Dhanansayan (Dhanu) Shanmuganayagam
Assistant Professor Co-Director, UW Center for Biomedical Swine Research and Innovation
Research
Dr. Shanmuganayagam’s research focuses on the development and utilization of pigs as homologous models to close the translational gap in human disease research, taking advantage of the similarities between pigs and humans in terms of genetics, anatomy, physiology, and immunology. He currently leads genetic engineering of swine at UW and is the Co-Director of the UW Center for Biomedical Swine Research and Innovation. His team has created numerous genetic porcine models, including ones for the study of xenotransplantation, and pediatric cancer-predisposition disorders such as neurofibromatosis type 1 (NF1). In the context of NF1, his lab is studying the role of alternative splicing of the nf1 gene on the tissue-specific function of neurofibromin and whether gene therapy to modulate the regulation of this splicing can be used as a viable treatment strategy for children with the disorder. Broadly, Dr. Shanmuganayagam’s program has numerous collaborations within and outside of UW in which swine models are used to drive research in other biomedical fields such as wound infections, heart disease, liver cirrhosis, metabolic disorders, imaging-guided radiotherapy systems, tumor ablation and resection devices, and ultrasound technologies.
Selected Peer-Reviewed Articles
Rubinstein CD, McLean DT, Lehman BP, Meudt JJ, Schomberg DT, Krentz KJ, Reichert JL, Meyer MB, Adams M, Konsitzke CM, Shanmuganayagam D. Assessment of Mosaicism and Detection of Cryptic Alleles in CRISPR/Cas9-Engineered Neurofibromatosis Type 1 and TP53 Mutant Porcine Models Reveals Overlooked Challenges in Precision Modeling of Human Diseases. Frontiers in Genetics 2021; 12. doi: 10.3389/fgene.2021.721045 (In Press).
Hanna A, Hellenbrand D, Schomberg D, Salamat S, Loh M, Wheeler L, Hanna B, Ozaydin B, Shanmuganayagam D. Brachial Plexus Anatomy of Miniature Swine Compared to Human. Journal of Anatomy 2021; doi: 10.1111/joa.13525 (In Press).
Schachtschneider KM, Schook LB, Meudt JJ, Shanmuganayagam D, Zoller JA, Haghani A, Li CZ, Zhang J, Yang A, Raj K, Horvath S. Epigenetic clock and DNA methylation analysis of porcine models of aging and obesity. GeroScience 2021. doi.org/10.1007/s11357-021-00439-6 (In Press).
Wuschner AE, Wallat EM, Flakus MJ, Shanmuganayagam D, Meudt J, Christensen GE, Reinhardt JM, Miller JR, Lawless MJ, Baschnagel AM, Bayouth JE. Radiation-induced Hounsfield unit change correlates with dynamic CT perfusion better than 4DCT-based ventilation measures in a novel-swine model. Science Reports 2021; 11(1):13156. doi: 10.1038/s41598-021-92609-x.
Schachtschneider KM, Jungersen G, Schook LB, Shanmuganayagam D. Editorial: “Humanized” Large Animal Cancer Models: Accelerating Time and Effectiveness of Clinical Trials. Frontiers in Oncology 2019; 9:793. doi: 10.3389/fonc.2019.00793.
Horton MV, Johnson CJ, Kernien JF, Patel TD, Lam BC, Cheong JZA, Meudt JJ, Shanmuganayagam D, Kalan LR, Nett JE. Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin. mSphere. 2020 Jan 22;5(1). doi: 10.1128/mSphere.00910-19.
Miranpuri GS, Schomberg DT, Stan P, Chopra A, Buttar S, Wood A, Radzin A, Meudt JJ, Resnick DK, Shanmuganayagam D. Comparative Morphometry of the Wisconsin Miniature Swine™ Thoracic Spine for Modeling Human Spine in Translational Spinal Cord Injury Research. Annals of Neurosciences 2018; 25(4): 210-218. doi: 10.1159/000488022.
Bekiares NA, Chen AS, Shanmuganayagam D, Meyers AD, Crenshaw TD, Krueger CG, Reed JD. Effect of Caloric Restriction on Metabolic Dysfunction of Young Rapacz Familial Hypercholesterolemic Swine (Sus scrofa). Comparative Medicine 2017; 67 (6):1-10.
Schomberg D, Miranpuri G. Chopra A, Patel K, Meudt JJ, Tellez A, Resnick DK, Shanmuganayagam D. Translational relevance of swine models of spinal cord injury. Journal of Neurotrauma 2016; 34(3):541-551. doi: 10.1089/neu.2016.4567.
Schomberg D, Tellez A, Meudt JJ, Brady D, Dillon KN, Arowolo FK, Wicks J, Rousselle SD, Shanmuganayagam D. Miniature swine for preclinical modeling of complexities of human disease for translational scientific discovery and accelerated development of therapies and medical devices. Toxicologic Pathology 2016; 44(3) 299-314.
Porras AM, Shanmuganayagam D, Meudt JJ, Krueger CG, Hacker TA, Rahko PS, Reed JD, Masters KS. Development of aortic valve disease in familial hypercholesterolemic swine: Implications for elucidating disease etiology. Journal of the American Heart Association 2015;4(10):e002254. doi: 10.1161/JAHA.115.002254.
Porras AM, Shanmuganayagam D, Meudt JJ, Krueger C, Reed JD, Masters KS. Gene expression profiling of valvular interstitial cells in Rapacz Familial Hypercholesterolemic swine. Genomic Data 2014; 2:261-263.
Johnson LL, Tekabe Y, Kollaros M, Eng G, Bhatia K, Li C, Krueger C, Shanmuganayagam D, Schmidt AM. Imaging RAGE expression in atherosclerotic plaques in hyperlipidemic pigs. European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI) Research 2014; 4:26.
Wentland AL, Wieben O, Shanmuganayagam D, Krueger CG, Meudt JJ, Consigny D, Rivera L, McBride PE, Reed JD, Grist TM. Measurements of wall shear stress and aortic pulse wave velocity in swine with familial hypercholesterolemia. Journal of Magnetic Resonance Imaging 2015; 41(5):1475-85.
Ge W, Krueger CG, Weichmann AJ, Shanmuganayagam D, Varghese T. Displacement and strain estimation for evaluation of arterial wall stiffness using a familial hypercholesterolemia swine model of atherosclerosis. Medical Physics 2012; 39 (7): 4483-92.
Selected Book Chapters
Shanmuganayagam D, Folts JD. Effect of polyphenolic flavonoid compounds on platelets. In: Packer L, ed. Methods in Enzymology (Volume 335): Flavonoids and Other Polyphenols: Academic Press; 2001: 369–380
Selected Popular Press Articles
Wisconsin State Journal: “Pigs into people: UW joins renewed effort to use animals as organ donors”
The Atlantic: “Turning Piglets into Personalized Avatars for Sick Kids”
Technology feature article in Nature Lab Animal: “Cancer Modeling Thinks Big with the Pig”
UW News: “To Help Kids Battling a Rare Disease, Scientists Forge a Genetic Link Between People and Pigs”
Selected Videos
Mini-documentary by New York filmmaker (“Super Human” series): “Can Genetically Modified Pigs Be the Key to Treating Rare Diseases?”
“Pig Avatars: Models for Precision Medicine” PBS Wisconsin – University Place. Aired May 2, 2018.
“Personalized Medicine” PBS Wisconsin – University Place; Aired March 4, 2019. UW School of Medicine and Public Health faculty: Elizabeth Burnside, Lee Gravatt Wilke, Dustin Deming, Stephen Meyn, and Dhanansayan Shanmuganayagam, from the Department of Animal Sciences at UW-Madison, discuss how to create individualized medical care plans.
Undergraduate Courses
AN SCI 320 – Animal Health and Disease (3 credits, Spring)
Course Description: Develops the students’ knowledge and appreciation for immunology and the interconnected role of multiple factors in heath and disease (with a focus on infectious disease).
INTER-AG 388 – Fundamentals of Scientific Research (1 credit, Spring)
Course Description: This course is for second-year students in the CALS Honors Program (Honors in Research track) about to begin independent research at UW-Madison. Students will learn the fundamentals of research: scientific process, using the scientific literature, and preparation of research proposals.
AN SCI 375 – Integrative Animal Physiology Laboratory (1 credit, Fall)
Course Description: Develops the students’ knowledge and appreciation for the interconnectivity and the interdependence between physiological processes of the various organ systems by teaching students basic skills in animal handling, blood collection, sedation/anesthesia techniques and surgical procedures.