Photo of Galit Lahav,

Galit Lahav

Harvard Medical School

Harvard Medical School
Phone: (617) 432-5621
Fax: (617) 432-5012

Galit Lahav

Harvard Medical School


  • Professor, Systems Biology, Harvard Medical School


Research Abstract

Our lab studies how individual cells translate internal and external signals into decisions such as growth, death, movement or differentiation. We quantitatively measure the changes in level, activity, or localization of proteins in single cells at high temporal resolution and correlate these behaviors with specific cellular fates. By visualizing how dynamical behaviors vary between different cells, we aim to tease out the reasons for varying behavior both in cell populations and in different cell types. Understanding these issues will be enormously important for understanding how drugs act on different cell types and organs, and to begin to gain insight into the reasons why different cells and people respond differently to specific drugs.

We focus on the p53 signaling pathway. p53 is the protein most frequently inactivated in human cancer; more than half of all human cancers contain mutations in the p53 gene, and in almost all cancers the p53 regulatory circuit is functionally inactivated. Earlier work on p53 dynamics used techniques that average the behavior of millions of cells together (e.g. Western blots). We are interested in examining how individual cells behave. We use live single-cell imaging system and fluorescently labeled reporter proteins to determine how p53’s dynamic behavior is controlled, why different cells show different dynamical behaviors and what consequences these behaviors have on cell survival. We apply the same approaches and techniques to study additional networks in human cells such as the networks controlling DNA repair and cell growth.

Publications from Harvard Catalyst Profiles

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  • Oren Y, Tsabar M, Cuoco MS, Amir-Zilberstein L, Cabanos HF, Hütter JC, Hu B, Thakore PI, Tabaka M, Fulco CP, Colgan W, Cuevas BM, Hurvitz SA, Slamon DJ, Deik A, Pierce KA, Clish C, Hata AN, Zaganjor E, Lahav G, Politi K, Brugge JS, Regev A. Cycling cancer persister cells arise from lineages with distinct programs. Nature 2021. PubMed
  • Tsabar M, Lovitch SB, Jambhekar A, Lahav G. Connecting Timescales in Biology: Can Early Dynamical Measurements Predict Long-Term Outcomes? Trends Cancer 2021. PubMed
  • Stewart-Ornstein J, Iwamoto Y, Miller MA, Prytyskach MA, Ferretti S, Holzer P, Kallen J, Furet P, Jambhekar A, Forrester WC, Weissleder R, Lahav G. p53 dynamics vary between tissues and are linked with radiation sensitivity. Nat Commun 2021; 12:898. PubMed
  • Tsabar M, Mock CS, Venkatachalam V, Reyes J, Karhohs KW, Oliver TG, Regev A, Jambhekar A, Lahav G. A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest. Cell Rep 2020; 32:107995. PubMed
  • Hafner A, Reyes J, Stewart-Ornstein J, Tsabar M, Jambhekar A, Lahav G. Quantifying the Central Dogma in the p53 Pathway in Live Single Cells. Cell Syst 2020; 10:495-505.e4. PubMed
  • Granada AE, Jiménez A, Stewart-Ornstein J, Blüthgen N, Reber S, Jambhekar A, Lahav G. The effects of proliferation status and cell cycle phase on the responses of single cells to chemotherapy. Mol Biol Cell 2020; 31:845-857. PubMed
  • Hafner A, Kublo L, Tsabar M, Lahav G, Stewart-Ornstein J. Identification of universal and cell-type specific p53 DNA binding. BMC Mol Cell Biol 2020; 21:5. PubMed
  • Heltberg ML, Chen SH, Jiménez A, Jambhekar A, Jensen MH, Lahav G. Inferring Leading Interactions in the p53/Mdm2/Mdmx Circuit through Live-Cell Imaging and Modeling. Cell Syst 2019; 9:548-558.e5. PubMed
  • Hafner A, Bulyk ML, Jambhekar A, Lahav G. The multiple mechanisms that regulate p53 activity and cell fate. Nat Rev Mol Cell Biol 2019; 20:199-210. PubMed
  • Gilad T, Reyes J, Chen JY, Lahav G, Raviv TR. Fully Unsupervised Symmetry-Based Mitosis Detection in Time-Lapse Cell Microscopy. Bioinformatics 2018. PubMed
  • Reyes J, Chen JY, Stewart-Ornstein J, Karhohs KW, Mock CS, Lahav G. Fluctuations in p53 Signaling Allow Escape from Cell-Cycle Arrest. Mol Cell 2018; 71:581-591.e5. PubMed
  • Chakrabarti S, Paek AL, Reyes J, Lasick KA, Lahav G, Michor F. Hidden heterogeneity and circadian-controlled cell fate inferred from single cell lineages. Nat Commun 2018; 9:5372. PubMed
  • Reyes J, Lahav G. Leveraging and coping with uncertainty in the response of individual cells to therapy. Curr. Opin. Biotechnol. 2017; 51:109-115. PubMed
  • Stewart-Ornstein J, Cheng HWJ, Lahav G. Conservation and Divergence of p53 Oscillation Dynamics across Species. Cell Syst 2017; 5:410-417.e4. PubMed
  • Hafner A, Stewart-Ornstein J, Purvis JE, Forrester WC, Bulyk ML, Lahav G. p53 pulses lead to distinct patterns of gene expression albeit similar DNA-binding dynamics. Nat Struct Mol Biol 2017; 24:840-847. PubMed
  • Oppenheim A, Lahav G. The puzzling interplay between p53 and Sp1. Aging (Albany NY) 2017; 9:1355-1356. PubMed
  • Tsabar M, Lahav G. The Single-Cell Yin and Yang of Live Imaging and Transcriptomics. Cell Syst 2017; 4:375-377. PubMed
  • Stewart-Ornstein J, Lahav G. p53 dynamics in response to DNA damage vary across cell lines and are shaped by efficiency of DNA repair and activity of the kinase ATM. Sci Signal 2017. PubMed
  • Stewart-Ornstein J, Lahav G. Integrating genomic information and signaling dynamics for efficient cancer therapy. Curr Opin Syst Biol 2017; 1:38-43. PubMed
  • Chen SH, Lahav G. Two is better than one; toward a rational design of combinatorial therapy. Curr Opin Struct Biol 2016; 41:145-150. PubMed
  • Drayman N, Ben-Nun-Shaul O, Butin-Israeli V, Srivastava R, Rubinstein AM, Mock CS, Elyada E, Ben-Neriah Y, Lahav G, Oppenheim A. p53 elevation in human cells halt SV40 infection by inhibiting T-ag expression. 2016. PubMed
  • Paek AL, Liu JC, Loewer A, Forrester WC, Lahav G. Cell-to-Cell Variation in p53 Dynamics Leads to Fractional Killing. Cell 2016; 165:631-42. PubMed
  • Chen SH, Forrester W, Lahav G. Schedule-dependent interaction between anticancer treatments. Science 2016; 351:1204-8. PubMed
  • Stewart-Ornstein J, Lahav G. Dynamics of CDKN1A in Single Cells Defined by an Endogenous Fluorescent Tagging Toolkit. Cell Rep 2016; 14:1800-11. PubMed
  • Lande-Diner L, Stewart-Ornstein J, Weitz CJ, Lahav G. Single-cell analysis of circadian dynamics in tissue explants. Mol Biol Cell 2015. PubMed
  • Liu JC, Lerou PH, Lahav G. Stem cells: balancing resistance and sensitivity to DNA damage. Trends Cell Biol 2014; 24:268-74. PubMed
  • Gaglia G, Lahav G. Constant rate of p53 tetramerization in response to DNA damage controls the p53 response. Mol Syst Biol 2014; 10:753. PubMed
  • Liu JC, Guan X, Ryan JA, Rivera AG, Mock C, Agrawal V, Agarwal V, Letai A, Lerou PH, Lahav G. High mitochondrial priming sensitizes hESCs to DNA-damage-induced apoptosis. Cell Stem Cell 2013; 13:483-91. PubMed
  • Gaglia G, Guan Y, Shah JV, Lahav G. Activation and control of p53 tetramerization in individual living cells. Proc Natl Acad Sci U S A 2013; 110:15497-501. PubMed
  • Karanam K, Loewer A, Lahav G. Dynamics of the DNA damage response: insights from live-cell imaging. Brief Funct Genomics 2013; 12:109-17. PubMed
  • Ikeda F, Lahav G. Signal transduction and signaling networks. Mol Biol Cell 2013; 24:676. PubMed
  • Purvis JE, Lahav G. Encoding and decoding cellular information through signaling dynamics. Cell 2013; 152:945-56. PubMed
  • Kafri R, Levy J, Ginzberg MB, Oh S, Lahav G, Kirschner MW. Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle. Nature 2013; 494:480-3. PubMed
  • Loewer A, Karanam K, Mock C, Lahav G. The p53 response in single cells is linearly correlated to the number of DNA breaks without a distinct threshold. BMC Biol 2013; 11:114. PubMed
  • Karanam K, Kafri R, Loewer A, Lahav G. Quantitative live cell imaging reveals a gradual shift between DNA repair mechanisms and a maximal use of HR in mid S phase. Mol Cell 2012; 47:320-9. PubMed
  • Purvis JE, Lahav G. Decoding the insulin signal. Mol Cell 2012; 46:715-6. PubMed
  • Purvis JE, Karhohs KW, Mock C, Batchelor E, Loewer A, Lahav G. p53 dynamics control cell fate. Science 2012; 336:1440-4. PubMed
  • Orth JD, Loewer A, Lahav G, Mitchison TJ. Prolonged mitotic arrest triggers partial activation of apoptosis, resulting in DNA damage and p53 induction. Mol Biol Cell 2012; 23:567-76. PubMed
  • Loewer A, Lahav G. We are all individuals: causes and consequences of non-genetic heterogeneity in mammalian cells. Curr Opin Genet Dev 2011; 21:753-8. PubMed
  • Batchelor E, Loewer A, Mock C, Lahav G. Stimulus-dependent dynamics of p53 in single cells. Mol Syst Biol 2011; 7:488. PubMed
  • Toettcher JE, Mock C, Batchelor E, Loewer A, Lahav G. A synthetic-natural hybrid oscillator in human cells. Proc Natl Acad Sci U S A 2010; 107:17047-52. PubMed
  • Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q, Shaik S, Wan L, Ang XL, Mock C, Yin H, Stommel JM, Gygi S, Lahav G, Asara J, Xiao ZX, Kaelin WG, Harper JW, Wei W. Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase. Cancer Cell 2010; 18:147-59. PubMed
  • Geva-Zatorsky N, Dekel E, Batchelor E, Lahav G, Alon U. Fourier analysis and systems identification of the p53 feedback loop. Proc Natl Acad Sci U S A 2010; 107:13550-5. PubMed
  • Loewer A, Batchelor E, Gaglia G, Lahav G. Basal dynamics of p53 reveal transcriptionally attenuated pulses in cycling cells. Cell 2010; 142:89-100. PubMed
  • Tzur A, Kafri R, LeBleu VS, Lahav G, Kirschner MW. Cell growth and size homeostasis in proliferating animal cells. Science 2009; 325:167-71. PubMed
  • Batchelor E, Loewer A, Lahav G. The ups and downs of p53: understanding protein dynamics in single cells. Nat Rev Cancer 2009; 9:371-7. PubMed
  • Toettcher JE, Loewer A, Ostheimer GJ, Yaffe MB, Tidor B, Lahav G. Distinct mechanisms act in concert to mediate cell cycle arrest. Proc Natl Acad Sci U S A 2009; 106:785-90. PubMed
  • Batchelor E, Mock CS, Bhan I, Loewer A, Lahav G. Recurrent initiation: a mechanism for triggering p53 pulses in response to DNA damage. Mol Cell 2008; 30:277-89. PubMed
  • Lahav G. Oscillations by the p53-Mdm2 feedback loop. Adv Exp Med Biol 2008; 641:28-38. PubMed
  • Sigal A, Milo R, Cohen A, Geva-Zatorsky N, Klein Y, Alaluf I, Swerdlin N, Perzov N, Danon T, Liron Y, Raveh T, Carpenter AE, Lahav G, Alon U. Dynamic proteomics in individual human cells uncovers widespread cell-cycle dependence of nuclear proteins. Nat Methods 2006; 3:525-31. PubMed
  • Loewer A, Lahav G. Cellular conference call: external feedback affects cell-fate decisions. Cell 2006; 124:1128-30. PubMed
  • Geva-Zatorsky N, Rosenfeld N, Itzkovitz S, Milo R, Sigal A, Dekel E, Yarnitzky T, Liron Y, Polak P, Lahav G, Alon U. Oscillations and variability in the p53 system. Mol Syst Biol 2006; 2:2006.0033. PubMed
  • Lahav G. The strength of indecisiveness: oscillatory behavior for better cell fate determination. Sci STKE 2004; 2004:pe55. PubMed
  • Lahav G, Rosenfeld N, Sigal A, Geva-Zatorsky N, Levine AJ, Elowitz MB, Alon U. Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat Genet 2004; 36:147-50. PubMed
  • McFarland DJ, Baker FD, Hotchin J. Host and viral genetic determinants of the behavioral effects of scrapie encephalopathy. Physiol Behav 1980; 24:911-4. PubMed