 We are today talking about a recent paper that our group has published entitled Metabolic Reprogramming of glioblastoma cells by L. Aspariginase sensitizes for apoptosis in vitro and in vivo. The authors are Georg Kappel-Marsler, Dorontina Ramani, Cheng Xu, Mark Eric Hallach, Mike Andrew Westhoff, Jeffrey N. Bruce, Peter Knoll, and myself, Marcus Siegelin. I'm an assistant professor of pathology and cell biology at Columbia University. I have a basic research laboratory at this institution, and my main research focus here is on glioblastoma and the elucidation of novel treatments by specifically targeting apoptosis signaling. So my name is Georg Kappel-Marsler. I am an assistant clinical professor at the Department of Pathology and Cell Biology at Columbia University, and I'm working with Marcus Siegelin on developing novel therapeutic approaches against cancer. And as a neurosurgeon, I very early on in my career experienced patients suffering from terrible diseases of the brain and diseases where there is not much to do about. Glioblastoma is the most common primary brain tumor in adults, and even though one tries hard to help patients suffering from this disease, for form surgery, radiotherapy, chemotherapy, the majority of patients with this disease will not survive much longer than one and a half years after diagnosis. So in our work, we examined a new therapeutic approach tackling tumor cell protein metabolism combined with pro-apoptotic agents in a multi-targeting approach. And Marcus is going to touch on the thought behind that and our findings. So glioblastoma, as Georg pointed out, is a highly malignant disease. And one of the hallmarks is also the heterogeneity and the fact that multiple pathways are active or outwardly active in these tumors, which suggests that for efficient therapeutic targeting, you would need multiple lines of therapy. And as he pointed out, we followed that strategy here in our research paper and addressed essentially the heterogeneity that is found in these neoplasms. And our treatment approach targets apoptosis, and apoptosis mainly consists of two commonly known pathways, which is the extrinsic and the intrinsic apoptotic pathway. And in this paper, we have focused on the intrinsic apoptotic pathway by utilizing a novel class of drug compounds called BH3 mimetics that target the BCI2 family of proteins. And in particular, these agents, we focused on ABT263, which is an orally available BH3 mimetic that targets BCL2, BCLX1, and BCLW, but not one of the other anti-apoptotic molecules, which is called MCL1. And essentially by interference with protein synthesis through allospiricinase, what we found is that allospiricinase hotently suppressed protein levels of MCL1 in a variety of glioblastoma cells, which then in turn enables the BH3 mimetic ABT263 to act efficiently on these glioblastoma cells and to overcome apoptotic resistance in these cells and to lead to massive cell death. Aside from that, what we also found is that allospiricinase is not only regulating MCL1, it also regulates an interacting protein of MCL1, which is called USP9X. And by down-regulating USP9X, you have a further, even more efficient effect on MCL1 levels with almost a complete disappearance of MCL1 levels facilitating the proapoptotic effects of the BH3 mimetic ABT263. We also went on further, in fact, to demonstrate that this observation of combined treatment of ABT263 and allospiricinase is not only limited to a cell culture in vitro setting, moreover, we showed that this combination is also rather effective in an in vivo model of glioblastoma. And in our in vivo model system, we observed essentially that the combination treatment of ABT263 and allospiricinase even led to a regression of the tumors, which suggests that this potential treatment strategy might have additional implications and further studies, in fact, even in patients, might be necessary to validate whether this treatment approach might be useful in patients. And on a side note, allospiricinase is a reagent, a compound that is currently used and is an established treatment for acute lymphoblastic leukemia in various therapies, in particular in combination therapies. And so ABT263, on the other hand, as well, has reached clinical trials. So it is conceivable that these two reagents might be tested in glioblastoma patients. Yes, that would be, of course, the ultimate goal to take this approach into a clinical trial and hopefully this will turn out into a significant benefit for patients because that is our ultimate goal to help patients in need, patients suffering from devastating disease. That's why we wake up in the morning. That's why we go to the lab. That's why we go to the hospital. That's what's driving us. We also, of course, will try to identify certain biomarkers that might particularly predict which patients might benefit from such a therapy. And we know already from our data presented in our paper that, unfortunately, not every glioblastoma cell culture will be sensitive to allospiricinase. And we are also currently in the process of identifying factors that predict the response to allospiricinase. And this will also be covered in the future work that we are conducting. In summary, we have provided a potential framework for a clinical trial of BH3 mimetics and allospiricinase for patients suffering from a malignant glioblastoma. So it's our expectation that our research will influence other researchers to pick up our major findings and to continue and to further develop the work we have created and demonstrated in our paper. Which will ultimately, hopefully, turn out to be beneficial for patients who are in desperate need for a better therapy.