Sydney M. Shaffer, M.D., Ph.D.

Assistant Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania

Contact InformationUniversity of Pennsylvania
Philadelphia, PA, 19104

Specialty Division

Immunobiology and Experimental Pathology

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.

Graduate Groups

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

George Wingfield Semmes Memorial Scholarship, Georgia Institute of Technology, 2008
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

Memberships and Professional Organizations

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

Web Links

Selected Publications

Abstract LB-050: Memory sequencing reveals heritable single cell gene expression programs associated with therapy resistance

Sydney Shaffer, Benjamin Emert, Eduardo Torre, Arjun Raj, American Association for Cancer Research, Cancer Research 79(): LB-050-LB-050, 2019

Genetic screening for single-cell variability modulators driving therapy resistance

Eduardo A Torre, Eri Arai, Sareh Bayatpour, Lauren E Beck, Benjamin L Emert, Sydney M Shaffer, Ian A Mellis, Krista A Budinich, Ashani Weeraratna, Junwei Shi, Arjun Raj, bioRxiv, 2019

Validation of a next-generation sequencing oncology panel optimized for low input DNA.

Sussman RT, Shaffer SM, Azzato EM, DeSloover D, Farooqi MS, Meyer A, Liebeman DB, Bigdeli A, Paolillo C, Sukhadia S, Rosenbaum JN, Daber RD, Morrissette JD, Cancer Genetics 228-229(): 55-63, 2018

Memory sequencing heritable single cell gene expression programs associated with distinct cellular behaviors.

Shaffer SM, Emert B, Sizemore AE, Gupte R, Torre E, Bassert DS, Raj A., bioRxiv, 2018

SAVER: Gene expression recovery for single cell RNA sequencing

Huang M, Wang J, Torre EA, Dueck H, Shaffer SM, Bonasio R, Murray J, Raj A, Li M, Zhang NR., Nature Methods, 2018

Gene expression distribution deconvolution in single cell RNA sequencing.

Wang J, Huang M, Torre E, Dueck H, Shaffer SM, Murray J, Raj A, LI M, Zhang NR, Proceedings of National Academy of Sciences 115(28): E6437-E6446, 2018

Rare cell detection by single-cell RNA sequencing as guided by single-molecule RNA FISH.

Torre EA, Dueck H, Shaffer SM, Gospocic J, Gupte R, Bonasio R, Kim J, Murray J, Raj A., Cell Systems 6(2): 171-179.e5, 2018

A slow-cycling subpopulation of melanoma cells with highly invasive properties.

Perego M, Maurer M, Wang J, Shaffer SM, Muller A, Parapatics K, Li L, Hristova D, Shin S, Keeney F, Liu S, Xu X, Raj A, Jensen J, Bennett K, Wagner S, Somasundaram R, Herlyn M., Oncogene 37(3): 302-312, 2017

Resistance to targeted therapy arises from pre-existing rare-cell expression variability followed by drug-induced epigenetic reprogramming.

Shaffer SM, Dunagin M, Torborg SR, Torre E, Emert B, Krepler C, Beqiri M, Sproesser K, Bradford P, Xiao M, Eggan E, Anastopoulos I, Nathanson K, Vargas-Garcia C, Singh A, Herlyn M, Raj A., Nature 546(7658): 431-435, 2017

Transcriptional bursting explains the noise-versus-mean relationship in mRNA and Protein Levels.

Dar RD, Shaffer SM, Sigh A, Razooky BS, Simpson ML, Raj A, Weinberger LS, PLoS One 11(7): e0158298, 2016