Janet L Funk

Janet L Funk

Professor, Medicine
Professor, Nutritional Sciences
Professor, Cancer Biology - GIDP
Professor, Physiological Sciences - GIDP
Clinical Instructor, Pharmacy Practice-Science
Member of the Graduate Faculty
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-3242

Work Summary

Janet Funk's work includes a focus on metastatic breast cancer that spans the research spectrum from bench to bedside, translational arthritis studies of the pharmacokinetics and safety of turmeric, and collaborative endocrinological studies evaluating the effects of obesity and insulin resistance on bone development in Hispanic girls, as well as effects of obesity on breast cancer risk in older women.

Research Interest

Janet L. Funk, MD, FACP, is a Professor of Medicine at the University of Arizona College of Medicine. Dr. Funk leads a federally-funded research team that is focused on identifying new treatments for chronic diseases that have strong inflammatory components, including metabolic bone diseases, such as arthritis, bone tumors and osteoporosis, and cardiovascular diseases, including diabetes. Recent studies have focused on the use of medicinal plants that have historically been used to treat inflammatory conditions, such as arthritis. By understanding whether and how these plants work in blocking inflammatory pathways in the body, we are striving to harness the power of nature and the wisdom of our ancestors to indentify new treatments for diseases that are common in our modern society. Discoveries we have made at the lab bench have allowed us to move forward into the clinics, building upon the old to discover the new.

Publications

Wright, L. E., Frye, J. B., Lukefahr, A. L., Timmermann, B. N., Mohammad, K. S., Guise, T. A., & Funk, J. L. (2013). Curcuminoids block TGF-β signaling in human breast cancer cells and limit osteolysis in a murine model of breast cancer bone metastasis. Journal of natural products, 76(3), 316-21.

Effects of curcuminoids on breast cancer cell secretion of the bone-resorptive peptide parathyroid hormone-related protein (PTHrP) and on lytic breast cancer bone metastasis were evaluated. In vitro, transforming growth factor (TGF)-β-stimulated PTHrP secretion was inhibited by curcuminoids (IC50 = 24 μM) in MDA-MB-231 human breast cancer cells independent of effects on cell growth inhibition. Effects on TGF-β signaling revealed decreases in phospho-Smad2/3 and Ets-1 protein levels with no effect on p-38 MAPK-mediated TGF-β signaling. In vivo, mice were inoculated with MDA-MB-231 cells into the left cardiac ventricle and treated ip every other day with curcuminoids (25 or 50 mg/kg) for 21 days. Osteolytic bone lesion area was reduced up to 51% (p 0.01). Consistent with specific effects on bone osteolysis, osteoclast number at the bone-tumor interface was reduced up to 53% (p 0.05), while tumor area within bone was unaltered. In a separate study, tumor mass in orthotopic mammary xenografts was also unaltered by treatment. These data suggest that curcuminoids prevent TGF-β induction of PTHrP and reduce osteolytic bone destruction by blockade of Smad signaling in breast cancer cells.

Funk, J. L. (2018). From bedside to bench and back again: investigating medicinal effects of turmeric on bone.. Entorno UDLAP.