Melinda R. Dwinell, PhD

Associate Professor

Locations

Physiology

Contact Information

Biography

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 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.

Sdha+/- Rats Display Minimal Muscle Pathology Without Significant Behavioral or Biochemical Abnormalities.

(Siebers EM, Choi MJ, Tinklenberg JA, Beatka MJ, Ayres S, Meng H, Helbling DC, Takizawa A, Bennett B, Garces AM, Dias Duarte Machado LG, Dimmock D, Dwinell MR, Geurts AM, Lawlor MW.) J Neuropathol Exp Neurol. 2018 Aug 01;77(8):665-672.
A Primer for the Rat Genome Database (RGD).

(Laulederkind SJF, Hayman GT, Wang SJ, Smith JR, Petri V, Hoffman MJ, De Pons J, Tutaj MA, Ghiasvand O, Tutaj M, Thota J, Dwinell MR, Shimoyama M.) Methods Mol Biol. 2018;1757:163-209.
Rat Genome and Model Resources.

(Shimoyama M, Smith JR, Bryda E, Kuramoto T, Saba L, Dwinell M.) ILAR J. 2017 07 01;58(1):42-58.
Haploid embryonic stem cell lines derived from androgenetic and parthenogenetic rat blastocysts.

(Hirabayashi M, Hara H, Goto T, Takizawa A, Dwinell MR, Yamanaka T, Hochi S, Nakauchi H.) J Reprod Dev. 2017 Dec 15;63(6):611-616.
Host genetic modifiers of nonproductive angiogenesis inhibit breast cancer.

(Flister MJ, Tsaih SW, Stoddard A, Plasterer C, Jagtap J, Parchur AK, Sharma G, Prisco AR, Lemke A, Murphy D, Al-Gizawiy M, Straza M, Ran S, Geurts AM, Dwinell MR, Greene AS, Bergom C, LaViolette PS, Joshi A.) Breast Cancer Res Treat. 2017 Aug;165(1):53-64.
Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia.

(Densmore JC, Schaid TR, Jeziorczak PM, Medhora M, Audi S, Nayak S, Auchampach J, Dwinell MR, Geurts AM, Jacobs ER.) Exp Lung Res. 2017 02;43(1):38-48.
Exploring human disease using the Rat Genome Database.

(Shimoyama M, Laulederkind SJ, De Pons J, Nigam R, Smith JR, Tutaj M, Petri V, Hayman GT, Wang SJ, Ghiasvand O, Thota J, Dwinell MR.) Dis Model Mech. 2016 10 01;9(10):1089-1095.
Disease, Models, Variants and Altered Pathways-Journeying RGD Through the Magnifying Glass.

(Petri V, Hayman GT, Tutaj M, Smith JR, Laulederkind S, Wang SJ, Nigam R, De Pons J, Shimoyama M, Dwinell MR.) Comput Struct Biotechnol J. 2016;14:35-48.
Comprehensive coverage of cardiovascular disease data in the disease portals at the Rat Genome Database.

(Wang SJ, Laulederkind SJ, Hayman GT, Petri V, Smith JR, Tutaj M, Nigam R, Dwinell MR, Shimoyama M.) Physiol Genomics. 2016 08 01;48(8):589-600.
The Disease Portals, disease-gene annotation and the RGD disease ontology at the Rat Genome Database.

(Hayman GT, Laulederkind SJ, Smith JR, Wang SJ, Petri V, Nigam R, Tutaj M, De Pons J, Dwinell MR, Shimoyama M.) Database (Oxford). 2016;2016.
Report of the National Heart, Lung, and Blood Institute Working Group on Sex Differences Research in Cardiovascular Disease: Scientific Questions and Challenges.

(Maric-Bilkan C, Arnold AP, Taylor DA, Dwinell M, Howlett SE, Wenger N, Reckelhoff JF, Sandberg K, Churchill G, Levin E, Lundberg MS.) Hypertension. 2016 May;67(5):802-7.
Ndufc2 Gene Inhibition Is Associated With Mitochondrial Dysfunction and Increased Stroke Susceptibility in an Animal Model of Complex Human Disease.

(Rubattu S, Di Castro S, Schulz H, Geurts AM, Cotugno M, Bianchi F, Maatz H, Hummel O, Falak S, Stanzione R, Marchitti S, Scarpino S, Giusti B, Kura A, Gensini GF, Peyvandi F, Mannucci PM, Rasura M, Sciarretta S, Dwinell MR, Hubner N, Volpe M.) J Am Heart Assoc. 2016 Feb 17;5(2).

Melinda R. Dwinell, PhD