David H. Spencer, M.D., Ph.D.

Assistant Professor
Internal Medicine
Oncology

Molecular Genetics and Genomics Program
Developmental, Regenerative and Stem Cell Biology Program
Computational and Systems Biology Program

  • 314 273-0739

  • 8007

  • dspencer@wustl.edu

  • My research program studies epigenetic gene regulation in cancer, with a specific emphasis on understanding how mutations in acute myeloid leukemia (AML) perturb the epigenome to alter gene expression and cause leukemia.

Research Abstract:

My research to date has focsed on human genetics and genomics, cancer genomics, and clinical nextgeneration
sequencing for the detection of disease-causing mutations. I used early next-generation
sequencing instruments to sequence genomes from a range of species, including bacteria, nematodes, and
humans, and I coauthored one of the first studies using capture-hybridization enrichment to sequence a specific locus in the human genome to search for disease-causing mutations in a Mendelian disease. I was also involved in the development, validation, implementation and interpretation of a clinical next-generation sequencing-based test for somatic mutations in cancer. My scientific focus now involves the genomics and biology of acute myeloid leukemia. I have coauthored a study exploring the patterns of gene expression and methylation in primary AML samples in response to decitabine treatment and studying the unique functional properties of subclones in AML, and lead studies of DNA methylation in primary AML samples with mutations in the de novo methyltransferase DNMT3A, and of the patterns of HOX gene expression, DNA methylation, and chromatin structure in primary AML samples that provided new insights into the regulation of these genes in hematopoiesis and AML. My current research interests involve studying the genetic and epigenetic regulatory mechanisms controlling HOX gene expression in normal and malignant hematopoiesis, and using model systems to understand how common cancer mutations in epigenetic pathway genes alter the epigenome and gene expression to cause cancer. I am currently devoting 80% of my professional time to pursing these research projects, with the remaining time spent directing the CLIA sequencing lab at the McDonnell Genome Institute.

Selected Publications:

Klco JM*, Spencer DH*, Lamprecht TL, Sarkaria SM, Wylie T, Magrini V, et al. Genomic impact of
transient low-dose decitabine treatment on primary AML cells. Blood. 2013 Feb;121(9):1633–43. PMCID:
PMC3587326

Klco JM*, Spencer DH*, Miller CA, Griffith M, Lamprecht TL, O`Laughlin M, et al. Functional heterogeneity
of genetically defined subclones in acute myeloid leukemia. Cancer Cell. 2014 Mar;25(3):379–92. PMCID:
PMC3983786

Russler-Germain DA, Spencer DH, Young MA, Lamprecht TL, Miller CA, Fulton R, et al. The R882H
DNMT3A Mutation Associated with AML Dominantly Inhibits Wild-Type DNMT3A by Blocking Its Ability to
Form Active Tetramers. Cancer Cell. 2014 Apr;25(4):442–54. PMID: 24656771

Spencer DH, Young MA, Lamprecht TL, Helton NM, Fulton R, O`Laughlin M, Fronick C, Magrini V,
Demeter RT, Miller CA, Klco JM, Wilson RK, Ley TJ. Epigenomic analysis of the HOX gene loci reveals
mechanisms that may control canonical expression patterns in AML and normal hematopoietic cells.
Leukemia. 2015 Jun;29(6):1279-89. doi: 10.1038/leu.2015.6. Epub 2015 Jan 20. PubMed PMID:
25600023; PubMed Central PMCID: PMC4456213.

Klco JM, Miller CA, Griffith M, Petti A, Spencer DH, Ketkar-Kulkarni S, Wartman LD, Christopher M,
Lamprecht TL, Helton NM, Duncavage EJ, Payton JE, Baty J, Heath SE, Griffith OL, Shen D, Hundal J,
Chang GS, Fulton R, O`Laughlin M, Fronick C, Magrini V, Demeter RT, Larson DE, Kulkarni S, Ozenberger
BA, Welch JS, Walter MJ, Graubert TA, Westervelt P, Radich JP, Link DC, Mardis ER, DiPersio JF, Wilson
RK, Ley TJ. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute
Myeloid Leukemia. JAMA. 2015 Aug 25;314(8):811-822. doi: 10.1001/jama.2015.9643. PubMed PMID:
26305651. PMCID: PMC4621257

Spencer DH, Russler-Germain DA, Ketkar-Kulkarni S, Helton NM, Lamprecht TL, Fulton RS, Fronick CC,
O’Laughlin M, Heath SE, Shinawi M, Westervelt P, Payton JE, Wartman LD, Welch JS, Wilson RK, Walter
MJ, Link DC, DiPersio JF, Ley TJ. CpG island hypermethylation mediated by DNMT3A is a consequence of
AML progression. Cell. in press

Last Updated: 8/2/2017 3:42:41 PM

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