FA 5 Progress Report WV-INBRE - Joan C. Edwards School of ...

Program Director/Principal Investigator (Last, First, Middle): Rankin, Gary O 122(ERRα and cMyc) pathways were involved in the ovarian tumor growth inhibition. He has published theseresults. (3) Determine whether kaempferol inhibit ovarian tumor angiogenesis, and identify which signalingmolecules mediate kaempferol-inhibiting tumor angiogenesis. He found that kaempferol inhibits ovariantumor angiogenesis through inhibiting HIF-1α, VEGF, cMyc and ERRα signaling molecules. He alsopublished these results in peer-reviewed scientific journals. He has published three manuscripts and hasone in press since the last APR. He has also submitted an R15 application that was not funded. He hasrevised and resubmitted his application. Overall, Dr. Chen has been the most productive of the PUIinvestigators to date.Dr. Gerald Hankins, West Virginia State University, “ Sex steroid hormones and epigenetics inmeningiomas”Dr. Hankin’s central hypotheses are: (1) that meningioma tumorigenesis is driven in part by actions offemale steroid hormones and (2) that the tumorigenesis may be mediated in part by progesterone andestrogen receptor containing chromatin-modifying complexes. This past year one graduate student and anundergraduate student have focused on fibroblast growth factors and their receptors and havedemonstrated that both fibroblast growth factors and their receptors are expressed by meningioma cells.Further, growth factor message levels are modulated by steroid hormones. Treatment of meningioma cellswith antagonists of FGF receptors decreases the proliferation of the cells and the phosphorylation of ERK1and 2. Together, these results provide more evidence that steroid hormones may affect the expression offibroblast growth factors (FGF2 and FGF9) in meningiomas and also that an FGF autocrine loop plays a rolein meningioma cell proliferation, partially by signaling through ERK1/2.He has also found that the expression of the cyclin dependent kinase p27 kip1 (CDKN1B) is modulated inmeningioma cells by both the progesterone antagonist Mifepristone and the histone deacetylase inhibitorbutyric acid. The transcriptional repressor KLF10 (Krueppel-like factor 10 or TIEG-1) was down regulatedby a factor of 32 by the estrogen receptor antagonist, ZK164015 in more aggressive lines of meningioma,while Mifepristone had no effect. Since PR is typically higher in lower grades of meningioma while ERincreases in higher grades, he is examining this in cells from lower grade tumors.Although SLC20A2 (GLVR-2, Pit2) was not highlighted in the grant, he found that its expression wassignificantly down regulated by Mifepristone. Expression was also modulated by HDAC inhibitor treatment.The work of one graduate student who graduated during the past year was published during the summer(Manohar S et al. Cell Cycle 10 (15): 2529-2539, 2011). Dr. Hankin’s mentor Dr. Mayion Park has left MUand Dr. Travis Salisbury has replaced her as his mentor. However, he is still collaborating with her onstudies on chromatin modifying proteins. Dr. Salisbury’s research on the aryl hydrocarbon receptorcomplements the grant research given the parallels and crosstalk between AHR and steroid receptors.Dr. Tesfaye Belay, Bluefield State College, “Effect of stress on pathogenesis and immunity duringchlamydia genital infection”Dr. Belay’s hypothesis is that cold-stress increases the severity of chlamydia genital infection anddevelopment of complications by modulating the immune response against Chlamydia.To assess theinfluence of stress on distribution pattern of immune cells in different regions of the genital tract duringChlamydia trachomatis infection, Dr. Belay has used the mouse stress model and flow cytometry analysis. Ingeneral, the total number of immune cells in stressed mice was reduced; however, no statistically significantdifference between stressed and non-stressed was obtained. Increased infiltration of leukocytes into thegenital tract of stressed or non-stressed infected mice was obtained. Further flow cytometry experimentsare underway to localize neutrophils, lymphocytes and dendritic cells or adhesion molecules in the regions ofthe genital tract of stressed mice during chlamydia infection.Dr. Belay has begun to assess the effect of cold-stress on Chlamydia-induced infertility in the mouse model.His initial results suggest that stress may increase complications of immunopathogenesis resulting from C.trachomatis genital infection and infertility. Further experimentation is underway to determine the effect andmechanism of stress in modulation of fertility in mice. (Abstract submitted to the General Meeting ofAmerican Society for Microbiology, San Francisco, CA, June 2012).Dr. Belay is also determining the effect of cold-induced stress on the histopathological changes of thePHS 2590 (Rev. 06/09)Continuation Format Page