Innovative Research Grants 2009
SU2C's first thirteen Innovative Research Grants, awarded in December of 2009, support cutting-edge cancer research that might not receive funding through traditional channels. Innovative Research Grants support early-career scientists with novel ideas that have a strong potential to impact patient care - projects that are high-risk but could also be high-impact.
IRG Recipients at a Glance
An Emerging Tumor Suppressor Pathway to Human Cancer
The Hippo biochemical pathway is thought to regulate organ growth, bringing cell division to a halt once organs have reached maturation. One of the defining characteristics of cancer is rapid, unchecked cell growth. Dr. Fernando Camargo leads an IRG investigation into the promise of Hippo signaling and its possible role in suppressing cancer cell growth or providing model and material for new cancer therapies.
“Every once in a while you’re going to be the first person that notices something that nobody else in history of human kind has known, and I think that’s very exciting.”
Modeling Ewing Tumor Initiation in Human Neural Crest Stem Cells
This project will use an innovative model to generate neural crest stem cells in the laboratory and will look at the ways in which expression of EWS-FLI1, an abnormal gene found in Ewing sarcomas, affects the epigenetic state in these neural crest stem cells and initiates tumor formation.
“We need to develop drugs that are going to selectively kill the cancer cell and spare the normal developing tissue. So that when the child has finished their treatment, they’re not only free of cancer, but they can go back to school and know that they’re going to live a normal, healthy life.”
Cancer Cell Specific, Self-Delivering Pro-Drugs
Tailoring a type of molecule that is naturally attracted to cancer cells with an anti-cancer payload, Dr. Levy aims to minimize the toxic collateral damage inflicted on healthy tissue and cells by conventional cancer treatment methods. The innovation of a precise, self-delivering agent would greatly diminish commonly harsh side effects, representing a leap forward for cancer patients in treatment.
“I fight cancer because I think we can find a cure. It’s a very complicated disease, but I think we can stop it.”
Targeting Inhibition of BCL6 for leukemia Stem Cell Eradication
This IRG concentrates on the BCL6 protein—how it influences leukemia at onset and relapse, the protein's relationship to leukemia stem cells, and preliminary development of a new BCL6 inhibitor capable of eliminating dormant leukemia stem cells.
“The key to conquering cancer, if there’s any, and I hope there is, will be collaboration.”
Identifying Solid Tumor Kinase Fusions via Exon Capture and 454 Sequencing
The uncontrolled cell growth that is a common characteristic of cancer is often compared to a broken switch, as is sometimes the case with thetyrosine kinases (TK), a class of molecular switches controlling cell growth, which can cause cancer when altered, sometimes the result of fusion with cellular protein. Dr. Pao will lead a search for 100 such fusions in lung and breast cancers, offering fresh therapeutic targets based on the model of Gleevec, the highly effective drug which targets a specific alteration in leukemia.
“The government tends to fund more conservative proposals that may not lead to the next breakthrough. SU2C has committed to funding the most innovative grants that can really make a large impact on cancer and cancer outcomes in the next few years.”
Therapeutically Targeting the Epigenome in Aggressive Pediatric Cancers
Dr. Charles M. Roberts designed a model system which will now be used to examine epigenetic pathways in pursuit of therapies that can reverse the non-permanent epigentic effects of losing the SNF5 gene. The loss affects DNA packaging and often results in an extremely lethal pediatric cancer primarily affecting children under 2 years old. Discovery of a method of reversal would translate to hope for these young patients and have far reaching implications for almost every type of cancer.
“Why do I fight this disease? I’m a pediatric oncologist and I see firsthand the devastating effect that this disease can have on children and their families. And there’s nothing more motivating than seeing a child suffering to make me want to do better.”
Endogenous Small Molecules that Regulate Signaling Pathways in Cancer CellsRajat Rohatgi, M.D., Ph.D., Stanford University
This project will identify small molecules that regulate the Hedgehog signaling pathway, which drives the development of a large number of childhood and adult cancers. Dr. Rohatgi's integrative approach will use tools from cell biology and chemistry to find the influential molecules and a new hope in the treatment of a variety of cancers.
“The future of cancer research is going to come from breaking down traditional barriers and approaches to solving problems and not being afraid to embrace concepts from different fields. This project really forces me to think beyond my roles as a biologist and a physician who sees patients.”
Genetic Approaches for Next Generation of Breast Cancer Tailored Programs
The goal of this project is to open up a new frontier of targeted therapy development by identifying specific gene functions that only serve the existence of cancer cells, with no benefit to normal cells and healthy tissue.
“Every day I try to be better than I was the last day. I try to learn more than I knew the last day. I would like to provide the clinical community with noble targets so they can give more hope to the patients.”
Modulating Transcription Factor Abnormalities in Pediatric Cancer
This project will target the EWS-FLI protein, the “undruggable” cancer-promoting protein in Ewing sarcoma, screening a library of chemicals for those that induce the gene fingerprint of the inactive EWS-FLI protein to identify potential anti-cancer drugs.
“Our work focuses on new approaches to drug discovery. And so, as such, the hope is that molecules that emerge from the screen might someday actually become clinical drugs that are used in the treatment of patients.”
Noninvasive Molecular Profiling of Cancer via Tumor-Derived Microparticles
This project will develop a new approach to profiling tumors by capturing and examining “microparticles,” tiny genetic material-containing packets that are emitted by cells in the tumor tissue and circulate in the blood.
“We’re at this point where all of this knowledge that's been accumulated through really painstaking work is about to flip, and about to translate into new therapies, into new tests, and potentially into ways of preventing cancer.”
A Transformative Technology to Capture and Drug New Cancer Targets
This project will bring together multiple fields — chemistry, biology and cancer drug development — to deploy a technology that can rapidly and precisely identify cancer-causing proteins and their malignant interaction sites.
“Our job – and it's truly a quest – is to try to find the Achilles heel of these cancer cells. And there may be more than one Achilles heel, and the only way to find them is to use new technologies. And once we do find them then we can actually get on the path of developing drugs against them.”
Functional Oncogene Identification
Using a novel system that identifies the molecular abnormalities that drive cancer causation and growth directly from patient tumors, this project will make the molecular profiling process faster, more efficient and more precise.
“We want to look in a broad array of different tumor types and try to pull out new oncogene alterations. That’s something that is difficult and it’s high risk, but it’s extremely high reward.”
Probing EBV-LMP-1’s Transmembrane Activation Domain with Synthetic Peptide
The goal of this project is to demonstrate how the human Epstein-Barr virus (EBV), which infects 90 percent of the world population, contributes to cell survival and cell division.
“We’re definitely trying to help people. Trying to understand why people develop cancer and trying to give them our help for diagnosing cancers early and prevent them from the very beginning.”
Meet the Innovative Research Grants 2009 Recipients
- Defining the Mechanistic Connections Between Injury, Regeneration, & Cancer
- Defining the Metabolic Dependencies of Tumors
- Imaging Cell-Level Heterogeneity in Solid Tumors for Personalized Treatment
- Deubiquitinating Enzymes as Novel Anticancer Targets
- Algorithmically-driven Quantitative Combination Cancer Therapy Engineering
- “Weak Links” in Cancer Proteostasis Networks as New Therapeutic Targets
- Metabolic Reprogramming Using Oncolytic Viruses to Improve Immunotherapy
- Phospholipid Messengers as Drivers of Dendritic Cell Dysfunction in Cancer
- Uncovering How Rad51 Paralog Mutations Contribute to Cancer Predisposition
- Targeting Cellular Plasticity in Individual Basal-Type Breast Cancer Cells
- An Emerging Tumor Suppressor Pathway to Human Cancer
- Modeling Ewing Tumor Initiation in Human Neural Crest Stem Cells
- Cancer Cell Specific, Self-Delivering Pro-Drugs
- Targeting MLL in Acute Myeloid Leukemia
- Targeting Genetic and Metabolic Networks in T-ALL
- Targeting Protein Quality Control for Cancer Therapy
- Targeting PP2A and the Glutamine-Sensing Pathway as Cancer Treatment
- Chimeric RNAs Generated by Trans-Splicing and their Implications in Cancer
- Exome Sequencing of Melanomas with Acquired Resistance to BRAF Inhibitors
- Identification and Targeting of Novel Rearrangements in High-Risk ALL
- A Systems Approach to Understanding Tumor Specific Drug Response
- Targeting Sleeping Cancer Cells
- Inhibiting Innate Resistance to Chemotherapy in Lung Cancer Stem Cells
- Developing New Therapeutic Strategies for Soft-tissue Sarcoma
- Framing Therapeutic Opportunities in Tumor-activated Gametogenic Programs
- Coupled Genetic and Functional Dissection of Chronic Lymphocytic Leukemia
- Targeting Inhibition of BCL6 for leukemia Stem Cell Eradication
- Identifying Solid Tumor Kinase Fusions via Exon Capture and 454 Sequencing
- Therapeutically Targeting the Epigenome in Aggressive Pediatric Cancers
- Endogenous Small Molecules that Regulate Signaling Pathways in Cancer Cells
- Genetic Approaches for Next Generation of Breast Cancer Tailored Programs
- Modulating Transcription Factor Abnormalities in Pediatric Cancer
- Noninvasive Molecular Profiling of Cancer via Tumor-Derived Microparticles
- A Transformative Technology to Capture and Drug New Cancer Targets
- Functional Oncogene Identification
- Probing EBV-LMP-1’s Transmembrane Activation Domain with Synthetic Peptide