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The Johns Hopkins Kimmel Cancer Center earned $3.1 million, one of the largest amounts awarded, from the National Institutes of Health (NIH) share of stimulus funding. The awards represent two of just 35 NIH administrative supplement grants made across the country with funding received through the American Recovery and Reinvestment Act (ARRA). It is supporting recruitment of talented new faculty to the Kimmel Cancer Center.
When ARRA funding availability was announced by the NIH, Cancer Center leadership and senior investigators canvassed the Johns Hopkins Medical Institutions for cancer-related research proposals. Three projects from three different departments, radiation oncology and molecular radiation sciences, pharmacology, and oncology, were submitted, and two were selected by NIH.
“The new grants represent what we consider the perfect formula for advancing cancer discovery—adequate funding and varied expertise of gifted researchers and clinicians,” says William Nelson, M.D., Ph.D., Marion I. Knott professor and director of the Kimmel Cancer Center. “The addition of bright young investigators across many scientific disciplines is vital to the ongoing success of our Cancer Center. These new faculty grants are truly reflective of the comprehensive status of our Center and our multidepartmental approach to better understanding and treating cancer.”
The ARRA funding has allowed the Kimmel Cancer Center to recruit two new faculty members and support novel research focused on some of the most common and lethal cancers, including lung, prostate, and pancreatic cancers.
Phuoc Tran, M.D., Ph.D., comes to the department of radiation oncology and molecular radiation sciences from Stanford University Medical Center and is using a special mouse model to develop molecularly targeted drug and radiation therapies for lung cancer and prostate cancer.
Unlike traditional chemotherapy and radiation treatment, molecularly targeted therapies are specific to molecules important for cancer cells, and as a result, are more effective against cancer and less toxic to normal cells and tissue. Using these unique mouse models, Tran is able to turn cancer-associated genes on and off, evaluating the genes’ impact on cancer behavior. He can activate specific lung cancer genes in mice that cause the development of lung cancer, and then turn the genes off to see what effect they have on the tumor. If a tumor stops growing or begins to shrink it indicates that a gene would be a good target for therapy. “The model allows us to simulate what would happen in humans if we used a therapy to block a particular gene,” says Tran.
In addition, Tran is working with John Wong, Ph.D., who has developed new technologies and experimental tumor models in conformal radiation therapy, a technology that creates a 3-dimensional image of tumors so that the highest possible dose of radiation can be delivered precisely and directly to the cancer without harming surrounding normal tissue. Tran’s goal is to combine molecularly targeted drug therapy with targeted radiation therapy to improve lung cancer survival rates.
Trans also is using his mouse model to better understand a gene pathway known as EMT that is hijacked by cancer cells to help them develop and invade other tissues. The EMT pathway also has been linked to the development of scar tissue in the lungs, a late occurring side effect of lung cancer treatment known as pulmonary fibrosis. Deciphering the mechanisms of this pathway could lead to more effective and safer therapies for lung cancer and help clinicians prevent long-term and dangerous side effects of cancer treatment.
In prostate cancer, he is using similar mouse models to study a phenomenon known as oncogene addiction, in which researchers suspect that tumors become dependent on the activation of cell growth-promoting genes known as oncogenes for their survival and growth. Tran uses his mouse models to observe the effects on prostate tumors when these oncogenes are turned off. If oncogene addiction is proven in his studies, compounds that block the oncogenes would represent potential new molecularly targeted therapies for prostate cancer.
“Dr. Tran is a wonderful addition to Johns Hopkins, whose presence significantly augments the expanding research and clinical faculty in radiation oncology,” says Theodore DeWeese, director of the department of radiation oncology and molecular radiation sciences. “This successful grant application is an example of how the senior leaders of the Kimmel Cancer Center work together to enhance and advance cancer initiatives throughout multiple departments.”
An ARRA grant also is supporting the pancreatic cancer research of Lei Zheng, M.D., Ph.D., a new member of the department of oncology gastro-intestinal cancer program and cancer immunology program. In first ever studies, Zheng is investigating a new gene called Annexin 2. Researchers believe it makes pancreatic cancers spread. In laboratory studies, Zheng has found that Annexin 2 causes pancreatic cancer cells to undergo a biological change to take on the characteristics of cancer stem cells, treatment-resistant cells believed to fuel the growth and spread of cancer. Specifically, in so-called “knockout models” where Zheng is able to activate and deactivate the gene in the laboratory, he found that it was key to promoting cancer cells to spread from the pancreas to the liver. Therapeutically, Zheng hopes that using a monoclonal antibody to inhibit the gene, may help stop the spread of pancreatic cancer. He is currently studying several antibodies in mouse models.
Zheng also is working with the pancreatic cancer vaccine team to better understand how the immune system responds to the vaccine. A small number of patients were vaccinated two weeks prior to surgery, jumpstarting their immune systems and then allowing, for the first time, doctors to see and begin to understand exactly what the immune systems does in the pancreas. At surgery, the patients had developed collections of lymphoid or immune cells in the pancreas resembling a lymph node. “We can now see firsthand how the immune system behaves, get pathological studies of the lymphoid aggregates, and understand the immune reaction in the pancreas so that we can make immunotherapy work better,” says Elizabeth Jaffee, M.D., Ph.D., co-director of the cancer immunology program and gastro-intestinal cancer program.
“The new faculty appointments of Tran and Zheng will help the Kimmel Cancer Center fulfill its translational research mission and help uncover new therapies and move them rapidly to the clinical setting,” says Nelson. “ Their work is representative of the strength and depth of our Cancer Center initiatives which span the Johns Hopkins Medical Institutions.”