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
SpaceBar enables single-cell-resolution clone tracing with imaging-based spatial transcriptomics
Kinsler G, Fagan C, Li H, Kaster J, Dunne M, Vander Velde RJ, Boe RH, Shaffer S, Herlyn M, Raj A, Heyman Y, Nature Methods 23(2): 328-333, 2026, PMID:41413345
Multiplexed enrichment and tracking of lineages with CloneSweeper
Vander Velde RJ, Ng RWS., Coté C, Shaffer, SM, bioRxiv, 2026
Pre-existing cell states predict resistance to multiple treatments
Schaff DL, White PE, Cote CJ, Watterson GE, Lin KZ, Fasse AJ, Zhang NR, Shaffer SM, Cell Genomics, 2026
Clonal cell states link Barrett’s esophagus and esophageal adenocarcinoma
Gier RA, Bracht SA, Rong J, Reyes Hueros RA, Wahlsten ML, Cote C, DeMarshall M, Karakasheva TA, Strauss Starling A, Muir AB, Falk GW, Zhang NR, Shaffer SM, Nature Communications 16(): 10952, 2025, PMID:41360789
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 inhibition reduces IL-13-induced epithelial remodelling and inflammation in eosinophilic oesophagitis
Sasaki M, Wang JX, Teranishi R, Itami T, Zhou Y, Kennedy KV, Semeao A, Ishikawa S, Hara T, McMillan EA, Mahon M, Golden H, Dhakal D, Baccarella A, Winters H, Umeweni CN, Wilkins BJ, Karakasheva TA, Whelan KA, Shaffer SM, Ruffner MA, Muir AB, Gut, 2025, PMID:41266120
Recurrent ERBB2 alterations are associated with esophageal adenocarcinoma brain metastases
Lawson NM, Ye L, Cho CY, Zhao B, Mitchell T, Martín-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
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
