- A major research goal of Amanda’s laboratory is to determine at the molecular and cellular levels the mechanism by which the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-pdioxin dioxin causes developmental toxicity. For this purpose they use two vertebrate models, the zebrafish and rat or mouse.
- Prostate disease is prominent among the male population. Understanding the progression and cause of the disease is crucial in determining both treatment and prevention. One impending question to further understand prostate disease is to what extent susceptibility to prostate disease is affected by exposure to environmental contaminants. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a member of the halogenated aromatic hydrocarbon family of environmental contaminants and exposure to TCDD has been shown to result in a range of diseases including cancer, teratogenicity, immunosuppression, and endocrine disruption.In uteroand lactational TCDD exposure has been shown to negatively affect prostate development in rodents by inhibiting the growth of ventral prostatic buds and causing dorsal and lateral prostatic buds to form in inappropriate positions. The mechanism by which prenatal TCDD exposure leads to detrimental defects in prostate development is poorly understood. Recent evidence has shown thatâ-catenin is found within the urogenital sinus (UGS), the region where prostate is derived, andâ-catenin signaling is necessary for prostatic bud formation, the initial step in prostate formation. During my postdoctoral research, I propose to test hypotheses regarding the exact mechanism by whichin uteroTCDD exposure affects-catenin signaling in the UGS. My results will hopefully shed light both on how the prostate is formed as well as how TCDD exposure inhibits prostatic bud formation in the mouse fetus.
- Branam AM, Davis NM, Moore RW, Schneider AJ, Vezina CM, Peterson RE. (2013) TCDD inhibition of canonical Wnt signaling disrupts prostatic bud formation in mouse urogenital sinus. Toxicol Sci. 133:42-53. Epub 2013 Feb 20. PMID: 23429912 [PubMed – in process]
- Kim J, Woo AJ, Chu J, Snow J, Fujiwara Y, Kim CG, Cantor AB, and Orkin SH. (2010) A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs. Cell 143: 313-324.
- Branam AM, Davis NM, Moore RW, Schneider AJ, Vezina CM, Peterson RE.TCDD inhibition of canonical wnt signaling disrupts prostatic bud formation in mouse urogenital sinus. Toxicol Sci. 2013 May;133(1):42-53. doi: 10.1093/toxsci/kft027. Epub 2013 Feb 20. PMID:23429912
- Keil KP, Mehta V, Branam AM, Abler LL, Buresh-Stiemke RA, Joshi PS, Schmitz CT, Marker PC, Vezina CM. (2012) Wnt Inhibitory Factor 1 (Wif1) Is Regulated by Androgens and Enhances Androgen-Dependent Prostate Development. Endocrinology. 2012 Oct 18. [Epub ahead of print] PMID: 23087175
- Branam AM, Hoffman GG, Pelegri F, and Greenspan DS. (2010) Zebrafish Chordin-like and Chordin Are Functionally Redundant in Regulating Patterning of the Dorsoventral Axis. Dev Biol. 341:444-458. Epub 2010 Mar 11. PMCID: PMC2862114
- Hoffman GG, Branam AM, Huang G, Pelegri F, Cole WG, Wenstrup RM, and Greenspan DS. (2010) Characterization of the six zebrafish clade B fibrillar procollagen genes, with evidence for evolutionarily conserved alternative splicing within the pro-alpha1(V) C-propeptide. Matrix Biol. 29:261-275. Epub 2010 Jan 25. PMCID: PMC2862785
- Jasuja R, Ge G, Voss NG, Lyman-Gingerich J, Branam AM, Pelegri FJ, and Greenspan DS. (2007) Bone morphogenetic protein 1 prodomain specifically binds and regulates signaling by bone morphogenetic proteins 2 and 4. J Biol Chem. 282:9053-9062. PMID: 17255107