Cell Biology

Faculty and Research Interests

Jeremy Francis, PhD

Assistant Professor
Science Center 253
856-566-6050
francijs@rowan.edu

Education

University of Auckland School of Medicine,  Auckland, New Zealand
PhD (neuroscience) 2003

Research Interest

Leukodystrophies are a subclass of neurodegenerative disorders caused by genetic abnormalities that adversely affect how the brain produces or metabolizes constituent chemicals or proteins in myelin. Myelination is a core component of synaptic integrity and is a tightly regulated, complex biological process. Identifying causative pathogenic mechanisms in leukodystrophies requires a systems based approach that enables the extrapolation of discrete genetic, molecular and biochemical observations to a whole animal phenotype. The controlled manipulation of specific pathways and processes in animal models in our laboratory aims to characterize pathogenic mechanisms with a view to identifying possible targets for therapeutic intervention. A range of analytical techniques are employed to this end, from molecular to animal behavioral analyses.  Functional intervention via either gene therapy, transplantation of neural stem cells, or a combination of both forms a central component of proof of principal in vivo studies for future therapeutic development.

Transduction of neurons in the thalamus of a rat brain with an adeno-associated (AAV) viral vector containing an expression cassette for GFP. Intense fluorescence in neuronal soma can be seen at the site of injection (thal) with anterograde transport of vector resulting in GFP-positive axons throughout the internal capsule (ic). Viral vectors can deliver practically any gene of interest for functional interventions in vivo.

Transplanted GFP-transgenic cells in the subcortical white matter of a rat model of Canavan disease. GFP-positive cells indicate successful engraftment of transplant material, and co-labeling with the oligodendrocyte-specific marker APC indicates differentiation into myelin producing cells. Cell transplantation strategies can be used alone or in combination with gene therapy to develop therapeutic strategies in animal models of neurodegenerative disease

A major focus of our research is the inherited pediatric leukodystrophy Canavan disease, which is caused by inactivating mutations to the gene encoding for the oligodendrocyte specific enzyme, aspartoacylase. The sole function of aspartoacylase is the catabolism of the neuronal amino acid derivative, N-acetylaspartic acid (NAA), and loss of this function in rodents results in white matter degeneration that mirrors that seen in human patients. By characterizing the spatio-temporal regulation of the NAA metabolic cycle throughout development in the normal and aspa-null rodent brain, we hope to be able to identify key metabolic interactions between neurons and oligodendrocytes that are essential to the integrity of both cellular compartments during postnatal development.

Recent Publications

(Updated March 2013)

  1. Leone P, Shera D, McPhee SW, Francis JS, Kolodny EH, Bilaniuk LT, Wang DJ, Assadi M, Goldfarb O, Goldman HW, Freese A, Young D, During MJ, Samulski RJ, Janson CG. Long-term follow-up after gene therapy for canavan disease. Sci Transl Med, 19:4(165), 1-13, Dec 2012.
  2. Francis JS, Strande L, Markov V, Leone P. Aspartoacylase supports oxidative energy metabolism during myelination. J Cereb Blood Flow Metab, 32(9): 1725-36, Sep 2012.
  3. Francis JS, Strande L, Pu A, Leone P. Endogenous aspartoacylase expression is responsive to glutamatergic activity in vitro and in vivo. Glia, 59(10): 1435-46, Oct 2011.
  4. Wang J, Leone P, Wu G, Francis JS, Li H, Jain MR, Serikawa T, Ledeen RW. Myelin lipid abnormalities in the aspartoacylase-deficient tremor rat. Neurochem Res, 34(1):138-48, Jan 2009.
  5. Francis JS, Olariu A, Kobayashi E, Leone P. GFP-transgenic Lewis rats as a cell source for oligodendrocyte replacement. Exp Neurol, 205(1): 177-89, May 2007.
  6. Janson CG, McPhee SW, Francis J, Shera D, Assadi M, Freese A, Hurh P, Haselgrove J, Wang DJ, Bilaniuk L, Leone P. Natural history of Canavan disease revealed by proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted MRI. Neuropediatrics, 37(4): 209-21, Aug 2006.
  7. Francis JS, Olariu A, McPhee SW, Leone P. Novel role for aspartoacylase in regulation of BDNF and timing of postnatal oligodendrogenesis. J Neurosci Res, 84(1): 151-69, Jul 2006.
  8. Hageman JC, Uyeki TM, Francis JS, Jernigan DB, Wheeler JG, Bridges CB, Barenkamp SJ, Sievert DM, Srinivasan A, Doherty MC, McDougal LK, Killgore GE, Lopatin UA, Coffman R, MacDonald JK, McAllister SK, Fosheim GE, Patel JB, McDonald LC. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis,12(6): 894-9, Jun 2006.
  9. McPhee SW, Janson CG, Li C, Samulski RJ, Camp AS, Francis J, Shera D, Lioutermann L, Feely M, Freese A, Leone P. Immune responses to AAV in a phase I study for Canavan disease. J Gene Med, 8(5): 577-88, May 2006.
  10. Tavazzi B, Lazzarino G, Leone P, Amorini AM, Bellia F, Janson CG, Di Pietro V, Ceccarelli L, Donzelli S, Francis JS, Giardina B. Simultaneous high performance liquid chromatographic separation of purines, pyrimidines, N-acetylated amino acids, and dicarboxylic acids for the chemical diagnosis of inborn errors of metabolism. Clin Biochem, 38(11):997-1008, Nov 2005.
  11. McPhee SW, Francis J, Janson CG, Serikawa T, Hyland K, Ong EO, Raghavan SS, Freese A, Leone P. Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease. Brain Res Mol Brain Res, 135(1-2): 112-21, Apr 2005.
  12. Inoue H, Ohsawa I, Murakami T, Kimura A, Hakamata Y, Sato Y, Kaneko T, Takahashi M, Okada T, Ozawa K, Francis J, Leone P, Kobayashi E. Development of new inbred transgenic strains of rats with LacZ or GFP. Biochem Biophys Res Commun, 329(1): 288-95, Apr 2005.
  13. Francis JS, Dragunow M, During MJ. Over expression of ATF-3 protects rat hippocampal neurons from in vivo injection of kainic acid. Brain Res Mol Brain Res, 124(2):199-203, May 2004.
  14. During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med, 9(9): 1173-9, Sep 2003.

Professional Memberships

  • American Society of Gene Therapy
  • Society for Neuroscience

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