Melinda R. Dwinell, Ph.D.

During the past eight years, the PhysGen Program for Genomic Applications (http://pga.mcw.edu) was focused on understanding the genetic basis of fundamental mechanistic pathways of the heart, lung, kidney, blood and vasculature.  To achieve this goal, PhysGen developed two panels of consomic rat strains and ENU-induced mutant strains and physiologically characterized these unique animal models.  Comprehensive characterization of the consomic strains allows for immediate mapping of traits to a particular chromosome without the need for genetic crosses.  The genes targeted in the ENU strategy are genes thought to be involved in complex diseases of the heart, lung, blood, and vasculature.  This strategy allows for the testing of the “functionality” of relevant genes.  My current role in this program, through the Education and Bioinformatics components, is to provide users with tools and information to navigate and utilize the extensive phenotype data.

My current focus is on establishing methods to integrate large phenotypic datasets, such as the PhysGen phenotyping data, with genomic databases such as the Rat Genome Database (http://rgd.mcw.edu).  This integration will use standardized nomenclature to link the phenotypic data to the rat genomic sequence, allowing the user to query by gene ontology, phenotype ontology and disease pathway.  Developing tools to provide easy access to phenotype data for a variety of strains assists in the identification of appropriate disease models and allows for comparison with human data.  Integrated phenotype data sets couples with genomic resources and emerging SNP based genotypes for hundreds of strains will improve our ability to elucidate the genetic basis of disease. 

An additional area of research focus has been on the neurophysiological mechanisms controlling breathing during development.  Maturation of the ventilator control system takes place following birth, although the factors influencing the maturation remain under investigation.  Our studies use different animal models to gain insight into the time-course of normal development of the ventilatory control system, as well as the effect of environmental and genetic influences on these changes during development.

Dwinell MR, Worthey E, Shimoyama M, Bakir-Gungor B, DePons J, Laulederkind S, Lowry T, Nigam R, Petri V, Smith J, Stoddard A, Twigger S, Jacob HJ. The Rat Genome Database 2009: Variation, Ontologies, and Pathways. Nucleic Acids Research. 2009; 37(Database Issue): D744-9.

Mattson DL, Dwinell MR, Greene AS, Kwitek AE, Roman RJ, Jacob HJ, Cowley AW Jr. Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease. Am J Physiol Renal Physiol. 2008; 295(3):F837-42.

Kunert MP, Dwinell MR, Drenjancevic Peric I, Lombard JH. Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SSxBN cross. Am J Physiol Regul Integr Comp Physiol. 2008; 295(2):R516-27.

Dwinell MR. Physiological genomics: from bench to bedside. Exp Physiol. 2007; 92:987.

Davis SE, Solheid G, Castillo M, Dwinell M, Brozoski D, Forster HV. Postnatal developmental changes in CO2 sensitivity in rats. J Appl Physiol. 2006; 101:1097-103.

Forster HV, Dwinell MR, Hodges MR, Brozoski D, Hogan GE. Do genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to regulation of breathing? Respir Physiol Neurobiol. 2003 May 30;135(2-3):247-61.

Hodges MR, Forster HV, Papanek PE, Dwinell MR, Hogan GE. Ventilatory phenotypes among four strains of adult rats. J Appl Physiol. 2002 Sep;93(3):974-83.

Dwinell MR, Kazemi H, Lam JT, Powell FL. Central amino acid neurotransmitters, ventilatory output and metabolism during acute hypoxia in anesthetized rats. Adv Exp Med Biol. 2001;499:291-6.

Olson EB Jr, Bohne CJ, Dwinell MR, Podolsky A, Vidruk EH, Fuller DD, Powell FL, Mitchel GS. Ventilatory long-term facilitation in unanesthetized rats. J Appl Physiol. 2001 Aug;91(2):709-16.

NIH Biosketch