Dr. Brennen earned his Ph.D. with Dr. Samuel R. Denmeade, M.D. from the Pharmacology & Molecular Sciences department at the Johns Hopkins (JH) School of Medicine (SOM). Subsequently, he did a postdoctoral fellowship under the mentorship of Dr. John T. Isaacs, Ph.D. in the Department of Oncology at the JHSOM and was recruited to the faculty in 2014. He has secondary appointments in Urology and Pharmacology & Molecular Sciences. He is a member of the Genitourinary Oncology and Cancer Invasion & Metastasis programs in the School of Medicine and Sidney Kimmel Comprehensive Cancer Center (SKCCC) at JH, as well as the Biochemistry & Molecular Biology and Biotechnology programs in the School of Public Health at JH, and the Biomedical Engineering program in the JH Whiting School of Engineering. His work is translational in nature, and he works closely with clinical colleagues to move his discoveries towards near-term patient applications. He is an active member of the AACR, SBUR, and PCF research communities.
He has more than 20 yrs of experience in the development of novel therapeutic strategies for mCRPC. In addition to drug development, he has expertise in generating and characterizing advanced animal models, and alternative approaches for assessing therapeutic and efficacy and safety, including novel models of liver metastasis and patient-derived xenografts (PDXs). Indeed, over the last decade we have developed and characterized >15 new PDXs derived from mCRPC patients recapitulating each of the major phenotypes of lethal disease. Many of these PDXs represent emerging highly aggressive treatment-resistant phenotypes that are underrepresented in other prostate cancer PDX collections and thus, represent a valuable and unique resource that we share openly with other investigators.
He has mentored multiple trainees at all levels of career development from undergraduates through junior faculty. His overall lab group environment spans diverse cultural, professional, and religious backgrounds. He is committed to providing an inclusive, safe, and supportive research environment for all to conduct ethically sound and responsible scientific research that is rigorous, unbiased, and conforms to the highest standards of practice while promoting each trainee in an effort to fulfill their maximum potential and personalized advancement goals in diverse biomedical fields aligned with their personal skills, interests, and values. We have a weekly lab meeting as well as a weekly group lab meeting comprised of four (4) – seven (7) independent and diverse prostate cancer-focused labs with complementary expertise where we share ideas to “cross-pollinate” and try to build a sense of community and shared purpose towards a common goal.
We take a rigorous, multi-disciplinary, modality-agnostic, collaborative team science-based approach towards developing innovative therapeutic and prognostic strategies for prostate cancer. Towards these objectives, our team places an emphasis on exploiting vulnerabilities within the tumor microenvironment (TME), particularly focused on fibroblast activation protein (FAP), or inducing synthetic lethal pathways through epigenetic manipulation of essential regulatory programs. To accomplish such goals, we are strategically pursuing innovative therapeutic platforms, including stromal-targeted prodrugs, protoxins, small molecules, and antibodies, in addition to epigenetic modulators and novel drug delivery systems; all of which are designed to reduce toxicity to peripheral non-target tissue (i.e., side effects) while maximizing anti-tumor efficacy (i.e., therapeutic benefit).
My laboratory routinely performs biochemical assays related to target inhibition and enzyme kinetics, genetic manipulation for target validation, analysis of standard pharmacokinetic and pharmacodynamic (PK/PD) parameters to assess biodistribution, clearance, and target engagement, in addition to in vivo efficacy and toxicity using state-of-the-art and clinically-representative models such as those described above. I have an established track-record of productivity and history of collaboration with leaders not only at Johns Hopkins, but also leading academic centers and biopharmaceutical companies nationally and worldwide to facilitate efficient translation of promising therapeutic strategies from the preclinical space to the bedside. We maintain close relationships with our medical oncology colleagues to maximize translational potential and clinical relevance.
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