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  • Organization
    Washington University in St. Louis

  • Telephone
    314-935-8838

  • ORCID
    0000-0002-0285-3344

  • Address
    address1:1 Brookings Drive
    address2:Box 1137
    city:St Louis
    postal:63130
    region:Missouri
    country:US

  • Biography

    Hello! I’m Professor Doug Chalker. I joined the faculty of the Wash U Biology department in 2001. The courses that I teach focus on genetics, genomics, and molecular cell biology. These include an advanced laboratory course in which students perform original research.

    I am a married, cisgender male (pronouns: he/him/his; preferred name: Doug) who shares a house in University City with Debbie and two cats, Dextrose and Lola. I grew up in Southern California and completed my college education in the public University of California system (B.S. Biology – UC Riverside; PhD, Microbiology and Molecular Genetics – UC Irvine).

    After college, I moved to Seattle, WA to begin my post-doctoral research at the Fred Hutchinson Cancer Research Center. (This is also where I met Debbie, who also has a PhD in Molecular and Cellular Biology). I am a first generation college graduate and had no idea when I started in college that I would become a professor.  I am fortunate to get to continue to learn about biology with my students, both in the classroom and the research lab.

    In my research lab, we use molecular genetics and cell biology to uncover, and better understand, molecular mechanisms that operate within cells. Most of this research investigates the biology of a ciliated protozoan called Tetrahymena thermophila. Specifically, this research aims to understand the functional organization of eukaryotic genomes (how do cells pack one meter’s worth of DNA into each nucleus and still manage to read the information encoded). More recently, projects in the lab also aim to discover how cells develop elaborate structures that determine cellular shape and function.

     

    More about my laboratory research.

    The research of my laboratory aims to discover and characterize fundamental mechanisms that eukaryotes use to organize and maintain their genomes. These investigations focus on the genome-wide, programmed DNA rearrangements of the ciliated protozoan Tetrahymena thermophila, which remodel the developing somatic genome during development. Our work has helped establish that these DNA rearrangements are guided by small RNA-directed heterochromatin formation, which marks a third of the 150 Mbp germline-derived genome for elimination from the differentiating somatic chromosomes. We have identified key proteins that package the DNA to be eliminated into heterochromatin-like bodies and precisely define the boundaries of the excised heterochromatin. In addition, our research has revealed that DNA sequences present in the parental somatic genome, which are not directly inherited by progeny cells, can epigenetically regulate these DNA rearrangements. Our findings provide evidence that these genome-altering events evolved by modifying the roles of existing cellular machineries. Some novel proteins that we have characterized possess structures suggesting a transposon origin, which indicates that the very sequences that these DNA rearrangements target for elimination have, through evolution, contributed to the mechanism of their elimination. My lab continues to pursues two major research directions. One is to study the RNAi-related mechanism that Tetrahymena cells use to identify the regions of the genome that need to be silenced, directing specific heterochromatin modifications to those sequences during somatic genome differentiation. The other is to characterize the molecular machinery used to package loci into heterochromatin and subsequently eliminate them from the somatic genome. This proposal is based on our recent studies of Lia3, the first protein discovered that regulates the accuracy of DNA elimination. Lia3 binds to a guanine(G)-rich sequence that defines the boundaries of several loci, but only when that sequence forms a G quadruplex structure. We plan to elucidate how distal G-rich sequences can be brought together to form a non-canonical DNA structure that defines heterochromatin domains during development. While pursuing my research goals, I am committed to training the next generation of scientists at all levels. As a faculty member at Washington University, I have graduated six students from three different programs in the Division of Biology and Biological Sciences, who each earned their PhD’s through research in my laboratory. I currently serve on the steering committees for two graduate programs in: 1) Molecular Genetics and Genomics; and 2) Developmental, Regenerative & Stem Cell Biology and have served as a member of over 40 dissertation advisory committees. As a researcher/educator, I have developed curriculum that engages undergraduates in authentic research in the laboratory classroom. Student generated results have been published in peer-reviewed articles with enrolled students as authors. I use my time and energy to enhance a larger research community. I serve as a reviewer and/or editor for research journals and as a grant proposal panelist. In addition, I serve as a member of the Tetrahymena Research Advisor Board; I was elected to the inaugural term as President, serving from 2011-2013. The mission of the Board is to increase the impact a research performed using this important model organism. My expertise as a researcher and experience as an educator provide me with important insights that guide my mentorship of students at all levels as they prepare for future careers in science.


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