Medical College of Wisconsin
Medical College of Wisconsin Medical College of Wisconsin
Research Lab Bench
Physiology
Melinda Dwinell, PhD

Melinda R. Dwinell, PhD

Professor and Eminent Scholar; Associate Director, Education, Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine

Locations

  • Physiology

Contact Information

Education

MS/PhD, Veterinary Science, University of Wisconsin-Madison, 1996
Postdoctoral Fellowship, University of California-San Diego, 1996-2001
BS, Biology/Psychology, University of Michigan, 1990

Research Experience

  • Cardiovascular Physiological Phenomena
  • Circulatory and Respiratory Physiological Phenomena
  • Data Mining
  • Database Management Systems
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Genome
  • Phenotype
  • Rats, Inbred Strains
  • Respiratory Physiological Phenomena

Methodologies and Techniques

  • Airway Resistance
  • Monitoring, Physiologic
  • Plethysmography, Whole Body

MCW Program / Core Facilities

  • Rat Research Models Service Center

Research Interests

Bioinformatics  |  Physiological Genomics  | Respiratory Physiology

My interest in collecting, analyzing and integrating large phenotype datasets began nearly ten years ago with the PhysGen Program for Genomic Applications. This program was focused on understanding the genetic basis of fundamental mechanistic pathways of the heart, lung, kidney, blood and vasculature and achieved this goal by developing two panels of consomic rat strains and ENU-induced mutant strains and physiologically characterizing 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. To test the "functionality" of relevant genes found to be associated with cardiovascular and renal disease in human populations, the PhysGen Knockout program has been developing 100 knockout strains with phenotypic characterization to test the role of these genes in cardiovascular and renal disease mechanisms.

My current focus is on establishing methods to integrate large phenotypic datasets, such as the PhysGen and PhysGen Knockout phenotyping data, with genomic databases such as the Rat Genome Database. 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 coupled 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 developing and characterizing rat models for pulmonary diseases, including asthma and pulmonary hypertension. Many of the animal models developed as part of the PhysGen and PhysGen Knockout programs have phenotypes that mimic pulmonary disease traits and are ideal models to further understand the genetic and environmental influence in disease development. Integration of published phenotype data for pulmonary disease traits has allowed us to identify key phenotypes that can be used to characterize strains as disease models and identify missing data sets that would further refine ideal animal models of disease.

Publications

  • Construction and evaluation of a new rat reference genome assembly, GRCr8, from long reads and long-range scaffolding.

    (Li K, Smith ML, Blazier JC, Kochan KJ, Wood JMD, Howe K, Kwitek AE, Dwinell MR, Chen H, Ciosek JL, Masterson P, Murphy TD, Kalbfleisch TS, Doris PA.) Genome Res. 2024 Nov 08 PMID: 39516046

  • A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.

    (de Jong TV, Pan Y, Rastas P, Munro D, Tutaj M, Akil H, Benner C, Chen D, Chitre AS, Chow W, Colonna V, Dalgard CL, Demos WM, Doris PA, Garrison E, Geurts AM, Gunturkun HM, Guryev V, Hourlier T, Howe K, Huang J, Kalbfleisch T, Kim P, Li L, Mahaffey S, Martin FJ, Mohammadi P, Ozel AB, Polesskaya O, Pravenec M, Prins P, Sebat J, Smith JR, Solberg Woods LC, Tabakoff B, Tracey A, Uliano-Silva M, Villani F, Wang H, Sharp BM, Telese F, Jiang Z, Saba L, Wang X, Murphy TD, Palmer AA, Kwitek AE, Dwinell MR, Williams RW, Li JZ, Chen H.) Cell Genom. 2024 Apr 10;4(4):100527 PMID: 38537634 PMCID: PMC11019364 03/28/2024

  • The Power of the Heterogeneous Stock Rat Founder Strains in Modeling Metabolic Disease.

    (Wagner VA, Holl KL, Clark KC, Reho JJ, Lehmler HJ, Wang K, Grobe JL, Dwinell MR, Raff H, Kwitek AE.) Endocrinology. 2023 Nov 02;164(12) PMID: 37882530 PMCID: PMC10637104 SCOPUS ID: 2-s2.0-85176509096 10/26/2023

  • Rare disease research resources at the Rat Genome Database.

    (Kaldunski ML, Smith JR, Brodie KC, De Pons JL, Demos WM, Gibson AC, Hayman GT, Lamers L, Laulederkind SJF, Thorat K, Thota J, Tutaj MA, Tutaj M, Vedi M, Wang SJ, Zacher S, Dwinell MR, Kwitek AE.) Genetics. 2023 Aug 09;224(4) PMID: 37119810 PMCID: PMC10411567 SCOPUS ID: 2-s2.0-85167481442 04/30/2023

  • Divergent risky decision-making and impulsivity behaviors in Lewis rat substrains with low genetic difference.

    (Gabriel DBK, Liley AE, Franks HT, Minnes GL, Tutaj M, Dwinell MR, de Jong TV, Williams RW, Mulligan MK, Chen H, Simon NW.) Behav Neurosci. 2023 Aug;137(4):254-267 PMID: 37104777 PMCID: PMC10524952 SCOPUS ID: 2-s2.0-85158841983 04/27/2023

  • Genetic background in the rat affects endocrine and metabolic outcomes of bisphenol F exposure.

    (Wagner VA, Holl KL, Clark KC, Reho JJ, Dwinell MR, Lehmler HJ, Raff H, Grobe JL, Kwitek AE.) Toxicol Sci. 2023 Jun 28;194(1):84-100 PMID: 37191987 PMCID: PMC10306406 SCOPUS ID: 2-s2.0-85164065947 05/16/2023

  • The Rat Genome Database: Genetic, Genomic, and Phenotypic Data Across Multiple Species.

    (Laulederkind SJF, Hayman GT, Wang SJ, Kaldunski ML, Vedi M, Demos WM, Tutaj M, Smith JR, Lamers L, Gibson AC, Thorat K, Thota J, Tutaj MA, de Pons JL, Dwinell MR, Kwitek AE.) Curr Protoc. 2023 Jun;3(6):e804 PMID: 37347557 PMCID: PMC10335880 SCOPUS ID: 2-s2.0-85162756259 06/22/2023

  • 2022 updates to the Rat Genome Database: a Findable, Accessible, Interoperable, and Reusable (FAIR) resource.

    (Vedi M, Smith JR, Thomas Hayman G, Tutaj M, Brodie KC, De Pons JL, Demos WM, Gibson AC, Kaldunski ML, Lamers L, Laulederkind SJF, Thota J, Thorat K, Tutaj MA, Wang SJ, Zacher S, Dwinell MR, Kwitek AE.) Genetics. 2023 May 04;224(1) PMID: 36930729 PMCID: PMC10474928 SCOPUS ID: 2-s2.0-85159551813 03/18/2023

  • The Gene Ontology knowledgebase in 2023.

    (Gene Ontology Consortium, Aleksander SA, Balhoff J, Carbon S, Cherry JM, Drabkin HJ, Ebert D, Feuermann M, Gaudet P, Harris NL, Hill DP, Lee R, Mi H, Moxon S, Mungall CJ, Muruganugan A, Mushayahama T, Sternberg PW, Thomas PD, Van Auken K, Ramsey J, Siegele DA, Chisholm RL, Fey P, Aspromonte MC, Nugnes MV, Quaglia F, Tosatto S, Giglio M, Nadendla S, Antonazzo G, Attrill H, Dos Santos G, Marygold S, Strelets V, Tabone CJ, Thurmond J, Zhou P, Ahmed SH, Asanitthong P, Luna Buitrago D, Erdol MN, Gage MC, Ali Kadhum M, Li KYC, Long M, Michalak A, Pesala A, Pritazahra A, Saverimuttu SCC, Su R, Thurlow KE, Lovering RC, Logie C, Oliferenko S, Blake J, Christie K, Corbani L, Dolan ME, Drabkin HJ, Hill DP, Ni L, Sitnikov D, Smith C, Cuzick A, Seager J, Cooper L, Elser J, Jaiswal P, Gupta P, Jaiswal P, Naithani S, Lera-Ramirez M, Rutherford K, Wood V, De Pons JL, Dwinell MR, Hayman GT, Kaldunski ML, Kwitek AE, Laulederkind SJF, Tutaj MA, Vedi M, Wang SJ, D'Eustachio P, Aimo L, Axelsen K, Bridge A, Hyka-Nouspikel N, Morgat A, Aleksander SA, Cherry JM, Engel SR, Karra K, Miyasato SR, Nash RS, Skrzypek MS, Weng S, Wong ED, Bakker E, Berardini TZ, Reiser L, Auchincloss A, Axelsen K, Argoud-Puy G, Blatter MC, Boutet E, Breuza L, Bridge A, Casals-Casas C, Coudert E, Estreicher A, Livia Famiglietti M, Feuermann M, Gos A, Gruaz-Gumowski N, Hulo C, Hyka-Nouspikel N, Jungo F, Le Mercier P, Lieberherr D, Masson P, Morgat A, Pedruzzi I, Pourcel L, Poux S, Rivoire C, Sundaram S, Bateman A, Bowler-Barnett E, Bye-A-Jee H, Denny P, Ignatchenko A, Ishtiaq R, Lock A, Lussi Y, Magrane M, Martin MJ, Orchard S, Raposo P, Speretta E, Tyagi N, Warner K, Zaru R, Diehl AD, Lee R, Chan J, Diamantakis S, Raciti D, Zarowiecki M, Fisher M, James-Zorn C, Ponferrada V, Zorn A, Ramachandran S, Ruzicka L, Westerfield M.) Genetics. 2023 May 04;224(1) PMID: 36866529 PMCID: PMC10158837 SCOPUS ID: 2-s2.0-85164785564 03/04/2023

  • A Four Core Genotypes rat model to distinguish mechanisms underlying sex-biased phenotypes and diseases.

    (Arnold AP, Chen X, Grzybowski MN, Ryan JM, Sengelaub DR, Mohanroy T, Furlan VA, Grisham W, Malloy L, Takizawa A, Wiese CB, Vergnes L, Skaletsky H, Page DC, Reue K, Harley VR, Dwinell MR, Geurts AM.) bioRxiv. 2023 Feb 10 PMID: 36798326 PMCID: PMC9934672 02/18/2023

  • Ontological Analysis of Coronavirus Associated Human Genes at the COVID-19 Disease Portal.

    (Wang SJ, Brodie KC, De Pons JL, Demos WM, Gibson AC, Hayman GT, Hill ML, Kaldunski ML, Lamers L, Laulederkind SJF, Nalabolu HS, Thota J, Thorat K, Tutaj MA, Tutaj M, Vedi M, Zacher S, Smith JR, Dwinell MR, Kwitek AE.) Genes (Basel). 2022 Dec 07;13(12) PMID: 36553571 PMCID: PMC9777590 12/24/2022

Publications of Melinda R. Dwinell PhD from the Faculty Collaboration Database