UTEB 150 at Storrs & Videoconferenced to UCHC CG-079B
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BME Seminar Friday, February 12th, 2016 UTEB 150 at Storrs & Videoconferenced to UCHC CG-079B 12:00-12:50 pm *Refreshments will be served*
“Systems Pharmacology Mathematical Model Development to Provide Physiologically-Based Interpretation and Drug Development Decision Support in Osteoporosis and Other Bone-Related Diseases” Presented by: Matthew M. Riggs, R.Ph., Ph.D. - Metrum Research Group LLC, Tariffville, CT USA Abstract: Mathematical models describing pharmacokinetics-pharmacodynamics, disease progression, and systems biology provide the components for a multiscale systems pharmacology model (MSPM) with a goal to enable in silico exploration of the ramifications of system perturbations, e.g., those caused by disease, genetic variation, and therapeutic intervention(s). In doing so, the MSPM approach offers a continuum for translating experimental data with clinical biomarkers and outcomes allowing researchers to probe target pathways, understand potential patient-to-patient sensitivities, and ultimately design more efficient and informative clinical trials. Applied broadly, these models instill rapid, seamless knowledge transfer across the research scale by enabling colleagues from multiple disciplines to communicate with a common set of expectations and understanding of these oftentimes complex systems. MSPMs can thereby serve as repositories that contain and connect data, experimentations, overall comprehension, and assumptions of the system. A MSPM describing bone mineral homeostasis and bone remodeling will be used as an example of how to develop and apply such a model with a focus on MSPM extensibility to evolving and broadening research goals. A brief history of the model construction will be provided with its initial focus on osteoporosis treatment[1] and continued expansion to other natural progressions and diseases involving bone, e.g., natural estrogen loss during menopause transition and during endometriosis treatment,[2] as well as Chronic Kidney Disease-Mineral and Bone Disorder.[3] Additionally, a “middle-out'' approach[4] to ongoing research efforts include the translation of bone marker effects to BMD prediction and subsequent fracture risk,[5] sclerostin-mediated effects on bone remodeling,[6] and inclusion of Vitamin D kinetics.[7] An overview and update on this research, as well as future plans, will be provided. Bio: Dr. Riggs is a Principal Scientist II and Group Leader of Systems Pharmacology Modeling and Simulation at Metrum Research Group LLC (MetrumRG). He has been with MetrumRG for over 10 years. Dr. Riggs leads research efforts to develop and integrate multiscale, physiologic models within model-driven drug development. His current responsibilities also include training and mentorship of graduate students through the University of Connecticut Biomedical Engineering Department, where he has held an adjunct faculty appointment. Matthew is a registered pharmacist. He received his B.S. in Pharmacy, Magna Cum Laude and with distinction, and Ph.D. degrees from the University Of Connecticut School Of Pharmacy in 1994 and 2000, respectively. He completed a post- doctoral fellowship at GloboMax LLC (now ICON Development Solutions) in early 2001. Dr. Riggs then worked for nearly 5 years at Pfizer Global Research and Development and was an Associate Director and Clinical Pharmacology Team Leader prior to joining MetrumRG. Matthew has served as an invited peer reviewer for several clinical pharmacology-related journals. He is the past-chair of the American Association of Pharmaceutical Scientists System Pharmacology Focus Group and current chair of the American Society of Clinical Pharmacology and Therapeutics System Pharmacology Community.
[1] M. C. Peterson and M. M. Riggs. A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling. Bone, 46:49–63, Jan 2010. [2] M. Riggs, M. Bennetts, P. van der Graaf, and S. Martin. Integrated pharmacometrics and systems pharmacology model-based analyses to guide GnRH receptor modulator development for management of endometriosis. CPT Pharmacometrics Syst Pharmacol., 1(e10), 2012. [3] M. M. Riggs, M. C. Peterson, and M. R. Gastonguay. Multiscale physiology-based modeling of mineral bone disorder in patients with impaired kidney function. J Clin Pharmacol, 52(1 Suppl):45S–53S, Jan 2012. [4] M. M. Riggs. Multiscale systems models as a knowledge bridge between biology, physiology, and phar- macology. AAPS Newsmagazine, December 2011. [5] E. L. Plan, K. T. Baron, M. R. Gastonguay, J. L. French, W. R. Gillespie, and M. M. Riggs. Bayesian joint modeling of bone mineral density and repeated time-to- fracture event for multiscale bone systems model extension. In PAGE 21st Meeting, 2012. [6] R. Eudy, M. R. Gastonguay, K. T. Baron, and M. M. Riggs. Connecting the dots: Linking osteocyte activity and therapeutic modulation of sclerostin by extending a multiscale systems model. CPT Pharmacometrics Syst Pharmacol, 2015. [7] A. S. Ocampo-Pellend, M. R. Gastonguay, J. L. French, M. M. Riggs. Model-based meta-analysis for development of a population-pharmacokinetic (ppk) model for vitamin D3 and its 25OHD3 metabolite. In PAGE 24, 2015.