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
(520) 626-3242

Work Summary

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.


Wright, L. E., Frye, J. B., Lukefahr, A. L., Marion, S. L., Hoyer, P. B., Besselsen, D. G., & Funk, J. L. (2011). 4-Vinylcyclohexene diepoxide (VCD) inhibits mammary epithelial differentiation and induces fibroadenoma formation in female Sprague Dawley rats. Reproductive toxicology (Elmsford, N.Y.), 32(1).
BIO5 Collaborators
David G Besselsen, Janet L Funk

4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that targets ovarian follicles and accelerates ovarian failure in rodents, was used to test the effect of early-onset reproductive senescence on mammary fibroadenoma formation. One-month female Sprague Dawley rats were dosed with VCD (80 mg/kg or 160 mg/kg) and monitored for 22 months for persistent estrus and tumor development. Only high-dose VCD treatment accelerated the onset of persistent estrus relative to controls. However, both doses of VCD accelerated mammary tumor onset by 5 months, increasing incidence to 84% (vs. 38% in controls). Tumor development was independent of time in persistent estrus, 17 β-estradiol, androstenedione and prolactin. Delay in VCD administration until after completion of mammary epithelial differentiation (3 months) did not alter tumor formation despite acceleration of ovarian senescence. VCD administration to 1-month rats acutely decreased mammary alveolar bud number and expression of β-casein, suggesting that VCD's tumorigenic effect requires exposure during mammary epithelial differentiation.

Craig, Z. R., Marion, S. L., Funk, J. L., Bouxsein, M. L., & Hoyer, P. B. (2010). Retaining Residual Ovarian Tissue following Ovarian Failure Has Limited Influence on Bone Loss in Aged Mice. Journal of osteoporosis, 2010.
BIO5 Collaborators
Zelieann R Craig, Janet L Funk

Previous work showed that retaining residual ovarian tissue protects young mice from accelerated bone loss following ovarian failure. The present study was designed to determine whether this protection is also present in aged animals. Aged (9-12 months) C57BL/6Hsd female mice were divided into: CON (vehicle), VCD (160 mg/kg; 15d), or OVX (ovariectomized). Lumbar BMD was monitored by DXA and μCT used to assess vertebral microarchitecture. BMD was not different between VCD and CON at any time point but was lower (P

Wright, L. E., Christian, P. J., Rivera, Z., Van Alstine, W. G., Funk, J. L., Bouxsein, M. L., & Hoyer, P. B. (2008). Comparison of skeletal effects of ovariectomy versus chemically induced ovarian failure in mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 23(8), 1296-303.
BIO5 Collaborators
Zelieann R Craig, Janet L Funk

Bone loss associated with menopause leads to an increase in skeletal fragility and fracture risk. Relevant animal models can be useful for evaluating the impact of ovarian failure on bone loss. A chemically induced model of menopause in which mice gradually undergo ovarian failure yet retain residual ovarian tissue has been developed using the chemical 4-vinylcyclohexene diepoxide (VCD). This study was designed to compare skeletal effects of VCD-induced ovarian failure to those associated with ovariectomy (OVX). Young (28 day) C57Bl/6Hsd female mice were dosed daily with vehicle or VCD (160 mg/kg/d, IP) for 15 days (n = 6-7/group) and monitored by vaginal cytology for ovarian failure. At the mean age of VCD-induced ovarian failure (approximately 6 wk after onset of dosing), a different group of mice was ovariectomized (OVX, n = 8). Spine BMD (SpBMD) was measured by DXA for 3 mo after ovarian failure and OVX. Mice were killed approximately 5 mo after ovarian failure or OVX, and bone architecture was evaluated by microCT ex vivo. In OVX mice, SpBMD was lower than controls 1 mo after OVX, whereas in VCD-treated mice, SpBMD was not lower than controls until 2.9 mo after ovarian failure (p

Funk, J. L., Shigenaga, J. K., Moser, A. H., Krul, E. J., Strewler, G. J., Feingold, K. R., & Grunfeld, C. (1994). Cytokine regulation of parathyroid hormone-related protein messenger ribonucleic acid levels in mouse spleen: paradoxical effects of interferon-gamma and interleukin-4. Endocrinology, 135(1), 351-8.

Under normal physiological conditions, PTH-related protein (PTHrP) is produced in a wide variety of tissues and is thought to act locally in an autocrine or paracrine fashion more analogous to cytokines than to classic hormones such as PTH. In addition, we have recently shown that, like cytokines, PTHrP is induced in the spleen during the response to sublethal doses of endotoxin [lipopolysaccharide (LPS)] an effect that is mediated by tumor necrosis factor (TNF). As complex cytokine cascades are induced in response to infectious or inflammatory stimuli, the effects of other prototypical inflammatory [interferon-gamma (IFN gamma)] or antiinflammatory [interleukin-4 (IL-4)] cytokines on PTHrP gene expression were studied. Paradoxically, IFN gamma (50 micrograms), a cytokine that usually synergizes with TNF, inhibited LPS induction of splenic PTHrP messenger RNA (mRNA) levels in LPS-sensitive C3H/OuJ (OuJ) and LPS-resistant C3H/HeJ (HeJ) mice. The stimulation of splenic PTHrP mRNA levels caused by the administration of TNF alpha or interleukin-1 beta was similarly inhibited by IFN gamma, a type II interferon. In contrast, IFN alpha (50 micrograms), a type I interferon, stimulated splenic levels of PTHrP mRNA. IL-4, a prototypical antiinflammatory cytokine, also had a paradoxical effect on LPS induction of splenic PTHrP mRNA levels. Instead of inhibiting LPS induction of splenic PTHrP mRNA levels in OuJ or HeJ mice, IL-4 (200 ng) actually stimulated PTHrP mRNA levels. These complex cytokine interactions suggest that the expression of PTHrP in response to infectious or inflammatory stimuli depends on the counterbalancing effects of the specific cytokine networks induced by each stimulus.

Bea, J., Lee, V., Blew, R., Funk, J., & Going, S. (2015). Cardiovascular Risk Related to Body Fat and Physical Activity in Young Girls. FASEB JOURNAL, 29.