PI Career Goals

Throughout my doctoral studies, I have gained tremendous expertise in molecular biology techniques to better understand the molecular mechanism of tumorigenesis and metastasis of lethal cancers. I had a particular interest in pediatric cancers and thus, joined Dr. Meredith Irwin’s laboratory at The Hospital for Sick Children, a world-renowned research hospital. Although I have been working to dissect the molecular mechanisms of complex biological processes such as invasion and metastasis that involve basic science, I always had an eye toward translating my findings into the clinic. With this in mind, along with my desire to continue studying cancer biology in the context of pediatric cancer, I have joined Dr. Kimberly Stegmaier’s laboratory at the Dana-Farber Cancer Institute (DFCI). Dr. Stegmaier is a leader in the field of pediatric cancer biology, and her laboratory is dedicated to understanding the precise molecular mechanism underlying diseases to develop rationale therapeutics. Dr. Stegmaier and I have developed a comprehensive mentoring plan for me to achieve maximal potential for my research. This mentoring plan includes weekly meetings with Dr. Stegmaier to discuss my project’s progress and receive scientific input, attending and presenting at weekly Stegmaier laboratory meetings as well as bi-weekly joint lab meetings with laboratories of Drs. Scott Armstrong and Benjamin Ebert, taking courses such as bioinformatics courses to gain additional skill sets for analyzing data, attending and presenting at local and international scientific meetings, and to utilize rich scientific resources (both personal and technical) at DFCI, Harvard Medical School, and Broad Institute of Harvard/MIT. My ultimate career goal is to become a successful independent researcher in an academic university or research hospital.

Scientific Objective and Rationale

Current therapies for patients with Ewing sarcoma is a combination of cytotoxic chemotherapy, surgery, and radiation, and this has not changed in over a decade. Despite the fact that we know the driver oncogene for the disease, EWS/FLI, there are no targeted therapies against this target. This is due to the structural nature of the EWS/FLI protein that prevents traditional medicinal chemistry to develop small-molecule inhibitors. The proposed research for this Horizon Award aims to characterize the function of TRIM8, a potential novel regulator of EWS/FLI protein expression. TRIM8 is an E3 ligase that has an enzymatic activity which can be readily targeted by small-molecules. Thus, in-depth characterization of the mechanism by which TRIM8 regulates EWS/FLI allow us to gain more insights into how EWS/FLI protein levels are regulated and potentially develop targeted therapeutics against TRIM8 to indirectly target EWS/FLI protein. This will help patients with Ewing sarcoma, especially those who are unresponsive to current therapies, with a novel targeted therapy that directly inhibits the key oncogenic protein with less toxicity. In addition, this proposed project will open up new avenues for scientific community to target other fusion-oncoproteins that drive cancers such as MLL-AF9 fusion oncoprotein in acute myeloid leukemia (AML).

Benefit to Service Members and Families

Pediatric cancers are rare relative to adult cancers; however, thousands of children die of cancer every year, and there is a tremendous unmet clinical need in treatment. Due to the rarity of pediatric cancers, the pharmaceutical companies have less incentive to invest their effort into these cancers, because small markets are unprofitable. With the research training I have received, together with the opportunity that the Horizon Award will support, I will invest my research effort into discovering new therapeutic targets for pediatric cancers such as Ewing sarcoma. My ultimate goal is to translate new scientific knowledge in pediatric cancer biology into clinical care of patients to extend the survival of children with cancers and to increase their quality of life.