Programs > Fellowships > Fellows > June 2009 > Rebecca Mathew, Ph.D.

Rebecca Mathew, Ph.D.
The University of Chicago
Chicago, IL

Project Title: Characterization of the targets of promyelocytic leukemia zinc finger in NKT cells
Sponsor: Albert Bendelac, M.D., Ph.D. 

Natural Killer T (NKT) cells are a population of T lymphocytes with innate anti-cancer properties that are markedly depressed in cancer patients.  Their activation with the marine sponge-derived NKT ligand α-galactosylceramide induces strong anti-cancer effects in vivo.  Recent studies in our laboratory have identified Promyelocytic Leukemia Zinc Finger (PLZF) as the signature transcription factor directing the differentiation of NKT cells.  

Dr. Mathew’s project will use recently developed genome-scale approaches to characterize how PLZF orchestrates the transcriptional program of NKT cells.  Her studies have direct implications on current efforts to harness and enhance the anti-cancer properties of NKT cells in human clinical studies.

What are NKT cells?

Natural Killer T (NKT) cells are a distinct subset of T lymphocytes with anti-cancer properties.  These cells are highly reduced in cancer patients, and therefore, so are their anti-cancer effects.  When NKT cells are activated, we observe strong anit-cancer effects in cellular studies.  These cells have the capacity to rapidly expand and produce large amounts of cancer-fighting molecules and proteins.  Our lab recently identified a transcription factor called promyelocytic leukemia zinc finger (PLZF) as the signature transcription factor that regulates and differentiates NKT cells.  The absence of PLZF effects both expansion and function of NKT cells. 

How do you plan to study PLZF and NKT cells?

My main objective is to identify gene targets of PLZF and the components that PLZF uses to regulate NKT cell function.  I am using a genome-wide approach called gene sequencing, which helps me to identify the genes which are the targets of PLZF.  Once I identify these target genes, the next step will be to further examine them for their ability to restore anti-cancer function in PLZF-defficient NKT cells.  Identification of theses gene targets and their function will open up new approaches for understanding and correcting NKT cell development associated with the cancer.

While I was doing my Ph.D. in chemistry, I became interested in transcription factors and how they can regulate gene networks and the development and function of particular cell types.  I read a lot about transcription regulation and decided I wanted to learn more and work in immunology.  When I interviewed with Dr. Bendelac's lab, I came to know that they identified a transcription factor very specific for NKT cell development, but didn’t know its gene targets or how it regulated NKT cell development.  I became very interested and excited by the questions I could help to answer in this growing and exciting field.  We can learn a whole lot about how the immune system works through immunology research.