People

David Pincus, PhD

David Pincus is an Assistant Professor in the Dept. of Molecular Genetics and Cell Biology. The Pincus lab is located in the Center for Physics of Evolving Systems on the 5th floor of GCIS.



The Pincus Lab studies "System Mechanics of Cellular Stress Responses", defined as quantitative control processes cells employ to sense and respond to environmental and endogenous perturbations.



David is trained in approaches in biochemistry, biophysics, genetics, and molecular, cell, computational, systems and synthetic biology. The lab uses budding yeast and cultured human cells as experimental models, and applies this toolkit to investigate three interconnected areas:



1) Hsf1, chaperones, and proteostasis networks

2) Stress responsive kinase signaling

3) Stress responsive gene expression



The goal of the research program is to understand the establishment and maintenance of cell-level homeostasis.

Whitehead Institute
Cambridge, MA

2018

UCSF
San Francisco, CA
PhD - Biochemistry
2012

UC Berkeley
Berkeley, CA
BA - Molecular & Cell Biology
2004

Strategies for Engineering and Rewiring Kinase Regulation.
McCormick JW, Pincus D, Resnekov O, Reynolds KA. Strategies for Engineering and Rewiring Kinase Regulation. Trends Biochem Sci. 2020 Mar; 45(3):259-271.
PMID: 31866305

m6A modification of a 3' UTR site reduces RME1 mRNA levels to promote meiosis.
Bushkin GG, Pincus D, Morgan JT, Richardson K, Lewis C, Chan SH, Bartel DP, Fink GR. m6A modification of a 3' UTR site reduces RME1 mRNA levels to promote meiosis. Nat Commun. 2019 07 30; 10(1):3414.
PMID: 31363087

Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness.
Tye BW, Commins N, Ryazanova LV, Wühr M, Springer M, Pincus D, Churchman LS. Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness. Elife. 2019 03 07; 8.
PMID: 30843788

Heat Shock Factor 1 Drives Intergenic Association of Its Target Gene Loci upon Heat Shock.
Chowdhary S, Kainth AS, Pincus D, Gross DS. Heat Shock Factor 1 Drives Intergenic Association of Its Target Gene Loci upon Heat Shock. Cell Rep. 2019 01 02; 26(1):18-28.e5.
PMID: 30605674

Lipidomic Analysis of a-Synuclein Neurotoxicity Identifies Stearoyl CoA Desaturase as a Target for Parkinson Treatment.
Fanning S, Haque A, Imberdis T, Baru V, Barrasa MI, Nuber S, Termine D, Ramalingam N, Ho GPH, Noble T, Sandoe J, Lou Y, Landgraf D, Freyzon Y, Newby G, Soldner F, Terry-Kantor E, Kim TE, Hofbauer HF, Becuwe M, Jaenisch R, Pincus D, Clish CB, Walther TC, Farese RV, Srinivasan S, Welte MA, Kohlwein SD, Dettmer U, Lindquist S, Selkoe D. Lipidomic Analysis of a-Synuclein Neurotoxicity Identifies Stearoyl CoA Desaturase as a Target for Parkinson Treatment. Mol Cell. 2019 03 07; 73(5):1001-1014.e8.
PMID: 30527540

Engineering allosteric regulation in protein kinases.
Pincus D, Pandey JP, Feder ZA, Creixell P, Resnekov O, Reynolds KA. Engineering allosteric regulation in protein kinases. Sci Signal. 2018 11 06; 11(555).
PMID: 30401787

Genetic and epigenetic determinants establish a continuum of Hsf1 occupancy and activity across the yeast genome.
Pincus D, Anandhakumar J, Thiru P, Guertin MJ, Erkine AM, Gross DS. Genetic and epigenetic determinants establish a continuum of Hsf1 occupancy and activity across the yeast genome. Mol Biol Cell. 2018 12 15; 29(26):3168-3182.
PMID: 30332327

Hierarchical Organization Endows the Kinase Domain with Regulatory Plasticity.
Creixell P, Pandey JP, Palmeri A, Bhattacharyya M, Creixell M, Ranganathan R, Pincus D, Yaffe MB. Hierarchical Organization Endows the Kinase Domain with Regulatory Plasticity. Cell Syst. 2018 10 24; 7(4):371-383.e4.
PMID: 30243563

Hsf1 Phosphorylation Generates Cell-to-Cell Variation in Hsp90 Levels and Promotes Phenotypic Plasticity.
Zheng X, Beyzavi A, Krakowiak J, Patel N, Khalil AS, Pincus D. Hsf1 Phosphorylation Generates Cell-to-Cell Variation in Hsp90 Levels and Promotes Phenotypic Plasticity. Cell Rep. 2018 03 20; 22(12):3099-3106.
PMID: 29562166

Translocon Declogger Ste24 Protects against IAPP Oligomer-Induced Proteotoxicity.
Kayatekin C, Amasino A, Gaglia G, Flannick J, Bonner JM, Fanning S, Narayan P, Barrasa MI, Pincus D, Landgraf D, Nelson J, Hesse WR, Costanzo M. Translocon Declogger Ste24 Protects against IAPP Oligomer-Induced Proteotoxicity. Cell. 2018 03 22; 173(1):62-73.e9.
PMID: 29526462

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Stewart Trust Cancer Fellowship
Alexander and Margaret Stewart Trust
2013 - 2015

Early Independence Award (DP5)
NIH Office of the Director
2013 - 2018

Graduate Research Felloship
NSF
2007 - 2010