1. Can Expression of VACM-1 Enhance Effects of Thalidomide on Endothelial Cell Growth? Drake Harper Zeeland East High School John Pelton Maria Burnatowska-Hledin Hope College

2. VACM-1 (Vasopressin-Activated Ca 2+ -mobilizing receptor) Isolated and studied by Hledin’s Lab Inhibits Cell growth by regulating cAMP and MAPK phosphorylation, and p53 concentration, signaling pathways involved in cell growth that lead to cancer In vivo VACM-1 is expressed in endothelial cells (cells in vasculature) Mutation in VACM-1 sequence (where one amino acid is changed) creates a dominant negative phenotype (reverse the effect) ie. Cell growth increases

3. Thalidomide Originally created to help pregnant women with “morning sickness” Caused Birth Defects (Physical deformities on limbs and organs), Later banned Reason for Study: Inhibits Angiogenesis (the growth of blood vessels) Cellular targets for Thalidomide’s effects are unknown

4. Hypothesis In normal endothelial cells expressing VACM- 1 protein, thalidomide will decrease cell growth by inducing VACM-1 protein expression. In cells expressing a dominant negative VACM-1 (VACM-S730A), Thalidomide will increase the mutated VACM-1 but will not inhibit growth.

5. Uses on cancer VACM-1 stops cell growth, therefore, if used on cancer cells, it should stop the growth of cancerous tumors on cells.

6. Methods Cell Culture Western Blot Wound Healing Assay Immunostaining

7. Western Blot GAPDH

8. Data

9. Summary Thalidomide increases VACM-1 protein concentration which results in decreased growth. When VACM-1 is mutated, it is unable to inhibit cell growth Conclusion Anticancer effect of Thalidomide may involve induction of VACM-1

10. Acknowledgements Dr. Hledin John Pelton Dr. Hledin’s lab group REACH Hope College