Photo of Kathleen H. Burns,  MD, PhD

Kathleen H. Burns, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (857) 215-0126

Kathleen H. Burns, MD, PhD

Dana-Farber Cancer Institute


  • Professor, Pathology, Harvard Medical School
  • Chair, Department of Pathology, Dana-Farber Cancer Institute



  • Deputy Associate Director, Shared Resources, Executive Committee
  • Member, Center Scientific Council

Research Abstract

The majority of our genome is highly repetitive sequence derived from the activities of self-propagating retrotransposons. My research focuses on roles these mobile genetic elements play in human disease. Despite their enormous impact on genome composition over evolutionary time and across virtually all eukaryotic taxa, transposons are often presumed to be inert, non-functional ‘junk DNA’, and I am one of few physician-scientists bridging this area of fundamental biology with biomedical research.

Specific types of transposons are active in modern humans, and my lab was one of the first to develop strategies to map insertion sites of these elements in the human genome. Our observations underscored that transposons are major sources of genetic structural variation in human populations (Cell, 2010). Over the next decade, catalogs of commonly-occurring mobile element insertion alleles grew, and my group led efforts to identify those variants that may be relevant to disease risk by integrating information about these insertions with findings of genome wide association studies (GWAS) (PNAS, 2017). We found scores of Alu insertions on haplotypes associated with risk for developing diseases, including the most common form of childhood cancer, precursor B-cell acute lymphoblastic leukemia (ALL) and the common autoimmune disease of the central nervous system, multiple sclerosis (MS). My group has since developed experimental systems to show that inherited transposable element insertion alleles can affect gene expression and mRNA splicing (NAR, 2019), demonstrating molecular mechanisms for how transposons may impact phenotypes. Together, these avenues of investigation have shown that we each inherit a unique compliment of transposon insertions – thousands of LINE-1, Alu, SVA, and ERV alleles – and that a specific subset of these sequences potentially affects our likelihood to develop disease. I have authored related reviews in Cell (2012) and Nature Reviews Genetics (2019).

My laboratory has also had a long-standing interest in transposable element expression in human malignancies. Many cancers undergo epigenetic changes that permit the expression of otherwise silenced transposable elements. Here, we are best known for our research on Long INterspersed Element-1 (LINE-1, L1), the only protein-coding retrotransposon active in modern humans. We were the first to develop and commercialize a monoclonal antibody to detect the LINE-1-encoded RNA-binding protein, open reading frame 1 protein (ORF1p). Using this reagent, we showed that LINE-1 expression is a hallmark of human cancers, including many of the most lethal of these diseases – lung, prostate, breast, colon, pancreatic, and ovarian cancers (Am J Path, 2014). We are exploring whether ORF1p has utility as a marker for cancer detection. We have shown that ORF1p expression is an indicator of LINE-1 activity as a mobile genetic element, i.e., cancers that express ORF1p have somatically-acquired insertions of genomic LINE-1 sequences that distinguish tumor genomes from a patient’s constitutional genetic make-up. I have led collaborations to map acquired LINE-1 insertion sites in pancreatic (Nature Medicine, 2015) and ovarian cancers (PNAS, 2017) at Johns Hopkins School of Medicine, and I have participated in larger efforts to identify somatically-acquired insertions as part of the International Cancer Genome Consortium (Nature Genetics, 2020). Together, these studies have shown that LINE-1 expression is commonplace in human cancers, and that it contributes to genome instability. I recently authored a review on this topic for Nature Reviews Cancer (2017).

We are now devoting significant efforts to understand implications of LINE-1 expression for cancer cell biology. We have found that non-transformed cells undergo a p53-dependent growth arrest when LINE-1 expression is forced, and that LINE-1 can induce interferon responses similar to those elicited by viral infection. In vitro studies in my lab show that in cells that mutate p53 and other tumor suppressor genes, LINE-1 enhances the relative growth advantage gained by those mutations. Meanwhile, LINE-1 expression makes p53-deficient cells especially vulnerable to loss of replication-coupled DNA repair pathways, and DNA-damaging chemotherapies (Nature Structural and Molecular Biology, 2020). Together, these findings indicate that LINE-1 expression may promote cancerous transformation, and that in transformed cells, retrotransposition may conflict with DNA replication in a manner that can be exploited for cancer therapeutics. Ultimately, we aim to leverage this understanding of LINE-1 biology to inform approaches to cancer treatment.

Publications from Harvard Catalyst Profiles

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  • Mendez-Dorantes C, Burns KH. LINE-1 retrotransposition and its deregulation in cancers: implications for therapeutic opportunities. Genes Dev 2023; 37:948-967. PubMed
  • Baldwin ET, van Eeuwen T, Hoyos D, Zalevsky A, Tchesnokov EP, Sánchez R, Miller BD, Di Stefano LH, Ruiz FX, Hancock M, Işik E, Mendez-Dorantes C, Walpole T, Nichols C, Wan P, Riento K, Halls-Kass R, Augustin M, Lammens A, Jestel A, Upla P, Xibinaku K, Congreve S, Hennink M, Rogala KB, Schneider AM, Fairman JE, Christensen SM, Desrosiers B, Bisacchi GS, Saunders OL, Hafeez N, Miao W, Kapeller R, Zaller DM, Sali A, Weichenrieder O, Burns KH, Götte M, Rout MP, Arnold E, Greenbaum BD, Romero DL, LaCava J, Taylor MS. Structures, functions, and adaptations of the human LINE-1 ORF2 protein. Nature 2023. PubMed
  • Jazaeri AA, Grisham R, Knisely A, Spranger S, Zamarin D, Hillman RT, Lawson BC, Burns KH, Lee S, Westin SN, Moiso E, Williams MJ, Bardhan NM, Pisanic T, Matulonis U, Weigelt B, Shih I, Konstantinopoulos PA, Gaillard S, Wang L, Aghajanian C, D'Andrea AD, Hammond P, Shah S, Wucherpfennig KW, Lu KH. Transforming ovarian cancer care by targeting minimal residual disease. 2023; 4:755-760. PubMed
  • Cheng KCL, Frost JM, Sánchez-Luque FJ, García-Canãdas M, Taylor D, Yang WR, Irayanar B, Sampath S, Patani H, Agger K, Helin K, Ficz G, Burns KH, Ewing A, García-Pérez JL, Branco MR. Vitamin C activates young LINE-1 elements in mouse embryonic stem cells via H3K9me3 demethylation. Epigenetics Chromatin 2023; 16:39. PubMed
  • Chu C, Lin EW, Tran A, Jin H, Ho NI, Veit A, Cortes-Ciriano I, Burns KH, Ting DT, Park PJ. The landscape of human SVA retrotransposons. Nucleic Acids Res 2023. PubMed
  • Taylor MS, Wu C, Fridy PC, Zhang SJ, Senussi Y, Wolters JC, Cajuso T, Cheng WC, Heaps JD, Miller BD, Mori K, Cohen L, Jiang H, Molloy KR, Chait BT, Goggins MG, Bhan I, Franses JW, Yang X, Taplin ME, Wang X, Christiani DC, Johnson BE, Meyerson M, Uppaluri R, Egloff AM, Denault EN, Spring LM, Wang TL, Shih IM, Fairman JE, Jung E, Arora KS, Yilmaz OH, Cohen S, Sharova T, Chi G, Norden BL, Song Y, Nieman LT, Pappas L, Parikh AR, Strickland MR, Corcoran RB, Mustelin T, Eng G, Yilmaz OH, Matulonis UA, Skates SJ, Rueda BR, Drapkin R, Klempner SJ, Deshpande V, Ting DT, Rout MP, LaCava J, Walt DR, Burns KH. Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker. 2023. PubMed
  • AlJabban A, Paik H, Aster JC, Berliner N, Brouillard J, Brown JR, Burns KH, Castillo JJ, Card J, Dal Cin P, DeAngelo DJ, Dorfman DM, Ebert BL, Garcia JS, Jacobson CA, Lakhani H, Laubach JP, Ligon AH, Lindeman NI, Lindsley RC, Lovitch SB, Luskin MR, Morgan EA, Nowak A, Petrides A, Pinkus GS, Pozdnyakova O, Steensma DP, Stone RM, Weinberg OK, Winer ES, Kim AS. Optimization of Advanced Molecular Genetic Testing Utilization in Hematopathology: A Goldilocks Approach to Bone Marrow Testing. JCO Oncol Pract 2023. PubMed
  • Kanholm T, Rentia U, Hadley M, Karlow JA, Cox OL, Diab N, Bendall ML, Dawson T, McDonald JI, Xie W, Crandall KA, Burns KH, Baylin SB, Easwaran H, Chiappinelli KB. Oncogenic Transformation Drives DNA Methylation Loss and Transcriptional Activation of Transposable Element Loci. Cancer Res 2023. PubMed
  • Sato S, Gillette M, de Santiago PR, Kuhn E, Burgess M, Doucette K, Feng Y, Mendez-Dorantes C, Ippoliti PJ, Hobday S, Mitchell MA, Doberstein K, Gysler SM, Hirsch MS, Schwartz L, Birrer MJ, Skates SJ, Burns KH, Carr SA, Drapkin R. LINE-1 ORF1p as a candidate biomarker in high grade serous ovarian carcinoma. Sci Rep 2023; 13:1537. PubMed
  • Tao J, Wang Q, Mendez-Dorantes C, Burns KH, Chiarle R. Frequency and mechanisms of LINE-1 retrotransposon insertions at CRISPR/Cas9 sites. Nat Commun 2022; 13:3685. PubMed
  • Rajurkar M, Parikh AR, Solovyov A, You E, Kulkarni AS, Chu C, Xu KH, Jaicks C, Taylor MS, Wu C, Alexander KA, Good CR, Szabolcs A, Gerstberger S, Tran AV, Xu N, Ebright RY, Van Seventer EE, Vo KD, Tai EC, Lu C, Joseph-Chazan J, Raabe MJ, Nieman LT, Desai N, Arora KS, Ligorio M, Thapar V, Cohen L, Garden PM, Senussi Y, Zheng H, Allen JN, Blaszkowsky LS, Clark JW, Goyal L, Wo JY, Ryan DP, Corcoran RB, Deshpande V, Rivera MN, Aryee MJ, Hong TS, Berger SL, Walt DR, Burns KH, Park PJ, Greenbaum BD, Ting DT. Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer. 2022. PubMed
  • McKerrow W, Wang X, Mendez-Dorantes C, Mita P, Cao S, Grivainis M, Ding L, LaCava J, Burns KH, Boeke JD, Fenyö D. LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint. Proc Natl Acad Sci U S A 2022. PubMed
  • Rotter LK, Berisha N, Hsu HT, Burns KH, Andreou C, Kircher MF. Visualizing surface marker expression and intratumoral heterogeneity with SERRS-NPs imaging. Nanotheranostics 2022; 6:256-269. PubMed
  • Ardeljan D, Steranka JP, Liu C, Li Z, Taylor MS, Payer LM, Gorbounov M, Sarnecki JS, Deshpande V, Hruban RH, Boeke JD, Fenyö D, Wu PH, Smogorzewska A, Holland AJ, Burns KH. Cell fitness screens reveal a conflict between LINE-1 retrotransposition and DNA replication. Nat Struct Mol Biol 2020; 27:168-178. PubMed
  • Rodriguez-Martin B, Alvarez EG, Baez-Ortega A, Zamora J, Supek F, Demeulemeester J, Santamarina M, Ju YS, Temes J, Garcia-Souto D, Detering H, Li Y, Rodriguez-Castro J, Dueso-Barroso A, Bruzos AL, Dentro SC, Blanco MG, Contino G, Ardeljan D, Tojo M, Roberts ND, Zumalave S, Edwards PAW, Weischenfeldt J, Puiggròs M, Chong Z, Chen K, Lee EA, Wala JA, Raine K, Butler A, Waszak SM, Navarro FCP, Schumacher SE, Monlong J, Maura F, Bolli N, Bourque G, Gerstein M, Park PJ, Wedge DC, Beroukhim R, Torrents D, Korbel JO, Martincorena I, Fitzgerald RC, Van Loo P, Kazazian HH, Burns KH, , Campbell PJ, Tubio JMC, . Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition. Nat Genet 2020; 52:306-319. PubMed
  • Ardeljan D, Wang X, Oghbaie M, Taylor MS, Husband D, Deshpande V, Steranka JP, Gorbounov M, Yang WR, Sie B, Larman HB, Jiang H, Molloy KR, Altukhov I, Li Z, McKerrow W, Fenyö D, Burns KH, LaCava J. LINE-1 ORF2p expression is nearly imperceptible in human cancers. Mob DNA 2020; 11:1. PubMed