Galit Lahav

Professor of Systems Biology

Harvard Medical School, Department of Systems Biology
Alpert Building, Room 555
200 Longwood Ave.
Boston, MA 02115
Tel: 617-432-5621
Email: galit_lahav@hms.harvard.edu

Website:

http://lahav.med.harvard.edu/index.html
Lab Size: Between 10 to 15

Summary

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 insights into the reasons why different cells and people respond differently to specific drugs.

We mainly focus on two networks; the p53 network and the DNA damage response. In the p53 network we are investigating the dynamics of the tumor suppressor protein p53 in response to irradiation and chemotherapeutics drugs in individual cells and ask how p53’s dynamic behavior is controlled, why different cells show different dynamical behaviors and what consequences these behaviors have on cell survival. In the DNA damage response we ask how the kinetics of DNA repair and the choice of repair mechanism are affected by the cell cycle and what are the consequences of activating one repair mechanism versus the other under various cellular backgrounds.

In the long term we are optimistic that these studies will help us predict how signaling networks in human cells will behave in response to new stimuli; how they can be modified or rebuilt to give a desired cellular output; and how to selectively increase the tendency for cancer cells to go in the direction of apoptosis by modulating the dynamics of the networks controlling this decision.

Publications

Giorgio Gaglia, Yinghu Guana, Jagesh V. Shaha, and Galit Lahav. Activation and control of p53 tetramerization in individual living cells PNAS, 2013; PDF.

Giorgio Gaglia and Galit Lahav Constant rate of p53 tetramerization in response to DNA damage controls the p53 response. Molecular Systems Biology, 2014, 10:753:1.

Julia C. Liu, Xiao Guan, Jeremy A. Ryan, Ana G. Rivera, Caroline Mock, Vishesh Agarwal, Anthony Letai, Paul H. Lerou, and Galit Lahav. High Mitochondrial Priming Sensitizes hESCs to DNA-Damage-Induced Apoptosis Cell Stem Cell, 2013; 13: 1-9 PDF.

Jeremy Purvis and Galit Lahav. Encoding and Decoding Cellular Information through Signaling Dynamics Cell, 2013; 152:945-956 PDF.

Ketki Karanam, Ran Kafri, Alexander Loewer and Galit Lahav. Quantitative Live Cell Imaging Reveals a Gradual Shift between DNA Repair Mechanisms and a Maximal Use of HR in Mid S Phase. Molecular Cell, 2012; 47:320-329 PDF

Jeremy E. Purvis, Kyle W. Karhohs, Caroline Mock, Eric Batchelor,Alexander Loewer, Galit Lahav. p53 Dynamics Control Cell Fate. Science 2012: 336:1440-4 PDF

Ketki Karanam, Ran Kafri, Alexander Loewer and Galit Lahav. Quantitative live cell imaging reveals a gradual shift between DNA repair mechanisms and maximal use of HR in mid S phase. Molecular Cell 2012; 47(2):320-329.

Eric Batchelor, Alexander Loewer, Caroline Mock and Galit Lahav. Stimulus-dependent dynamics of p53 in single cells. Molecular Systems Biology 2011; 7: 488.

Alexander Loewer, Eric Batchelor, Giorgio Gaglia and Galit Lahav. Basal dynamics of p53 reveals transcriptionally attenuated pulses in cycling cells. Cell 2010; 142(1):89-100.

Andrew Paek, Julia Liu, Alexander Loewer, William Forrester and Galit Lahav. Cell-to-cell variation in p53 dynamics leads to fractional killing. Cell 2016.

Sheng-hong Chen, William Forrester and Galit Lahav. Schedule-dependent interaction between anticancer treatments. Science, 2016, 351:1204-1208; Full text PDF

Jacob Stewart-Ornstein and Galit Lahav. Dynamics of CDKN1A in Single Cells Defined by an Endogenous Fluorescent Tagging Toolkit. Cell Reports, 2016, 14:1-12; PDF

Laura Lande-Diner, Jacob Stewart-Ornstein, Charles J. Weitz and Galit Lahav. Single cell analysis of circadian dynamics in tissue explants. Molecular Biology of the Cell, 2015; PDF