Download FACULTY SPONSOR`S NAME AND DEGREE:

Summer Student Research Program
Project Description
FACULTY SPONSOR’S NAME AND DEGREE: Betsy J. Barnes, Ph.D.
PHONE: (973) 972 -3319
DEPARTMENT AND INTERNAL MAILING ADDRESS: Biochemistry & Molecular Biology,
NJMS-UH Cancer Center, G1224
E-MAIL:[email protected]
PROJECT TITLE (200 Characters max):
Cell type-specific role for IRF-5 in cancer cell growth regulation and death receptor signaling
HYPOTHESIS:
We hypothesize that IRF-5 is a key regulator of cell cycle and apoptosis that is dependent on its cell
type-specific expression.
PROJECT DESCRIPTION (Include design, methodology, data collection, techniques, data analysis to be
employed and evaluation and interpretation methodology)
Interferon regulatory factor 5 (IRF-5) is a transcription factor with multiple, distinct biological
functions. It is a key mediator of type I interferon (IFN) signaling, Toll-like receptor (TLR) signaling,
and apoptotic cell signaling. As a result, IRF-5 plays a critical role in the immune response to
pathogens, as well as the cellular response to extracellular stressors, such as DNA damage. IRF-5 is a
candidate tumor suppressor gene and expression is lacking in multiple cancers such as lymphoma,
breast cancer and lung cancer. We showed that overexpression of human IRF-5 in a B cell lymphoma
lacking the tumor suppressor p53 could induce a G2/M cell cycle arrest and apoptosis. These cells were
further sensitized to DNA damage-induced apoptosis (Barnes et al. 2003). To make the story a little
more complicated, IRF-5 appears to function in a cell-type specific manner. We had hypothesized this
early on after completing a detailed analysis of human IRF-5 cell type-specific expression and
transcriptional regulation (Mancl et al. 2005). Similar results were reported in IRF-5-/- mice when
examining type I IFN levels in mouse embryonic fibroblasts (MEFs) versus splenic macrophages.
While loss of IRF-5 expression in MEFs had no effect on type I IFN gene expression after viral
infection, splenic macrophages lacking IRF-5 expression were deficient in their IFN response. More
recently, it was reported that IRF-5 does not play a role in DNA damage-induced cell cycle arrest after
analyzing cell cycle in MEFs from wt and IRF-5-/- mice exposed to DNA damage. However, MEFs
from knockout mice were resistant to undergo apoptosis in response to DNA damage. The fact that
IRF-5 is not well expressed in fibroblasts (human or mouse), may explain its loss of certain biological
functions, such as type I IFN signaling or cell cycle regulation. We are specifically interested in
determining cell types in which IRF-5 may regulate the cell cycle and/or respond to different death
receptor stimuli, such as Fas ligand or TRAIL (Hu and Barnes 2008). For these studies, we will use
both human immortalized cell lines and cells from wt and IRF-5 ko mice to determine IRF-5 cell typespecific function(s).
SPONSOR’S MOST RECENT PUBLICATIONS RELEVANT TO THIS RESEARCH:
This is a new project in the lab.
IS THIS PROJECT SUPPORTED BY EXTRAMURAL FUNDS?
Yes
or
No
(IF YES, PLEASE SUPPLY THE GRANTING AGENCY’S NAME)
This is supported by internal funds.
Summer Student Research Program
Project Description
THIS PROJECT IS:
Clinical
Laboratory
Behavioral
Other
THIS PROJECT EMPLOYS RADIOISOTOPES
THIS PROJECT INVOLVES THE USE OF ANIMALS
PENDING
APPROVED
IACUC PROTOCOL #07068D0910
THIS PROJECT INVOLVES THE USE OF HUMAN SUBJECTS
PENDING
APPROVED
IRB PROTOCOL #
WHAT WILL THE STUDENT LEARN FROM THIS EXPERIENCE?
The student will be exposed to a variety of molecular and cell biology techniques to analyze IRF-5
function, including, but not limited to, Western blot analysis, FACS, fluorescent microscopy, and cell
culture.