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

Contact InformationUniversity of Pennsylvania
Philadelphia, PA, 19104

Specialty Division

Cancer and Immunobiology

Itmat Expertise

Biomedical engineering
Systems Biology
Tissue engineering

Graduate Groups

Biochemistry and Molecular Biophysics
Cell and Molecular Biology


B.S. (Chemical and Biomolecular Engineering), Georgia Institute of Technology , 2010
Ph.D. (Bioengineering), University of Pennsylvania, 2017
M.D. (Medicine), Perelman School of Medicine, University of Pennsylvania, 2018

Specialty Certification

Postgraduate Training

Research Intern, Eli, Lilly and Company, Research and Development, 2007-2008
Hartwell Foundation Postdoctoral Fellowship, University of Pennsylvania, 2018-2019

Awards and Honors

John G. Clark Research Paper Award, University of Pennsylvania, 2014
NIH Ruth L. Kirschstein National Research Service Award (F30), 2015-2018
Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research/University of Pennsylvania, 2018
NIH Director's Early Independence Award DP5, 2019
Society for Melanoma Research, Christopher Marshall Award, 2023

Memberships and Professional Organizations

Biomedical Engineering Society, Member, 2017 - Present
American Association for Cancer Research, Associate Member, 2018 - Present

Web Links

Selected Publications

Disrupting cellular memory to overcome drug resistance

Harmange G, Reyes Hueros RA, Schaff D, Emert B, Saint-Antoine M, Nellore S, Fane ME, Alicea GM, Weeraratna AT, Singh A, Shaffer SM, Nature Communications 14(7130): , 2023

Detection of blood–brain barrier disruption in brains of patients with COVID-19, but no evidence of brain penetration by SARS-CoV-2

Hailong Song, Alexandra Tomasevich, Kofi K Acheampong, Dylan L Schaff, Sydney M Shaffer, Jean-Pierre Dolle, Victoria E Johnson, Bailey Mikytuck, Edward B Lee, Amber Nolan, C Dirk Keene, Susan R Weiss, William Stewart, Douglas H Smith, Acta Neuropathologica 146(5): 771-775, 2023

Non-genetic differences underlie variability in proliferation among esophageal epithelial clones

Reyes Hueros RA, Gier RA, Shaffer SM, BioRxiv [Pre-print], 2023

Patterns of tumour transcriptional variability

Raymond W S Ng, Sydney M Shaffer, Nature 618(7965): 464-465, 2023, PMID:37258729

Read article

Clonal differences underlie variable responses to sequential and prolonged treatment

Schaff DL*, Fasse AJ*, White PE, Vander Velde R, Shaffer SM, BioRxiv [Pre-print], 2023

Clonal cell states link Barrett’s esophagus and esophageal adenocarcinoma

Gier RA, Reyes Hueros RA, Rong J, DeMarshall M, Karakasheva TA, Muir AB, Falk GW, Zhang NR, Shaffer SM, BioRxiv [Pre-print], 2023

Integrating mutational and nonmutational mechanisms of acquired therapy resistance within the Darwinian paradigm

Robert Vander Velde, Sydney Shaffer, Andriy Marusyk, Trends in Cancer 8(6): 456-466, 2022

Variability within rare cell states enables multiple paths toward drug resistance

Benjamin L Emert, Christopher J Cote, Eduardo A Torre, Ian P Dardani, Connie L Jiang, Naveen Jain, Sydney M Shaffer, Arjun Raj, Nature Biotechnology 39(7): 865-876, 2021

Subcellular Detection of SARS-CoV-2 RNA in Human Tissue Reveals Distinct Localization in Alveolar Type 2 Pneumocytes and Alveolar Macrophages

Kofi K Acheampong, Dylan L Schaff, Benjamin L Emert, Jonathan Lake, Sam Reffsin, Emily K Shea, Courtney E Comar, Leslie A Litzky, Nigar A Khurram, Rebecca L Linn, Michael Feldman, Susan R Weiss, Kathleen T Montone, Sara Cherry, Sydney M Shaffer, mBio 13(1): e0375121, 2021, PMID:35130722

Read article

Genetic screening for single-cell variability modulators driving therapy resistance

Eduardo A Torre, Eri Arai, Sareh Bayatpour, Connie L Jiang, Lauren E Beck, Benjamin L Emert, Sydney M Shaffer, Ian A Mellis, Mitchell E Fane, Gretchen M Alicea, Krista A Budinich, Ashani T Weeraratna, Junwei Shi, Arjun Raj, Nature Genetics 53(1): 76-85, 2021