Ming Lei

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Assistant Professor, Biological Chemistry

Phone: 734.647.5839
leim@umich.edu

  • About

    Research Profile
    The goal of our laboratory is to understand the organization and dynamics of macromolecular assemblies important for genome regulation and stability. A combination of structural analyses, such as X-ray crystallography and electron microscopy, coupled with biophysical and biochemical experimentation, forms the core of our methodological approach. Active areas of investigation includes:

    (1). Telomere protection and regulation. Telomeres are higher order nucleoprotein complexes that cap the ends of chromosomes and play essential roles in conferring genome stability and cell proliferation capacity in all eukaryotes. Changes in telomere functions and the associated chromosomal abnormalities have been implicated in human aging and cancer. Work from our group is revealing important information about the mechanisms of telomere organization and telomere end protection by a group of specialized telomeric proteins. We are now biochemically and structurally characterizing the interactions of these telomeric proteins, both individually and complexed with various targets, to better model their molecular activity.

    (2). We are searching small molecular inhibitors of the interaction between the single-stranded telomeric DNA and its binding protein POT1 using high-throughput chemical genomics approach. These small molecular inhibitors will provide insights into the interaction between POT1 and the telomeric ssDNA and address the feasibility of the POT1-ssDNA complex as a therapeutic target. We will biochemically characterize the interactions between the identified inhibitors and POT1. Using X-ray crystallography, we aim to understand how the inhibitors bind specifically to POT1 and to guide improvements in their binding affinity and specificity.

    (3). Molecular mechanism of histone dymethylase. Histone modifications mediate changes in gene expression by altering the chromatin structure or by serving as a binding platform to recruit other proteins. One such modification, histone methylation, was thought to be irreversible until recently when a new class of enzymes, lysine-specific histone demethylase (LSD1), was identified. LSD1 is a bona fide histone H3 lysine 4 and lysine 9 demethylase. Its activity and specificity is regulated by associated protein factors. In order to understand the molecular mechanisms of LSD1 enzymatic activity and regulation, we are determining the structures of LSD1 in complex with H3 peptide substrate and with small molecular inhibitors.

    PubMed Search Term: lei+m[au]+telomere

  • Education
    • B.S. Tsinghua University
    • M.Sc. McGill University
    • Ph.D. Harvard University
    • Postdoctoral, University of Colorado at Boulder
  • Awards
    • 1990 – 1994 Guanghua Scholarship – Tsinghua University
    • 1994 – Max Stern Scholarship – McGill University
    • 2001 Paul Sigler/Agouron Institute Fellow, Helen Hay Whitney
    • 2004 Biological Science Scholar – UM
    • 2006 American Cancer Society Scholar (ACS)
    • 2006 Sidney Kimmel Scholar
  • Selected Publications:
  • Articles