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Petr Kalab, Ph.D.

Portait Photo of Petr Kalab
Laboratory of Cellular and Molecular Biology
Investigator
National Cancer Institute
37 Convent Drive, MSC 4256
Building 37, Room 2050
Bethesda, MD 20892-4256
Phone:  
 301-496-1572
Fax:  
 301-496-8479
E-Mail:  
 kalab@mail.nih.gov

Biography

Dr. Petr Kalab received C.Sc. (Ph.D. equivalent) from the Institute of Animal Physiology and Genetics of the Czech Academy of Sciences in 1990. During his postdoctoral visit at the University of Pennsylvania, Philadelphia, and in his own lab in Czech Republic, he studied signal transduction in mammalian reproduction. In 1997, Dr. Kalab redirected his career and as a visiting fellow at NICHD, NIH, Bethesda, and later as staff researcher at the University of California, Berkeley, focused on the mitotic functions of the small GTPase Ran. In 2008, Dr. Kalab joined the Laboratory of Cellular and Molecular Biology, NCI, NIH as a tenure-track investigator.

Research

My research focuses on two organelles that are characteristic of the internal structure of eukaryotic cells: the nucleus and the mitotic spindle. In particular, it is fascinating that the essential roles of both these organelles require the contribution of a single signaling network controlled by the small GTPase Ran. Because of its fundamental influence, the analysis of Ran-regulated functions provides unparalleled opportunities to study how the nucleus and mitotic spindle are assembled and how they function.

Ran is an evolutionarily conserved key regulator of the nucleo-cytoplasmic transport and has an essential role in the mitotic spindle assembly and in the reformation of the nuclear envelope at the exit from mitosis. The common principle of Ran function is the genome-centered concentration gradient of RanGTP. As Ran GEF (RCC1) binds to DNA and is imported to the nuclei while RanGAP is cytoplasmic, more RanGTP exists around the position of the genome inside the cells, compared to the cell periphery. The functions of the RanGTP gradient are mediated by the interaction of RanGTP with members of the family of nuclear transport receptors (NTRs) of the importin beta superfamily.

Although the role of the Ran-NTR system as a genome positioning system (GPS) is conserved in eukaryotes, its contribution to mitotic spindle assembly differs in comparison of various types of cells (e.g., in meiotic vs. mitotic somatic cells in vertebrates). Importantly, some components of the Ran-NTR system, including Ran and some of the importins, are overexpressed or mislocalized in a variety of human cancers. Many well known 'cancer proteins' such as BRCA1, HTOG, TACC3, HURP, Aurora A, TPX2, NPM1, survivin, and others are either targets of mitotic Ran regulation or are required for Ran mitotic functions.

The approach of my laboratory is to consider the Ran-NTR system as a research tool to address important questions in cell biology and in the development of disease. For example, by taking advantage of published molecular structures of the Ran-NTR system components, we devised FRET-based molecular biosensors reporting on Ran function in live cells. The results we obtained with such tools revealed an unexpected mechanism of mitotic spindle regulation by chromatin signals, encouraging the development of strategies to inhibit cell division by subtle modulation of the mitotic Ran pathways. Ongoing and future projects involve quantitative imaging of Ran function in live cells, reconstitution of Ran functions with defined components, chemical biology approaches, and functional proteomic screens to analyze mitotic Ran pathways. Besides the powerful Xenopus egg extract system, we are using computational systems modeling, tissue culture cells, and we are developing animal models to study the RanGTP gradient function.

Postdoctoral or Research Fellow Position is Available

Position is open to study the mitotic spindle assembly. This position is intended for a project focusing on the mitotic spindle pole formation and its relevance for mitosis progression in vivo. The initial objective will be to elucidate the molecular mechanism of a so far uncharacterized Ran-regulated pathway controlling mitotic spindle pole dynamics that we have discovered. In a longer term, this project will contribute to the reconstitution of mitotic spindle assembly from defined components in vitro. The experimental approaches will include a variety of techniques from molecular biology, protein biochemistry and cell biology, combined with live microscopy (including FRET and FLIM/FRET), as needed. Our favorite models for mitotic spindle assembly analysis are Xenopus egg extracts, tissue culture cells and in vitro reconstitution experiments. This project requires solid background in protein biochemistry and cell biology, good understanding of the mitotic spindle assembly and interest in mitotic regulation. Being demonstrably a creative researcher, being comfortable with microscopy or having an additional background in physics or chemistry would be an advantage.

Contact: kalab@mail.nih.gov

This page was last updated on 1/5/2010.