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
McAlpine CS, Kiss MG, Zuraikat FM, Cheek D, Schiroli G, Amatullah H, Huynh P, Bhatti MZ, Wong LP, Yates AG, Poller WC, Mindur JE, Chan CT, Janssen H, Downey J, Singh S, Sadreyev RI, Nahrendorf M, Jeffrey KL, Scadden DT, Naxerova K, St-Onge MP, Swirski FK Sleep exerts lasting effects on hematopoietic stem cell function and diversity. J Exp Med. 2022;219(11):ePub - PMID: 36129517 - PMCID: PMC9499822 - DOI: 10.1084/jem.20220081
Schloss MJ, Hulsmans M, Rohde D, Lee IH, Severe N, Foy BH, Pulous FE, Zhang S, Kokkaliaris KD, Frodermann V, Courties G, Yang C, Iwamoto Y, Knudsen AS, McAlpine CS, Yamazoe M, Schmidt SP, Wojtkiewicz GR, Masson GS, Gustafsson K, Capen D, Brown D, Higgins JM, Scadden DT, Libby P, Swirski FK, Naxerova K, Nahrendorf M B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis. Nat Immunol. 2022;23(4):605-618 - PMID: 35352063 - PMCID: PMC8989652 - DOI: 10.1038/s41590-022-01165-7
Rohde D, Vandoorne K, Lee IH, Grune J, Zhang S, McAlpine CS, Schloss MJ, Nayar R, Courties G, Frodermann F, Wojtkiewicz G, Honold L, Chen Q, Schmidt S, Iwamoto Y, Sun Y, Cremer S, Hoyer FF, Iborra-Egea O, Muñoz-Guijosa C, Fei Ji F, Zhou B, Adams RH, Wythe JD, Hidalgo J, Watanabe H, Jung Y, van der Laan AM, Piek JJ, Kfoury Y, Désogère PA, Vinegoni C, Dutta P, Sadreyev RI, Caravan P, Bayes-Genis A, Libby P, Scadden DT, Lin CP Naxerova K, Swirski FK, Nahrendorf M Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease. Nat Cardiovasc Res. 2022;1:28–44 - PMID: 35747128 - PMCID: PMC9216333 - DOI: 10.1038/s44161-021-00002-8
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