Name: Steven Kosak
Title: Assistant Professor
Research area: Nuclear Form and Function in Cell Fate Decisions

Degree: Ph.D.

Voice: 312.503.9582

Fax: 312.503.7912
E-mail: s-kosak@northwestern.edu

Detailed Research description:

Nuclear function and nuclear organization are inextricably linked.  For example, gene expression is related to nuclear localization, with silenced genes frequently positioned at heterochromatin and the nuclear periphery, and active genes enriched in the nuclear interior.  Moreover, we have established a relationship between gene expression and genomic organization during cellular differentiation by contrasting the linear arrangement of co-regulated genes and the organization of all chromosomes in a hematopoietic progenitor and derived cell types. 

 

We suggest that the inter-linked functions of the nucleus results in its self-organization, defined as the emergence of a global structure from combined local activities.  Stem cells represent an ideal model to examine the functional role of nuclear self-organization, since their unique cellular properties are likely reflected in shared nuclear characteristics.  My lab intends to both describe and probe the role of nuclear organization in stem cell maintenance and differentiation.  We aim to characterize the mechanistic role transcription plays in organizing the nucleus during the renewal and commitment of stem cells and determine the ability of the nucleoskeleton to dynamically integrate cellular signals that yield these two fates.  We suggest that these studies will be relevant to our understanding of the role stem cells play in aging and disease states such as cancer.

 

Representative publications:

Rajapakse I, Perlman MD, Scalzo D, Kooperberg C, Groudine M, and Kosak ST.  The emergence of lineage-specific chromosomal topologies from coordinate gene regulation.  Proc Natl Acad Sci USA, 106:6679-6684, 2009.  (A commentary was written about this manuscript:  Misteli, T.  Self-organization in the genome.  PNAS 106:6885-6886, 2009.) 

 

Kosak ST, Scalzo D, Alworth SV, Li F, Palmer S, Enver T, Lee, JSJ, and Groudine M.  Coordinate gene regulation during hematopoiesis is related to genomic organization.  PLoS Biology 5(11):e309, 2007.

 

Kosak ST and Groudine M.  Gene order and dynamic domains.  Science 306:644-647, 2004.

 

Kosak ST and Groudine M.  Form follows function:  the genomic organization of cellular differentiation.  Genes & Development 18:1371-1384, 2004.

 

Ragoczy T, Telling A, Sawado T, Groudine M, and Kosak ST.  A genetic analysis of chromosome territory looping:  diverse roles for distal regulatory elements.  Chromosome Research 11:513-25, 2003.

 

Kosak ST and Groudine M.  The undiscovered country:  chromosome territories and the organization of transcription.  Developmental Cell 2:690-92, 2002.

 

Kosak ST, Skok JA, Medina KL, Riblet R, Le Beau MM, Fisher AG, Singh H.  Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development.  Science 296:158-62, 2002.