Melinda R. Dwinell, PhD
Professor and Eminent Scholar; Associate Director, Education, Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine
Postdoctoral Fellowship, University of California-San Diego, 1996-2001
BS, Biology/Psychology, University of Michigan, 1990
- Cardiovascular Physiological Phenomena
- Circulatory and Respiratory Physiological Phenomena
- Data Mining
- Database Management Systems
- Disease Models, Animal
- Genetic Predisposition to Disease
- 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
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.
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
Lack of xanthine dehydrogenase leads to a remarkable renal decline in a novel hypouricemic rat model.
(Dissanayake LV, Zietara A, Levchenko V, Spires DR, Burgos Angulo M, El-Meanawy A, Geurts AM, Dwinell MR, Palygin O, Staruschenko A.) iScience. 2022 Sep 16;25(9):104887 PMID: 36039296 PMCID: PMC9418856 08/31/2022
Btg2 mutation induces renal injury and impairs blood pressure control in female rats.
(Hoffman MJ, Takizawa A, Jensen ES, Schilling R, Grzybowski M, Geurts AM, Dwinell MR.) Physiol Genomics. 2022 Jul 01;54(7):231-241 PMID: 35503009 PMCID: PMC9208437 SCOPUS ID: 2-s2.0-85132453480 05/04/2022
Hybrid Rat Diversity Program (HRDP): A rat resource for mapping complex traits.
(Dwinell M, Takizawa A, Lazcares L, Tutaj M, Schilling R, Geurts A, Kwitek A.) FASEB J. 2022 May;36 Suppl 1 PMID: 35560431 SCOPUS ID: 2-s2.0-85130045442 05/14/2022
MOET: a web-based gene set enrichment tool at the Rat Genome Database for multiontology and multispecies analyses.
(Vedi M, Nalabolu HS, Lin CW, Hoffman MJ, Smith JR, Brodie K, De Pons JL, Demos WM, Gibson AC, Hayman GT, Hill ML, Kaldunski ML, Lamers L, Laulederkind SJF, Thorat K, Thota J, Tutaj M, Tutaj MA, Wang SJ, Zacher S, Dwinell MR, Kwitek AE.) Genetics. 2022 Apr 04;220(4) PMID: 35380657 PMCID: PMC8982048 SCOPUS ID: 2-s2.0-85128160560 04/06/2022
The Rat Genome Database (RGD) facilitates genomic and phenotypic data integration across multiple species for biomedical research.
(Kaldunski ML, Smith JR, Hayman GT, Brodie K, De Pons JL, Demos WM, Gibson AC, Hill ML, Hoffman MJ, Lamers L, Laulederkind SJF, Nalabolu HS, Thorat K, Thota J, Tutaj M, Tutaj MA, Vedi M, Wang SJ, Zacher S, Dwinell MR, Kwitek AE.) Mamm Genome. 2022 Mar;33(1):66-80 PMID: 34741192 PMCID: PMC8570235 SCOPUS ID: 2-s2.0-85118526605 11/07/2021
Body Composition and Metabolic Changes in a Lyon Hypertensive Congenic Rat and Identification of Ercc6l2 as a Positional Candidate Gene.
(Clark KC, Wagner VA, Holl KL, Reho JJ, Tutaj M, Smith JR, Dwinell MR, Grobe JL, Kwitek AE.) Front Genet. 2022;13:903971 PMID: 35812759 PMCID: PMC9263446 07/12/2022
The NIH Somatic Cell Genome Editing program.
(Saha K, Sontheimer EJ, Brooks PJ, Dwinell MR, Gersbach CA, Liu DR, Murray SA, Tsai SQ, Wilson RC, Anderson DG, Asokan A, Banfield JF, Bankiewicz KS, Bao G, Bulte JWM, Bursac N, Campbell JM, Carlson DF, Chaikof EL, Chen ZY, Cheng RH, Clark KJ, Curiel DT, Dahlman JE, Deverman BE, Dickinson ME, Doudna JA, Ekker SC, Emborg ME, Feng G, Freedman BS, Gamm DM, Gao G, Ghiran IC, Glazer PM, Gong S, Heaney JD, Hennebold JD, Hinson JT, Khvorova A, Kiani S, Lagor WR, Lam KS, Leong KW, Levine JE, Lewis JA, Lutz CM, Ly DH, Maragh S, McCray PB Jr, McDevitt TC, Mirochnitchenko O, Morizane R, Murthy N, Prather RS, Ronald JA, Roy S, Roy S, Sabbisetti V, Saltzman WM, Santangelo PJ, Segal DJ, Shimoyama M, Skala MC, Tarantal AF, Tilton JC, Truskey GA, Vandsburger M, Watts JK, Wells KD, Wolfe SA, Xu Q, Xue W, Yi G, Zhou J, SCGE Consortium.) Nature. 2021 Apr;592(7853):195-204 PMID: 33828315 PMCID: PMC8026397 SCOPUS ID: 2-s2.0-85103997956 04/09/2021
The Gene Ontology resource: enriching a GOld mine.
(Gene Ontology Consortium.) Nucleic Acids Res. 2021 Jan 08;49(D1):D325-D334 PMID: 33290552 PMCID: PMC7779012 SCOPUS ID: 2-s2.0-85099428896 12/09/2020
The genome sequence of the Norway rat, Rattus norvegicus Berkenhout 1769
(Howe K, Dwinell M, Shimoyama M, Corton C, Betteridge E, Dove A, Quail MA, Smith M, Saba L, Williams RW, Chen H, Kwitek AE, McCarthy SA, Uliano-Silva M, Chow W, Tracey A, Torrance J, Sims Y, Challis R, Threlfall J, Blaxter M).) Wellcome Open Res. 2021, 6:118 05/18/2021
Sexual Dimorphic Role of CD14 (Cluster of Differentiation 14) in Salt-Sensitive Hypertension and Renal Injury.
(Fehrenbach DJ, Abais-Battad JM, Dasinger JH, Lund H, Keppel T, Zemaj J, Cherian-Shaw M, Gundry RL, Geurts AM, Dwinell MR, Mattson DL.) Hypertension. 2021 Jan;77(1):228-240 PMID: 33249861 PMCID: PMC9732708 SCOPUS ID: 2-s2.0-85097815793 12/01/2020