About

Polly Fordyce is an Associate Professor of Genetics and Bioengineering and a fellow of the ChEM-H Institute at Stanford University. Her laboratory focuses on developing and applying new microfluidic platforms for quantitative, high-throughput biophysics and biochemistry and single-cell genomics. She earned her undergraduate degrees in physics and biology from the University of Colorado at Boulder and completed her Ph.D. in physics at Stanford University, where she worked with Professor Steve Block on developing instrumentation and assays for single-molecule studies of kinesin motor proteins. For her postdoctoral research at the University of California San Francisco, she collaborated with Professor Joe DeRisi to develop a microfluidic platform for understanding transcription factor-DNA interactions and a technology for bead-based multiplexing. She has received numerous awards, including the NIH New Innovator and Pioneer Awards, an NSF CAREER Award, the 2023 Eli Lilly Award in Biological Chemistry, the 2025 Schmidt Sciences Polymath Award, and is a Chan Zuckerberg Biohub Investigator.

Research topics

• Biology
• Computer Science
• Computational biology
• Biochemistry
• Chemistry
• Cell biology
• Biophysics
• Nanotechnology
• Physics
• Materials science
• Immunology
• Genetics

Selected publications

• Large-scale mapping and mutagenesis of human transcriptional effector domains

  Nature · 2023 · 132 citations

  • Biology
  • Computational biology
  • Genetics
  DOI

• Tuning T cell receptor sensitivity through catch bond engineering

  Science · 2022 · 157 citations

  • Chemistry
  • Cell biology
  • Biology

  Adoptive cell therapy using engineered T cell receptors (TCRs) is a promising approach for targeting cancer antigens, but tumor-reactive TCRs are often weakly responsive to their target ligands, peptide-major histocompatibility complexes (pMHCs). Affinity-matured TCRs can enhance the efficacy of TCR-T cell therapy but can also cross-react with off-target antigens, resulting in organ immunopathology. We developed an alternative strategy to isolate TCR mutants that exhibited high activation signals coupled with low-affinity pMHC binding through the acquisition of catch bonds. Engineered analogs of a tumor antigen MAGE-A3-specific TCR maintained physiological affinities while exhibiting enhanced target killing potency and undetectable cross-reactivity, compared with a high-affinity clinically tested TCR that exhibited lethal cross-reactivity with a cardiac antigen. Catch bond engineering is a biophysically based strategy to tune high-sensitivity TCRs for T cell therapy with reduced potential for adverse cross-reactivity.

  DOI

• Revealing enzyme functional architecture via high-throughput microfluidic enzyme kinetics

  Science · 2021 · 229 citations

  Senior authorCorresponding
  • Computer Science
  • Chemistry
  • Biochemistry

  Systematic and extensive investigation of enzymes is needed to understand their extraordinary efficiency and meet current challenges in medicine and engineering. We present HT-MEK (High-Throughput Microfluidic Enzyme Kinetics), a microfluidic platform for high-throughput expression, purification, and characterization of more than 1500 enzyme variants per experiment. For 1036 mutants of the alkaline phosphatase PafA (phosphate-irrepressible alkaline phosphatase of Flavobacterium), we performed more than 670,000 reactions and determined more than 5000 kinetic and physical constants for multiple substrates and inhibitors. We uncovered extensive kinetic partitioning to a misfolded state and isolated catalytic effects, revealing spatially contiguous regions of residues linked to particular aspects of function. Regions included active-site proximal residues but extended to the enzyme surface, providing a map of underlying architecture not possible to derive from existing approaches. HT-MEK has applications that range from understanding molecular mechanisms to medicine, engineering, and design.

  DOI

Recent grants

• Using Microfluidic Affinity Analysis to Probe Transcriptional Regulation

  NIH · $249k · 2012–2017

• NIH Grant K99GM099848

  NIH · $178k · 2014

• Leveraging spectral encoding for high dimensional biological multiplexing

  NIH · $2.4M · 2016–2021

• Using Microfluidic Affinity Analysis to Probe Transcriptional Regulation

  NIH · $498k · 2012–2017

Frequent coauthors

• Kara K. Brower

  Stanford University

  47 shared

• Jamin B. Hein

  Novo Nordisk Foundation

  37 shared

• Joseph L. DeRisi

  University of California, San Francisco

  36 shared

• Kara Brower

  34 shared

• Scott A. Longwell

  Stanford University

  32 shared

• Arjun K. Aditham

  Fred Hutch Cancer Center

  28 shared

• Adam K. White

  Stanford University

  27 shared

• Daniel A. Mokhtari

  Stanford University

  23 shared

Awards & honors

• NIH New Innovator Award
• NIH Pioneer Award
• NSF CAREER Award
• 2023 Eli Lilly Award in Biological Chemistry
• 2025 Schmidt Sciences Polymath Award

Similar researchers at Stanford University

• Yi Cuih-287
• Zhenan Baoh-224
• Karl Deisserothh-218
• Michael Snyderh-215
• Roger Blandfordh-205