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Steve Attle


Identification of a Sphingosine-1-Phosphate Receptor in Drosophila.

The American Society for Cell Biology, 49th Annual Meeting

December 2009, San Diego, CA


Sphingosine-1-phosphate (S1P) has become one of the most studied bioactive lipids in recent years.Initially thought of as simply a structural lipid it has emerged as major mediator of many vital cellular processes including lymphocyte trafficking, cytoskeletal rearrangements, angiogenesis and suppression of apoptosis.†† S1P regulates these processes by stimulating a subclass of five g-protein coupled receptors known as S1PR1-5.Aberrant expression of S1P receptors contributes to the metastatic nature and proliferation of many types of tumors. All eukaryotic organisms have a well conserved sphingolipid metabolic pathway.However, a S1P receptor has yet to be discovered in an invertebrate system.†† The studies presented here set out to identify a S1P receptor in Drosophila (fruit fly).The discovery of a S1P receptor in this organism could provide valuable insight to the evolutionary development of S1P receptors. In addition, Drosophila is very well characterized and genetically tractable.The identification of an S1P receptor in this organism could provide a new model organism to study S1P receptors.



Joshua Theisen

Methyl CpG Binding Protein 2- (MeCP2-) Mediated Repression of Transcription.

The American Society for Cell Biology, 49th Annual Meeting

December 2009, San Diego, CA


Many types of cancer are caused by mutations in or reduced expression from tumor suppressor genes. In addition, the loss of expression of other important genes has significant consequences for patientsí prognoses and treatment outcomes. One of the mechanisms linked to loss of tumor suppressor gene expression is DNA methylation. DNA methylation is a chemical modification of DNA. This modification causes gene to be repressed, or turned off, and has been linked to reduced expression of genes involved in cancer. However, this mark is not sufficient, by itself, to cause repression. DNA methylation must be recognized by proteins, including methyl CpG binding protein 2 (MeCP2), which then cause repression.


Our research strives to determine how MeCP2, which binds to methylated DNA, is able to reduce gene expression. Specifically, we are studying how MeCP2 recognizes which genes should be turned off and the mechanisms that MeCP2 uses to turn off these genes. By increasing our knowledge of how MeCP2 functions, this work will lead to a greater understanding of how gene expression goes wrong in cancer and may improve future cancer therapies.



Matt Niederst


The PHLPP Phosphatases negatively regulate EGFR levels and signaling of the Ras/Raf/Mek/Erk pathway.

The American Society for Cell Biology, 48th Annual Meeting

December 2008, San Francisco, CA


Cells receive signals from their nearby environment that regulate important cell processes such as cell division.One of the hallmarks of cancer formation is the cell gaining the ability to divide independent of these external signals.This independence often results when the cell becomes unable to turn off its cell division machinery.Our lab has recently discovered a new gene family, the PHLPP family that acts as a brake to stop cell division.The goal of my research is to understand exactly how PHLPP normally prevents cells from dividing, and more importantly, what the role of PHLPP is in preventing the onset and progression of cancer.To date, I have discovered that PHLPP inhibits one of the key proteins involved in promoting cell division, and that loss of PHLPP in tumor cells leads to increased levels of another protein that is found to be high in many human tumors, particularly glioblastomas.Better understanding of the tumor-suppressing function of PHLPP in cancer cells may pave the way for its use as a therapeutic target for treatment of cancer.In addition, studying PHLPP will shed light on the broader process of oncogenesis and provide information that will be valuable in preventing, diagnosing and curing cancer in the future.



Amber Miller


Elucidating the Role of Txnip Ablation in Development of a Cancer Phenotype.

The American Society for Cell Biology, 47th Annual Meeting

December 2007, Washington D.C.


The transformation of a normal healthy cell into a proliferating cancer cell is a complicated process that can arise from numerous genetic aberrations as well as external damage.Almost all cancers exhibit altered metabolism (energy consumption) that not only allows them to survive in the low oxygen microenvironment of the tumor but also makes them resistant to many chemotherapeutics.Determining what causes this metabolic shift is an important step in the understanding of cellular transformation, which will in turn aid in the development of new therapeutics.The deletion of the gene encoding thioredoxin interacting protein (Txnip) causes a metabolic shift which emulates that seen in cancer cells both in mice and in cell culture, as well as increasing the development of liver cancer.Loss of Txnip expression has also been shown in multiple human cancers, while its overexpression has been shown to slow cancer cell growth and induce cell death.Understanding the mechanism by which deletion of Txnip alters metabolism as well as cellular growth rate will not only further the general knowledge of cancer development but may also yield potential molecular targets to modulate for the development of new cancer therapeutics or to increase the efficacy of current treatments.



Sukanya Patra


Cancer cells are hypersensitive to structure specific DNA repair inhibitors

The American Society for Cell Biology, 47th Annual Meeting

December 2007, Washington D.C.


Cancer comprises a group of diseases characterized by uncontrolled growth and spread of abnormal cells. The DNA in all cells, normal and tumor, is continuously bombarded with DNA damaging chemicals, both endogenous and exogenous, and must have repair machinery to fix this damage. Any deficiency in the genome surveillance machinery (mostly due to malfunctioning of one or more of the players in the cell cycle checkpoint pathway) leads either to cell death or cancer. Cells with abnormal DNA that have escaped cell cycle controls often become cancer cells.


Most of the chemotherapeutic treatments available are fairly general in the sense that they cause DNA damage to cells irrespective of their genetic background. Since cancer cells have much higher proliferation capacity, they are the cells that are most susceptible to these damaging treatments, which block DNA replication. However, these treatments can cause severe side effects, partly by inhibiting the growth of other rapidly growing cells like gut epithelium, hair follicles, etc., or by other even less specific toxic effects. The uniqueness of the hexapeptides I am studying is that they target specific DNA damage repair pathways and thus should be very specific in its action. For instance, our preliminary results show that p53 deficient cells are much more sensitive to peptide wrwycr treatment than cells containing the wild type p53 protein [L.Su and A. Segall, manuscript in preparation; S.Patra and A. Segall, unpublished results]. This signifies that this peptide may be very useful for treating those tumors in which p53 has been mutated. p53 is just one example of proteins which, when mutated, may be synergistic with peptide toxicity. Identifying more proteins that exacerbate peptide-mediated toxicity should reveal even more potential chemotherapeutic applications for the peptide.



Angela C. Cone


A neural crest-like cell lineage in the invertebrate chordate Ciona intestinalis.

The American Society for Cell Biology, 46th Annual Meeting

December 2006, Can Diego, CA


When vertebrates evolved from invertebrates, they acquired a specialized cell type called the neural crest.These cells give rise to a variety of cell types including skin pigment cells (melanocytes), but it is still not clear if these cells are truly unique to vertebrates.We show for the first time that the pigment cells of the ascidian, an invertebrate closely related to vertebrates, are surprisingly similar to neural crest cells, especially with regards to how these cells are programmed during embryonic development.It has been demonstrated that improper activation of embryonic regulatory genes in adult melanocytes is important for the pathogenesis of melanoma.Many of the genes we have examined in the developing pigment cell lineage in ascidians, such as Snail and MITF, are implicated in the progression of malignant melanoma in humans.Melanocyte development in the ascidian, Ciona intestinalis, occurs in less than 16 hours and can be observed with single-cell resolution unlike any vertebrate model system.This simplified model will allow for more careful dissection of the gene regulation that is involved in the development of chordate pigment cells and in turn help determine new targets that can be pursued to fight the progression of melanoma.