Jacob Sloane Laboratory
Multiple sclerosis (MS) is characterized by an initial relapsing remitting course followed by a secondary progressive phase. The Sloane lab is interested in understanding the mechanisms behind progression in MS. This secondary progressive phase appears to be unaffected by immunosuppressive or immunomodulatory medications, suggesting an entirely different pathogenesis when compared to relapsing remitting MS. There are several possible substrates for progressive MS, including axonal injury and loss, impaired remyelination, and cortical lesions.
We have recently identified an important molecular pathway which blocks remyelination in MS lesions. This pathway depends on inflammatory production of hyaluronan, partial degradation by hyaluronidases, and subsequent Toll-like receptor 2 stimulation by low molecular weight hyaluronan. We are currently investigating whether inhibition of this pathway by various drugs improves outcomes and pathology in animal models of MS. Also, we are studying mechanisms behind axonal spheroid formation in relation to autophagy, an central way axons deal with injury. Understanding the molecular basis of each should lead to new therapeutic approaches to progressive MS.
About Jacob Sloane
Jacob Sloane is a graduate of Harvard University and Boston University Medical School. His PhD in pathology was performed in Carmela Abraham's laboratory at Boston University. He completed an internship at Beth Israel Deaconess Medical Center and a Neurology residency at Massachusetts General Hospital and Brigham & Women's Hospital. He finished his MS fellowship under the tutelage of Drs. Timothy Vartanian and Rip Kinkel. He recently started his own laboratory in 2009.
- Harris Z, Sloane JA. Axonal injury in Multiple Sclerosis. Neurodegeneration. Hauppauge: Nova Science, 2010. In preparation.
Sloane JA, Batt C, Ma Y, Harris ZM, Trapp B, and Vartanian T. Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2. Proc Natl Acad Sci U S A. 2009. In revision.
- Sloane JA, Blitz D, Margolin Z, Vartanian T. A Clear and Present Danger: Endogenous Ligands of Toll-like Receptors. Neuromolecular Med. 2009.
- Cameron JS, Alexopoulou L, Sloane JA, DiBernardo AB, Ma Y, Kosaras B, Flavell R, Strittmatter SM, Volpe J, Sidman R, Vartanian T. Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals. J Neurosci. 2007;27(47):13033-41.
- Sloane JA, Vartanian TK. Myosin Va controls oligodendrocyte morphogenesis and myelination. J Neurosci. 2007;27(42):11366-75.