Faculty Book
PANTELIS TSOULFAS, M.D.
Associate Professor, Neurological Surgery
Neurotrophins: Specificity of Action
Research
Interests
The research in my laboratory is currently focused on two major areas. The first area explores the early events of neurotrophin receptor activation and their effects on neural stem cells and the second explores the biological mechanisms involved in the maintenance and differentiation of neural stem cells.
Neurotrophins and trk mediated signaling
The NGF family of growth factors mediate their effects through the trk family of receptor tyrosine kinase and through p75 a member of the TNF family of receptors. Neurotrophins induce the receptors to dimerize.
Following dimerization, the receptors autophosphorylate on specific tyrosine residues that serve as docking sites for other signaling molecules that initiate several signaling cascades, leading to the activation of different key proteins important for biological responses. We are using new visualization techniques to map the dynamic interactions of the receptors and signaling molecules and their trafficking in vivo. Additional ongoing projects include the role that neurotrophins have on the regeneration of specific nerve tracks in spinal cord injury.
Maintanance and differentiation of neural stem cells
We are investigating how cell fate is controlled by intrinsic and exogenous factors and which molecules are involved in maintaining the stem cell characteristics. Our laboratory uses several approaches including in vitro and in vivo techniques to manipulate the expression of molecules that act as dominant negative or constitutively active. We are taking advantage of techniques such as microarray analysis and subtractive hybridization to isolate genes involved at different stages of stem cell differentiation.
Mammolenti M, Gajavelli S, Tsoulfas P, Levy R (2004) Absence of major histocompatibility complex class I on neural stem cells does not permit natural killer cell killing and prevents recognition by alloreactive cytotoxic T lymphocytes in vitro. Stem Cells. 22: 1101-1110. [Abstract]
Baez JC, Gajavelli S, Thomas CK, Grumbles RM, Aparicio B, Byer D, Tsoulfas P
(2004) Embryonic cerebral cortex cells retain CNS phenotypes after transplantation into peripheral nerve. Exp Neurol. 189:422-425. [Abstract]
Gajavelli S, Wood PM, Pennica D, Whittemore SR, Tsoulfas P (2004) BMP signaling initiates a neural crest differentiation program in embryonic rat CNS stem cells. Exp Neurol. 188:205-223. [Abstract]
Urfer R, Tsoulfas P, O'Connell L and Presta LG (1997) Specificity determinants in neurotrophin-3 and design of nerve growth factor-based trkC angonists by changing central ß-strand bundle residues to their neurotrophin-3 analogs. Biochem 36:4775-4781. [Abstract]
Tsoulfas P, Stephens RM, Kaplan DR and Parada LF (1996) TrkC isoforms with inserts in the kinase domain show impaired signaling responses. J Biol Chem 271: 5691-5697. [Abstract]
Urfer R, Tsoulfas P, O’Connell L, Shelton DL, Parada LF and Presta LG (1995) An immunoglobulin-like domain determines the specificity of neurotrophin receptors. EMBO J 14: 2795-2805. [Abstract]
Last updated March 10, 2005
Back to the Faculty Page
