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Faculty Profile

Steven U. Walkley, D.V.M., Ph.D.

Dr. Steven U. Walkley

Professional Interests


Pathobiology and Treatment of Lysosomal Disorders of Brain

Training in Comparative Medicine and Neuroscience provided the basis for my career interests in neurogenetic disease, particularly those disorders impacting neuronal homeostatic mechanisms and resulting in intellectual disability and related neurobehavioral abnormalities.  My lab has published extensively in the area of pathogenic cascade analysis in lysosomal disease, defining key changes in neuronal structure and function as a consequence of lysosomal compromise.  Current interests include the causes and consequences of neuroaxonal dystrophy and ectopic dendritogenesis, altered synaptic function underlying intellectual compromise, the involvement of autophagy and the ubiquitin/proteasomal system in disease progression, and the importance of metabolite salvage in lysosomal processing.  A most recent study has shown lysosomal involvement in a newly discovered X-linked Angelman-like syndrome, further illustrating the importance of the lysosomal system to a wide range of human neurobehavioral conditions. 

My lab is also significantly involved in therapy development for neurological disease.  We were the first to show essentially complete correction of CNS disease in the lysosomal disorder known as alpha-mannosidosis through the use of bone marrow transplantation and this treatment approach is now the standard of care for children diagnosed with this rare disorder.  A disease of current focus is Niemann-Pick type C (NPC), a fatal cholesterol-glycosphingolipid lysosomal storage disorder of children.  Based on our studies of glycosphingolipid processing abnormalities in NPC disease we developed the first and presently only approved (by EMEA; FDA pending) therapy for this disorder.  This is the imino sugar known as N-butyldeoxynojirimycin, or miglustat, which is a partial inhibitor of glycosphingolipid synthesis.  

More recently we discovered that the FDA approved excipient known as hydroxypropyl beta-cyclodextrin is efficacious in limiting intraneuronal accumulation of both unesterified cholesterol and glycosphingolipids, and dramatically extends the lifespan in animal models of NPC disease.  Research and clinical trial development was subsequently pursued through a unique scientist/clinician/parent consortium known as SOAR (Support Of Accelerated Research) for NPC disease (SOAR-NPC) and through collaboration with TRND (Therapeutics for Rare and Neglected Diseases) and NCATS (National Center for Advancing Translational Sciences) at NIH. Phase I trials of this compound in NPC patients began in February, 2013.


Selected Publications

  1. Damme M, Stroobants S, Walkley SU, Lullmann-Rauch R, D'Hooge R, Fogh J, et al. Cerebellar alterations and gait defects as therapeutic outcome measures for enzyme replacement therapy in alpha-mannosidosis. Journal of neuropathology and experimental neurology. 2011;70(1):83-94. Epub 2010/12/16. doi: 10.1097/NEN.0b013e31820428fa. PubMed PMID: 21157375; PubMed Central PMCID: PMC3077051.
  2. Strømme P, Dobrenis K, Sillitoe RV, Gulinello M, Ali NF, Davidson C, Micsenyi MC, Stephney G, Ellevog L, Klungland A, Walkley SU. X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits evidence of endosomal-lysosomal dysfunction. Brain: a journal of neurology. 2011;134(Pt 11):3369-83. Epub 2011/10/04. doi: 10.1093/brain/awr250. PubMed PMID: 21964919; PubMed Central PMCID: PMC3212719.
  3. Ulatowski L, Parker R, Davidson C, Yanjanin N, Kelley TJ, Corey D, Atkinson J, Porter F, Arai H, Walkley SU, et al. Altered vitamin E status in Niemann-Pick type C disease. Journal of lipid research. 2011;52(7):1400-10. Epub 2011/05/10. doi: 10.1194/jlr.M015560. PubMed PMID: 21550990; PubMed Central PMCID: PMC3122910.
  4. Zhou S, Davidson C, McGlynn R, Stephney G, Dobrenis K, Vanier MT, Walkley SU. Endosomal/lysosomal processing of gangliosides affects neuronal cholesterol sequestration in Niemann-Pick disease type C. The American journal of pathology. 2011;179(2):890-902. Epub 2011/06/29. doi: 10.1016/j.ajpath.2011.04.017. PubMed PMID: 21708114; PubMed Central PMCID: PMC3157170.
  5. Cluzeau CV, Watkins-Chow DE, Fu R, Borate B, Yanjanin N, Dail MK, Davidson CD, Walkley SU, et al. Microarray expression analysis and identification of serum biomarkers for Niemann-Pick disease, type C1. Human molecular genetics. 2012;21(16):3632-46. Epub 2012/05/24. doi: 10.1093/hmg/dds193. PubMed PMID: 22619379; PubMed Central PMCID: PMC3406758.
  6. Kollmann K, Damme M, Markmann S, Morelle W, Schweizer M, Hermans-Borgmeyer I, Rochert AK, Pohl S, Lubke T, Michalski JC, Kakela R, Walkley SU, et al. Lysosomal dysfunction causes neurodegeneration in mucolipidosis II 'knock-in' mice. Brain : a journal of neurology. 2012;135(Pt 9):2661-75. Epub 2012/09/11. doi: 10.1093/brain/aws209. PubMed PMID: 22961545; PubMed Central PMCID: PMC3437033.
  7. Lieberman AP, Puertollano R, Raben N, Slaugenhaupt S, Walkley SU, Ballabio A. Autophagy in lysosomal storage disorders. Autophagy. 2012;8(5):719-30. Epub 2012/06/01. doi: 10.4161/auto.19469. PubMed PMID: 22647656; PubMed Central PMCID: PMC3378416.
  8. Stein VM, Crooks A, Ding W, Prociuk M, O'Donnell P, Bryan C, Sikora T, Dingemanse J, Vanier MT, Walkley SU, et al. Miglustat improves purkinje cell survival and alters microglial phenotype in feline Niemann-Pick disease type C. Journal of neuropathology and experimental neurology. 2012;71(5):434-48. Epub 2012/04/11. doi: 10.1097/NEN.0b013e31825414a6. PubMed PMID: 22487861; PubMed Central PMCID: PMC3352323.
  9. Xu M, Liu K, Swaroop M, Porter FD, Sidhu R, Finkes S, Ory DS, Marugan JJ, Xiao J, Southall N, Pavan WJ, Davidson C, Walkley SU, et al. delta-Tocopherol reduces lipid accumulation in Niemann-Pick type C1 and Wolman cholesterol storage disorders. The Journal of biological chemistry. 2012;287(47):39349-60. Epub 2012/10/05. doi: 10.1074/jbc.M112.357707. PubMed PMID: 23035117; PubMed Central PMCID: PMC3501083.
  10. Micsenyi MC, Sikora J, Stephney G, Dobrenis K, Walkley SU. Lysosomal membrane permeability stimulates protein aggregate formation in neurons of a lysosomal disease.  J Neurosci. 2013 Jun 26;33(26):10815-27. doi:10.1523/JNEUROSCI.0987-13.2013. PMID: 23804102 [PubMed - in process]

More Information About Dr. Steven Walkley

Department of Neuroscience

Rose F. Kennedy Intellectual and Developmental Disabilities Research Center

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Albert Einstein College of Medicine
Rose F. Kennedy Center
1410 Pelham Parkway South , Room 618
Bronx, NY 10461

Tel: 718.430.4025
Fax: 718.430.8821

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Media Coverage

The Wall Street Journal highlights groundbreaking research by Dr. Steven Walkley that has led to treatment options for the rare condition Niemann-Pick Type C.

The New York Daily News interviews Drs. Robert Marion and Steven Walkley about Einstein’s leap year event showcasing the talents of young people with rare diseases in order to raise awareness of their conditions.

More media coverage