Photo of Kamila Naxerova,  PhD

Kamila Naxerova, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone:


Kamila_Naxerova@hms.harvard.edu

Kamila Naxerova, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Genetics, Harvard Medical School
  • Assistant Professor, Genetics, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Naxerova 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.

Publications from Harvard Catalyst Profiles

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  • Hulsmans M, Schloss MJ, Lee IH, Bapat A, Iwamoto Y, Vinegoni C, Paccalet A, Yamazoe M, Grune J, Pabel S, Momin N, Seung H, Kumowski N, Pulous FE, Keller D, Bening C, Green U, Lennerz JK, Mitchell RN, Lewis A, Casadei B, Iborra-Egea O, Bayes-Genis A, Sossalla S, Ong CS, Pierson RN, Aster JC, Rohde D, Wojtkiewicz GR, Weissleder R, Swirski FK, Tellides G, Tolis G, Melnitchouk S, Milan DJ, Ellinor PT, Naxerova K, Nahrendorf M. Recruited macrophages elicit atrial fibrillation. Science 2023; 381:231-239. PubMed
  • Janizek JD, Dincer AB, Celik S, Chen H, Chen W, Naxerova K, Lee SI. Uncovering expression signatures of synergistic drug responses via ensembles of explainable machine-learning models. Nat Biomed Eng 2023; 7:811-829. PubMed
  • Küçükköse E, Laoukili J, Gorelick AN, Degner S, Lacle M, van den Bent L, Peters NA, Verheem A, Hung WT, Frenkel NC, Wassenaar E, Lansu N, Lenos KJ, Vermeulen L, Koopman M, Roodhart JML, Kops GJPL, Borel Rinkes IHM, Hagendoorn J, Naxerova K, Kranenburg O. Lymphatic invasion of plakoglobin-dependent tumor cell clusters drives formation of polyclonal lung metastases in colon cancer. Gastroenterology 2023. PubMed
  • Datta M, Chatterjee S, Perez EM, Gritsch S, Roberge S, Duquette M, Chen IX, Naxerova K, Kumar AS, Ghosh M, Emblem KE, Ng MR, Ho WW, Kumar P, Krishnan S, Dong X, Speranza MC, Neagu MR, Iorgulescu JB, Huang RY, Youssef G, Reardon DA, Sharpe AH, Freeman GJ, Suvà ML, Xu L, Jain RK. Losartan controls immune checkpoint blocker-induced edema and improves survival in glioblastoma mouse models. Proc Natl Acad Sci U S A 2023; 120:e2219199120. PubMed
  • 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. PubMed
  • 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. Author Correction: B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis. Nat Immunol 2022. PubMed
  • 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; 23:605-618. PubMed
  • Rohde D, Vandoorne K, Lee IH, Grune J, Zhang S, McAlpine CS, Schloss MJ, Nayar R, Courties G, Frodermann V, Wojtkiewicz G, Honold L, Chen Q, Schmidt S, Iwamoto Y, Sun Y, Cremer S, Hoyer FF, Iborra-Egea O, Muñoz-Guijosa C, 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. PubMed
  • Cheek DM, Naxerova K. Mapping the long road to cancer. Cell 2022; 185:939-940. PubMed
  • Gorelick AN, Naxerova K. Mutational clocks tick differently across species. Nature 2022; 604:435-436. PubMed
  • 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. PubMed
  • 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; 35:1527-1547. PubMed
  • 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. PubMed
  • 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. 2021; 2:414-428. PubMed
  • 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. PubMed
  • Naxerova K. Mutation fingerprints encode cellular histories. Nature 2021; 597:334-336. PubMed
  • 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; 117:23684-23694. PubMed
  • Naxerova K. Defining the role of lymph node metastasis in systemic breast cancer evolution. EBioMedicine 2020; 57:102852. PubMed
  • Naxerova K. Clonal competition in a confined space. Nat Genet 2020; 52:553-554. PubMed
  • 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. PubMed
  • Hoyer FF, Zhang X, Coppin E, Vasamsetti SB, Modugu G, Schloss MJ, Rohde D, McAlpine CS, Iwamoto Y, Libby P, Naxerova K, Swirski FK, Dutta P, Nahrendorf M. Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes. Circulation 2020. PubMed
  • Hoyer FF, Naxerova K, Schloss MJ, Hulsmans M, Nair AV, Dutta P, Calcagno DM, Herisson F, Anzai A, Sun Y, Wojtkiewicz G, Rohde D, Frodermann V, Vandoorne K, Courties G, Iwamoto Y, Garris CS, Williams DL, Breton S, Brown D, Whalen M, Libby P, Pittet MJ, King KR, Weissleder R, Swirski FK, Nahrendorf M. Tissue-Specific Macrophage Responses to Remote Injury Impact the Outcome of Subsequent Local Immune Challenge. Immunity 2019; 51:899-914.e7. PubMed
  • Frodermann V, Rohde D, Courties G, Severe N, Schloss MJ, Amatullah H, McAlpine CS, Cremer S, Hoyer FF, Ji F, van Koeverden ID, Herisson F, Honold L, Masson GS, Zhang S, Grune J, Iwamoto Y, Schmidt SP, Wojtkiewicz GR, Lee IH, Gustafsson K, Pasterkamp G, de Jager SCA, Sadreyev RI, MacFadyen J, Libby P, Ridker P, Scadden DT, Naxerova K, Jeffrey KL, Swirski FK, Nahrendorf M. Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells. Nat Med 2019; 25:1761-1771. PubMed
  • Heyde A, Reiter JG, Naxerova K, Nowak MA. Consecutive seeding and transfer of genetic diversity in metastasis. Proc Natl Acad Sci U S A 2019. PubMed
  • Chauhan VP, Chen IX, Tong R, Ng MR, Martin JD, Naxerova K, Wu MW, Huang P, Boucher Y, Kohane DS, Langer R, Jain RK. Reprogramming the microenvironment with tumor-selective angiotensin blockers enhances cancer immunotherapy. Proc Natl Acad Sci U S A 2019; 116:10674-10680. PubMed
  • Sack LM, Davoli T, Li MZ, Li Y, Xu Q, Naxerova K, Wooten EC, Bernardi RJ, Martin TD, Chen T, Leng Y, Liang AC, Scorsone KA, Westbrook TF, Wong KK, Elledge SJ. Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns. Cell 2018. PubMed
  • Hulsmans M, Sager HB, Roh JD, Valero-Muñoz M, Houstis NE, Iwamoto Y, Sun Y, Wilson RM, Wojtkiewicz G, Tricot B, Osborne MT, Hung J, Vinegoni C, Naxerova K, Sosnovik DE, Zile MR, Bradshaw AD, Liao R, Tawakol A, Weissleder R, Rosenzweig A, Swirski FK, Sam F, Nahrendorf M. Cardiac macrophages promote diastolic dysfunction. J Exp Med 2018; 215:423-440. PubMed
  • Naxerova K, Reiter JG, Brachtel E, Lennerz JK, van de Wetering M, Rowan A, Cai T, Clevers H, Swanton C, Nowak MA, Elledge SJ, Jain RK. Origins of lymphatic and distant metastases in human colorectal cancer. Science 2017; 357:55-60. PubMed
  • Liu H, Naxerova K, Pinter M, Incio J, Lee H, Shigeta K, Ho WW, Crain JA, Jacobson A, Michelakos T, Dias-Santos D, Zanconato A, Hong TS, Clark JW, Murphy JE, Ryan DP, Deshpande V, Lillemoe KD, Fernandez-Del Castillo C, Downes M, Evans RM, Michaelson J, Ferrone CR, Boucher Y, Jain RK. Use of Angiotensin System Inhibitors Is Associated with Immune Activation and Longer Survival in Nonmetastatic Pancreatic Ductal Adenocarcinoma. Clin Cancer Res 2017. PubMed
  • Kodack DP, Askoxylakis V, Ferraro GB, Sheng Q, Badeaux M, Goel S, Qi X, Shankaraiah R, Cao ZA, Ramjiawan RR, Bezwada D, Patel B, Song Y, Costa C, Naxerova K, Wong CSF, Kloepper J, Das R, Tam A, Tanboon J, Duda DG, Miller CR, Siegel MB, Anders CK, Sanders M, Estrada MV, Schlegel R, Arteaga CL, Brachtel E, Huang A, Fukumura D, Engelman JA, Jain RK. The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation. Sci Transl Med 2017. PubMed
  • Hulsmans M, Clauss S, Xiao L, Aguirre AD, King KR, Hanley A, Hucker WJ, Wülfers EM, Seemann G, Courties G, Iwamoto Y, Sun Y, Savol AJ, Sager HB, Lavine KJ, Fishbein GA, Capen DE, Da Silva N, Miquerol L, Wakimoto H, Seidman CE, Seidman JG, Sadreyev RI, Naxerova K, Mitchell RN, Brown D, Libby P, Weissleder R, Swirski FK, Kohl P, Vinegoni C, Milan DJ, Ellinor PT, Nahrendorf M. Macrophages Facilitate Electrical Conduction in the Heart. Cell 2017; 169:510-522.e20. PubMed
  • Gupta N, Badeaux M, Liu Y, Naxerova K, Sgroi D, Munn LL, Jain RK, Garkavtsev I. Stress granule-associated protein G3BP2 regulates breast tumor initiation. Proc Natl Acad Sci U S A 2017; 114:1033-1038. PubMed
  • Askoxylakis V, Ferraro GB, Kodack DP, Badeaux M, Shankaraiah RC, Seano G, Kloepper J, Vardam T, Martin JD, Naxerova K, Bezwada D, Qi X, Selig MK, Brachtel E, Duda DG, Huang P, Fukumura D, Engelman JA, Jain RK. Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment. Journal of the National Cancer Institute 2016. PubMed
  • Dutta P, Sager HB, Stengel KR, Naxerova K, Courties G, Saez B, Silberstein L, Heidt T, Sebas M, Sun Y, Wojtkiewicz G, Feruglio PF, King K, Baker JN, van der Laan AM, Borodovsky A, Fitzgerald K, Hulsmans M, Hoyer F, Iwamoto Y, Vinegoni C, Brown D, Di Carli M, Libby P, Hiebert SW, Scadden DT, Swirski FK, Weissleder R, Nahrendorf M. Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells. Cell Stem Cell 2015; 16:477-87. PubMed
  • Naxerova K, Jain RK. Using tumour phylogenetics to identify the roots of metastasis in humans. Nat Rev Clin Oncol 2015. PubMed
  • Naxerova K, Elledge SJ. Taking the brakes off telomerase. Elife 2015. PubMed
  • Naxerova K, Brachtel E, Salk JJ, Seese AM, Power K, Abbasi B, Snuderl M, Chiang S, Kasif S, Jain RK. Hypermutable DNA chronicles the evolution of human colon cancer. Proc Natl Acad Sci U S A 2014. PubMed
  • Rogers MS, Novak K, Zurakowski D, Cryan LM, Blois A, Lifshits E, Bø TH, Oyan AM, Bender ER, Lampa M, Kang SY, Naxerova K, Kalland KH, Straume O, Akslen LA, Watnick RS, Folkman J, Naumov GN. Spontaneous reversion of the angiogenic phenotype to a nonangiogenic and dormant state in human tumors. Mol Cancer Res 2014. PubMed
  • Liu J, Liao S, Diop-Frimpong B, Chen W, Goel S, Naxerova K, Ancukiewicz M, Boucher Y, Jain RK, Xu L. TGF-β blockade improves the distribution and efficacy of therapeutics in breast carcinoma by normalizing the tumor stroma. Proc Natl Acad Sci U S A 2012; 109:16618-23. PubMed
  • Liu J, Liao S, Huang Y, Samuel R, Shi T, Naxerova K, Huang P, Kamoun W, Jain RK, Fukumura D, Xu L. PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer. Clin Cancer Res 2011; 17:3638-48. PubMed
  • Naxerova K,Bult CJ,Peaston A,Fancher K,Knowles BB,Kasif S,Kohane IS. Analysis of gene expression in a developmental context emphasizes distinct biological leitmotifs in human cancers. Genome Biol 2008; 9:R108. PubMed
  • Otu HH, Naxerova K, Ho K, Can H, Nesbitt N, Libermann TA, Karp SJ. Restoration of liver mass after injury requires proliferative and not embryonic transcriptional patterns. J Biol Chem 2007; 282:11197-204. PubMed
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