Photo of Kamila Naxerova,  PhD

Kamila Naxerova, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 643-8446


naxerova.kamila@mgh.harvard.edu

Kamila Naxerova, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Radiology, Harvard Medical School
  • Principal Investigator, Center for Systems Biology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Naxerova lab is mainly interested in somatic evolution. We are using a variety of systems-level approaches to study the origins and consequences of somatic variation, blending computational and high-throughput wet lab methods. Our main focus is carcinogenesis. We are interested in understanding how processes of mutation and selection in normal (stem) cells set the stage for cancer evolution. 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? We are particularly interested in the evolution of metastasis. 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? The answers to these questions 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

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  • 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 2015. 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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