Roger L Miesfeld

Roger L Miesfeld

Distinguished Professor, Chemistry and Biochemistry
Professor, Chemistry and Biochemistry
Professor, Molecular and Cellular Biology
Professor, Entomology / Insect Science - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
(520) 626-2343

Research Interest

Roger L. Miesfeld, Ph.D., Professor and Co-Chair, Dept. of Chemistry & Biochemistry, College of Science, University of Arizona. Mosquitoes are human disease vectors that transmit pathogens through blood feeding. One of these disease vectors is the Aedes aegypti mosquito, which have rapidly expanded their habitat and are contributing annually to 500,000 cases of Dengue hemorrhagic fever. On an even greater scale, Anopheline mosquitoes account for 250 million cases of malaria/yr, with up to 1 million deaths annually. The most common adult insecticides used for mosquito control are pyrethroids, which inhibit evolutionarily conserved sodium channels in the mosquito nervous system. Although these compounds have proven to be effective, mosquito resistance is an increasing problem and there is a pressing need to develop the next generation of safe and effective agents. Since blood meal feeding creates a unique metabolic challenge as a result of the extremely high protein and iron content of blood, it is possible that interfering with blood meal metabolism could provide a novel control strategy for mosquito born diseases. Our long term goal is to identify small molecule inhibitors that block blood meal metabolism in vector mosquitoes, resulting in feeding-induced death of the adult female, or a significant reduction in egg viability, as a strategy to control vector mosquito populations in areas of high disease transmission.


Miesfeld, R., Briehl, M. M., & Miesfeld, R. L. (1991). Isolation and characterization of transcripts induced by androgen withdrawal and apoptotic cell death in the rat ventral prostate. Molecular endocrinology (Baltimore, Md.), 5(10).

A variety of stimuli have been identified which initiate transcription-dependent programmed cell death (apoptosis) in specific target cells. Since the withdrawal of androgens induces regression and apoptosis in rat ventral prostate (RVP) epithelial cells, and it is known that the androgen receptor is a transcriptional regulator, we used subtraction cDNA cloning to isolate differentially expressed transcripts from the RVP of androgen ablated rats. In addition to sulfated glycoprotein-2 and glutathione S-transferase (GST), which had been previously described, several other transcripts were found to be elevated 3- to 8-fold in the regressing RVP. DNA sequencing revealed that two of these cDNA clones encode matrix carboxyglutamic acid and gamma-actin, respectively. A third cDNA contained novel sequence information and was named RVP.1. The RVP.1 transcript is expressed at very low levels in the RVP and epididymis of normal adult rats (less than 0.01% of the total mRNA) and is undetectable in other tissues, such as kidney, liver, and muscle. RVP.1 encodes a putative 280-amino acid protein, which shares no significant homology with previously described protein functional domains. We examined the expression of these transcripts in serum-starved NIH 3T3 cells to determine whether any of them are elevated in cells that are growth arrested. It was found that only GST mRNA levels are increased under these conditions. These data may suggest that induction of some genes, such as RVP.1, could be associated with apoptosis, whereas other transcripts, such as GST, may be up-regulated in response to altered rates of cellular metabolism.

Marcu, K. B., Arnheim, N., Banerji, J., Penncavage, N. A., Seperack, P., Lang, R., Miesfeld, R., Harris, L., & Greenberg, R. (1981). Studies on the nature and germ-line stability of DNA sequences flanking the mouse immunoglobulin heavy-chain constant-region genes.. Cold Spring Harbor Symposia on Quantitative Biology, 45 Pt 2, 899-911.
Adkins, K. K., Levan, T. D., Miesfeld, R. L., & Bloom, J. W. (1998). Glucocorticoid regulation of GM-CSF: Evidence for transcriptional mechanisms in airway epithelial cells. American Journal of Physiology - Lung Cellular and Molecular Physiology, 275(2 19-2), L372-L378.

PMID: 9700099;Abstract:

Inflammation plays a central role in the pathogenesis of asthma. Glucocorticoids are first-line anti-inflammatory therapy in the treatment of asthma and are effective inhibitors of inflammatory cytokines. Clinical data demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF) production by airway epithelial cells may be an important target of inhaled glucocorticoid therapy. We examined the regulatory mechanisms of GM-CSF expression by interleukin-1β (IL-1β) and the synthetic glucocorticoid dexamethasone in the BEAS-2B human bronchial epithelial cell line. IL-1β stimulation resulted in a 15-fold induction of GM-CSF protein, which was associated with a corresponding 47-fold maximal induction of GM-CSF mRNA levels. Treatment with the transcriptional inhibitor actinomycin D before IL- 1β stimulation completely abolished induction of GM-CSF mRNA, whereas incubation with cycloheximide had no effect. Taken together, these data demonstrate that IL-1β induction of GM-CSF is mediated through transcriptional mechanisms. Dexamethasone treatment of BEAS-2B cells produced an 80% inhibition of IL-1β-induced GM-CSF protein and a 51% inhibition of GM-CSF mRNA. GM-CSF mRNA was rapidly degraded in these cells, and dexamethasone treatment did not significantly affect this decay rate. We conclude that, in the BEAS-2B bronchial epithelial cell line, IL-1β induction and dexamethasone repression of GM-CSF expression are mediated predominantly through transcriptional mechanisms.

Bloom, J. W., Chacko, J., Lohman, I. C., Halonen, M., Martinez, F. D., & Miesfeld, R. L. (2004). Differential control of eosinophil survival by glucocorticoids. Apoptosis, 9(1), 97-104.

PMID: 14739603;Abstract:

Glucocorticoids are effective drugs for eosinophil-related disorders, such as asthma and allergy. Previous studies have demonstrated that glucocorticoids increase eosinophil apoptosis and block the survival effect of submaximal concentrations of interleukin-5 (IL-5). We investigated the effect of glucocorticoids on eosinophil survival in the presence of a higher concentration of IL-5 (1 ng/ml), comparable to IL-5 levels in bronchoalveolar lavage and sputum specimens from patients with asthma. In contrast to incubation in the presence of submaximal concentrations of IL-5, the addition of dexamethasone (DEX) to media containing I ng/ml IL-5 led to a significant increase in eosinophil cell viability from 58 ± 6.9% to 87 ± 2.4% (p 0.005) after 72 hours in culture. We found that RU486 blocked the DEX effect on cell viability confirming that glucocorticoid receptor functions are required. We Investigated the possibility that the glucocorticoid enhancement of eosinophil survival may be due to an effect on IL-5 receptor expression. Our results show that the IL-5 associated decrease in IL-5 receptor α-subunit expression was blocked significantly after 24 hrs in culture with media containing IL-5 plus DEX compared to IL-5 alone. It is tempting to speculate that the observed glucocorticoid enhancement of eosinophil survival in the presence of elevated concentrations of IL-5 could be a mechanism that contributes to glucocorticoid resistance in asthma.

Miesfeld, R., Godowski, P. J., Maler, B. A., & Yamamoto, K. R. (1987). Glucocorticoid receptor mutants that define a small region sufficient for enhancer activation. Science, 236(4800), 423-427.

PMID: 3563519;Abstract:

Transcriptional enhancement is a general mechanism for regulation of gene expression in which particular proteins bound to specific DNA sequences stimulate the efficiency of initiation from linked promoters. One such protein, the glucocorticoid receptor, mediates enhancement in a glucocorticoid hormone-dependent manner. In this study, a region of the 795-amino acid rat glucocorticoid receptor that is active in transcriptional enhancement was identified. The active region was defined by expression various receptor deletion mutants in stably and transiently transfected cells and examining the regulated transcription of hormone-responsive genes. Mutant receptors lacking as many as 439 amino-terminal amino acids retained activity, as did those with as many as 270 carboxyl-terminal amino acids deleted. This suggests that the 86-amino acid segment between the most extensive terminal deletions, which also includes sequences required for specific DNA binding in vitro, is sufficient for enhancer activation. In fact, a 150-amino acid receptor fragment that encompasses this segment mediates constitutive enhancement.