The Morales lab is investigating the mechanism(s) by which glioblastoma multiforme (GBM) become therapy resistant and invasive.Patients with GBM have a poor 5-year survival rate of 4-10% due to development of therapy resistance and cancer cells metastasizing to inoperable areas of the brain.Therefore, there is an urgent need to develop novel therapies that can combat resistance and/or metastasis.The Morales lab uses mouse models, reporter cell lines, synergetic survival protocols, invasion and motility assays, and molecular biology techniques to discover weak points in cancer therapy resistance and metastasis.
DNA Repair: Cancer cells often have heightened DNA repair capabilities to circumvent toxic therapies.The Morales lab is interested how cancer cells can up regulate DNA repair efficiencies, in particular DNA double stranded break (DSB) repair capacities during cancer progression and cancer treatment.
Invasion: Metastasis is a multi-step process and is often the source of relapsed disease.Even though brain metastatic growths rarely occur in other organs, cancer cells have a high propensity of invading into other areas of brain.Invasion is the initial step of metastasis.The Morales lab is interested in discovering novel molecular targets of invasion.
XRN2: From his post-doctoral training, Dr. Julio Morales found that XRN2, a 5’-3’ exoribonuclease is required for cancer cell survival during DNA damaging events. XRN2 is classically associated with transcription termination, specifically resolving DNA:RNA hybrids (R-loops). The Morales lab has found that XRN2 is required for the efficient repair of DSB lesions and that loss of XRN2 either through genetic knockdown or chemical inhibition sensitizes cancer cells to conventional therapeutics. Recently, the Morales lab has found that XRN2 regulates a pro-metastatic program in GBMs
Keywords: DNA repair, DNA double stranded breaks, XRN2, metastasis, invasion, brain cancer, glioblastoma multiforme, R-loops, DNA:RNA hybrids, transcription