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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 
Ann  Richmond

Ann Richmond, Ph.D.

Ingram Professor of Cancer Research
Professor of Cancer Biology
Vice Chair, Department of Cancer Biology
VICC Member
Researcher

Contact Information:

Vanderbilt University Medical Center
432-B Preston Building
Nashville, TN 37232-6840
615-343-7777

Profile

Ann Richmond, Ph.D. is a Professor in the Department of Cancer Biology at Vanderbilt University School of Medicine. Her research interests include transcriptional regulation of chemokines, the role of chemokines in chronic inflammatory conditions, wound healing and tumor progression, as well as signal transduction mechanisms involved in chemokine mediated chemotaxis.
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Ann Richmond, Ph.D. is a Professor in the Department of Cancer Biology at Vanderbilt University School of Medicine. Her research interests include transcriptional regulation of chemokines, the role of chemokines in chronic inflammatory conditions, wound healing and tumor progression, as well as signal transduction mechanisms involved in chemokine mediated chemotaxis. Her laboratory has extensively studied the factors contributing to the constitutive transcription of angiogenic chemokines during tumor progression. They are currently testing the utility of targeting the transcription factor, NF-kB, as a therapeutic approach for treatment of malignant melanoma. Work from her lab has also elucidated the role of ligand mediated receptor phosphorylation in the facilitation of chemokine receptor desensitization. Moreover, her research team has shown that ligand mediated receptor internalization is associated with cessation of burst of chemokine signaling mediated through the chemokine receptor, CXCR2, which is required for continuous response to a chemokine. Mutation of the receptor such that ligand no longer mediates internalization of the receptor is accompanied by prolonged response to ligand with regard to generation of IP3, calcium mobilization, and other intracellular signals. However, loss of receptor internalization is accompanied by a loss of the chemotactic response, even through there is an increased length and strength of intracellular signals. Data to date suggest that it is the oscillation of signals that is required for a chemotactic response. Moreover, the activation signals need to localize at the leading edge or the uropod of the migrating cell. Using state of the art microfluid devices, time lapse video microscopy, FRET analysis of localized activation of Rac-1, Cdc42 and Rho GTPases, Richmond's research group is characterizing the mechanism by which altered adaptor binding to chemokine receptors or altered internalization of receptors alters the chemotactic response. Ongoing research is aimed at examination of the mechanism by which receptor internalization facilitates the establishment of an intracellular gradient of signals to establish polarity oscillations required for response to a chemotactic gradient with the end result leading to a better understanding of how chemokines mediate cancer cell metastasis as well as chronic inflammatory conditions.

Research Description

A major question we are trying to answer in my laboratory is "What is the role of the inflammatory response in tumor progression". We are studying the role of proteins that promote the migration of inflammatory cells into tissues. These "chemotactic" proteins can educate leukocytes to either stimulate or inhibit tumor progression. These factors can also stimulate the growth of the tumor and recruit blood vessels into the tumor to provide a continuous supply of nutrients to feed tumor growth. We have tested with a variety of pharmaceutical drugs that shut down the inflammatory process and alter the expression of genes that recruit inflammatory cells into the tumor microenvironment. We are also evaluating how to deliver therapies that teach the patient's leukocytes to fight the growth of the tumor and switch from a pro-tumorigenic to an anti-tumorigenic state.

We have also learned that this inflammatory process, combined with other genetic and environmental factors, contributes to mutations in genes that regulate the growth of cells. Some of these mutations make the cells capable of continuous growth and enable the cancer cells to spread throughout the body and grow in distant organs. By determining what genes become mutated or amplified in each patient's tumor and then providing therapies that specifically inhibit the activity of that mutated or amplified gene, we can deliver "personalized cancer treatment" that addresses the problem in that persons specific cancer. This works so much better than the "one size fits all" approach often used previously in chemotherapy. Recently we have determined that inhibition of aurora kinases induce tumor cells to undergo senescence and when we inhibit aurora kinases while at the same time activate the tumor suppressor p53 or the death receptor DR5, melanoma cells die and tumors regress. We are also interested in evaluating how therapeutic agents that target driver mutations such as PI3K, RAS or BRAF affect the tumor microenvironment and the immune response to the tumor. We postulate that in some instances drug resistance comes in part due to deleterious effects of the therapy on the tumor microenvironment. We collaborate with medical oncologists, surgical oncologists, bioengineers, cellular and molecular biologists, and scientists in pharmaceutical companies to address the scientific questions we are asking. This TEAM interaction enables us to optimize our studies to make important breakthroughs in tumor biology and tumor therapy. Our research is funded by the TVHS Department of Veterans Affairs, the National Cancer Institute, and the Department of Defense. I work with a wonderful group of postdoctoral fellows, students, and laboratory scientists who dedicate their lives to providing better treatments for cancer patients.

Publications