Ph.D., University of Wisconsin-Madison, Molecular and Cellular Biology, 1986.
B.S., Ohio State University, Biochemistry, 1981.
HIV host cell interactions
This laboratory studies the regulatory and structural genes of the human immunodeficiency virus (HIV) in order to understand the molecular basis for its pathogenicity. Much of our focus is on identifying and characterizing host cell functions that are used to serve specific functions for viral replication and the evolution and function of intrinsic host defenses against retroviruses.
Intrinsic host defense: Primates have evolved a number of gene families that limit or restrict retroviral infections. In collaboraton with the lab of Harmit Malik at the FHCRC we are studying the evolution of function of these intrinsic anti-viral genes. We have found that some of these genes have been rapidly evolving throughout the history of primates and some have been under selective pressure in recent human history. We study how these genes function in humans and why they are or are not active against current viruses such as HIV.
HIV infection of non-dividing cells: HIV is unusual in its ability to infect non-dividing cells such as terminally differentiated macrophages. With most retroviruses, the cell must pass through mitosis for the viral DNA to enter the nucleus. However, HIV can enter the nucleus at any stage of the cell cycle. We are trying to understand events that occur immediately after the virus has entered the cell that allow HIV to subsequently enter the nucleus
(Reading, Writing, Speaking)
French: (Functional, Basic, Functional)
American Association for the Advancement of Science
American Society for Microbiology
American Society for Virology
Identification and antiviral activity of common polymorphisms in the APOBEC3 locus in human populations.. Virology. 443(2):329-37.. 2013.
An evolutionary perspective on the broad antiviral specificity of MxA.. Current opinion in microbiology.. 2013.
Gene loss and adaptation to hominids underlie the ancient origin of HIV-1.. Cell host & microbe. 14(1):85-92.. 2013.
Evolutionary toggling of Vpx/Vpr specificity results in divergent recognition of the restriction factor SAMHD1.. PLoS pathogens. 9(7):e1003496.. 2013.
Birth, decay, and reconstruction of an ancient TRIMCyp gene fusion in primate genomes.. Proceedings of the National Academy of Sciences of the United States of America. 110(7):E583-92.. 2013.
Antagonism of SAMHD1 is actively maintained in natural infections of simian immunodeficiency virus.. Proceedings of the National Academy of Sciences of the United States of America. 110(52):21136-41.. 2013.
The mongoose, the pheasant, the pox, and the retrovirus.. PLoS biology. 11(8):e1001641.. 2013.
An Evolutionary Screen Highlights Canonical and Noncanonical Candidate Antiviral Genes within the Primate TRIM Gene Family.. Genome biology and evolution. 5(11):2141-54.. 2013.
Host gene evolution traces the evolutionary history of ancient primate lentiviruses.. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 368(1626):20120496.. 2013.
Evolution-Guided Identification of Antiviral Specificity Determinants in the Broadly Acting Interferon-Induced Innate Immunity Factor MxA.. Cell host & microbe. 12(4):598-604.. 2012.
Evolutionary conflicts between viruses and restriction factors shape immunity.. Nature reviews. Immunology. 12(10):687-95.. 2012.
The host restriction factor APOBEC3G and retroviral Vif protein coevolve due to ongoing genetic conflict.. Cell host & microbe. 11(1):91-8.. 2012.
The Ability of Primate Lentiviruses to Degrade the Monocyte Restriction Factor SAMHD1 Preceded the Birth of the Viral Accessory Protein Vpx.. Cell host & microbe. 11(2):194-204.. 2012.
Paleovirology - Ghosts and gifts of viruses past.. Current opinion in virology. 1(4):304-309.. 2011.
The DEAD-box RNA helicase DDX6 is required for efficient encapsidation of a retroviral genome.. PLoS pathogens. 7(10):e1002303.. 2011.
The breadth of antiviral activity of Apobec3DE in chimpanzees has been driven by positive selection.. Journal of virology. 85(21):11361-71.. 2011.
Trim5 TAKes on pattern recognition.. Cell host & microbe. 9(5):349-50.. 2011.
Human Trim5α has additional activities that are uncoupled from retroviral capsid recognition.. Virology. 409(1):113-20.. 2011.
Polymorphism in human APOBEC3H affects a phenotype dominant for subcellular localization and antiviral activity.. Journal of virology. 85(16):8197-207.. 2011.
Ancient adaptive evolution of tetherin shaped the functions of Vpu and Nef in human immunodeficiency virus and primate lentiviruses.. Journal of virology. 84(14):7124-34.. 2010.
The range of human APOBEC3H sensitivity to lentiviral Vif proteins.. Journal of virology. 84(1):88-95.. 2010.
Paleovirology--modern consequences of ancient viruses.. PLoS biology. 8(2):e1000301.. 2010.
Cellular restriction targeting viral capsids perturbs human immunodeficiency virus type 1 infection of nondividing cells.. Journal of virology. 83(19):9835-43.. 2009.