Our lab’s research spans a variety of topics in cancer genetics and somatic evolution. We use interdisciplinary approaches to study the origins and consequences of somatic variation. We blend computational analysis, experimental work and mathematical modeling - whatever it takes!
We are interested in understanding how processes of mutation and selection in normal (stem) cells set the stage for cancer evolution over long periods of time. Then, once a tumor develops, how does tissue-specific selection shape the cancer genome? How can we take advantage of genetic intra-tumor heterogeneity to gain insights into the life history of a cancer? Finally, the evolution of metastasis is a particular focus of the lab. Do metastases arise from distinct clones with special, genetically encoded properties or do they represent random samples of the primary tumor? Does metastatic spread happen early or late in tumor development? Do all metastases arise independently from the primary tumor, or do they give rise to each other? How heterogeneous are metastases?
The answers to the questions above have important clinical implications but are difficult to study in human patients because it is challenging to reconstruct occult events that happened years before diagnosis. We have developed genetic techniques to determine the clonal architecture and lineage of cancer cells in human specimens and collaborate with clinicians in utilizing these tools to further our understanding of cancer evolution.
- Experimental investigation and mathematical modeling of somatic evolution in normal tissues and cancers
- Cancer phylogenetics
- Metastasis evolution
- High-throughput genetic screening
- Integrative data analysis
Leong SP, Naxerova K, Keller L, Pantel K, Witte M Molecular mechanisms of cancer metastasis via the lymphatic versus the blood vessels. Clin Exp Metastasis. 2021;:ePub - PMID: 34767139 - DOI: 10.1007/s10585-021-10120-z
Naxerova K, Di Stefano B, Makofske JL, Watson EV, de Kort MA, Martin TD, Dezfulian M, Ricken D, Wooten EC, Kuroda MI, Hochedlinger K, Elledge SJ Integrated loss- and gain-of-function screens define a core network governing human embryonic stem cell behavior. Genes Dev. 2021;35(21-22):1527-1547 - PMID: 34711655 - PMCID: PMC8559676 - DOI: 10.1101/gad.349048.121
Zhang Y, Kohrn BF, Yang M, Nachmanson D, Soong TR, Lee IH, Tao Y, Clevers H, Swisher EM, Brentnall TA, Loeb LA, Kennedy SR, Salk JJ, Naxerova K, Risques RA PolyG-DS: An ultrasensitive polyguanine tract-profiling method to detect clonal expansions and trace cell lineage. Proc Natl Acad Sci U S A. 2021;118(31):ePub - PMID: 34330826 - PMCID: PMC8346827 - DOI: 10.1073/pnas.2023373118
Ferraro GB, Ali A, Luengo A, Kodack DP, Deik A, Abbott KL, Bezwada D, Blanc L, Prideaux B, Jin X, Possada JM, Chen J, Chin CR, Amoozgar Z, Ferreira R, Chen I, Naxerova K, Ng C, Westermark AM, Duquette M, Roberge S, Lindeman NI, Lyssiotis CA, Nielsen J, Housman DE, Duda DG, Brachtel E, Golub TR, Cantley LC, Asara JM, Davidson SM, Fukumura D, Dartois VA, Clish CB, Jain RK, Vander Heiden MG Fatty acid synthesis is required for breast cancer brain metastasis. Nat Cancer. 2021;2(4):414-428 - PMID: 34179825 - PMCID: PMC8223728 - DOI: 10.1038/s43018-021-00183-y
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