Steven Kosak

Steven Kosak, PhD
Assistant Professor
Cell and Molecular Biology

The Relationship between Nuclear Form and Function during Cellular Differentiation and Disease

Research Clusters: Developmental Systems and Stem Cell Biology
Genetics and Genomics

E-mail:   
s-kosak@northwestern.edu

To visit the Kosak Lab web site, click here.


Growing evidence supports the idea that the nucleus is organized according to the varied functions it performs.  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 nuclear organization during differentiation by examining the relationship between the linear arrangement of co-regulated genes and the organization of all chromosomes in a hematopoietic stem cell and derived cell types. 

We hypothesize 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 may be 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 directly relevant in developing more refined induced pluripotent stem (iPS) cell strategies as well as our understanding of the role stem cells play in organismal aging and disease states such as cancer.

Publications:
Rajapakse I, Perlman MD, Scalzo D, Kooperberg C, Groudine M, Kosak ST.  (2009)  The emergence of lineage-specific chromosomal topologies from coordinate gene regulation.  PNAS 106:6679-6684.

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

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

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

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

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

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


Pub med

View Publications by Steven Kosak listed in the National Library of Medicine (PubMed).