Phyllis L. Faust, M.D., Ph.D.


Associate Professor of Clinical Pathology and Cell Biology
Columbia University, PH Stem 15-124
630 West 168th Street, New York, NY 10032


Phone: 212-305-7345
Fax: 212-305-4548

Research Summary

We are studying a PEX2 mouse model for the human neuronal migration disorder Zellweger syndrome. The defective assembly of the peroxisomal organelle in this disease leads to widespread metabolic disarray in selected cellular lipid pathways and results in severe neurologic dysfunction.

Our in vivo analyses in PEX2-/- mice clearly demonstrate that peroxisomes are necessary for normal neuronal migration, differentiation and proliferation in the developing brain. However, due to the essentially ubiquitous cellular distribution of peroxisomes, it is not yet clear to what extent these defects are intrinsic to abnormalities in CNS cells versus secondary to extrinsic, systemically derived organ defects. The use of in vitro cultures, in which the migration of neurons is examined by real-time videomicroscopy in the absence of extrinsic organ defects, has allowed us to define that intrinsic defects are clearly present in migrating peroxisome-deficient neurons. We will further utilize these assays to gain an understanding of the mechanism for the neuronal migration defect. By comparing the migration of PEX2 mutant neurons with that of neurons derived from mice having defects limited to peroxisomal beta-oxidation and/or plasmalogen pathways we can evaluate the role of whole peroxisomal organelle dysfunction versus defects in these specific peroxisomal lipid pathways. Our studies on the in vitro development of PEX2-/- cerebellar Purkinje cells also demonstrates the presence of CNS intrinsic defects for neuronal differentiation, which will be further characterized in these various peroxisomal defect mouse lines.

We are also examining the effect of bile acid and cholesterol dysfunction in PEX2-/- mice. When PEX2-/- mice are fed bile acids, there is significant improvement in postnatal survival of these mutant mice. We are studying how the bile acid treatment affects both bile acid and cholesterol biosynthetic pathways by combined use of RNA expression, enzymatic and protein assays. Recent studies also suggest that bile acid products may play a role in the pathogenesis of CNS defects. We are studying how the bile acid therapy affects in vivo CNS development in PEX2-/- mice, which will further define extrinsic peroxisomal defects that may alter CNS development.

Selected Publications


  • Faust, PL, and Hatten, ME. Targeted deletion of the PEX2 peroxisome assembly gene in mice provides a model for Zellweger syndrome, a human neuronal migration disorder. J. Cell Biol. 139: 1293-1305 (1997).
  • Pearlman, AL, Faust, PL, Hatten, ME, and Brunstrom, JE. New directions for neuronal migration. Curr. Opinion Neurobiol. 8: 45-54 (1998).
  • Faust PL, Su H-M, Moser, A and Moser H (2001). The Peroxisome Deficient PEX2 Zellweger Mouse: Pathologic and Biochemical Correlates of Lipid Dysfunction. J. Mol. Neurosci. 16:289-297.
  • Kovacs WJ, Faust PL, Keller G-A and Krisans SK (2001). Purification of Brain Peroxisomes and Localization of 3-hydroxy-3-methylglutary Coenzyme A Reductase. Eur. J. Biochem. 268:4850-4859.
  • Faust PL (2003). Abnormal Cerebellar Histogenesis in PEX2 Zellweger Mice Reflects Multiple Neuronal Defects Induced by Peroxisome Deficiency. The J. Comp. Neurol. 461:394-413.
  • Kovacs WJ, Shackelford JE, Tape KN, Richards MJ, Faust PL, Fliesler SJ, and Krisans SK (2004) Disturbed cholesterol homeostasis in a peroxisome-deficient PEX2 knockout mouse model. Mol. Cell. Biol. 24:1-13.

Honors and Awards:


  • Frederica Clarkson Award (valedictorian), Clarkson University, 1981
  • United States Public Health Service Medical Scientist Training Award, RSA GM-07200
  • Carl T. and Gerty F. Cori Prize in Biochemistry, Washington University, 1981
  • Spencer T. and Ann W. Olin Medical Scientist Fellow, Washington University, 1987
  • Howard Hughes Postdoctoral Research Fellowship for Physicians, 1993 - 1996
  • The American Association of Neuropathologists Weil Award, for the best paper on Experimental Neuropathology, June 1996
  • Basil O'Connor Starter Scholar Research Award, March of Dimes Foundation, 1998
  • Board Certification in Anatomic Pathology/Neuropathology, 1999

Committees , Council, and Professional Society Memberships

  • American Association of Neuropathologists
  • Society for Neuroscience

Education and Training


  • 1989, M.D., Ph.D. Washington University