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Promise and Progress - Greenberg Bladder Cancer Institute Awards First Research Grant

Promise & Progress - A Spectrum of Achievements

Greenberg Bladder Cancer Institute Awards First Research Grant

Date: January 15, 2015

L to R: Paul Rothman, Dean of the Johns Hopkins University School of Medicine, Erwin and Stephanie Greenberg.

A urine-based test for early detection and monitoring of bladder cancer and nanoparticles that can deliver chemotherapy drugs to bladder tissue are among the first projects awarded research grants by the Johns Hopkins Greenberg Bladder Cancer Institute.

The institute, which aims to develop new clinical strategies for combating bladder cancer through intensive, collaborative and innovative research, awards grants of up to $50,000 each year to encourage young investigators to take on research that advances the science and treatment of bladder cancer and to leverage existing resources and expertise.

“We’re very excited about these projects, which potentially could lead to novel therapies for bladder cancer, or to optimizing and characterizing existing therapies and improving their efficacy,” says William B. Isaacs, Ph.D., a genitourinary cancer expert and interim director of the Greenberg Institute.

The Johns Hopkins Greenberg Bladder Cancer Institute was established in May 2014, with a $15 million gift from Baltimore-area commercial real estate developer Erwin L. Greenberg and his wife, Stephanie Cooper Greenberg, along with a $30 million investment from The Johns Hopkins University.

The institute is the first of its kind in the world dedicated to advancing the scientific understanding of bladder cancer and improving its treatment. Its experts include multidisciplinary research teams from the Johns Hopkins Kimmel Cancer Center and faculty from the Johns Hopkins University School of Medicine’s Department of Radiation Oncology and Molecular Radiation Sciences, the James Buchanan Brady Urological Institute of The Johns Hopkins Hospital, and Johns Hopkins’ departments of Pathology and Surgery.

“Drawing upon the extraordinary resources available at Johns Hopkins and working with physicians at other world-class centers, the institute will continuously and rapidly elevate the state of the science in bladder cancer, moving ever closer toward the goals of preventing, effectively treating, and ultimately curing bladder cancer,” says Erwin Greenberg

The 2014 awardees and projects:

Trinity Bivalacqua, M.D., Ph.D.:  Bivalacqua’s project will investigate the development of nonadhesive, biodegradable nanoparticles loaded with chemotherapy and other solutions. His team will compare the effectiveness of these nanoparticles with standard ways of delivering chemotherapy in a mouse model of bladder cancer to determine whether nanoparticles better sustain delivery of chemotherapy into bladder tissue, preventing tumor recurrence and progression.

Charles Drake, M.D., Ph.D.: This study involves a catalogue of the sequences of RNA—strings of chemical letters that form the “readout” of DNA and help construct proteins—from bladder cancer samples of people with advanced disease.  Drake’s goal is 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 lead to discovery of new targets for cancer immunotherapy.

George Netto, M.D.: Netto 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.

Peter H. O’Donnell, M.D.: This study will test whether progressing bladder cancers acquire 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.

Armine Smith, M.D.:  This animal study will explore stimulation of a protein called TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), which kick starts the process of cell death, as a potential way to increase the effectiveness of BCG (Bacillus Calmette-Guerin), the main biological treatment for nonmuscle invasive bladder cancer. Investigators also will collect tissue from patients with bladder cancer to identify levels of TRAIL receptors before and after BCG treatment, then correlate them with treatment outcomes.

Dan Theodorescu, M.D., Ph.D.:  His research will investigate 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 also will study mice that do not express AGL to see if they are more susceptible to bladder cancer.