Padres Pedal 2019 Summer Grants

 

Grant #1: Accelerating knowledge of genetic mutations in neuroblastoma. 

Type of Cancer:

Pediatric

Awardees:

Dr. Graham McVicker, Salk Institute for Biological Studies

Dr. Jennifer Elster, Rady’s Children’s Hospital

About the project:

Neuroblastoma is a devastating cancer of the sympathetic nervous system that most commonly affects very young children; 90% of patients are diagnosed by 5 years of age and the highest rate of diagnosis in the first month of life. Neuroblastoma patients are currently stratified into low-, intermediate- and high-risk groups based on their age at diagnosis, pattern of metastases, and the genetic mutations in their tumor. Unfortunately the accuracy of risk stratification is hampered by limited genetic understanding of the mutations that drive disease progression and relapse. Improved knowledge of the genetic mutations that are important for neuroblastoma could lead to advances both in neuroblastoma risk stratification and to new therapeutic approaches. This study will focus on learning how mutations affect genes indirectly by changing their expression instead of the genes themselves. It will identify mutations in neuroblastoma tumors that occurred in the parents or early in embryonic development. These types of mutations may be more important in neuroblastoma than other cancers because of its extremely early age of onset.


Grant #2: Overcoming resistance to current bone cancer chemotherapy. 

Type of Cancer:

Pediatric

Awardees:

Dr. Jean Wang, UC San Diego Health

Dr. Richard Kolodner, UC San Diego Health

Dr. Sun Choo, Rady’s Children’s Hospital

About the project:

Ewing sarcoma (ES) is a bone cancer that affects children and young adults. Despite aggressive treatment survival remains poor because of resistance to chemotherapy. This study will investigate a new drug target, FEN1, to overcome resistance to current therapy. FEN1 is an enzyme that helps with DNA replication. Other research has shown that ES cells behave like BRCA- deficient cells, which are known to be hypersensitive to FEN1 inhibition. ES cells are also sensitive to removal of FEN1 by a process that uses CRISPR, a gene editing technology, to knockout genes. Further, ES cells from at least one patient are hypersensitive to the FEN1 inhibitor, SMD2485. This project will provide the necessary pre-clinical data for evaluating FEN1 as a drug target to treat ewing sarcoma.


Grant #3: Targeting new treatments for children with neuroblastoma. 

Type of Cancer:

Pediatric

Awardees:

Dr. Tony Hunter, Salk Institute for Biological Studies

Dr. Peter Zage, UC San Diego Health

About the project:

Children with aggressive neuroblastoma have poor cure rates despite intensive treatment, and new therapies are needed. Treatments that inhibit important proteins and pathways in neuroblastoma tumors are likely to be more effective with fewer side effects. We have identified an association between expression of the NME1 gene and the survival rates of children with neuroblastoma, suggesting that NME1 may be a good candidate target for new neuroblastoma treatments. NME1 can act as a histidine kinase by adding phosphate to the amino acid histidine in other proteins in neuroblastoma cells, representing a previously undiscovered way for cells to control the function of proteins required for neuroblastoma growth and survival. We propose to explore how the NME1 histidine kinase affects neuroblastoma tumor cell maturation, growth, survival, and spread. The results of these studies will likely identify new proteins that could serve as targets for new types of treatment, leading to improved success of neuroblastoma therapy and improved chances of survival for children with neuroblastoma.


Grant #4: Protecting the gut and halting colon cancer growth.

Type of Cancer:

Colorectal

Awardees:

Dr. Soumita Das, UC San Diego Health

Dr. Svasti Haricharan, Sanford Burnham Prebys

Dr. Pradipta Ghosh, UC San Diego Health

Dr. Debashis Sahoo, UC San Diego Health, Rady’s Children Hospital

Dr. Sherry C. Huang, Rady’s Children Hospital

Dr. Scott Peterson, Sanford Burnham Prebys

About the project:

Chronic infections, stemming from an abnormal immune response, fuels inflammation, tissue destruction and DNA damage. Infection-associated inflammation can even initiate and fuel cancers. This grant revolves around the discovery, characterization, disease modeling and harnessing the diagnostic and therapeutic potential of a novel tumor suppressive pathway in the gut that normally protects the gut barrier from the luminal microbes but is lost during the initiation of colon cancers. The combined synergy of several transdisciplinary approaches is used to reveal when and how the microbes may alter host cell properties to ultimately fuel cancer initiation. The grant promises to deliver a therapeutic target/therapy for protecting the gut from these cancer-causing microbes and halt the formation and progression of colon polyps, and to validate a novel set of markers for predicting which polyps in the colons are at highest risk for progressing to colon cancers.


Grant #5: Driving progress in gioblastoma.

Type of Cancer: 

Brain

Awardees:

Dr. Joseph Ecker, Salk Institute for Biological Studies

Dr. Jeremy Rich, UC San Diego Health

Dr. Jess Dixon, Salk Institute for Biological Studies

About the project:

Glioblastoma (GBM) is the most lethal malignant brain tumor with a dismal median survival of less than 15 months. GBMs contain heterogeneous cell populations, including a glioblastoma stem cell (GSC) population that drives tumor growth and mediates therapeutic resistance. Cell type heterogeneity is a major contributor to the therapeutic resistance of glioblastoma. The goal of this project is to understand the molecular identity of different cell types in glioblastoma tumors. Using single-cell strategies, the project will reveal the gene regulatory programs that drive the progression of glioblastoma.


Grant #6: A new pathway to fractioning cancer.

Type of Cancer:

All

Awardees:

Dr. Seth Field, UC San Diego Health

Dr. Michael Jackson, Sanford Burnham Prebys

About the project:

To more effectively combat cancer, we need new therapies directed at new targets. This project discovered a signaling pathway involving a protein called GOLPH3 that drives a high fraction of cancers that together cause a high proportion of cancer deaths, including lung, breast, prostate, and colorectal cancers. The GOLPH3 pathway is unlike other pathways that drive cancer, and so inhibitors of the pathway provide a unique approach to cancer treatment. Existing data indicate that inhibition of the GOLPH3 pathway preferentially kills cancer. This project has identified a potent inhibitor of the pathway, and proposes experiments to better define its mechanism of action. This will enable further development to produce a compound that would be suitable as a novel therapeutic agent, completely unlike all current therapeutic strategies for cancer.

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