Contact
Email: mbredel@miami.edu
Roles
Chairman of Radiation Oncology
Professor of Radiation Oncology
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Biography
I am an (American Board of Radiology) board-certified German-American radiation oncologist who practices as a physician-scientist at The University of Miami. I focus clinically and scientifically on central nervous system (CNS) tumors. I have a broad background in basic, translational, and clinical investigations of primary brain tumors and brain metastases. My research is dedicated to understanding the genetics and molecular mechanisms driving glioblastoma (GBM) pathogenesis and to identifying new cancer targets and therapeutic leads for these neoplasms.
Our work integrates complex molecular tumor data generated by the complementary and iterative application of data-driven (systems biology) and hypothesis-driven molecular biology and molecular genetics research approaches and corresponding clinical patient profiles. In this particular application, we are building up on our previous work illustrating that NFKBIA-encoded I?Ba functions as a haploinsufficient tumor suppressor in GBM that portends unfavorable prognosis in patients. We have new data to suggest that, besides its role as a master regulator of NF-?B, I?Ba exerts an alternative nuclear function in various tissue stem cells where it binds chromatin and acts as a transcriptional switch for a subset of polycomb repressive complex 2 (PRC2)-regulated differentiation genes.
We are collaborating with Dr. Lluís Espinosa at the Hospital del Mar Medical Research Institute (IMIM) in Barcelona to characterize the dynamic regulation of chromatin by I?Ba, and its malfunction during lineage specification and cell fate transitions en route to tumorigenesis. Therefore, this dual PI R01 application represents the natural extension of our collaborative work, where we combine our complementary expertise.
As a result of my training and faculty positions at Stanford University, Northwestern University, University of Freiburg, and the University of Alabama at Birmingham, I have a broad background in cancer molecular biology, and cancer genetics and genomics, with specific expertise in key research areas for this application. Previous research of my laboratories, with immediate relevance to the current application, has been published in several high-profile peer-reviewed journals, including The New England Journal of Medicine, JAMA, Lancet Oncology, Journal of Clinical Investigation, Journal of Clinical Oncology, and Oncogene. With a demonstrated record of successful and productive research in a cancer area of unmet need for scientific and clinical progress, I have the expertise, leadership skills, and motivation necessary to successfully carry out the proposed work as part of an interdisciplinary team. -
Education & Training
Education
Post Graduate Training
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Research Interests
My basic and translational research is dedicated to understanding the genetics of brain tumorswith a particular focus on human gliomas. This incredibly challenging disease highlights both theapplication of cutting-edge scientific medicine and its limitations as these tumors evade the mosttargeted therapies. Yet, advances in genome-wide analyses, an ever-increasing production ofmolecularly targeted/immune directed therapies, and building momentum for understanding thestem-cell component of this disease all mark the present as a time of great promise for newtreatment benefits to arise.
Our work integrates complex molecular tumor data generated by thecomplementary and iterative application of data-driven (systems biology) and hypothesis-drivenresearch (functional genetics/molecular biology) approaches and corresponding clinical patientprofiles. Our work aims to translate to the clinic. Our focus lies on the characterization ofcooperative and compensatory gene alterations and their roles and mechanisms in signalingpathway deregulation and pathogenesis of brain tumors. We combine complex genomicnetwork analysis from patient tumor samples with both in vitro and in vivo models to identify newtherapeutic strategies. We also aim to use high-dimensional tumor profiling to benefit the patientin providing prognostic information and adding in therapeutic decision-making.
As a member ofthe NRG Brain Tumor Working Group, I have been involved in the profiling of glioma studypatient samples for prognostic and predictive biomarkers. I have been the PI on high-impactmedical publications in The New England Journal of Medicine, JAMA, The Lancet Oncology, The Journal of Clinical Investigation, and Journal of Clinical Oncology. My research has beenhonored by multiple research awards, including awards from ASCO, AACR, and AANS. Ourcharacterization of a novel tumor suppressor gene in brain cancer (published in NEJM) hasbeen named one of the top clinical cancer research advances of the year by ASCO. Ourresearch is highly collaborative in nature as we maintain a very interactive network of nationaland international research alliances and work within the brain tumor field to offer patients newhope, educate and train the next generation of brain tumor scientists, and advance the generalbody of knowledge concerning the origins and nature of these challenging neoplasms.
In terms of clinical research, I’m particularly interested in advanced radiosurgery applicationsfor brain metastases and movement disorders. As such, I’m currently leading a prospectivephase I dose escalation/de-escalation study of pre-operative stereotactic radiosurgery for brainmetastases that has been completed and showed a substantially reduced risk of leptomeningealdissemination compared to post-operative radiosurgery. I have also developed an advancedstereotactic radiosurgery program for movement disorders at UAB that couples novel, framelesslinear-accelerator-based radiosurgery technologies and cutting-edge image-guided targeting.
Iam currently the Principal Investigator of an investigator-initiated, funded functional radiosurgeryclinical trial for patients with medically refractory essential tremor and tremor-dominantParkinson’s Disease. This trial led to the FDA 510(K) approval of the Varian TrueBeam/Edgeradiosurgery platform for the treatment of essential tremor. I have performed the first framelessradiosurgical pallidotomy for dystonia worldwide. -
Publications
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