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
Heyde A, Rohde D, McAlpine CS, Zhang S, Hoyer FF, Gerold JM, Cheek D, Iwamoto Y, Schloss MJ, Vandoorne K, Iborra-Egea O, Muñoz-Guijosa C, Bayes-Genis A, Reiter JG, Craig M, Swirski FK, Nahrendorf M, Nowak MA, Naxerova K Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis. Cell. 2021;184:1-14 - PMID: 33636128 - DOI: 10.1016/j.cell.2021.01.049
Chen IX, Newcomer K, Pauken KE, Juneja VR, Naxerova K, Wu MW, Pinter M, Sen DR, Singer M, Sharpe AH, Jain RK A bilateral tumor model identifies transcriptional programs associated with patient response to immune checkpoint blockade. Proc Natl Acad Sci U S A. 2020;117(38):23684-23694 - PMID: 32907939 - PMCID: PMC7519254 - DOI: 10.1073/pnas.2002806117
Reiter JG, Hung WT, Lee IH, Nagpal S, Giunta P, Degner S, Liu G, Wassenaar ECE, Jeck WR, Taylor MS, Farahani AA, Marble HD, Knott S, Kranenburg O, Lennerz JK, Naxerova K Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases. Nat Genet. 2020;52(7):692-700 - PMID: 32451459 - PMCID: PMC7343611 - DOI: 10.1038/s41588-020-0633-2
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