Photo of Galit Lahav,

Galit Lahav

Harvard Medical School

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


galit@hms.harvard.edu

Galit Lahav

Harvard Medical School

EDUCATIONAL TITLES

  • Associate Professor, Systems Biology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

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

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  • Liu JC, Lerou PH, Lahav G. Stem cells: balancing resistance and sensitivity to DNA damage. Trends Cell Biol 2014; 24:268-274. 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
  • Ikeda F, Lahav G. Signal transduction and signaling networks. Mol Biol Cell 2013; 24:676. 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
  • 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
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