PUMA

Who we are

PUMA (Pathway-driven Pharmacogenomics, University of Minnesota Alliance) is a coordinated effort by experienced investigators with expertise in multiple disciplines including pharmacology, genetics, pharmacogenomics, bioinformatics, pharmacometrics, oncology, and cardiology. 

Our common goals include identification and development of polygenic, pathway based approaches which will advance our understanding of the role for pharmacogenomics in drug response variability. Investigators within PUMA are currently using this approach to identify molecular mechanisms underlying variable response and/or drug-related adverse events for various diseases with an emphasis on cancer, transplantation, epilepsy, asthma and cardiovascular diseases.

The formation of PUMA attempts to address an urgent need to integrate the scattered genetic data from different sources/platforms onto common human pathways and functionalities. The aim of PUMA is to identify comprehensive panels of potentially functional and clinically relevant genetic polymorphisms in pharmacokinetic (ADME) and pharmacodynamic pathways important for treatment of human diseases with a long term goal to move pharmacogenetic testing into the clinical setting to improve safety and efficacy of drug therapy. An initial prototype of one such panel was recently developed here at the University of Minnesota (Bank on A Cure SNP Panel).

Plans

Our strategy consists of the following:

• Preparing lists of candidate genes and/or pathways important for drug pharmacokinetics and pharmacodynamics by using a wide variety of bioinformatic/pathway analysis tools and information from the published literature. 
  
• Identifying and/or discovering polymorphisms in the key candidate genes by using databases and/or resequencing followed by in silico analysis and prioritization of SNPs (eg. coding SNPs, SNPs in regions of transcriptional regulatory potential, miR binding sites and in motifs important in splicing) as well as in vitro functional studies to evaluate potentially functional polymorphisms. 
  
• Conducting studies ascertaining associations between functional polymorphisms or haplotypes and phenotypic response. We will also screen for copy number variations (CNVs) in the key candidate genes using information from the published literature and structural variant databases. 
  
• Determining clinical significance of the potentially functional variants by conducting translational studies in relevant patient populations. 
  
• Utilize both established and novel statistical approaches to assess the contributions of multiple genes/genetic variants towards observed phenotypes.

PUMA is registered with the Pharamacogenetics Research Network. More information can be found here.