Research in Dr. James Waschek’s laboratory centers on three broad but related topics:
- Central nervous system development, degeneration, injury and repair
- Brain tumor pathogenesis
- Neuroinflammatory conditions such as multiple sclerosis and maternal inflammation-induced perinatal white matter disease.
Although a past and continuing objective has been to better understand the biological roles of neuropeptides in these processes (especially two related peptides VIP and PACAP), current efforts have expanded considerably to investigate general processes impacted by neuropeptides, including innate immune mechanisms that operate in astrocytes and microglia, adaptive immune mechanisms that involve T-helper subsets and myeloid cells and mechanisms that mediate tumor immunoeradication and immunoescape.
As critical tools in its investigations, Waschek’s laboratory has generated several neuropeptide-deficient and reporter mice and has utilized several transgenic and conditional knockout mouse strains that alter the phenotype of astrocytes and myeloid cells. These have been applied to models of pediatric brain tumors nerve trauma, premature infant white matter injury, multiple sclerosis and Parkinson's Disease.
Selected Cancer-Related Publications:
Abad C, Tan YV, Lopez R, Nobuta H, Dong H, Phan P, Feng JM, Campagnoni AT, Waschek JA. Vasoactive intestinal peptide loss leads to impaired CNS parenchymal T-cell infiltration and resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19555-60. Epub 2010 Oct 26.
Tan YV, Abad C, Lopez R, Dong H, Liu S, Lee A, Gomariz RP, Leceta J, Waschek JA. Pituitary adenylyl cyclase-activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2012-7. Epub 2009 Feb 3.
Nemetz N, Abad C, Lawson G, Nobuta H, Chhith S, Duong L, Tse G, Braun J, Waschek JA. Induction of colitis and rapid development of colorectal tumors in mice deficient in the neuropeptide PACAP. Int J Cancer. 2008 Apr 15;122(8):1803-9.
Niewiadomski P, Coûté-Monvoisin AC, Abad C, Ngo D, Menezes A, Waschek JA. Mice deficient in both pituitary adenylyl cyclase-activating polypeptide and vasoactive intestinal peptide survive, but display growth retardation and sex-dependent early death. J Mol Neurosci. 2008 Nov;36(1-3):200-7. Epub 2008 May 20.
Lelievre V, Seksenyan A, Nobuta H, Yong WH, Chhith S, Niewiadomski P, Cohen JR, Dong H, Flores A, Liau LM, Kornblum HI, Scott MP, Waschek JA. Disruption of the PACAP gene promotes medulloblastoma in ptc1 mutant mice. Dev Biol. 2008 Jan 1;313(1):359-70. Epub 2007 Nov 26.