Skip to content

Josh Bonkowsky

Professor of Pediatric Neurology, Adjunct Professor of Neurobiology, Adjunct Professor and of Neurology

Chief, Division of Pediatric Neurology
Director, Primary Children's Center for Pediatric Personalized Medicine

Function of Human Disease Genes in CNS Development



Molecular Biology Program


B.A. Harvard University

M.D./Ph.D. University of California, San Diego



Axon pathfinding and development of CNS connectivity; function of human disease genes in CNS development 

Our research is centered on studying the development of CNS connectivity and neurodevelopmental disorders. Neurodevelopmental disorders are very common, but poorly understood in terms of their pathophysiology and effects on CNS development. 

1. Developmental functions of human disease genes. 
  • We are studying human leukodystrophies. Inherited leukodystrophies are diseases of the myelin, including abnormal myelin development, hypomyelination, or degeneration of myelin.  The incidence of leukodystrophies is almost 1 in 7500 live births.  Typical disease presentation occurs in the first three years of life with a 34% risk of death by age 8 years (Bonkowsky et al., 2010). 
  • Vanishing white matter disease (VWMD) is a frequent cause of leukodystrophies with no known cure.  VWMD is an autosomal recessive leukodystrophy caused by mutations in the eukaryotic initiation factor 2B (eif2B) gene family.  
  • We are developing zebrafish models of VWMD, as well as of other common leukodystrophies including ALD, MLD, and PMD.
2. Effects of hypoxia on CNS Development. 
  • Hypoxic injury to the developing human brain causes life-long intellectual and behavioral deficits. These serious outcomes include autism spectrum disorders, cerebral palsy, depression, epilepsy, and intellectual disabilities. Currently there are no treatments to protect against the effects of prematurity and chronic hypoxic injury to the central nervous system (CNS). The ultimate goal of our research is to understand the fundamental molecular and neurobiological mechanisms by which hypoxia disrupts connectivity.
  • We use a combination of novel transgenic lines and innovative chemical and imaging approaches. Elucidation of these mechanisms offers the potential for designing effective and targeted therapeutic approaches.
3.  Genomic medicine, big data, and novel therapeutics including gene therapy.
  • We are collaborating closely with our clinical colleagues to understand the roles and contributions of genetic changes to pediatric disease, particularly in patients with leukodystrophies and epilepsy.
  • We have several gene therapy projects in process; as well as the development of novel therapeutic approaches to pediatric disease.
  • Using large national databases, we are studying hidden patterns of disease and new potentials to improve pediatric health.

References (Selected Publications)

  1. Son JH, Gerenza AK, Bingener GM, Bonkowsky JL. Hypoplasia of dopaminergic neurons by hypoxia-induced neurotoxicity is associated with disrupted swimming development of larval zebrafish. Front Cell Neurosci. 2022 Sep 23;16:963037. doi: 10.3389/fncel.2022.963037. PMID: 36212692; PMCID: PMC9540391.
  2. Baker M, Olsen JC, Wilkes J, Sweney M, Soisson S, Bonkowsky JL. Similar antiseizure medication refill characteristics in Hispanic and White pediatric patients. Epilepsy Res. 2022 Aug;184:106970. doi: 10.1016/j.eplepsyres.2022.106970. Epub 2022 Jun 17. PMID: 35779465.
  3. Baker M, Mason CC, Wilkes J, Sant D, Sweney M, Bonkowsky JL. Long-Term Health Outcomes of Infantile Spasms Following Prednisolone vs. Adrenocorticotropic Hormone Treatment Characterized Using Phenome-Wide Association Study. Front Neurol. 2022 Apr 13;13:878294. doi: 10.3389/fneur.2022.878294. PMID: 35493808; PMCID: PMC9043313.
  4. Derksen A, Shih HY, Forget D, Darbelli L, Tran LT, Poitras C, Guerrero K, Tharun S, Alkuraya FS, Kurdi WI, Nguyen CE, Laberge AM, Si Y, Gauthier MS, Bonkowsky JL, Coulombe B, Bernard G. Variants in LSM7 impair LSM complexes assembly, neurodevelopment in zebrafish and may be associated with an ultra-rare neurological disease. HGG Adv. 2021 May 5;2(3):100034. 
  5. Bonkowsky JL, Keller S; AAP Section on Neurology, Council on Genetics. Leukodystrophies in Children: Diagnosis, Care, and Treatment. Pediatrics. 2021 Aug 23:e2021053126.
  6. Nuebel E, Morgan JT, Fogarty S, Winter JM, Lettlova S, Berg JA, Chen YC, Kidwell CU, Maschek JA, Clowers KJ, Argyriou C, Chen L, Wittig I, Cox JE, Roh-Johnson M, Braverman N, Bonkowsky J, Gygi SP, Rutter J. The biochemical basis of mitochondrial dysfunction in Zellweger Spectrum Disorder. EMBO Rep. 2021 Aug 5:e51991.
  7. Russell KL, Downie JM, Gibson SB, Tsetsou S, Keefe MD, Duran JA, Figueroa KP, Bromberg MB, Murtaugh LC, Bonkowsky JL*, Pulst SM*, Jorde LB*. Pathogenic effect of TP73 Gene Variants in People With Amyotrophic Lateral Sclerosis. Neurology. 2021 Jun 16;97(3):e225–35. *co-senior authors
  8. Raas Q, van de Beek MC, Forss-Petter S, Dijkstra IM, Deschiffart A, Freshner BC, Stevenson TJ, Jaspers YR, Nagtzaam L, Wanders RJ, van Weeghel M, Engelen-Lee JY, Engelen M, Eichler F, Berger J, Bonkowsky JL*, Kemp S*. Metabolic rerouting via SCD1 induction impacts X-linked adrenoleukodystrophy. J Clin Invest. 2021 Apr 15;131(8):e142500. *co-senior authors       
  9. Keefe MD, Soderholm HE, Shih HY, Stevenson TJ, Glaittli KA, Bowles DM, Scholl E, Colby S, Merchant S, Hsu EW, Bonkowsky JL. Vanishing white matter disease expression of truncated EIF2B5 activates induced stress response. Elife. 2020 Dec 10;9:e56319. 
  10. Bonkowsky JL, Wilkes J, Ying J, Wei WQ. Novel and known morbidities of leukodystrophies identified using a phenome-wide association study. Neurol Clin Pract. 2020 Oct;10(5):406-414. 
  11. Urbik VM, Schmiedel M, Soderholm H, Bonkowsky JL. Expanded Phenotypic Definition Identifies Hundreds of Potential Causative Genes for Leukodystrophies and Leukoencephalopathies. Child Neurol Open. 2020 Jul 8;7:2329048X20939003. 
  12. Soderholm HE, Chapin AB, Bayrak-Toydemir P, Bonkowsky JL. Elevated Leukodystrophy Incidence Predicted From Genomics Databases. Pediatr Neurol. 2020 Oct;111:66-69. doi: 10.1016/j.pediatrneurol.2020.06.005. Epub 2020 Jun 17. 
  13. Grineski S, Morales DX, Collins T, Wilkes J, Bonkowsky JL. Geographic and Specialty Access Disparities in US Pediatric Leukodystrophy Diagnosis. J Pediatr. 2020 May;220:193-199.
  14. Son JH, Stevenson TJ, Bowles MD, Scholl EA, Bonkowsky JL. Dopaminergic Co-Regulation of Locomotor Development and Motor Neuron Synaptogenesis is Uncoupled by Hypoxia in Zebrafish. eNeuro. 2020 Jan 30.
  15. Bonkowsky JL, Wilkes J, Bardsley T, Urbik VM*, Stoddard G. Association of Diagnosis of Leukodystrophy With Race and Ethnicity Among Pediatric and Adolescent Patients. JAMA Netw Open. 2018 Nov 2;1(7):e185031. 
  16. Bonkowsky JL, Son JH. Hypoxia and connectivity in the developing vertebrate nervous system. Dis Model Mech. 2018 Dec 12;11(12). 
  17. Bonkowsky JL, Wilkes J, Shyr DC. Scope and Burden of Non-Standard of Care Hematopoietic Stem Cell Transplantation in Pediatric Leukodystrophy Patients. J Child Neurol. 2018 Dec;33(14):882-887.
  18. Bakian AV, Bilder DA, Korgenski EK, Bonkowsky JL. Autism Spectrum Disorder and Neonatal Serum Magnesium Levels in Preterm Infants. Child Neurol Open. 2018 Sep 18;5:2329048X18800566. 
  19. Ostrander BEP, Butterfield RJ, Pedersen BS, Farrell AJ, Layer RM, Ward A, Miller C, DiSera T, Filloux FM, Candee MS, Newcomb T, Bonkowsky JL^, Marth GT^, Quinlan AR^. Whole-genome analysis for effective clinical diagnosis and gene discovery in early infantile epileptic encephalopathy. NPJ Genom Med. 2018 Aug 13;3:22. ^ co-senior authors.
  20. Gao J, Stevenson TJ, Douglass AD, Barrios JP, Bonkowsky JL. The Midline Axon Crossing Decision Is Regulated through an Activity-Dependent Mechanism by the NMDA Receptor. ENeuro. 2018. 17;5(2).
  21. Lambert CJ, Freshner BC, Chung A, Stevenson TJ, Bowles DM, Samuel R, Gale BK, Bonkowsky JL. An automated system for rapid cellular extraction from live zebrafish embryos and larvae: Development and application to genotyping. PLoS One. 2018. 15;13(3):e0193180.
  22. Strachan LR, Stevenson TJ, Freshner B, Keefe MD, Miranda Bowles D, Bonkowsky JL. A zebrafish model of X-linked adrenoleukodystrophy recapitulates key disease features and demonstrates a developmental requirement fro abcdl in oligodenrocyte patterning and myelination. Hum Mol Genet. 2017. 15;26(18):3600-3614.
  23. Keefe MD, Bonkowsky JL. Transvection Arising from Transgene Interactions in Zebrafish. Zebrafish. 2017. 14(1):8-9.
  24. Chen YC, Semenova S, Rozov S, Sundvik M, Bonkowsky JL, Panula P. A Novel Developmental Role for Dopminergic Signaling to Secify Hypothalamic Neurotransmitter Identity. J Biol Chem. 2016. 14;291(42):21880-21892.
  25. Milash B, Gao J, Stevenson TJ, Son JH, Dahl T, Bonkowsky JL. Temporal Dysynchrony in brain connectivity gene expression following hypoxia. BMC Genomics. 2016. 17(1):334.
  26. Son JH, Keefe MD, Stevenson TJ, Barrios JP, Anjewierden S, Newton JB, Douglass AD, Bonkowsky JL. Transgenic FingRs for Live Mapping of Synaptic Dynamics in Genetically-Defined Neurons. Scientific Reports (Nature). 2016. 6:18734.
  27. Xing L, Son JH, Stevenson TJ, Lillesaar C, Bally-Cuif L, Dahl T, Bonkowsky JL. A Serotonin Circuit Acts as an Environmental Sensor to Mediate Midline Axon Crossing through EphrinB2. Journal of Neuroscience. 2015. 35(44):14794-808.
  28. Samuel R, Stephenson R, Roy P, Pryor R, Zhou L, Bonkowsky JL*, Gale BK*. Microfluidic-aided genotyping of zebrafish in the first 48 h with 100% viability. Biomedical Microdevices. 2015. 17(2):43.
  29. Anderson HM, Wilkes J, Korgenski EK, Pulsipher MA, Blaschke AJ, Hersh AL, Srivastava R, Bonkowsky JL. Preventable Infections in Children with Leukodystrophy. Annals of Clinical and Translational Neurology. 2014. 1(5):370-374.
  30. Purnell SM, Bleyl SB, Bonkowsky JL. Clinical exome sequencing identifies a novel TUBB4A mutation in a child with static hypomyelinating leukodystrophy. Pediatric Neurology. 2014. 50(6):608-11.
  31. Xing, L., Quist, T., Stevenson, T., Dahlem, T., Bonkowsky JL. Rapid and Efficient Zebrafish Genotyping Using PCR with High-resolution Melt Analysis. Journal of Visualized Experiments. 2014 Feb 5;(84):e51138.
  32. Schweitzer J, Löhr H, Bonkowsky JL, Hübscher K, Driever W. Sim1a and Arnt2 contribute to hypothalamo-spinal axon guidance by regulating Robo2 activity via a Robo3-dependent mechanism. Development. 2013. 140(1):93-106.
  33. Xing L, Hoshijima K, Grunwald DJ, Fujimoto E, Quist TS, Sneddon J, Chien CB, Stevenson TJ, Bonkowsky JL. Zebrafish foxP2 zinc finger nuclease mutant has normal axon pathfinding. PLoS One. 2012. 7(8):e43968.
  34. Lambert AM, Bonkowsky JL, Masino MA. The dopaminergic diencephalospinal tract mediates a developmental switch in the locomotor pattern of larval zebrafish. Journal of Neuroscience. 2012. 32:13488-13500
  35. Stevenson TJ, Trinh T, Kogelschatz C, Fujimoto E, Lush ME, Piotrowski T, Brimley CJ, Bonkowsky JL. Hypoxia disruption of vertebrate CNS pathfinding through EphrinB2 is rescued by magnesium. PLoS Genetics. 2012. 8(4):e1002638.
  36. Lakhina V, Maraccio C, Shao X, Lush M, Jain R, Fujimoto E, Bonkowsky JL, Granato M, Raper J. Netrin/DCC signaling guides olfactory sensory axons to their correct location in the olfactory bulb. Journal of Neuroscience. 2012. 32(13):4440-56.
  37. Gutnick A, Blechman J, Kaslin J, Affolter M, Bonkowky JL, Levkowitz G. The hypothalamic neuropeptide oxytocin is required for formation of the neuro-vascular interface of the pituitary. Developmental Cell. 2011. 18:642-54.
  38. Fujimoto E, Gaynes B, Brimley CJ, Chien CB, Bonkowsky JL. Gal80 Intersectional Regulation of Cell-Type Specific Expression in Vertebrates. Developmental Dynamics. 2011. 240(10):2324-34.
  39. Fujimoto E, Stevenson TJ, Chien CB, Bonkowsky JL. Identification of a dopaminergic enhancer indicates complexity in vertebrate dopamine neuron phenotype specification. Developmental Biology. 2011. 352(2):393-404.
  40. Kastenhuber E, Kern U, Bonkowsky JL, Chien CB, Driever W, Schweitzer J. Netrin-DCC, Robo-Slit and HSPGs coordinate lateral positioning of longitudinal dopaminergic diencephalospinal axons. Journal of Neuroscience. 2009. 29:8914-26.
  41. Bonkowsky JL, Wang X, Fujimoto E, Lee EJ, Chien CB, Dorsky RI. Domain-specific regulation of foxP2 CNS expression by lef1. BMC Developmental Biology. 2008. 8:103.
  42. Bonkowsky JL, Chien CB. Isolation and cloning of zebrafish foxP2. Developmental Dynamics. 2005. 234:740-6.
  43. Bonkowsky JL, Bohnsack, JF, Pennington MJ, Viskochil D, Thompson JA. Leukoencephalopathy, arthritis, colitis, and hypogammaglobulinemia (LACH) in two brothers: a novel syndrome? American Journal of Medical Genetics. 2004. 128:52-56.
  44. Bonkowsky JL, Johnson J, Carey J, Smith AD, Swoboda K. An infant with primary tooth loss and palmar hyperkeratosis: a novel mutation in the NTRK1 gene causing congenital insensitivity to pain with anhidrosis. Pediatrics. 2003. 112:e237-241. 
  45. Bonkowsky JL*, Yoshikawa S*, O’Keefe DD, Scully AL, Thomas JB. Axon routing across the midline controlled by the Drosophila Derailed receptor. Nature. 1999. 402: 540-4.
  46. Yoshikawa S*, Bonkowsky JL*, Kokel M, Shyn S, Thomas, JB. The Derailed guidance receptor does not require kinase activity in vivo. Journal of Neuroscience. 2001. 21: RC119.
Last Updated: 7/31/23