UC-wide Committee Awards Grants to Two UC Merced Stem Cell Projects

MERCED - University of California, Merced faculty members in the School of Natural Sciences have won two important grants from the UC Cancer Research Coordinating Committee for the 2007-08 fiscal year.

Dean Maria Pallavicini and her team will receive $40,000 to study how stem cells in the breast differentiate into the two major mammary cell types. They expect the knowledge they gain may shed light on how some stem cells in the breast may contribute to the development of breast cancer.

Professor Jennifer O. Manilay and her team will receive $50,000 to study the role of a specific hormone/receptor pair in the development of T cells - knowledge that can be applied to how that pair interacts with many forms of cancer.

"Cancer research by faculty members like Dean Pallavicini and Professor Manilay are contributing to the strong biomedical sciences program that is evolving at UC Merced," said Vice Chancellor for Research Sam Traina. "This program is one of the foundations for the developing medical school at UC Merced."

"Understanding how stem cells make decisions is a critical question in stem cell biology," said Dean Pallavicini of the university's School of Natural Sciences. "While the potential role of stem cells for regenerative medicine is a goal for many, it has only been recognized recently that stem cells are also involved in cancer.

"My study and Professor Manilay's are both examples of science that may be used later by researchers working to increase understanding of how stem cells are altered in cancer. While the studies to be carried out in Professor Manilay's laboratory and my group do not have immediate goals to develop treatments, the knowledge we gain by studying how stem cells make decisions will lay the foundations for later research that we hope will directly benefit cancer patients."

Pallavicini and grad student Heather Bryan will study the role of notch signaling in the differentiation of mammary gland stem cells - cells present even in adult breasts.

"Recently researchers have identified a stem cell-like population that contributes to breast cancer," Bryan explained. "We're looking at the basic biology of normal cells so we can better understand what goes wrong when cancer develops."

Bryan said they will explore the notch signaling process using flow cytometry to examine cell-surface markers, microscopy to look at intracellular markers, gene expression studies and a three-dimensional differentiation culture assay that has shown in the past that breast stem cells can develop into milk-producing or duct cells, depending on what hormones and other factors are present in vitro.

Pallavicini and Bryan are cooperating with Amy Hiddessen, a researcher at Lawrence Livermore National Laboratory. Hiddessen is a chemical engineer who develops cell arrays that they will use in their research.

Manilay and staff researcher Bryce McLelland are working on a project studying the role of CXCL16 - a specific protein belonging to a group called chemokines - and its associated receptor, CXCR6. Chemokines (chemotactic cytokines) are proteins which are produced by cells in the immune system and influence cell trafficking within the same tissue where they are produced.

CXCL16 is overexpressed in many kinds of tumor cells, and T-cells with the CXCR6 receptor seem to be directed to migrate to those tumors. It's unknown whether the T-cells are there to fight the tumor, or whether their presence is just a side effect of the overexpression of CXCL16 in tumor cells.

Manilay and McLelland are studying how this cytokine/receptor pair functions during normal T-cell development in the thymus. Manilay said they may then be able to apply what they learn to how CXCL16 and CXCR6 function in cancer.

Just from her preliminary data, Manilay produced a presentation for the American Association of Immunologists meeting in Miami Beach in May. She expects a paper will follow later this year.

For more information about the UC Cancer Research Coordinating Committee, see http://crcc.ucdavis.edu/.

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