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, Nobuta H, Li J, Kasai A, Yong WH, Waschek JA. Targeted STAT3 disruption in myeloid cells alters immunosuppressor cell abundance in a murine model of spontaneous medulloblastoma. J Leukoc Biol. 2014 Feb;95(2):357-67. doi: 10.1189/jlb.1012531. Epub 2013 Sep 25.
Niewiadomski P, Zhujiang A, Youssef M, Waschek JA. Interaction of PACAP with Sonic hedgehog reveals complex regulation of the hedgehog pathway by PKA. Cell Signal. 2013 Nov;25(11):2222-30. doi: 10.1016/j.cellsig.2013.07.012. Epub 2013 Jul 18.
Yan Y, Zhou X, Pan Z, Ma J, Waschek JA, DiCicco-Bloom E. Pro- and anti-mitogenic actions of pituitary adenylate cyclase-activating polypeptide in developing cerebral cortex: potential mediation by developmental switch of PAC1 receptor mRNA isoforms. J Neurosci. 2013 Feb 27;33(9):3865-78. doi: 10.1523/JNEUROSCI.1062-12.2013.
Hirose M, Niewiadomski P, Tse G, Chi GC, Dong H, Lee A, Carpenter EM, Waschek JA. Pituitary adenylyl cyclase-activating peptide counteracts hedgehog-dependent motor neuron production in mouse embryonic stem cell cultures. J Neurosci Res. 2011 Sep;89(9):1363-74. doi: 10.1002/jnr.22675. Epub 2011 Jun 14.
Cohen JR, Resnick DZ, Niewiadomski P, Dong H, Liau LM, Waschek JA. Pituitary adenylyl cyclase activating polypeptide inhibits gli1 gene expression and proliferation in primary medulloblastoma derived tumorsphere cultures. BMC Cancer. 2010 Dec 9;10:676. doi: 10.1186/1471-2407-10-676.