Benjamin W. Purow
- MD, Johns Hopkins University-Baltimore, MD
- BA, Harvard University-Cambridge, MA
- Professor, Neurology
- Phone: 434-924-5545
- Email: email@example.com
Novel therapeutic approaches to brain cancers and to other neurologic diseases
The Purow laboratory is dedicated to developing innovative approaches to treating not only brain tumors but cancer as a whole.
We have focused now and in recent years on the following areas:
--We have shown that a pathway important in stem cells, called the Notch pathway, is a potential target for gliomas, the most common and lethal brain tumors. We have further demonstrated that a class of drugs in clinical trials for other functions also acts to inhibit Notch.
--microRNAs are small RNA molecules that are found throughout our DNA but that are not used to generate proteins. They do, however, play powerful roles in regulating expression of genes that do code for proteins, and have been found to be important in almost every area in biology—including cancer. We have found a number of microRNAs that can promote or suppress survival in glioblastoma, the most aggressive gliomas. Delivery of tumor-suppressive microRNAs is showing potential to treat brain tumors in our mouse models, and we hope to eventually move these studies forward to clinical trials.
--In a project arising from our microRNA work, we have shown that a protein called DGKalpha is a promising cancer target in brain cancers but also in other cancers as well. Our first paper on this was recently published in Cancer Discovery. DGKalpha inhibition appears to have exciting potential to boost the effects of other anti-cancer therapies, such as radiation and possibly immunotherapy as well. Chemical blockers of this protein already exist, and we have identified a nearly identical compound that has already been found safe in clinical trials in people as a psychiatric medication. We have confirmed that this compound also functions as a DGKalpha inhibitor, potentially allowing this strategy to proceed rapidly to clinical trials in patients.
--In the same vein of repurposing old drugs, we are also investigating anti-cancer functions of medications approved for other indications. These studies could allow rapid translation to patients in the clinic. In one such project in the early stages, we have followed leads from the recently-released online database CellMiner to show that a widely-used class of medications effectively inhibits the TGF-beta signaling pathway, and appears particularly toxic to cancer cells with a more mesenchymal phenotype.
- Floyd D, Zhang Y, Dey B, Kefas B, Breit H, Marks K, Dutta A, Herold-Mende C, Synowitz M, Glass R, Abounader R, Purow B. Novel anti-apoptotic microRNAs 582-5p and 363 promote human glioblastoma stem cell survival via direct inhibition of caspase 3, caspase 9, and Bim. PloS one. 2014;9(5): e96239. PMID: 24805821 | PMCID: PMC4013090
- Dominguez C, Floyd D, Xiao A, Mullins G, Kefas B, Xin W, Yacur M, Abounader R, Lee J, Wilson G, Harris T, Purow B. Diacylglycerol kinase α is a critical signaling node and novel therapeutic target in glioblastoma and other cancers. Cancer discovery. 2013;3(7): 782-97. PMID: 23558954 | PMCID: PMC3710531
- Notch inhibition as a promising new approach to cancer therapy. Advances in experimental medicine and biology. 2012;727 305-19. PMID: 22399357 | PMCID: PMC3361718
- Floyd D, Kefas B, Seleverstov O, Mykhaylyk O, Dominguez C, Comeau L, Plank C, Purow B. Alpha-secretase inhibition reduces human glioblastoma stem cell growth in vitro and in vivo by inhibiting Notch. Neuro-oncology. 2012;14(10): 1215-26. PMID: 22962413 | PMCID: PMC3452340
- Sherman J, Redpath G, Redick J, Purow B, Laws E, Jane J, Shaffrey M, Hussaini I. A novel fixative for immunofluorescence staining of CD133-positive glioblastoma stem cells. Journal of neuroscience methods. 2011;198(1): 99-102. PMID: 21402102 | PMCID: PMC3126626
- Kefas B, Comeau L, Erdle N, Montgomery E, Amos S, Purow B. Pyruvate kinase M2 is a target of the tumor-suppressive microRNA-326 and regulates the survival of glioma cells. Neuro-oncology. 2010;12(11): 1102-12. PMID: 20667897 | PMCID: PMC3098027
- Purow B, Schiff D. Glioblastoma genetics: in rapid flux. Discovery medicine. 2010;9(45): 125-31. PMID: 20193638 | PMCID: PMC3365574
- Notch inhibitors as a new tool in the war on cancer: a pathway to watch. Current pharmaceutical biotechnology. 2009;10(2): 154-60. PMID: 19199947 | PMCID: PMC3365567
- Kefas B, Comeau L, Floyd D, Seleverstov O, Godlewski J, Schmittgen T, Jiang J, diPierro C, Li Y, Chiocca E, Lee J, Fine H, Abounader R, Lawler S, Purow B. The neuronal microRNA miR-326 acts in a feedback loop with notch and has therapeutic potential against brain tumors. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009;29(48): 15161-8. PMID: 19955368 | PMCID: PMC2823067
- Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen T, Lopes B, Schiff D, Purow B, Abounader R. MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer research. 2009;69(19): 7569-76. PMID: 19773441 | PMCID: PMC2756313
- Purow B, Schiff D. Advances in the genetics of glioblastoma: are we reaching critical mass? Nature reviews. Neurology. 2009;5(8): 419-26. PMID: 19597514 | PMCID: PMC3387541