Angela Phillips, PhD
Assistant Professor
Microbiology and Immunology
School of Medicine
We are broadly interested in how the molecular properties of viral proteins and antibodies constrain their evolution and co-evolution.
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Viral proteins and antibodies acquire amino acid substitutions at a rate orders of magnitude above most eukaryotic proteins. These substitutions can have pleiotropic consequences on protein stability, folding, and function. Our lab is developing high-throughput evolution and phenotyping assays to determine how these properties, and trade-offs between them, constrain and potentiate the evolution of viral proteins and antibodies, and how this varies between distinct selection environments. These experimental platforms will enable us to (1) determine key constraints on protein evolution, (2) predict the emergence of new viral variants, and (3) design therapeutic strategies that are refractory to the development of resistance.
Education & Training
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- Post-doc Evolutionary Biology Harvard University 09/2022
- Ph.D. Biological Chemistry Massachusetts Institute of Technology 06/2018
Interests
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- antibody maturation
- viruses
- protein folding
- fitness landscapes
- evolution
Websites
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- The Phillips Lab at UCSF (aphillipslab.ucsf.edu)
Grants and Projects
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- Mapping constraints on protein evolution at the host-virus interface, HHMI, 2022-2026
Publications (20)
Top publication keywords:
Genetic FitnessInfluenza, HumanAntibodies, NeutralizingInfluenza A Virus, H3N2 SubtypeOseltamivirHemagglutinin Glycoproteins, Influenza VirusImmune EvasionAntibody AffinityProteostasisTemperatureOrthomyxoviridaeMolecular ChaperonesNeuraminidaseHost-Pathogen InteractionsAntibodies, Viral
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Binding affinity landscapes constrain the evolution of broadly neutralizing anti-influenza antibodies.
eLife 2021 Phillips AM, Lawrence KR, Moulana A, Dupic T, Chang J, Johnson MS, Cvijovic I, Mora T, Walczak AM, Desai MM -
Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones.
PLoS biology 2018 Phillips AM, Ponomarenko AI, Chen K, Ashenberg O, Miao J, McHugh SM, Butty VL, Whittaker CA, Moore CL, Bloom JD, Lin YS, Shoulders MD -
Protein sequence landscapes are not so simple: on reference-free versus reference-based inference.
bioRxiv : the preprint server for biology 2024 Dupic T, Phillips AM, Desai MM -
Genotype-phenotype landscapes for immune-pathogen coevolution.
Trends in immunology 2023 Moulana A, Dupic T, Phillips AM, Desai MM -
The landscape of antibody binding affinity in SARS-CoV-2 Omicron BA.1 evolution.
eLife 2023 Moulana A, Dupic T, Phillips AM, Chang J, Roffler AA, Greaney AJ, Starr TN, Bloom JD, Desai MM
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Hierarchical sequence-affinity landscapes shape the evolution of breadth in an anti-influenza receptor binding site antibody.
eLife 2023 Phillips AM, Maurer DP, Brooks C, Dupic T, Schmidt AG, Desai MM -
Compensatory epistasis maintains ACE2 affinity in SARS-CoV-2 Omicron BA.1.
Nature communications 2022 Moulana A, Dupic T, Phillips AM, Chang J, Nieves S, Roffler AA, Greaney AJ, Starr TN, Bloom JD, Desai MM -
Compensatory epistasis maintains ACE2 affinity in SARS-CoV-2 Omicron BA.1
BioRxiv 2022 Alief Moulana*, Thomas Dupic*, Angela M. Phillips*†, Jeffrey Chang*, Serafina Nieves, Anne A. Roffler, Allison J. Greaney, Tyler N. Starr, Jesse D. Bloom, Michael M. Desai† -
The endoplasmic reticulum proteostasis network profoundly shapes the protein sequence space accessible to HIV envelope.
PLoS biology 2022 Yoon J, Nekongo EE, Patrick JE, Hui T, Phillips AM, Ponomarenko AI, Hendel SJ, Sebastian RM, Zhang YM, Butty VL, Ogbunugafor CB, Lin YS, Shoulders MD -
Dynamics and variability in the pleiotropic effects of adaptation in laboratory budding yeast populations.
eLife 2021 Bakerlee CW, Phillips AM, Nguyen Ba AN, Desai MM -
The genetic basis of differential autodiploidization in evolving yeast populations.
G3 (Bethesda, Md.) 2021 Tung S, Bakerlee CW, Phillips AM, Nguyen Ba AN, Desai MM -
Phenotypic and molecular evolution across 10,000 generations in laboratory budding yeast populations.
eLife 2021 Johnson MS, Gopalakrishnan S, Goyal J, Dillingham ME, Bakerlee CW, Humphrey PT, Jagdish T, Jerison ER, Kosheleva K, Lawrence KR, Min J, Moulana A, Phillips AM, Piper JC, Purkanti R, Rego-Costa A, … -
Enhanced ER proteostasis and temperature differentially impact the mutational tolerance of influenza hemagglutinin.
eLife 2018 Phillips AM, Doud MB, Gonzalez LO, Butty VL, Lin YS, Bloom JD, Shoulders MD -
Host proteostasis modulates influenza evolution.
eLife 2017 Phillips AM, Gonzalez LO, Nekongo EE, Ponomarenko AI, McHugh SM, Butty VL, Levine SS, Lin YS, Mirny LA, Shoulders MD -
The Path of Least Resistance: Mechanisms to Reduce Influenza's Sensitivity to Oseltamivir.
Journal of molecular biology 2015 Phillips AM, Shoulders MD -
Potency enhancement of the κ-opioid receptor antagonist probe ML140 through sulfonamide constraint utilizing a tetrahydroisoquinoline motif.
Bioorganic & medicinal chemistry 2014 Frankowski KJ, Slauson SR, Lovell KM, Phillips AM, Streicher JM, Zhou L, Whipple DA, Schoenen FJ, Prisinzano TE, Bohn LM, Aubé J -
Quantifying Drosophila food intake: comparative analysis of current methodology.
Nature methods 2014 Deshpande SA, Carvalho GB, Amador A, Phillips AM, Hoxha S, Lizotte KJ, Ja WW -
Development of functionally selective, small molecule agonists at kappa opioid receptors.
The Journal of biological chemistry 2013 Zhou L, Lovell KM, Frankowski KJ, Slauson SR, Phillips AM, Streicher JM, Stahl E, Schmid CL, Hodder P, Madoux F, Cameron MD, Prisinzano TE, Aubé J, Bohn LM -
Oxidative folding and preparation of α-conotoxins for use in high-throughput structure-activity relationship studies.
Journal of peptide science : an official publication of the European Peptide Society 2012 Gyanda R, Banerjee J, Chang YP, Phillips AM, Toll L, Armishaw CJ -
Vitamin D-dependent non-type 1, non-type 2 rickets in a 3-month-old Cornish Rex kitten.
Journal of feline medicine and surgery 2011 Phillips AM, Fawcett AC, Allan GS, Wilkinson M, Fraser DR, Malik R