Rana Sayroo

Mentor: Dr. Georgiy Aslanidi
Pediatrics
 
"After taking various labs for my required classes I realized I really enjoyed being and working in the lab . During my sophomore year I searched and emailed many different research labs in hopes of possibly getting a position. I was contacted by Georgiy Aslanidi and upon meeting him and listening to his research interests I was intrigued. Ever since joining the lab I have found that I am capable of doing many things I did not think I was capable of and I enjoy the topics that we focus on. "

Major

Biology

Minor

N/A

Research Interests

  • Gene therapy
  • Cancer research
  • AAV vector research

Academic Awards

  • University Scholars

Organizations

  • Indian Student Association
  • Alpha Kappa Delta Phi
  • Alpha Epsilon Delta

Volunteer

  • Shands Hospital

Hobbies and Interests

  • Dancing (bollywood)
  • Going to the gym
  • Playing the violin
  • Listen to music

Research Description

Development of the novel AAV-based vectors with selective tropism for human prostate cancer cells.
Background and significance: Cancer is a leading cause of human death worldwide. Commonly used methods of treatment such as surgery, radiation and chemotherapy tend to be largely successful but are extremely invasive and have serious toxic side effects. The possibility of manipulating viral genomes and the natural ability of viruses to efficiently infect various cell types has increased an interest in using a virus-based delivery system to express cytotoxic products within target cells. Thus, oncolotic viruses represent an attractive alternative to currently used anti-cancer treatments. Among different viral methods for gene delivery, vectors based on a human parvovirus, the adeno-associated virus (AAV), has attracted much attention mainly because of its non-pathogenic nature, and its ability to mediate long-term, sustained therapeutic gene expression. AAV vectors serve as a safe and efficient delivery vehicle and are currently used in a number of clinical trials, such as Parkinson`s disease, muscular dystrophy, and ocular diseases. I have recently identified one out of ten commonly used AAV serotypes being particularly effective in transduction of several human prostate cancer cell lines. However, the vector promiscuity makes it difficult to use in vivo. The recent studies in our lab on AAV crystal structure, combined with various site-directed and insertion mutagenesis studies of the capsid gene, have identified specific regions of the capsid proteins that are surface-exposed and tolerant to mutations. More specifically, incorporation of an Arg-Gly-Asp (RGD) containing peptide at specific sites enables AAV to infect integrin-expressing cells-independent of heparin sulfate proteoglycan (HSPG). Thus, this approach potentially can lead to the development of novel AAV vectors with selective tropism for cancer cells Specific aim: Optimization of the AAV capsid for selective transduction of human prostate cancer cell lines. In the currently proposed studies, we are planning to develop novel AAV-based vectors for selective targeting of human prostate cancer cells for the potential application as delivery vehicle of the cytotoxic transgene. Research design: 1. First, the ligand Arg-Gly-Asp (RGD) will be cloned into AAV6 capsid (Fig.1). As a result of the insertion of the particular ligand the novel chimeric capcid will produce AAV vectors with alternative cellular receptor usage and significantly increase the specificity of the virus to human prostate cancer cell. 2. Next, the efficiency novel AAV vector encoding a reporter gene such as firefly luciferase will be evaluated in human prostate cancer cell lines (LNcap, PC3 and DU145) in vitro. 3. Finally, human prostate cell will be engrafted to immune-deficient mice to develop tumor and then AAV-RGD vector will be injected to prove specificity.