PIPages
Labs

Kevin McCarthy

University of Pittsburgh, PA·Microbiology & Immunology

Roughly eight percent of the human genome is leftover viral DNA. Over millions of years, retroviruses inserted copies of themselves into the DNA of egg and sperm cells, so their sequences became inherited like any other gene.

Fields

Microbiology & Immunology

Genetics

Biochemistry

Topics

endogenous retrovirus

EnvP(b)1

env gene

Grants
1 known grant, through Apr 2029

What they work on

  1. Define, in cultured cells, which tissues and which primate versions of EnvP(b)1 can fuse membranes, using human, ape, and monkey copies of this ERV-derived protein that merges cells into multi-nucleated sheets.
  2. Reconstruct how EnvP(b)1 activity changed over more than 40 million years of primate evolution by building and testing inferred ancestral versions of the protein.
  3. Map where EnvP(b)1 protein is made in healthy human and nonhuman primate tissues, including placenta, using validated antibodies, and test whether cell-cell fusion occurs at those sites.
  4. Generate and quality-control protein-detection reagents for at least eight distinct endogenous retroviral Env proteins expressed in the placenta so their roles and regulation can be dissected.

More about the research

These are called endogenous retroviruses, or ERVs. Almost all of them are broken, but a handful of ERV genes have been kept intact for tens of millions of years, which strongly suggests they do something useful for the host. The gene kept most often is env, which in a live virus encodes a surface protein that latches onto a cell and fuses the viral membrane with it. In humans, two ERV env genes have been repurposed to fuse placental cells together into the syncytiotrophoblast, the fused cell layer at the boundary between mother and fetus. What is known about ERVs has come almost entirely from reading their DNA and RNA, while the proteins that actually do the work remain largely unstudied, in part because good protein-detecting reagents such as antibodies barely exist.

Why it matters

Inherited viral genes are part of normal human biology and have been linked to both healthy functions, such as building the placenta, and to disease. Because the field has worked mostly with DNA and RNA sequences, the proteins themselves have been hard to study. The antibodies, assays, and primate models generated here could let many labs determine where these proteins act in healthy tissue and in disease, and could clarify parts of human and placental biology that mouse models miss entirely.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Hosts Going Viral: Building The Tools And Systems To Determine How Human-Relevant Biology Evolved Through The Capture Of Viral Genes In Our Distant Ancestors

NIH · Jul 2024 – Apr 2029

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William Murphy

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Reconstruct how mammalian chromosomes and their recombination rates changed from a roughly 100-million-year-old inferred ancestor to living species, by pairing chromosome-level genome assemblies with recombination maps.

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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