COBRE Research Projects

5 Research Projects, each with funding for up to 3 years, are currently underway.

Project 1:

Organization of the Nerve Terminal by Synaptic Cleft Components
(Hiroshi Nishimune, Ph.D., P.I.)

We hypothesize that voltage gated calcium channels (VGCCs) at nerve terminals are important scaffolding proteins that help organize active zones.  Our Specific Aims are to:  1)  Identify the direct interaction of active zone proteins and VGCC at presynaptic terminals; 2) Assess the role of N-type VGCCs in presynaptic differentiation; and 3) Identify ligands for VGCCs at synapses in the brain.

Project 2:

Preimplantation Embryonic Secreted/Released Proteins:  Embryo Quality Predictors
(Lane Christenson, Ph.D., PI)

We hypothesize that the early embryo secretes/releases proteins that reflect the quality status of that embryo.    Our Specific Aims are to:  1)  Develop a methodology for identifying protein secreted/released by the early mammalian embryo abd establish a set of protein markers associated with healthy/unhealthy embryos; 2) Validate whether murine secreted/released proteins can predict murine embryonic quality and test whether these proteins are translatable to the human system.

Project 3:

Genetic Models of Congenital Vascular Malformations
(Jay Vivian, Ph.D., P.I.)

Klippel-Trenaunay Syndrome (KTS) is a congenital vascular disease with associated cutaneous vascular malformations, vein varicosity, and overgrowth of affected lims.  Recent human genetic studies have implicated the VG5Q locus in the etiology of KTS, but the mouse ortholog, Aggf1, has not yet been characterized experimentally.  Our Specific Aims are:  1) Define the expression pattern of murine Aggf1 during embryonic and fetal development; 2) Determine the functions of Aggf1 by analyzing null mutants; and 3) Overexpress Aggf1 in transgenic mice.

Project 4:

Regulation of Gene Expression in the TH2 Cytokine Locus
(Patrick E. Fields, Ph.D., P.I.)

Differentiation of Th2 cells, and their secretion of specific cytokines, are important for the development of humoral immune responses.  Th2 cytokine genes reside in a single, coordinately regulated locus (the Th2 cytokine locus), and we hypothesize that positive and negative regulatory elements coordinate cytokine gene expression within this locus.  Our Specific Aims are to: 1) Identify functional GATA3 and STAT6 binding sites in the Th2 locus; and 2) Generate a reporter system where Th2 cytokine gene transcription can be evaluated simultaneously.

Project 5:

Germ Cell Development in the atrichosis Mutant Mouse
(T. Rajendra Kumar, Ph.D., P.I.)

Spermatogenesis involves interactions between testicular germ cells and somatic cells and aberrations in these interactions can result in male infertility and testicular cancers.  The atrichosis mutant mouse has a primordial germ cell defect, which, we hypothesize, affects the migration /proliferation of these cells.  Our Specific Aims are to:  1) Analyze the migration and proliferation of atrichosis mutant primoridial germ cells in vivo; 2) Determine the contribution of the somatic cell niche to germ cell loss in the mutant testis; and 3)  Identify the candidate gene(s) at the atrichosis locus on mouse chromosome 10.