Douglas E. Feldman, PhD

TitleAssistant Professor of Research Pathology
InstitutionUniversity of Southern California
AddressHMR 2011 Zonal Ave
Health Sciences Campus
Los Angeles CA 90089-9092
Phone+1 323 442 3121
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    Collapse Biography 
    Collapse Education and Training
    Harvard College, Cambridge, MA. A.B. Magna cum laude Biochemistry
    Stanford University, Stanford, CA.Ph.DMolecular Cell Biology

    Collapse Overview 
    Collapse Overview
    Major Areas of Research Interest
    1. Our laboratory studies DNA base modifications and their erasure in the control of gene expression in stem cells and cancer. Our efforts extend to two distinct DNA modification systems: i) erasure of DNA cytosine methylation through Tet-oxidized 5-methylcytosine intermediates; and ii) DNA adenine-N6 methylation (6mA), a previously unrecognized form of DNA modification in mammals. We are particularly interested in understanding how writers, sensors and erasers of these marks modulate gene control in embryonic stem cells, and how this process goes awry in cancers such as myeloid leukemia. We use a combination of protein biochemistry, mouse genetics and next-generation sequencing strategies (MeDIP-seq, RNA-seq, RRBS-seq) to address these questions.

    We also seek to uncover previously unknown regulators of DNA base modifications in human cells by interrogating bacterial and phage restriction- and counter-restriction associated genes through a bioinformatics pipeline to identify candidate human orthologs.

    2. Protein engineering and synthetic signaling pathways
    A major focus of our research is the design and construction of controllable, synthetic signaling systems. We apply the design principles of synthetic biology and directed evolution of native protein sensors of modified DNA bases to create controllable signaling modules with user-defined inputs and outputs. These engineered signaling modules are being tested in a range of cell-based therapeutic applications.

    Categories: Gene Control, Stem Cells, Cancer, Epigenetics, and DNA Methylation

    Collapse Research 
    Collapse Research Activities and Funding
    Robert E. and May R. Wright Foundation Trust
    James H. Zumberge Faculty Research and Innovation Fund
    Keck School of Medicine of USC, Dean's Pilot Funding Program

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Kweon SM, Zhu B, Chen Y, Aravind L, Xu SY, Feldman DE. Erasure of Tet-Oxidized 5-Methylcytosine by a SRAP Nuclease. Cell Rep. 2017 Oct 10; 21(2):482-494. PMID: 29020633.
      View in: PubMed
    2. Feldman DE, Chen C, Punj V, Machida K. The TBC1D15 oncoprotein controls stem cell self-renewal through destabilization of the Numb-p53 complex. PLoS One. 2013; 8(2):e57312. PMID: 23468968; PMCID: PMC3584131.
    3. Feldman DE, Chen C, Punj V, Tsukamoto H, Machida K. Pluripotency factor-mediated expression of the leptin receptor (OB-R) links obesity to oncogenesis through tumor-initiating stem cells. Proc Natl Acad Sci U S A. 2012 Jan 17; 109(3):829-34. PMID: 22207628; PMCID: PMC3271911.
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