Description of Research Expertise

I established and direct the induced Pluripotent Stem Cell (iPSC) Core facility at the University of Pennsylvania. My group has over 10 years of experience in developing human cellular models of disease using iPSCs. We have generated hiPSC lines from more than 150 normal and diseased human subjects and have characterized some of these lines extensively. We also routinely employ CRISPR/Cas9 technology to create genetic modifications in PSCs including gene reporters, gene knock-outs and single base knock-in cell lines. Another major strength of my group is establishing robust and reproducible protocols based on published literature for differentiation of PSCs into various cell lineages, which include but not limited to cardiomyocytes, hepatocytes, endothelial cells, adipocytes, skeletal muscle cells and pancreatic beta cells. Of note, I played a key role in a NIH funded project (U01 HG006398) demonstrating stem cell derived hepatocyte-like-cells (HLCs) are a powerful and relevant model for discovering and interrogating functional variants and genes contributing to complex human diseases. My Core collaborates extensively with the Penn and external stem cell research communities to facilitate research in the areas of cardiomyocyte biology, lung regeneration, hepatocyte biology, muscle regeneration and type 1 diabetes using the above-mentioned research tools that we have developed. In addition to directing the Core, I have an active research program aimed at understanding the mechanisms of action through which type 2 diabetes (T2D) risk variants and their effector genes affect disease development. To this end, we develop and validate human PSC-cell models of adipose, muscle and liver in the context of establishing robust functional assays of insulin-action, which are lacking in the field. We collaborate with others using these models to link genotype to phenotype. In addition, my lab has a particular interest in the mechanisms of action of T2D-associated variants/genes/pathways expressed and relevant in skeletal muscle using human cell models, including stem cell models that we have developed.

Selected Publications

Trang KB, Pahl MC, Pippin JA, Su C, Littleton SH, Sharma P, Kulkarni NN, Ghanem LR, Terry NA, O'Brien JM, Wagley Y, Hankenson KD, Jermusyk A, Hoskins JW, Amundadottir LT, Xu M, Brown KM, Anderson SA, Yang W, Titchenell PM, Seale P, Cook L, Levings MK, Zemel BS, Chesi A, Wells AD, Grant SFA.: 3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity medRxiv : 2023.

Almad AA, Garcia L, Takanohashi A, Gagne A, Yang W, Ann McGuire J, French D, Vanderver A.: Generation of three induced Pluripotent Stem Cell lines from individuals with Hypomyelination with Atrophy of Basal Ganglia and Cerebellum caused by a c.745G>A (p.D249N) autosomal dominant mutation in TUBB4A Stem Cell Res 69 : 103083,2023.

Gawronski KAB, Bone WP, Park Y, Pashos EE, Wenz BM, Dudek MF, Wang X, Yang W, Rader DJ, Musunuru K, Voight BF, Brown CD.: Evaluating the Contribution of Cell Type-Specific Alternative Splicing to Variation in Lipid Levels Circ Genom Precis Med 16 (3): 248-257,2023.

Cotticelli MG, Xia S, Truitt R, Doliba NM, Rozo AV, Tobias JW, Lee T, Chen J, Napierala JS, Napierala M, Yang W, Wilson RB.: Acute frataxin knockdown in induced pluripotent stem cell-derived cardiomyocytes activates a type I interferon response Dis Model Mech 16 (5): dmm049497,2023.

Sakata Y, Cheng K, Mayama M, Seita Y, Detlefsen AJ, Mesaros CA, Penning TM, Shishikura K, Yang W, Auchus RJ, Strauss JF 3rd, Sasaki K.: Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells Dev Cell 57 (22): 2566-2583,2022.

Kee J, Thudium S, Renner DM, Glastad K, Palozola K, Zhang Z, Li Y, Lan Y, Cesare J, Poleshko A, Kiseleva AA, Truitt R, Cardenas-Diaz FL, Zhang X, Xie X, Kotton DN, Alysandratos KD, Epstein JA, Shi PY, Yang W, Morrisey E, Garcia BA, Berger SL, Weiss SR, Korb E.: SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry Nature 610 (7931): 381-388,2022.

Fernandez RJ, Gardner ZJG, Slovik KJ, Liberti DC, Estep KN, Yang W, Chen Q, Santini GT, Perez JV, Root S, Bhatia R, Tobias JW, Babu A, Morley MP, Frank DB, Morrisey EE, Lengner CJ, Johnson FB.: GSK3 inhibition rescues growth and telomere dysfunction in dyskeratosis congenita iPSC-derived type II alveolar epithelial cells Elife 11 : e64430,2022.

Jiang CL, Goyal Y, Jain N, Wang Q, Truitt RE, Coté AJ, Emert B, Mellis IA, Kiani K, Yang W, Jain R, Raj A.: Cell type determination for cardiac differentiation occurs soon after seeding of human-induced pluripotent stem cells Genome Biol 23 (1): 90,2022.

Ramachandran K, Maity S, Muthukumar AR, Kandala S, Tomar D, Abd El-Aziz TM, Allen C, Sun Y, Venkatesan M, Madaris TR, Chiem K, Truitt R, Vishnu N, Aune G, Anderson A, Martinez L, Yang W, Stockand JD, Singh BB, Srikantan S, Reeves WB, Madesh M.: SARS-CoV-2 infection enhances mitochondrial PTP complex activity to perturb cardiac energetics iScience 25 (1): 103722,2022.

Kim J, Ekstrom T, Yang W, Donahue G, Grygoryev D, Ngo TTM, Muschler JL, Morgan T, Zaret KS.: Longitudinal Analysis of Human Pancreatic Adenocarcinoma Development Reveals Transient Gene Expression Signatures Mol Cancer Res 19 (11): 1854-1867,2021.

Academic Contact Information

Department of Medicine
University of Pennsylvania School of Medicine
Smilow Center for Translational Research, 11th Floor, Rm 111
3400 Civic Center Boulevard
Philadelphia, PA 19104
Phone: 215-746-0589