As a member of Dr Sebti lab, the focus of my work was in understanding the biology of mutant (mt) KRAS driven cancers and why some tumors rely on oncogenic activity of mt KRAS, i.e., are addicted to KRAS, whereas other mt KRAS tumors are less dependent on KRAS. Using integrative analyses of CRISPR/Cas9 derived cancer cell sensitivity data and gene expression profiles of mt KRAS human cancer cell lines, my work led to the identification of a novel 30-gene transcriptome signature “KDS30” that predicts mt KRAS addiction, poor patient prognosis and drug response.

Subsequently, we have filed a provisional application for a patent on KDS30.

I am a Co-Investigator on 2 NIH NCI R01 grant applications which are build upon the work related to the derivation of KDS30:

• "Dissecting mechanisms of mutant KRAS dependency in human cancers" (re-submitted in July 2021)

• "KRAS dependency signature and drug response to KRAS G12C inhibitors sotorasib and adagrasib" (submitted in October 2021)

We are preparing this work for publication:

"Novel mutant KRAS addiction signature predicts prognosis and drug response to the combination of ERBB and MEK inhibitors in lung and pancreatic cancers." Tyc KM, Ranjan A, Kazi A, Wang R, Sebti SM. (Under review)

Check out my work on Hi-C data analysis guidelines here and all the scripts necessary to reproduce the results from this work here. I was also helping out with scRNA-seq data analysis. You can find the related scripts for scRNAseq data analysis, from the alignment step to the actual exploratory analysis here.

While at Rutgers University at the Department of Genetics I investigated genetic causes that predispose to aneuploid conceptions among IVF patients. Supported with WES data we were able to identify high risk genetic variants that drive mal-segregation of chromosomes during female meiosis.

Representative work:

• Tyc KM*, Yakoubi El W*, Bag A, Tao X, Landis J, Zhan Y, Treff N, Scott RT Jr., Schindler K, Xing J. (Hum Reprod. 2020) Exome sequencing links variants in centrosomal genes to maternally-derived aneuploid conception risk.

• Tyc KM, McCoy RC, Schindler K, Xing J. (PNAS 2020) Mathematical modeling of human oocyte aneuploidy.

• Tyc KM*, Wong A*, Scott RT Jr, Tao X, Schindler K, Xing J. (Lab Invest. 2021) Analysis of DNA variants in miRNAs and miRNA 3'UTR binding sites in female infertility patients.

* equal contribution

While at University of Utah and University of Toronto I dived into next-generation sequencing data analysis. During this time, I also gained experience with worms and basic molecular biology techniques (WB, qRT-PCR, etc.).

Related work:

• Reich DP, Tyc KM, Bass BL. C. elegans ADARs antagonize silencing of cellular dsRNAs by the antiviral RNAi pathway. Genes & development. 2018; 32(3-4):271-282. PMID: 29483152, PMCID: PMC5859968

• Tyc KM*, Nabih A*, Wu MZ*, Wedeles CJ, Sobotka JA, Claycomb JM. The Conserved Intron Binding Protein EMB-4 Plays Differential Roles in Germline Small RNA Pathways of C. elegans. Developmental cell. 2017; 42(3):256-270.e6. PMID: 28787592

* equal contribution

While at Humboldt University in Berlin, I used agent-based modeling to study host-pathogen interactions and ODE models to study the network dynamics of molecular interaction.

My doctoral research resulted in:

• Tyc KM, Herwald SE, Hogan JA, Pierce JV, Klipp E, Kumamoto CA. The game theory of Candida albicans colonization dynamics reveals host status-responsive gene expression. BMC systems biology. 2016; 10:20. PMID: 26927448, PMCID: PMC4772284

• Barros de Andrade E Sousa LC, Kühn C, Tyc KM, Klipp E. Dosage and Dose Schedule Screening of Drug Combinations in Agent-Based Models Reveals Hidden Synergies. Frontiers in physiology. 2016; 6:398. PMID: 26779031, PMCID: PMC4701919

• Tyc KM, Kühn C, Wilson D, Klipp E. Assessing the advantage of morphological changes in Candida albicans: a game theoretical study. Frontiers in microbiology. 2014; 5:41. PMID: 24567730, PMCID: PMC3915147

• Leach MD*, Tyc KM*, Brown AJ, Klipp E. Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans. PloS one. 2012; 7(3):e32467. PMID: 22448221, PMCID: PMC3308945

* equal contribution