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Sydney M Shaffer, M.D., Ph.D.
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Assistant Professor of Pathology and Laboratory Medicine
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Assistant Investigator, Abramson Family Cancer Research Institute
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Assistant Professor, Department of Pathology and Laboratory Medicine
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Assistant Professor, Department of Bioengineering
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Department: Pathology and Laboratory Medicine
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Graduate Group Affiliations
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Contact information
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BRB II/III, Room 452
31 421 Curie Blvd
Philadelphia, PA 19104
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31 421 Curie Blvd
Philadelphia, PA 19104
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Publications
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Education:
21 9 B.S. 32 (Chemical and Biomolecular Engineering) c
39 Georgia Institute of Technology , 2010.
21 a Ph.D. 1b (Bioengineering) c
33 University of Pennsylvania, 2017.
21 9 M.D. c
33 University of Pennsylvania, 2018.
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Permanent link21 9 B.S. 32 (Chemical and Biomolecular Engineering) c
39 Georgia Institute of Technology , 2010.
21 a Ph.D. 1b (Bioengineering) c
33 University of Pennsylvania, 2017.
21 9 M.D. c
33 University of Pennsylvania, 2018.
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103 Vander Velde RJ, Ng RWS., Coté C, Shaffer, SM: Multiplexed enrichment and tracking of lineages with CloneSweeper. bioRxiv January 2026 Notes: https://doi.org/10.64898/2026.01.30.700779.
10e Schaff DL, White PE, Cote CJ, Watterson GE, Lin KZ, Fasse AJ, Zhang NR, Shaffer SM: Pre-existing cell states predict resistance to multiple treatments. Cell Genomics 2026 Notes: Accepted, in press.
1ac 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: Clonal cell states link Barrett’s esophagus and esophageal adenocarcinoma. Nature Communications 16: 10952, December 2025 Notes: doi: 10.1038/s41467-025-66302-w. Article number: 10952. Open access.
206 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: Mitochondrial clone tracing within spatially intact human tissues. bioRxiv July 2025 Notes: doi: https://doi.org/10.1101/2025.07.11.664452.
18b 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: The H3K36M oncohistone inhibits NSD2 to activate a SETD2-dependent antiviral-like immune response in KRAS-driven lung cancer. bioRxiv May 2025.
216 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: FOXM1 inhibition reduces IL-13-induced epithelial remodelling and inflammation in eosinophilic oesophagitis. Gut Page: 1-15, May 2025 Notes: doi: 10.1136/gutjnl-2025-335163. Epub ahead of print 20 Nov 2025. Open access.
1ae 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: Recurrent ERBB2 alterations are associated with esophageal adenocarcinoma brain metastases. medRxiv February 2025.
e0 Wahlsten M, Shaffer SM: Unveiling heterogeneity in rare cells by combining RNA-based sorting and scRNA-seq. Nature Genetics 57: 283-284, February 2025.
1bb 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: Cancer-associated fibroblasts maintain critical pancreatic cancer cell lipid homeostasis in the tumor microenvironment. Cell Reports 43(11): 8-9, November 2024 Notes: doi: https://doi.org/10.1016/j.celrep.2024.114972.
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Selected Publications
17d Kinsler G, Fagan C, Li H, Kaster J, Dunne M, Vander Velde RJ, Boe RH, Shaffer S, Herlyn M, Raj A, Heyman Y: SpaceBar enables single-cell-resolution clone tracing with imaging-based spatial transcriptomics. Nature Methods 23(2): 328-333, February 2026 Notes: doi: 10.1038/s41592-025-02968-w. Epub 2025 Dec 18.103 Vander Velde RJ, Ng RWS., Coté C, Shaffer, SM: Multiplexed enrichment and tracking of lineages with CloneSweeper. bioRxiv January 2026 Notes: https://doi.org/10.64898/2026.01.30.700779.
10e Schaff DL, White PE, Cote CJ, Watterson GE, Lin KZ, Fasse AJ, Zhang NR, Shaffer SM: Pre-existing cell states predict resistance to multiple treatments. Cell Genomics 2026 Notes: Accepted, in press.
1ac 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: Clonal cell states link Barrett’s esophagus and esophageal adenocarcinoma. Nature Communications 16: 10952, December 2025 Notes: doi: 10.1038/s41467-025-66302-w. Article number: 10952. Open access.
206 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: Mitochondrial clone tracing within spatially intact human tissues. bioRxiv July 2025 Notes: doi: https://doi.org/10.1101/2025.07.11.664452.
18b 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: The H3K36M oncohistone inhibits NSD2 to activate a SETD2-dependent antiviral-like immune response in KRAS-driven lung cancer. bioRxiv May 2025.
216 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: FOXM1 inhibition reduces IL-13-induced epithelial remodelling and inflammation in eosinophilic oesophagitis. Gut Page: 1-15, May 2025 Notes: doi: 10.1136/gutjnl-2025-335163. Epub ahead of print 20 Nov 2025. Open access.
1ae 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: Recurrent ERBB2 alterations are associated with esophageal adenocarcinoma brain metastases. medRxiv February 2025.
e0 Wahlsten M, Shaffer SM: Unveiling heterogeneity in rare cells by combining RNA-based sorting and scRNA-seq. Nature Genetics 57: 283-284, February 2025.
1bb 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: Cancer-associated fibroblasts maintain critical pancreatic cancer cell lipid homeostasis in the tumor microenvironment. Cell Reports 43(11): 8-9, November 2024 Notes: doi: https://doi.org/10.1016/j.celrep.2024.114972.
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