Profile
Zebrafish (Danio rerio) have been extensively utilized for understanding mechanisms of development. These studies have led to a wealth of resources including genetic tools, informational databases, and husbandry methods. In spite of all these resources, zebrafish have been underutilized for exploring pathophysiology of disease and the aging process. Zebrafish offer several advantages over mammalian models for these studies, including the ability to perform saturation mutagenesis with relative ease and the capability to contain thousands of animals in a small space.
Dr. Keller’s research involves the development of the mature zebrafish as an animal model for studying late-life diseases and the biology of aging. She and her team are studying a family of proteins called heat shock proteins (Hsps), which play a critical role in maintaining cellular homeostasis. They have worked to characterize the heat shock response in mature zebrafish and how this response is altered during the aging process. In addition, they have an aging colony of zebrafish as part of an ongoing study to characterize the normal aging process in the zebrafish and the pathological changes that occur in zebrafish with aging. This includes examining morphological, histological, hematological, biochemical, and molecular changes that occur during the aging process in zebrafish. As part of this study, Dr. Keller’s team is also developing a web-based atlas of adult zebrafish anatomy and age-related changes. Future goals include using zebrafish as a model for cancer.
Dr. Keller’s second research focus involves studying the effects of metastasis-suppressing agents in the progression of prostate and breast cancer in a mouse model. Both prostate and breast cancer commonly metastasize to bone, leading to painful sequelae and significant impairment in health and well-being. Bone metastases incite osteoclastic activity in the bone. This suggests that osteoclast activity may be important in the initiation or progression of these metastases. Accordingly, blocking osteoclast activity may block the development or progression of bone metastases. Her team is examining compounds with the potential to mediate bone formation, which may inhibit the initiation or progression of bone metastases in cancer.
Professional Background
- Bachelor of Science, Michigan State University, 1996
- Doctor of Veterinary Medicine, Michigan State University, 1998
- Ph.D., University of Michigan, 2003
- Diplomate, American College of Laboratory Animal Medicine (DACLAM), 2005
SELECTED PUBLICATIONS
- Keller, J. M., Schade, G. R., Ives, K., Cheng, X., Rosol, T. J., Piert, M., Siddiqui, J., Roberts, W. W. and Keller, E. T. (2013), A novel canine model for prostate cancer. Prostate. doi: 10.1002/pros.22642.
- Schade GR, Keller JM, Ives K, Cheng X, Rosol TJ, Keller ET, and Roberts WW. 2012. Histotripsy Focal Ablation of Implanted Prostate Tumor in an ACE-1 Canine Cancer Model. The Journal of Urology, Volume 187, Issue 4, Supplement, April 2012, Page 325.
- Osisami M, Sottnik JL, Keller JM, and Keller ET. 2012. Cancer Biology Review: A Case Based Approach, Chapter 8b: Other Stromal Factors. Walter Stadler, ed.
- Dai J. Lu Y. Yu C. Keller JM. Mizokami A. Zhang J. Keller ET. 2010. Reversal of chemotherapy-induced leukopenia using granulocyte macrophage colony-stimulating factor promotes bone metastasis that can be blocked with osteoclast inhibitors. Cancer Research. 70(12):5014-23.
- Keller JM, Escara-Wilke JF, and Keller ET. 2008. Heat stress-induced heat shock protein 70 expression is dependent on ERK activation in zebrafish (Danio rerio) cells. Comparative Biochemistry & Physiology. Part A, Molecular & Integrative Physiology. 150(3):307-14.
- Dai J, Hall CL, Escara-Wilke J, Mizokami A, Keller JM, and Keller ET. 2008. Prostate cancer induces bone metastasis through Wnt-induced bone morphogenetic protein-dependent and independent mechanisms. Cancer Research. 68(14):5785-94.
- Keller ET, Dai J, Escara-Wilke JF, Hall CL, Ignatoski K, Keller JM. 2007. News trends in the in treatment of bone metastasis. Journal of Cellular Biochemistry. 102(5):1095-102.
- Keller ET, Keller JM, Gillespie G. 2006. Chapter 27: The Use of Mature Zebrafish (Danio rerio) as a Model for Human Aging and Disease. In Handbook of Models for Human Aging, pp. 309-315. Academic Press.
- Kitagawa Y, Dai J, Zhang J, Keller JM, Nor J, Yao Z, and Keller ET. 2005. Vascular endothelial growth factor contributes to prostate cancer-mediated osteoblastic activity. Cancer Research. 65(23): 10921-9.
- Dai J, Keller J, Zhang J, Lu Y, Yao Z, and Keller ET. 2005. Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Research. 65(18):8274-85.
- Murtha JM and Keller ET. 2004. The use of mature zebrafish (Danio rerio) as a model for human aging and disease. Comparative Biochemistry and Physiology. In Press.
- Murtha JM and Keller ET. 2004. Heat Shock Induces Heat Shock Protein 70 Expression Independent of ERK in Zebrafish (Danio rerio) Cells. Manuscript submitted to Zebrafish.
- Murtha JM and Keller ET. 2003. Characterization of the Heat Shock Response in Mature Zebrafish (Danio rerio). Experimental Gerontology. 38(6): 683-691.
- Murtha JM, Qi W, and Keller ET. 2003. Hematologic and Serum Biochemical Values for Zebrafish (Danio rerio). Comparative Medicine. 53(1): 37-41.
- Murtha JM, Dysko RC, and Decoster JL. 2000. Lethargy and hypothermia in a rhesus macaque. Contemporary Topics. 39 (4): 65.
- Keller ET and Murtha JM. 2004. The use of mature zebrafish (Danio rerio) as a model for human aging and disease. Comparative Biochemistry & Physiology. Toxicology & Pharmacology: Cbp. 138(3): 335-41.
- Kitagawa Y, Dai J, Zhang J, Keller JM, Nor J, Yao Z, and Keller ET. 2005. Vascular endothelial growth factor contributes to prostate cancer-mediated osteoblastic activity. Cancer Research. 65(23): 10921-9.
- Dai J, Keller J, Zhang J, Lu Y, Yao Z, and Keller ET. 2005. Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Research. 65(18):8274-85