Natalie Davidson, MSc. UCLA Computer Science

PhD Student

+41 43 254 0224
Biomedical Informatics Group
Schmelzbergstrasse 26
8006 Zürich
SHM 26 B 3

I am interested in extending statistical models to gain deeper understanding of transcriptional dysregulation in cancer.

I am interested in understanding the role transcriptional dysregulation plays in cancer. Through my collaborations during my Ph.D., I have been able to conduct single cancer and pan-cancer analyses using RNA-Seq and Ribosome Profiling data. I typically use generalized linear models and generalized linear mixed models, but I am interested in extending to other models as the numbers of samples in cancer analyses grow. I am currently a part of the International Cancer Genome Consortium, where I integrate multiple transcriptional aberrations such as splicing, fusions, over/under expression, allele specific expression, and others in over 1,000 samples to identify cancer relevant genes and alteration patterns. I received my B.Sc. in computer science and minor in mathematics from University of California, Santa Barbara.  I received my M.Sc. in computer science from University of California, Los Angeles under the advisement of Dr. Jason Ernst. I am currently obtaining my Ph.D from Tri-Institutional Program for Computational Biology and Medicine in New York, while conducting research at ETH Zürich.

Abstract Translation initiation is orchestrated by the cap binding and 43S pre-initiation complexes (PIC). Eukaryotic initiation factor 1A (EIF1A) is essential for recruitment of the ternary complex and for assembling the 43S PIC. Recurrent EIF1AX mutations in papillary thyroid cancers are mutually exclusive with other drivers, including RAS. EIF1AX is enriched in advanced thyroid cancers, where it displays a striking co-occurrence with RAS, which cooperates to induce tumorigenesis in mice and isogenic cell lines. The C-terminal EIF1AX-A113splice mutation is the most prevalent in advanced thyroid cancer. EIF1AX-A113spl variants stabilize the PIC and induce ATF4, a sensor of cellular stress, which is co-opted to suppress EIF2α phosphorylation, enabling a general increase in protein synthesis. RAS stabilizes c-MYC, an effect augmented by EIF1AX-A113spl. ATF4 and c-MYC induce expression of aminoacid transporters and enhance sensitivity of mTOR to aminoacid supply. These mutually reinforcing events generate therapeutic vulnerabilities to MEK, BRD4 and mTOR kinase inhibitors.

Authors Gnana P. Krishnamoorthy, Natalie R Davidson, Steven D Leach, Zhen Zhao, Scott W. Lowe, Gina Lee, Iñigo Landa, James Nagarajah, Mahesh Saqcena, Kamini Singh, Hans-Guido Wendel, Snjezana Dogan, Prasanna P. Tamarapu, John Blenis, Ronald Ghossein, Jeffrey A. Knauf, Gunnar Rätsch and James A. Fagin

Submitted Cancer Discovery

Link DOI