of Ligase 4 Syndrome. Am J Pathol. 2019 12; 189(12):2440-2449. View Abstract
  44. Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models. Cell. 2019 08 08; 178(4):867-886.e24. View Abstract
  45. Sister, Sister: Ependymal Cells and Adult Neural Stem Cells Are Separated at Birth by Geminin Family Members. Neuron. 2019 04 17; 102(2):278-279. View Abstract
  46. Sodium Channel SCN3A (NaV1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development. Neuron. 2018 09 05; 99(5):905-913.e7. View Abstract
  47. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Rep. 2018 07 24; 24(4):973-986.e8. View Abstract
  48. Downregulation of ribosome biogenesis during early forebrain development. Elife. 2018 05 10; 7. View Abstract
  49. Mice Expressing Myc in Neural Precursors Develop Choroid Plexus and Ciliary Body Tumors. Am J Pathol. 2018 06; 188(6):1334-1344. View Abstract
  50. Shining new light on migraine. Sci Transl Med. 2017 07 12; 9(398). View Abstract
  51. Say good night to your pain. Sci Transl Med. 2017 05 31; 9(392). View Abstract
  52. ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar granule neuron loss. Brain. 2017 05 01; 140(5):1267-1279. View Abstract
  53. Filtering more than light in the developing retina. Sci Transl Med. 2017 04 19; 9(386). View Abstract
  54. The brain's matchmakers. Sci Transl Med. 2017 03 08; 9(380). View Abstract
  55. CSF Makes Waves in the Neural Stem Cell Niche. Cell Stem Cell. 2016 11 03; 19(5):565-566. View Abstract
  56. Unverricht-Lundborg disease. Epileptic Disord. 2016 Sep 01; 18(S2):28-37. View Abstract
  57. Comment on "Multiple repressive mechanisms in the hippocampus during memory formation". Science. 2016 Jul 29; 353(6298):453. View Abstract
  58. Retrograde fibroblast growth factor 22 (FGF22) signaling regulates insulin-like growth factor 2 (IGF2) expression for activity-dependent synapse stabilization in the mammalian brain. Elife. 2016 04 15; 5. View Abstract
  59. Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells. Nat Cell Biol. 2016 Apr; 18(4):418-30. View Abstract
  60. Progressive Differentiation and Instructive Capacities of Amniotic Fluid and Cerebrospinal Fluid Proteomes following Neural Tube Closure. Dev Cell. 2015 Dec 21; 35(6):789-802. View Abstract
  61. Enlargement of choroid plexus in complex regional pain syndrome. Sci Rep. 2015 Sep 21; 5:14329. View Abstract
  62. Development and functions of the choroid plexus-cerebrospinal fluid system. Nat Rev Neurosci. 2015 Aug; 16(8):445-57. View Abstract
  63. Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway. Dev Neurobiol. 2016 Jan; 76(1):75-92. View Abstract
  64. Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production. J Neurosci. 2015 Mar 25; 35(12):4903-16. View Abstract
  65. The choroid plexus and cerebrospinal fluid: emerging roles in development, disease, and therapy. J Neurosci. 2013 Nov 06; 33(45):17553-9. View Abstract
  66. Isolation of cerebrospinal fluid from rodent embryos for use with dissected cerebral cortical explants. J Vis Exp. 2013 Mar 11; (73):e50333. View Abstract
  67. Adult neurogenesis: VCAM stems the tide. Cell Stem Cell. 2012 Aug 03; 11(2):137-8. View Abstract
  68. Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron. 2012 Apr 12; 74(1):41-8. View Abstract
  69. The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond. Cell Mol Life Sci. 2012 Sep; 69(17):2863-78. View Abstract
  70. Neurogenesis at the brain-cerebrospinal fluid interface. Annu Rev Cell Dev Biol. 2011; 27:653-79. View Abstract
  71. The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron. 2011 Mar 10; 69(5):893-905. View Abstract
  72. Proliferative and transcriptional identity of distinct classes of neural precursors in the mammalian olfactory epithelium. Development. 2010 Aug 01; 137(15):2471-81. View Abstract
  73. The apical complex couples cell fate and cell survival to cerebral cortical development. Neuron. 2010 Apr 15; 66(1):69-84. View Abstract
  74. Cystatin B deficiency sensitizes neurons to oxidative stress in progressive myoclonus epilepsy, EPM1. J Neurosci. 2009 May 06; 29(18):5910-5. View Abstract
  75. Regulation of neuronal cell death by MST1-FOXO1 signaling. J Biol Chem. 2009 Apr 24; 284(17):11285-92. View Abstract
  76. Demystifying MST family kinases in cell death. Curr Mol Med. 2008 Jun; 8(4):313-8. View Abstract
  77. Modeling oxidative stress in the central nervous system. Curr Mol Med. 2006 Dec; 6(8):871-81. View Abstract
  78. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006 Jun 02; 125(5):987-1001. View Abstract
  79. The transcription factor NFAT3 mediates neuronal survival. J Biol Chem. 2005 Jan 28; 280(4):2818-25. View Abstract
  80. Characterization of a neurotrophin signaling mechanism that mediates neuron survival in a temporally specific pattern. J Neurosci. 2003 Aug 13; 23(19):7326-36. View Abstract
  81. Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery. Mol Cell. 2002 May; 9(5):1005-16. View Abstract
  82. Agonists calcitonin, corticotropin-releasing hormone, and vasoactive intestinal peptide, but not prostaglandins or beta-adrenergic agonists, elevate cyclic adenosine monophosphate levels in oligodendroglial cells. J Neurosci Res. 2001 Jul 15; 65(2):165-72. View Abstract
  83. Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma. JAMA. 2001 Jan 03; 285(1):47-51. View Abstract
  84. Prerequisites for human papillomavirus vaccine trial: results of feasibility studies. J Clin Virol. 2000 Oct; 19(1-2):25-30. View Abstract
  85. Outcome for patients with leukemia, multiple myeloma and lymphoma who relapse after high dose therapy and autologous stem cell support. Leuk Lymphoma. 1996 Dec; 24(1-2):81-91. View Abstract
  86. Serum antibodies and subsequent cervical neoplasms: a prospective study with 12 years of follow-up. Am J Epidemiol. 1993 Jan 15; 137(2):166-70. View Abstract
  87. Quantity of nuclear DNA in malignancies and benign lymphadenopathies associated with Epstein-Barr virus. J Clin Pathol. 1989 Jul; 42(7):699-704. View Abstract

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