AACR-Takeda Oncology Fellowships
The AACR-Takeda Oncology (formerly Millennium Pharmaceuticals) Fellowships represent a joint effort to promote and support mentored young investigators to conduct cancer research and to establish successful career paths in this field. Eligibility is limited to postdoctoral and clinical research fellows who will have completed their most recent doctoral degree within the past five years. The research proposed for funding may be basic, translational, clinical, or epidemiological in nature.
Metabolic reprogramming occurs during tumorigenesis; however, metabolic therapies to treat cancer are generally lacking. Cysteine has a crucial role in cancer proliferation and survival through the generation of multiple functional biomolecules to promote translation, redox homeostasis, bioenergetic processes, TCA cycle metabolism, and electron transport. Promisingly, Dr. Kang has found that NSCLC cells are highly dependent on cystine (oxidized cysteine), suggesting they may be vulnerable to an engineered and pharmacologically optimized enzyme to deplete systemic cyst(e)ine that was recently developed. However, the mechanism by which cysteine depletion impairs NSCLC viability is not well understood. Surprisingly, preliminary results indicate that cysteine limitation antagonizes serine metabolism and may induce serine dependency. Therefore, Dr. Kang proposes that cysteine starvation and the resulting reliance on serine metabolism in NSCLC leads to lethal consequences and that synergistic therapy targeting serine metabolism may increase anti-cysteine therapeutic efficacy.
Dr. Kang is currently a postdoctoral fellow in Dr. Gina DeNicola’s laboratory at Moffitt Cancer Center. He received his BS and PhD degrees from Seoul National University, College of Pharmacy. During his PhD studies, he received training in GC-MS and LC-MS based metabolomics and lipidomics technologies under the guidance of Dr. Sung Won Kwon. Now, applying these high-throughput techniques, he is exploring the role of metabolism during lung cancer progression mentored by Dr. DeNicola. Dr. Kang’s ultimate research goal is development of efficacious cancer therapy targeting cancer metabolism.
Acknowledgment of Support
I am greatly honored to receive the AACR-Takeda Oncology Lung Cancer Research Fellowship. This opportunity will greatly support me on my path to become an independent scientist, aiming towards the development of efficacious cancer therapy.
The histone methyltransferase NSD2 is overexpressed in 15-20 percent of multiple myeloma (MM) patients due to the t(4:14) chromosomal translocation. NSD2 overexpression in MM cells drives an oncogenic epigenetic and transcriptional program. Dr. Sobh will test the hypothesis that different genetic lesions commonly detected in MM differentially impact histone methylation and transcriptional profiles driven by NSD2 overexpression. He will generate and characterize several genetically-distinct t(4:14) MM cell lines where degradation of the rearranged NSD2 allele product can be selectively induced. RNAseq and H3K36/H3K27 methylation ChIPseq in the different NSD2-high and NSD2-low isogenic pairs will define key genes deregulated by NSD2 overexpression in the context of mutations recurrently found in MM. He will further perform genome-wide CRISPR-based loss-of-function screens to identify genetic liabilities and synthetic-lethal drug-gene interactions associated with NSD2 overexpression in MM cells. This work will provide better understanding of how NSD2 contributes to MM pathogenesis and reveal insight into novel molecular-based treatment options for t(4;14) MM.
Dr. Sobh is a postdoctoral researcher in the laboratory of Dr. Jonathan Licht at the University of Florida. He received a BSc in biochemistry from the Lebanese University, a MSc in biotechnology from the American University of Science and Technology, and a PhD in comparative biochemistry from the University of California, Berkeley. His research in graduate school focused on implementing functional genomics tools to study various cellular processes, including nutrient homeostasis as well as susceptibility to chemical carcinogens and chemotherapeutic agents. As a postdoctoral researcher, Dr. Sobh is studying the molecular consequences and vulnerabilities associated with NSD2 overexpression in multiple myeloma.
Acknowledgement of Support
Receiving the 2019 AACR-Takeda Oncology Myeloma Research Fellowship is a key milestone in establishing a career in cancer research. I am pleased and grateful to be a recipient of this fellowship that will provide support for my professional development to become an independent researcher in the field of hematologic malignancies.