K-T Varley

Assistant Professor of Oncological Sciences

K-T Varley

B.S. Cornell University

Ph.D. Washington University School of Medicine

Research

References

kt.varley@hci.utah.edu

K-T Varley's Lab Page

K-T Varley's PubMed Literature Search

Molecular Biology Program

Genomics, Breast Cancer, Epigenetics, Gene Regulation, DNA methylation, Biomarkers, CRISPR, Ovarian Cancer, Cancer Immunotherapy, Cancer Immunology

Research

Genomic technology has revolutionized our ability to study the molecular defects that occur in cancer. We use next-generation sequencing assays and computational analysis to study the gene expression, transcription factor binding and DNA methylation patterns in breast cancer. Our goals are to answer fundamental questions about how epigenetic gene regulation is disrupted in cancer cells, and to discover pathways and biomarkers that have a more immediate impact on breast cancer treatment. Our projects involve the development of new molecular methods and bioinformatics approaches to explore the cancer genome and translate our discoveries into clinical tools that improve patient care. 

Specific projects in the lab include:

  1. Developing epigenome engineering / genome editing tools to test whether the DNA methylation defects we observe across patient’s tumors are sufficient to induce tumor formation and whether they are necessary for tumor cell proliferation.
  2. Investigating novel transcripts that we have identified in RNA-seq data from patients’ tumors to determine how these uncharacterized RNAs are associated with disease progression and resistance to therapy. These novel transcripts include new long non-coding RNAs and fusion transcripts.
  3. Exploring the role of transcription factors in driving the gene expression programs that cause cancer and metastasis. These studies include identifying transcription factors responsible for the gene expression signatures that we observe in cancer, and performing functional assays to determine if inhibiting these factors stops tumor cell proliferation, migration and invasion.
  4. Developing non-invasive biomarker tests to detect circulating tumor DNA in patients’ blood plasma, and determining how sensitive and specific these tests are for detecting resistance to therapy and disease progression in patients.
  5. Analyzing genomic data collected from patients enrolled in clinical drug trials to identify genomic signatures in their tumors that predict response to therapy. This project includes the development of clinical-scale biomarker tests that can be used to selectively enroll patients in subsequent trials who are most likely to respond to therapy.

References

  1. Forero A, Li Y, Chen D, Grizzle WE, Updike KL, Merz ND, Downs-Kelly E, Burwell TC, Vaklavas C, Buchsbaum DJ, Myers RM, LoBuglio AF, Varley KE (2016). Expression of the MHC Class II Pathway in Triple-Negative Breast Cancer Tumor Cells Is Associated with a Good Prognosis and Infiltrating Lymphocytes. Cancer Immunol Res, 4(5), 390-9. PMCID: PMC4878913
  2. Forero-Torres A, Varley KE, Abramson VG, Li Y, Vaklavas C, Lin NU, Liu MC, Rugo HS, Nanda R, Storniolo AM, Traina TA, Patil S, Van Poznak CH, Nangia JR, Irvin WJ Jr, Krontiras H, De Los Santos JF, Haluska P, Grizzle W, Myers RM, Wolff AC (2015). Translational Breast Cancer Research Consortium (TBCRC). TBCRC 019: A Phase II Trial of Nanoparticle Albumin-Bound Paclitaxel with or without the Anti-Death Receptor 5 Monoclonal Antibody Tigatuzumab in Patients with Triple-Negative Breast Cancer. Clin Cancer Res, 21(12), 2722-9.
  3. Varley KE, Gertz J, Roberts BS, Davis NS, Bowling KM, Kirby MK, Nesmith AS, Oliver PG, Grizzle WE, Forero A, Buchsbaum DJ, LoBuglio AF, Myers RM (2014). Recurrent read-through fusion transcripts in breast cancer. Breast Cancer Res Treat, 146(2), 287-97. PMCID: PMC4085473
  4. Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE, Pauli-Behn F, Cross MK, Williams BA, Stamatoyannopoulos JA, Crawford GE, Absher DM, Wold BJ, Myers RM (2013). Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res, 23(3), 555-67. PMCID: PMC3589544
  5. Wang H, Maurano MT, Qu H, Varley KE, Gertz J, Pauli F, Lee K, Canfield T, Weaver M, Sandstrom R, Thurman RE, Kaul R, Myers RM, Stamatoyannopoulos JA (2012). Widespread plasticity in CTCF occupancy linked to DNA methylation. Genome Res, 22(9), 1680-8. PMCID: PMC3431485
  6. Gertz J, Varley KE, Davis NS, Baas BJ, Goryshin IY, Vaidyanathan R, Kuersten S, Myers RM (2012). Transposase mediated construction of RNA-seq libraries. Genome Res, 22(1), 134-41. PMCID: PMC3246200
  7. ENCODE Project Consortium (2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489(7414), 57-74.
  8. Gertz J*, Varley KE*, Reddy TE, Bowling KM, Pauli F, Parker SL, Kucera KS, Willard HF, Myers RM (2011). Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation. PLoS Genet, 7(8), e1002228. PMCID: PMC3154961
  9. Varley KE, Mitra RD (2010). Bisulfite Patch PCR enables multiplexed sequencing of promoter methylation across cancer samples. Genome Res, 20(9), 1279-87. PMCID: PMC2928506
  10. Varley KE, Mutch DG, Edmonston TB, Goodfellow PJ, Mitra RD (2009). Intra-tumor heterogeneity of MLH1 promoter methylation revealed by deep single molecule bisulfite sequencing. Nucleic Acids Res, 37(14), 4603-12. PMCID: PMC2724279
  11. Varley KE, Mitra RD (2008). Nested Patch PCR enables highly multiplexed mutation discovery in candidate genes. Genome Res, 18(11), 1844-50. PMCID: PMC2577855

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Last Updated: 11/2/16