Tatyana Golovkina received her M.S. in Biochemistry from Moscow State University, Moscow, former USSR. She pursued graduate studies at the USSR Academy of Medical Sciences Cancer Research Center, Moscow, USSR in the laboratory of Andrei Gudkov. Her doctoral thesis describes studies on evolution of endogenous retroviruses in mammalian genome. She then joined Susan Ross’ laboratory at the Department of Biochemistry, University of Illinois at Chicago and later moved with the lab to University of Pennsylvania, Department of Microbiology. She obtained an independent position at The Jackson Laboratory in Bar Harbor, ME in 1997 where she studied genetics of resistance to viral infection and in 2005, she re-located her laboratory to the Department of Microbiology at the University of Chicago.
The primary goal of Golovkina’s laboratory is to understand how the innate immune system detects retroviral infection and initiates virus-neutralizing adaptive immune responses. In addition, she is also interested in mechanisms evolved by retroviruses to overcome host protective responses. To investigate these important questions, Golovkina’s lab employ virus-resistant mice capable of controlling retroviruses from distinct genera. Using mice from retrovirus-resistant strains, her lab found that endosomal Toll-like receptor 7 (TLR7) is an innate immune receptor that detects mouse retroviruses and signals to stimulate the production of virus-neutralizing antibodies (Kane et al, Immunity 2011).
Most viruses enter the host through surfaces exposed to the microbiota that protect the host from incoming pathogens. Golovkina’s lab performed pioneering work showing that orally transmitted retroviruses exploit the microbiota for their own benefit (Kane et al, Science 2011). An enveloped mouse retrovirus acquired host Lipopolysaccharide (LPS)-binding factors during budding to bind LPS produced by Gram-negative commensal bacteria (Wilks et al, Cell Host and Microbe 2015). Virion-associated LPS activates Toll-like receptor 4 (TLR4), stimulating production of the immunosuppressive cytokine IL-10 and virus evasion of host immunity (Kane et al, Science, 2011). Julie Pffeifer’s group at University of UT Southwestern simultaneously showed that picornavirus and reovirus transmission also depends on the gut microbiota. Noraviruses and rotaviruses have been recently added to the list of viruses which replication and transmission is completely dependent on the gut microbiota.
Retroviruses earned their notoriety by inducing a broad range of tumors in vertebrates. Whereas some retroviruses carry oncogenes in their genome, the vast majority of retroviruses do not encode such elements and thus, must integrate near cellular proto-oncogenes and up-regulate them to induce tumors. Many cellular genes involved in tumorigenesis were first identified as viral oncogenes (v-onc) or genes up-regulated upon retroviral insertion. They are now known to be involved in various types of spontaneous tumors in humans. Up-regulation of cellular protooncogenes via insertional mutagenesis or insertion of v-oncs constitutes a necessary step for tumor induction. However, up-regulation of an oncogene alone is not sufficient for tumor induction and other events are required for tumor development. Preliminary data generated in Golovkina’s lab suggest that the gut commensal bacteria serve as an epigenetic factor that contributes to virally-induced cancer. Using well-defined animal models, Golovkina’s lab is searching for the mechanism(s) by which the commensal microbiota promotes virally induced tumorigenesis.