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Kathleen Burns, MD, PhD


Oncologic Pathology

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Physician

  • Chair, Department of Oncologic Pathology, Dana-Farber Cancer Institute

Contact Information

  • Office Phone Number857-215-0216

Bio

Dr. Burns is a physician-scientist and practicing hematopathologist. Her research laboratory studies roles transposable elements play in human disease. Her lab was one of the first to develop a targeted method for amplifying mobile DNA insertion sites in the human genome, and show that these are a significant source of structural variation (Cell, 2010). Her group continues to characterize these understudied sequences in genomes and to describe the expression and genetic stability of interspersed repeats in normal and malignant tissues.

The lab has described the overexpression of Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) in a wide array of human cancers (American Journal of Pathology, 2014). They have mapped somatically-acquired LINE-1 insertion sites incurred during the evolution of pancreatic ductal adenocarcinomas (Nature Medicine, 2015) and ovarian cancers (Proceedings of the National Academy of Sciences, 2017). The lab has ongoing projects focused on the functional consequences of inherited mobile element insertions (Proceedings of the National Academy of Sciences, 2017) and LINE-1 expression in cancers (Nature Structural and Molecular Biology, 2020).

Dr. Burns has authored reviews on human transposons (Cell, 2012), their activities in cancer (Nature Reviews Cancer, 2017), and their impact on gene expression (Nature Reviews Genetics, 2019). She has organized several national and international meetings in the field, and has been continuously funded by the National Institutes of Health for her research.

Dr. Burns received her M.D., Ph.D. from Baylor College of Medicine. She completed a clinical pathology (CP) residency and hematopathology fellowship at Johns Hopkins School of Medicine, and thereafter joined the faculty and progressed through the academic ranks to Professor. She served as Vice Chair for Research in the Pathology Department and Director of the Physician Scientist Training Program at Johns Hopkins. She was recruited to Dana-Farber as Chair of the Department of Oncologic Pathology in 2020.

Fellowship:

  • Johns Hopkins School of Medicine

Residency:

  • Johns Hopkins School of Medicine

Medical School:

  • Baylor College of Medicine

Recent Awards:

  • American Society for Clinical Investigation (ASCI) – 2018
  • Scriver Family Visiting Professorship in Genetic Medicine, McGill University – 2019

Research

     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.

Research Departments:

Location

Dana-Farber Cancer Institute
450 Brookline Avenue
Jimmy Fund JF-220
Boston, MA 02215
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