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 15 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, Sharma P, Cook L, Mount Z, Thomas RM, Kulkarni NN, Pahl MC, Pippin JA, Su C, Kaestner KH, 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, Zemel BS, Chesi A, Romberg N, Levings MK, Grant SFA, Wells AD.: 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility medRxiv : 2024.

Trang KB, Chesi A, Toikumo S, Pippin JA, Pahl MC, O'Brien JM, Amundadottir LT, Brown KM, Yang W, Welles J, Santoleri D, Titchenell PM, Seale P, Zemel BS, Wagley Y, Hankenson KD, Kaestner KH, Anderson SA, Kayser MS, Wells AD, Kranzler HR, Kember RL, Grant SFA.: Shared and unique 3D genomic features of substance use disorders across multiple cell types medRxiv : 2024.

Zhao G, Zhang HM, Nasseri AR, Yip F, Telkar N, Chen YT, Aghakeshmiri S, Küper C, Lam W, Yang W, Zhao J, Luo H, McManus BM, Yang D.: Heart-specific NFAT5 knockout suppresses type I interferon signaling and aggravates coxsackievirus-induced myocarditis Basic Res Cardiol : 2024.

Vishnu N, Venkatesan M, Madaris TR, Venkateswaran MK, Stanley K, Ramachandran K, Chidambaram A, Madesh AK, Yang W, Nair J, Narkunan M, Muthukumar T, Karanam V, Joseph LC, Le A, Osidele A, Aslam MI, Morrow JP, Malicdan MC, Stathopulos PB, Madesh M.: ERMA (TMEM94) is a P-type ATPase transporter for Mg(2+) uptake in the endoplasmic reticulum Mol Cell 84 : 1321-1337,2024.

Das S, Hilman MC, Yang F, Mourkioti F, Yang W, Cullen DK.: Motor neurons and endothelial cells additively promote development and fusion of human iPSC-derived skeletal myocytes Skelet Muscle 14 : 5,2024.

Pahl MC, Liu L, Pippin JA, Wagley Y, Boehm K, Hankenson KD, Wells AD, Yang W, Grant SFA.: Variant to gene mapping for carpal tunnel syndrome risk loci implicates skeletal muscle regulatory elements EBioMedicine : 2024.

Jain N, Goyal Y, Dunagin MC, Cote CJ, Mellis IA, Emert B, Jiang CL, Dardani IP, Reffsin S, Arnett M, Yang W, Raj A.: Retrospective identification of cell-intrinsic factors that mark pluripotency potential in rare somatic cells Cell Syst 15 : 109-133,2024.

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.

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