Cynthia McMillen
University of Pittsburgh, PA·Microbiology & Immunology·Early-career
Some viruses carried by insects can cross the placenta, the organ that connects a pregnancy to the mother's bloodstream, and harm the developing fetus. In livestock, this causes waves of miscarriage; in people, it can cause stillbirth, newborn death, or abnormally small heads.
- Fields
Microbiology & Immunology
Physiology
Medicine & Clinical Research
- Topics
Oropouche virus
bunyavirus
Rift Valley fever virus
- Grants
- 2 known grants, through Jul 2028
What they work on
- Compare mother-to-offspring transmission of four Oropouche virus strains (BeAn19991, BeH759021, LET2083, AM0088) from four genetically distinct lineages, to test whether genomic reassortment underlies changes in tissue targeting and virulence.
- Define Oropouche virus tropism, pathology and host responses at the maternal-fetal interface using human placenta explants and a pregnant mouse model, and establish these as systems for future vaccine and therapeutic testing.
- Test whether La Crosse, Cache Valley, Schmallenberg and Rift Valley fever viruses infect placenta explants from humans, sheep and rats, to determine which viruses and host species support congenital infection.
- Determine whether the viral virulence protein NSm drives host and cell tropism, antiviral immune responses, programmed cell death and congenital pathology, by comparing wild-type with NSm-knockout viruses.
- Compare cell-specific immune and cell death responses to bunyavirus infection in two-dimensional human trophoblast cultures and three-dimensional trophoblast organoids, the first use of human placenta organoids for congenital bunyavirus infection.
More about the research
Why certain viruses make that crossing and others do not is largely unknown. Both projects here tackle that question for bunyaviruses, a large family of insect-spread viruses, by infecting living placenta tissue and lab-grown placenta models and comparing what happens across virus strains and host species.
Why it matters
Oropouche virus is spreading and has no vaccine or treatment, and its effects on pregnancy are largely unknown; defining how it and related bunyaviruses reach the fetus could identify targets for prevention and provide validated models in which candidate vaccines and antivirals can be tested. Clarifying whether Cache Valley, Schmallenberg and La Crosse viruses cross the human placenta could also change how pregnancies are monitored during outbreaks, while work in sheep addresses abortion losses that strain livestock producers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Vertical Transmission of Past and Present Oropouche Virus Isolates: Comparing Tropism and Pathogenesis using Human Ex Vivo and Rodent in Vivo Models
NIH · Aug 2026 – Jul 2028
Host and Viral Determinants of Orthobunyavirus Vertical Transmission: Novel Model Systems to Understand the Mechanisms of Congenital Disease in Humans and Ruminants
NIH · Aug 2023 – Jul 2028
Closest labs
Natasha Tilston
Indiana University-Purdue University-Indianapolis, IN·Microbiology & Immunology
Identify, using cell culture infection experiments, how the different glycoproteins carried by circulating Oropouche virus reassortants change viral phenotypes such as entry into host cells.
Anita McElroy
University of Pittsburgh, PA·Microbiology & Immunology
Determine the route by which Rift Valley fever virus spreads from a peripheral site to the central nervous system, using mouse models in which virus is injected into the footpad to mimic a mosquito bite.
Adam Bailey
University of Wisconsin-Madison, WI·Microbiology & Immunology
Map which parts of the neonatal Fc receptor (FcRn), a molecule that normally ferries antibodies across barriers, arteriviruses need for cell entry, by building chimeric FcRn molecules combining virus-permissive and virus-resistant versions from different species.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
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