Robert M. Nissen, Ph.D.
Associate Professor
Department of Biological Sciences
California State University
5151 State University Drive
Los Angeles, CA 90032
office: 323-343-2039

Education
B.A. (94) Molecular Biology and Biochemistry, UC Berkeley
Ph.D. (00) Biochemistry and Molecular Biology, UC San Francisco
Postdoc (00-05) Developmental Genetics, MIT

RESEARCH FOCUS  

The long-term goal of my research program is to understand the mechanisms by which an initially pluripotent cell becomes restricted to specific fates and subsequently how it is maintained in the differentiated state. Progress in developing directed differentiation therapeutics is hindered by an incomplete understanding of the Nodal-signaling pathway. The current focus of the Nissen lab is aimed at revealing the roles that the Wdr68 and Dyrk1b proteins play in the Nodal-signaling pathway using zebrafish as a model organism. The Nodal-signaling pathway is required for specification of mesoderm, endoderm, and establishing left-right asymmetry. Although it is clear that different downstream target genes are induced in these three different Nodal-signaling contexts, knowledge about how the pathway mediates context-specific transcriptional responses is limited. This limitation in understanding the mechanisms that parse Nodal signal transduction into discrete context-specific transcriptional outcomes poses a significant problem. Identifying the factors responsible for parsing Nodal signaling into discrete promoter-specific transcriptional outcomes and understanding how those factors function will reveal new avenues for developing directed differentiation therapeutics.

Our recent findings suggest that the Wdr68-Dyrk1b protein complex plays a critical role in the specific branch of the Nodal-signaling pathway leading to the expression of the Nodal antagonists lefty1 (lft1) and lefty2 (lft2). The wdr68 gene was originally identified as a gene required for craniofacial development in the zebrafish. The Wdr68 protein physically interacts with two members of the dual-specificity tyrosine-regulated kinase gene family, dyrk1a and dyrk1b. Our current central hypothesis is that Wdr68 and Dyrk1b are members of a transcriptional co-regulator complex required for activation of the specific branch of the Nodal signaling pathway leading to lft1/2 gene expression. Through a combination of genomic and developmental methods using zebrafish mutants and antisense gene knockdown models, we are characterizing these genes and how they function in pathways essential for normal vertebrate development. Ultimately, we hope these studies will shed new and valuable light on the mechanisms driving cell specification and differentiation in vertebrates.