Janet L Funk
Clinical Instructor, Pharmacy Practice-Science
Professor, BIO5 Institute
Professor, Medicine
Professor, Nutritional Sciences
Professor, Physiological Sciences - GIDP
Primary Department
Department Affiliations
(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.


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., Shoback, D. M., & Genant, H. K. (1995). Transient osteoporosis of the hip in pregnancy: natural history of changes in bone mineral density. Clinical endocrinology, 43(3), 373-82.

A 31-year-old white female developed severe bilateral hip pain during the third trimester of pregnancy that persisted after parturition. Laboratory abnormalities (elevated alkaline phosphatase and erythrocyte sedimentation rate) and radiographic changes (faint demineralization of the femur in the more symptomatic hip on plain films with evidence of bone marrow oedema and small joint effusions bilaterally on MRI) in the absence of other causes of focal osteoporosis were consistent with the diagnosis of transient osteoporosis of the hip in pregnancy. Although loss of bone mineral density (BMD) characterizes this syndrome, serial BMD measurements in symptomatic transient osteoporosis of the hip in pregnancy have not previously been reported. In the case reported here, serial bone density measurements were obtained over a 4-year period following the onset of symptoms. BMD in both femoral necks, which initially was approximately 20% lower than the average for age matched controls, increased markedly during the first year, plateaued during the following year, and then rapidly increased again following cessation of lactation. Unexpectedly, BMD in the lumbar spine, an asymptomatic site, was also markedly decreased at the time of presentation (31% lower than the mean of age-matched controls). Recovery of spinal density did not occur during the first year. However, spinal BMD did begin to increase during the second year and continued to rise after the cessation of lactation. In contrast to the marked reduction in bone density at these site of trabecular bone, cortical bone density in the forearm was normal. Possible aetiologies of pregnancy associated osteoporosis are discussed.

Funk, J. L. (2001). A role for parathyroid hormone-related protein in the pathogenesis of inflammatory/autoimmune diseases. International immunopharmacology, 1(6), 1101-21.

Our increased understanding of the critical role of cytokines in chronic inflammatory/autoimmune diseases has led to the recent development of effective anti-cytokine treatments. In particular, agents blocking the function of TNF-alpha, a cytokine first identified as an endotoxin-inducible mediator of tumor cell necrosis, are now licensed for the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease. However, TNF-alpha is but one member of a cytokine network that is responsible for mediating these inflammatory disorders. Therefore, as our understanding of the pathophysiologic role of other members of this inflammatory network increases, other cytokines may similarly be identified as effective targets for treatment. In this article, we will review evidence which suggests that parathyroid hormone-related protein (PTHrP), a peptide which, like TNF-alpha, was first identified because of its effects in the setting of malignancy, may in fact serve an important non-neoplastic, physiologic function by mediating the inflammatory/autoimmune host response. Data identifying PTHrP as a member of the cytokine network induced in multi-organ inflammation and rheumatoid arthritis will be summarized, initial evidence comparing the therapeutic efficacy of PTHrP- vs. TNF-alpha-blockade in the treatment of endotoxemia will be reviewed, and potential future areas of research, including assessment of the effects of PTHrP blockade in the treatment of RA, will be discussed.