BBS Faculty Member - Galit Lahav

Galit Lahav

Department of Systems Biology

Harvard Medical School
Warren Alpert Building, Room 555B
200 Longwood Avenue
Boston, MA 02115
Tel: 617-432-5621
Fax: 617-432-5012
Visit my lab page here.

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. Some of the questions we are currently interested in include:

• How does the cell evaluate the level of its DNA damage and transfer this information to p53?

• What combination of p53 dynamics and p53 modifications triggers a given cell fate program?

• What is the dynamical behavior of wild-type and mutant p53 in response to different stresses?

• Can we ‘rewire’ the p53 network to affect p53 behavior and the cell fate?

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.

Last Update: 8/22/2013


For a complete listing of publications click here.



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

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

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

Jared Toettcher, Caroline Mock, Eric Batchelor, Alexander Loewer and Galit Lahav. A synthetic-natural hybrid oscillator in human cells.
PNAS 2010; 107(36): 17047-52

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

Eric Batchelor, Alexander Loewer and Galit Lahav. The ups and downs of p53: understanding protein dynamics in single cells.
Nature Reviews Cancer 2009; 9: 371-377

Jared E. Toettcher, Alexander Loewer, Gerard J. Ostheimerd, Michael B. Yaffe, Bruce Tidor and Galit Lahav. Distinct mechanisms act in concert to mediate cell cycle arrest.
PNAS 2009; 106 (3): 785-790

Eric Batchelor, Caroline S Mock. Irun Bhan, Alexander Loewer, and Galit Lahav, Recurrent initiation: a mechanism for triggering p53 pulses in response to DNA damage.
Mol Cell. 2008 30(3):277-289.

© 2013 by the President and Fellows of Harvard College