Mitch A. Phelps, PhD
Assistant Professor of Pharmaceutics,
College of Pharmacy
Technical Director, Pharmacoanalytical Shared Resource
The Ohio State University Comprehensive Cancer Center
Office: 230 Parks Hall
500 W 12th Ave, Columbus, OH 43210
Phone: (614) 688-4370, Fax: (614) 292-7766
Education
- PhD Biophysics, 2005, Biophysics Program, The Ohio State University, Columbus, OH
- MLHR, 1999, Business Management/Labor and Human Resources, The Ohio State University, Columbus, OH
- BA Physics, 1992, Ohio Wesleyan University, Delaware, OH
Research Interests
- Anti-cancer drug development
- Functional polymorphisms in transporters and metabolizing enzymes and their effects on gene/protein expression and interaction with anti-cancer therapeutic agents
- Role of genetic polymorphisms on inter-individual variation in drug disposition and clinical outcomes (response and toxicity)
Our group is involved in both pre-clinical and clinical development of numerous small molecule anti-cancer and immuno-modulatory agents under development here at OSU. Our work aims to understand the mechanisms involved in the absorption, distribution, metabolism, and excretion (i.e. pharmacokinetics, PK) of these agents, and how both the PK and pharmacodynamic (PD) effects of these agents are altered by genetic differences (polymorphisms) among individuals (i.e. pharmacogenetics, PG).
From a pre-clinical standpoint, we model the relationship between PK and PD to facilitate selection and optimization of compounds for further development. We aim to elucidate the processes for absorption, metabolism and excretion to enable predictions of how these processes may impact drug efficacy in humans given the prevalence of known polymorphisms of genes involved in these processes. Much of our work includes the development and validation of liquid chromatography/mass spectrometry assays or other sensitive and selective assays to achieve this.
With respect to clinical development, our lab is pursuing several avenues to identify, characterize and/or confirm novel PK-PG relationships. Heterogeneity in response and toxicity among individuals treated with anti-cancer drugs is undoubtedly multi-factorial, and fully modeling this diversity has been, and will continue to be, a complex endeavor. The ability to accurately and rapidly genotype individuals for specific polymorphisms in genes coding for target proteins and enzymes and transporters involved in a drug's disposition has confirmed the role of genetics in this complexity. While a few clinically relevant examples exist where the presence of a single polymorphism is adequate to explain a major portion of observed inter-individual variability (e.g. TPMT and thiopurine metabolism), most drugs will require more information to achieve a similar level of understanding. For example, polymorphisms in a gene coding for a drug metabolizing enzyme may describe only 20% of observed variability in drug exposure and/or activity within a given population. The remaining 80% may be described by other polymorphisms or mutations in the primary drug target, in other metabolizing enzymes or transporters contributing to drug elimination, varying expression levels of these proteins (perhaps caused by yet other polymorphisms), mutations or epigenetic modifications in tumor survival pathways, varying tumor sensitivities, and numerous other possible factors. Our efforts in PK/PG/PD data analysis and modeling, combined with collaborations and other resources here at OSU to incorporate clinical outcomes and genetics, enables us to probe various portions of this puzzle. In particular, we can use PK as a direct phenotype for evaluation with respect to pharmacogenetics of enzymes and transporters. Active projects in our group involve agents such as flavopiridol and lenalidomide for which we are evaluating the role of pharmacogenetics in inter-individual differences in PK and outcomes for patients enrolled in clinical studies at OSU. We are also pursuing studies with well-characterized agents, such as dexamethasone and tamoxifen, to evaluate the impact of novel polymorphisms in CYP enzymes recently identified by our collaborators at OSU.
Teaching
Instructor, Advanced Pharmacokinetics (Pharmacy 802) 2007
The Ohio State University, College of Pharmacy
Professional Experience
2009 to Present: Assistant Professor, Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH
2006 to Present: Manager, Pharmacoanalytical Shared Resource, The Ohio State University Comprehensive Cancer Center, Columbus, OH
November, 1992 – June, 2000: Chemist and Group Leader, Polymer Coatings PPG Industries, Inc., Springdale, PA and Delaware, OH
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