Ann Richmond, Ph.D.
Professor of Pharmacology
Ingram Professor of Cancer Biology
Senior Career Scientist, VA Medical Center, Nashville, TN
- : firstname.lastname@example.org
- : (615) 343-7777
432 Preston Research Building
2220 Pierce Avenue
Nashville, Tennessee - 37232-6600
- : Ann Richmond, Ph.D. - CV
My laboratory investigates the intracellular signals that are important in the tumor microenvironment and in the pre-metastatic niche to reduce the establishment of metastatic lesions. We have worked to investigate the role of inflammatory mediators in cancer progression and mechanisms for controlling the negative impact of inflammatory mediators using basic cancer biology principals that can be translated to the clinic. Recently, following basic discoveries on the pathways involved in tumor growth, we have developed translational studies using patient derived xenograft models to explore new therapeutic approaches for breast cancer and melanoma. We have shown that pan-phosphoinositide 3-kinase (PI3K) inhibitors inhibit tumor growth in part through modulation of the immune cell infiltrate in the tumor and inhibition of PI3Kγ as well as PI3Kα are crucial for inhibiting tumor growth directly and for reprogramming the tumor associated macrophages to an anti-tumor phenotype. The result is a significant increase in M1-like macrophages with elevated NF-κB activity, enhanced tumor infiltrating CD8+T effector cells, reduction in Tregs, and enhanced macrophage anti-tumor activity). In melanoma, we have previously shown that while targeted deletion of IKKβ in tumor cells blocks oncogene mediated transformation, targeted deletion of IKKβ in myeloid cells leads to enhanced tumor growth and metastasis for melanoma tumors. Moreover, we have characterized the role of CXCR2 and CXCR4 in the aggressiveness of breast cancer, demonstrating that inhibition of CXCR2 and CXCR4 blocks the recruitment of myeloid-derived suppressor cells (MDSCs) to the pre-metastatic niche and inhibits metastasis. We have shown that targeted deletion of CXCR2 in myeloid cells markedly inhibits the growth of both melanoma and breast tumors by altering the tumor immune microenvironment and suppressing recruitment and activity of myeloid-derived suppressor cells (MDSCs). We have worked to determine how inflammatory signals from tumors induce the chronic and elevated expression of chemokines and/or their receptors to recruit leukocytes that enhance or inhibit tumorigenesis and metastasis. We are experienced in the characterization of leukocyte interaction with the tumor microenvironment and in identification of subsets of these cells within the tumor using multi-color FACS and RNAseq analysis. Moreover, we are currently characterizing the role of immune checkpoint inhibitors in combination with several small molecule inhibitors that affect melanoma and breast cancer growth and metastasis using GEM models, patient derived xenografts and tumor organoid cultures. We have an outstanding group of collaborators and access to phenomenal infrastructure for acquiring patients, obtaining informed consent, tissue collection, patient follow-up, and access to patients in clinical trials.
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