Collaborative Research Program
The Forbeck Foundation asked itself a few years ago how could it further its commitment to collaboration towards a cure for cancer, the answer was the Collaborative Research Program. Funding of research projects is based upon collaborations between two laboratory fellows/scholars/MDs in their early years of scientific development. Preference is given to scholars that are developing their own laboratories and need funding to enable them to establish themselves as independent investigators capable of receiving major funding from alternative bodies. The projects so far have been basic research projects that have great potential in the fight against cancer.
Current Collaborative Research Projects
Project: Immune Cell Genomic and Metabolic Profiling in Renal Cell Carcinoma
Dr. Kimryn Rathmell, M.D., Ph.D. – University of North Carolina
Dr. Benjamin Vincent, M.D. – University of North Carolina
The scientific collaborators have demonstrated that immune cells invade these kidney tumors, which suggests that the immune system attempts to attack the cancer and halt its growth. Their data indicates that, in many cases, the tumor wins its battle over the immune system because it continues to grow, despite the presence of the immune cells. By understanding precisely which immune cells invade the tumor, it is hoped that the ‘balance of power’ between the tumor and immune cells can be changed so that the patient’s own defence system can be made more efficient and hence destroy the malignancy. This is no easy task, as it is known that tumor cells can produce special molecules that inhibit the immune system. This is one way in which the tumor cells have learned to outwit the body’s defence mechanisms.
This project, funded by the Forbeck Foundation, has already resulted in scientific advances.
Drs. Vincent and Rathmell have published one scientific paper on their work, and others will follow shortly. The research carried out by the two investigators funded by the Foundation has been so fruitful that two post-doctoral fellows have recently been recruited to work on the program. The Foundation’s Scientific Advisory Board (SAB) has reviewed the one-year progress report presented by Drs. Vincent and Rathmell, and the SAB members are all delighted with their progress. This is exactly the type of collaborative grant that we set out to fund, and the project has all the characteristics of one that will grow into something substantial in the future.
Project: Comprehensive Structure-Function Analysis of Mutant IDH
Dr. Julie-Aurore Losman, M.D., Ph.D. – Dana-Farber Cancer Institute
Dr. Cory Johannessen, Ph.D. – The Broad Institute of MIT
The pathways by which cells break down sugars and convert them to energy have been well known for many years. Recently, scientists have realized that the process of energy generation in the cell is far more complicated than we had imagined. One of the proteins involved in this process is called isocitrate dehydrogenase. Errors in the structure of this protein have been found in certain tumors, such as glioblastoma (a brain tumor) and acute myeloid leukemia (a blood borne cancer). These changes can impact the proteins functionally and this may further contribute to the malignant process. When the mutated protein malfunctions, it can cause changes in the cells' DNA that contribute to the emergence of malignant cells.
Drs Losman and Johannessen are comprehensively mapping mutations in the gene that encodes the isocitrate dehydrogenase protein. The aim is to determine which mutations lead to the generation of a malignant cell type. This is a major piece of research, which involves complex molecular technologies that the two groups have great expertise in. Progress in the first year has been excellent, with both groups meeting their research goals. The Foundation’s SAB is extremely pleased with the progress that Drs Losman and Johannessen have made.
Identifying Epigenetic Vulnerabilities in Pre-Malignant Hematopoietic Stem Cells
Dr. Grant Challen, Ph.D. - Washington University
Dr. Christpopher Vakoc, Ph.D. - Cold Spring Harbor Laboratory
Dr. Challen and Dr. Vakoc will be working together to identify the genetic mutations that can lead to the development of certain blood borne malignancies. The DNA that makes up our genetic material is the blueprint that controls cell division and enables cells to perform their specific functions. During our lifetime, cells divide over and over again. Exposure to various toxic agents throughout our lives damages our DNA: these changes are called mutations. The presence of mutations in the genome can have serious medical consequences, such as the development of malignancies. Cancers are more common in older people, possibly due to the accumulated burden of genetic changes. Damage to our DNA may be a random event or it may occur at specific sites within the cell’s genome. If one or more mutation affects the production of key proteins that control cell division, this can lead to the uncontrolled production of cells, which is a simplified description of cancer. It is hoped that the mutated proteins identified will become targets for novel drug-based therapies. If their research is successful, they may be able to devise new therapeutic strategies for patients with these life threatening cancers.