Sydney M. Shaffer, MD, PhD
Assistant Professor of Pathology and Laboratory Medicine
Assistant Professor of Bioengineering
Perelman School of Medicine at the University of Pennsylvania
Associate Vice Chair for Basic Research
Department of Pathology and Laboratory Medicine
Contact InformationPerelman School of Medicine at the University of Pennsylvania
Department of Pathology and Laboratory Medicine
John Morgan Building, Rm. 163
3620 Hamilton Walk
Philadelphia, PA 19104
Email: shaffers@pennmedicine.upenn.edu
Specialty Division
Cancer and Immunobiology
Research Expertise
Understanding how differences between single-cells generate phenotypes such as drug resistance, oncogenesis, differentiation, and invasion, using cutting-edge technologies including high-throughput imaging, single-molecule RNA FISH, fluorescent protein tagging, CRISPR/Cas9 screening, and flow cytometry to investigate rare single-cell phenomena
Itmat Expertise
Biomedical engineering
Systems Biology
Tissue engineering
Microfludics
Diagnostics
Graduate Groups
Biochemistry and Molecular Biophysics
Cell and Molecular Biology
Education
BS (Chemical and Biomolecular Engineering), Georgia Institute of Technology, 2010
PhD (Bioengineering), University of Pennsylvania, 2017
MD (Medicine), Perelman School of Medicine, University of Pennsylvania, 2018
Specialty Certification
Postgraduate Training
Research Intern, Research and Development, Eli, Lilly and Company, 2007-08
Fellow, Hartwell Foundation Postdoctoral Fellowship, University of Pennsylvania, 2018-19
Awards and Honors
John G. Clark Research Paper Award, University of Pennsylvania, 2014
NIH Ruth L. Kirschstein National Research Service Award (F30), 2015-18
Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research/University of Pennsylvania, 2018
Hartwell Foundation Postdoctoral Fellowship, 2018
NIH Director's Early Independence Award DP5, 2019
Society for Melanoma Research, Christopher Marshall Award, 2023
American Cancer Society Research Scholar Grant, 2024
Damon Runyon-Rachleff Innovation Award, 2024
Memberships and Professional Organizations
Biomedical Engineering Society, Member, 2017- present
American Association for Cancer Research, Associate Member, 2018-present
Web Links
Selected Publications
Mitochondrial clone tracing within spatially intact human tissues
Bracht SA*, Rong J*, Gier RA, DeMarshall M, Golden H, Dhakal D, McDevitt JC, Mo F, Furth EE, Strauss Starling A, Muir AB, Falk GW, Katona BW, Stanger BZ, Zhang NR**, Shaffer SM** *equal contributions, **corresponding authors, BioRxiv, 2025
The H3K36M oncohistone inhibits NSD2 to activate a SETD2-dependent antiviral-like immune response in KRAS-driven lung cancer
Gladstein AC, Poltorack CD, Solomon AMC, Venkatesh S, Adler KM, Robertson MR, Stransky S, Irizarry-Negron VM, Ruiz DA, Freeburg NF, Sidoli S, Asangani IA, Shaffer SM, Feldser DM, BioRxiv, 2025
FOXM1 Modulation Alleviates Epithelial Remodeling and Inflammation in Eosinophilic Esophagitis
Sasaki M, Wang JX, Zhou Y, Kennedy KV, Teranishi R, Itami T, Ishikawa S, Hara T, Winters H, McMillan EA, Mahon M, Golden H, Dhakal D, Bacarella A, Umeweni CN, Wilkins BJ, Karakasheva TA, Whelan KA, Shaffer SM, Ruffner MA, Muir AB, BioRxiv, 2025
Recurrent ERBB2 alterations are associated with esophageal adenocarcinoma brain metastases
Lawson NM, Ye L, Cho CY, Zhao B, Mitchell T, MartÃn-Barrio I, Beernaert B, Gupta A, Banu M, Lissanu Y, Shaffer S, Tawbi H, Li J, Gule-Monroe MK, Alvarez-Breckenridge CA, Huse JT, Murphy MB, Yin F, Lang FF, Parkes EE, Weinberg JS, Akdemir KC, medRxiv, 2025
SpaceBar enables clone tracing in spatial transcriptomic data
Kinsler G, Fagan C, Li H, Kaster J, Dunne M, Vander Velde RJ, Boe RH, Shaffer S, Herlyn M, Raj A, Heyman Y, bioRxiv, 2025
Unveiling heterogeneity in rare cells by combining RNA-based sorting and scRNA-seq
Wahlsten M, Shaffer SM, Nature Genetics 57(): 283-284, 2025
Cancer-associated fibroblasts maintain critical pancreatic cancer cell lipid homeostasis in the tumor microenvironment
Han X, Burrows M, Kim LC, Xu JP, Vostrejs W, Le TNV, Poltorack C, Jiang Y, Cukierman E, Stanger BZ, Reiss KA, Shaffer SM, Mesaros C, Keith B, Simon MC, Cell Reports 43(11): 8-9, 2024, PMID:114972
Non-genetic differences underlie variability in proliferation among esophageal epithelial clones
Reyes Hueros RA, Gier RA, Shaffer SM, PLOS Computational Biology, 2024
Development of a functional beige fat cell line uncovers independent subclasses of cells expressing UCP1 and the futile creatine cycle
Vargas-Castillo A, Sun Y, Smythers AL, Grauvogel L, Dumesic PA, Emont MP, Tsai LT, Rosen ED, Zammit NW, Shaffer SM, Ordonez M, Chouchani ET, Gygi SP, Wang T, Sharma AK, Balaz M, Wolfrum C, Spiegelman BM, Cell Metabolism, 2024, PMID:39084217
Clonal differences underlie variable responses to sequential and prolonged treatment
Schaff DL*, Fasse AJ*, White PE, Vander Velde R, Shaffer SM, Cell Systems, 2024
