Rice bioengineering graduate student Manuela Sushnitha has been selected for a 2018 Ruth L. Kirschstein National Research Service Award (NRSA) by the National Cancer Institute to develop a biomimetic nanotherapy that attacks cancer stem cells.
Triple-negative breast cancer (TNBC) remains a clinical and therapeutic challenge, because of its stem-cell like phenotype and ability to produce lineages of aggressive cancer cells that drive metastases.
â€śMuch of the decline in death rates associated with other subtypes of breast cancer has been due to the development of therapies that target the estrogen, progesterone and HER2 receptors,â€ť said Sushnitha, who is in her third-year of doctoral studies in bioengineering. â€śIn contrast, patients diagnosed with TNBC have not benefited from these targeted treatments because the biomarker profile of this specific cancer is not the same.â€ť
In addition, Sushnitha explains, â€śThe aggressiveness of TNBC has been attributed to the presence of breast cancer stem cells â€“ a population of tumor initiating cells that reside within the tumor and are highly resistant to conventional chemotherapy and radiation.â€ť
Sushnitha is jointly advised by Houston Methodist Professor Ennio Tasciotti and Rice University Assistant Professor Omid Veiseh. She received her B.S. in biomedical engineering from the Georgia Institute of Technology where she conducted research in Associate Professor Susan Thomasâ€™ laboratory developing microfluidic-based devices for nanoparticle drug delivery testing.
Although a targeted therapy specific to TNBC remains to be developed, Sushnitha says recent research has focused on understanding the role of the Janus kinase (JAK) and STAT3 signaling pathway in supporting the growth of these breast cancer stem cells and driving TNBC metastasis.
Using this knowledge, she will use her NRSA Fellowship to apply immunoengineering techniques to develop a nanoparticle that integrates the proteins found on the membranes of leukocytes, or white blood cells, as a means to the target these particles to the tumor, while encapsulating inhibitory drugs against the JAK/STAT3 pathway to reduce the cancer stem cell population within the tumor.
Sushnitha and her advisors will also work with Houston Methodist breast medical oncology specialist Jenny Chang, who is also the Emily Herrmann Chair in Cancer Research and director of the Houston Methodist Cancer Center, to develop a patient-derived model of TNBC to further evaluate the success of the drug delivery system and its ability to overcoming barriers posed by the bodyâ€™s immune system.
Kirschstein NRSA fellows are selected after rigorous peer-review and scoring of the proposed work by a panel of established and senior scientists. Students are selected various stages of their education by the National Institutes of Health, which is made up of 27 different institutional components. The program honors the late Kirschstein for her pioneering research, which led to the development of improved, safer polio vaccines.