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2014 Grant Recipients

The Greenberg Bladder Cancer Institute announced its first six research grant recipients in November 2014, four of which were renewed in 2015.

Grants were awarded for projects in the following research areas:

Cancer Genetics

Genetic Diversity of T Cell Receptors Impacting Antitumor Effects in Bladder Cancer

 
Peter O'Donnell, M.D.

Peter H. O’Donnell, M.D., assistant professor of medicine at the University of Chicago Medicine Comprehensive Cancer Center

O’Donnell’s study will test the idea that as some bladder cancers progress, they acquire certain mutations that may activate and expand the number of tumor-infiltrating T lymphocytes (TILs), white blood cells found in tumors that kill cancer cells. Investigators will look for genetic changes in TILs that predict robustness of immune responses against bladder cancer to see if they contribute to better recurrence-free and overall survival.

Immunotherapy

Dissecting the Phenotype of CD4 and CD8 Tumor-Infiltrating Lymphocytes in Advanced Bladder Cancer

 
Charles Drake, M.D., Ph.D.

Charles Drake, M.D., Ph.D., associate professor of oncology, urology and immunology at the Johns Hopkins University School of Medicine

Drake and others will catalog the sequences of RNA — strings of chemical letters that form the “read out” of DNA and help construct proteins — from bladder cancer samples of people with advanced disease. He aims to identify new and existing molecules on the surface of lymphocytes — white blood cells that penetrate tumors and kill cancer cells — that regulate how the immune system identifies and marks cancer cells for destruction. The findings could help discover new targets for cancer immunotherapy.

Pilot Study of TRAIL and BCG Combination Therapy in Bladder Cancer

 
Armine Smith, M.D.

Armine Smith, M.D., assistant professor of urology at the Johns Hopkins University School of Medicine

Smith’s study will see if stimulating a protein called TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), which kick-starts the process of cell death, will increase the effect of BCG (Bacillus Calmette-Guerrin), the main biological treatment for nonmuscle-invasive bladder cancer, in mice. Investigators also will collect tissue from patients with bladder cancer to identify levels of TRAIL receptors before and after BCG treatment, and correlate them with treatment outcomes.

Genetic Diversity of T Cell Receptors Impacting Antitumor Effects in Bladder Cancer

 
Peter O'Donnell, M.D.

Peter H. O’Donnell, M.D., assistant professor of medicine at the University of Chicago Medicine Comprehensive Cancer Center

O’Donnell’s study will test the idea that as some bladder cancers progress, they acquire certain mutations that may activate and expand the number of tumor-infiltrating T lymphocytes (TILs), white blood cells found in tumors that kill cancer cells. Investigators will look for genetic changes in TILs that predict robustness of immune responses against bladder cancer to see if they contribute to better recurrence-free and overall survival.

Biomarkers

TERT-Promoter Mutations Urine Assay for Early Detection and Monitoring of Bladder Cancer

 
Georges Netto, M.D.

Georges Netto, M.D., director of surgical pathology molecular diagnostics and professor of pathology, oncology and urology at the Johns Hopkins University School of Medicine

Netto’s project will continue work on a noninvasive, urine-based test to identify mutations in the “on-off switch” of a gene called telomerase reverse transcriptase (TERT), which is present in a range of bladder cancer precursor lesions. New experiments will determine how well a test for TERT mutations can detect bladder cancer in urine samples of individuals at high risk for bladder cancer, determine the utility of detecting TERT mutations among urine samples taken during follow-up of bladder cancer patients to monitor disease recurrence and see if it is worth expanding the test to include additional genetic mutations found in bladder cancer.

New Technologies

Nanomedicine Approaches for Improving Intravesical Delivery of Chemotherapeutic Agents

 
Trinity Bivalacqua, M.D., Ph.D.

Trinity Bivalacqua, M.D., Ph.D., associate professor of urology, surgery and oncology at the Johns Hopkins University School of Medicine and director of urologic oncology at the Johns Hopkins Kimmel Cancer Center

Bivalacqua and colleagues will develop nonadhesive, biodegradable nanoparticles loaded with chemotherapy and other solutions. They will compare the effectiveness of their nanoparticles with standard ways of delivering chemotherapy in a mouse model of bladder cancer. The hypothesis is that the nanoparticles will better sustain delivery of chemotherapy into bladder tissue, preventing tumor recurrence and progression.

Patient Care, Prevention and Screening

The Role of AGL, a Glycogen Debranching Enzyme in Bladder Cancer

 
Dan Theodorescu, M.D., Ph.D.

Dan Theodorescu, M.D., Ph.D., professor of urology and director of the University of Colorado Cancer Center

Theodorescu’s research will study the role of AGL, an enzyme that suppresses bladder tumor growth. Patients with metastatic bladder cancer have lower levels of AGL. Scientists will track levels of AGL and another enzyme called HAS2 to determine their correlation with patient outcomes. The researchers will also study mice that do not express AGL to see if they are more susceptible to bladder cancer.

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