- Advisers: Stephen J. Russell, M.D., Ph.D., and Evanthia Galanis, M.D.
- Areas of emphasis: Oncolytic virotherapy and gene therapy
- Research areas: 1. Engineering the sodium iodide symporter for enhanced vector-mediated imaging capabilities, and 2. Designing oncolytic virotherapies for glioblastoma
What are your research interests?
One of my projects focuses on the sodium iodide symporter (NIS). NIS is a potent tool for imaging animals and humans. The gene can be delivered by viral vectors, such as measles, vesicular stomatitis virus and adeno-associated virus, to any tissue in the organism where the virus replicates.
NIS primarily functions to concentrate iodine in the thyroid but also transports technetium, tetrafluoroborate and several other substrates. Radioactive isotopes of these substrates allow for imaging with positron emission tomography (PET), single-photon emission computerized tomography (SPECT) and MRI.
Viral infection and replication in infected tissues, such as tumors, can be imaged and tracked by detecting NIS substrate uptake in the whole organism. However, systemic administration of the isotopes causes a problem: Endogenous NIS expressed in the thyroid, salivary glands, stomach and breast tissue also takes up the isotope and reduces the resolution with which sites of interests can be imaged.
My project focuses on directed evolution of the NIS transporter to be resistant to NIS inhibitors such as perchlorate and to preferentially uptake one substrate over another. With endogenous NIS inhibited, the vector-delivered inhibitor-resistant NIS will exclusively concentrate the radioisotope, allowing for clearer images and enhanced image resolution, aiding in the detection, tracking and treatment of disease.
My other project is centered on glioblastoma, the most aggressive and common form of brain cancer in adults. The five-year survival rate was less than 3 percent prior to the introduction of temozolomide (TMZ), and it now stands at less than 10 percent.
The current course of treatment consists of surgery, along with TMZ treatment and radiation therapy. This treatment route is complicated by several factors: tumor location, tumor infiltration into the surrounding brain tissue and MGMT promoter demethylation, which protects the tumor from TMZ.
Patients have few options for treatment, especially in the event of recurrence, which is generally inevitable. The cancer itself is marked by widespread invasiveness, angiogenesis, tumor necrosis, resistance to therapy, immune shielding, dense extracellular matrix composition and a significant ability to self-renew.
A major problem for effective glioblastoma treatment is that the effects of MGMT promoter demethylation and TMZ resistance are clinically relevant. DNA repair is upregulated in response to treatment and is especially active in recurrent tumors. Reduced expression of DNA repair proteins has been shown to reverse TMZ resistance and radioresistance, even in demethylated MGMT tumors. Several microRNAs have been shown to target these repair proteins and reverse TMZ resistance and radioresistance.
My project seeks to incorporate microRNAs and NIS into oncolytic herpes simplex virus 1 (oHSV-1) and oncolytic measles vectors to improve treatment sensitivity in glioblastoma.
Why did you choose Mayo Clinic Graduate School of Biomedical Sciences' Virology and Gene Therapy track?
When I was a junior in college, I fell in love with the idea of oncolytic virotherapy. To me, it represented a brilliant way to use nature's weapons against one of society's greatest enemies: cancer.
I only applied to graduate programs that had faculty working on oncolytic virotherapy. During my interview, I saw that Mayo had the highest concentration of high-caliber oncolytic virotherapists of any institution. Taking into account the amazing art-filled campus, the top-of-the-line technology available to students, ensured funding for five years and personable faculty, my decision was easy.
I am very happy with my choice. My experience so far has been more than I could have hoped for, and I look forward to continuing my education here.
Nov. 17, 2015