In the News:
Castro/Lowenstein lab publishes a significant paper in a major journal: Science Translational Medicine "ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma". Follow this link to read the whole article:
Press releases have been issued to share this important publication. See the links below for more information.
The current focus of our research program is to discover the cellular, molecular, and mathematical basis underlying the growth patterns of malignant brain tumors (glioma, GBM), and the interactions between cancer cells with the tumor microenvironment, in both experimental models and in human patients.
Understanding the precise molecular basis of glioma tumor cell growth and invasive behavior, will uncover novel therapeutic targets aiming at inactivating the essential mechanisms used by tumors to grow and destroy normal brain tissue, and thus, kill the host.
We are also developing novel immunotherapies for primary and metastatic brain cancer. Research within our labs stem all the way from basic immunobiology mechanisms to translational immune-therapeutics.
Another active research area is related to the tumor immune-microenvironment: its role in tumor progression and response to therapeutics; cross talk between cancer cells and hematopoietic stem/progenitor cells; and mechanisms affecting the migration of immune cells from peripheral lymphoid organs to the tumor microenvironment.
Our lab has recently focused its research efforts on DNA repair pathways, the epigenetic regulation of cancer progression, uncovering the role of oncometabolites in the brain tumor microenvironment and in mediating the response to immunotherapies. To this end, we are developing novel rodent models of malignant brain cancer using in vivo gene transfer technologies. To accomplish this, we are using the Sleeping Beauty Transposase System to insert specific genetic lesions in the genome of stem cells lining the third ventricle. These genetically engineered murine models harboring genetic lesions present in the human disease have proven to be powerful platforms to uncover the molecular mechanisms that mediate tumor progression and implement novel immune-mediated gene and/or cell based therapeutic approaches. These approaches will lead to the development of novel therapeutic approaches and their implementation in Phase I clinical trials for GBM.
Pioneering work from our lab has led to an FDA approved Phase I clinical trial for malignant brain cancer which is ongoing at the University of Michigan, Department of Neurosurgery.