It is not the regenerative potential of neural stem cells that interests Donghong Zhao, Ph.D. Instead, Zhao — a postdoctoral fellow in the laboratory of Karen Aboody, M.D. — is more intrigued by the stem cells’ attraction to malignant tumors and how they migrate specifically to cancer cells.
The American Association for Cancer Research (AACR) and the American Brain Tumor Association (ABTA) have recognized this deep interest, and both recently funded her studies in the field. The grants will allow Zhao to continue her ongoing research into the attraction of neural stem cells to tumors as well as the cells’ usefulness in delivering anticancer therapies directly to tumor sites.
“Dr. Zhao is an exceptionally capable and devoted scientist who has significantly broadened the scope of our investigations related to stem cell mediated tumor-selective gene delivery,” said Aboody, assistant professor in the divisions of Hematology & Hematopoietic Cell Transplantation and Neurosciences. “I believe her studies investigating the role of hypoxia in stem cell targeting of tumor sites have significant clinical implications for optimizing stem cell based therapies of brain tumors and metastatic cancers.”
Zhao is the first recipient of the AACR-National Brain Tumor Foundation Fellowship and was granted a one-year, $40,000 award to support her studies on hypoxia, or low oxygen levels, and stem cell migration.
The fellowship was established in honor of Bonnie Brooks, who died of brain cancer. It was creatively funded by her daughter, Karen Brooks, who raised money by accepting pledges and donations to climb Mt. Everest. When she reached the summit, she planted a small flag bearing the picture of her mother to commemorate the moment and her success. AACR matches funds she raises dollar for dollar. (To read her story, visit www.firstgiving.com/kbb.)
Zhao explained that oxygen levels are directly related to how strongly neural stem cells migrate to tumors, according to the lab’s earlier studies in neuroblastoma and current work in glioma and breast carcinoma. “My goal is to identify the specific signaling pathways involved in this process,” she said, “and investigate the role hypoxia has in directing the migration of neural stem cells.”
Zhao also received the ABTA Basic Research Fellowship, a two-year $80,000 award, for related research. She seeks to into optimize the use of neural stem cells in delivering targeted therapeutics to gliomas.
The targeted therapy works this way: It relies on a certain enzyme to convert a prodrug — which is an inactive or less active form of a drug — into an effective chemotherapeutic agent. Neural stem cells, which converge on tumors, would be engineered to express the converting enzyme. After the patient receives the prodrug, the enzyme would metabolize the drug into an active form of chemotherapy directly at the tumor site.
“Neural stem cells could serve as a vehicle for targeted delivery of therapeutic agents directly to the invasive tumor cells, sparing the surrounding brain tissue and potentially minimizing side effects,” said Zhao.
She added that ths form of therapy “may also improve delivery of a given therapeutic to hypoxic tumor regions, which are often poorly accessible by current treatments.”
Aboody noted that since neural stem cells show an affinity for invasive cancer cells, this therapy has potential for broader applications to other metastatic solid tumors beyond those in the brain. Zhao already is contributing to new studies of targeted neural stem cell therapy for breast cancer under way in collaboration with the laboratory of Carlotta Glackin, Ph.D., associate professor in the Division of Molecular Biology.
The grants are a testimony to the work’s potential, and Zhao is honored by the recognition. Said Zhao: “I have been engaged in cancer research for over 10 years and truly see it as my lifetime career.”