# Darrel W. Stafford
**Darrel W. Stafford** (also published as D.W. Stafford) is a Professor Emeritus in the Department of Biology at the [University of North Carolina at Chapel Hill](https://www.edgepedia.org/university-of-north-carolina-at-chapel-hill), where his office is in Wilson Hall.[1](https://bio.unc.edu/faculty-profile/stafford/) He came to Carolina in 1965 and has spent his career there, working on the two enzymes of the vitamin K cycle.[2](https://endeavors.unc.edu/thick_and_thin) He is known for identifying the gene for vitamin K epoxide reductase, the target of the anticoagulant warfarin, published in *Nature* in 2004,[3](https://www.ovid.com/journals/natr/fulltext/00006056-200402050-00047~identification-of-the-gene-for-vitamin-k-epoxide-reductase) and for cloning the cDNA for human gamma-glutamyl carboxylase, published in *[Science](https://www.edgepedia.org/science-journal)* in 1991.[4](https://wfhcongress2024.eventscribe.net/fsPopup.asp?efp=V1hPU09CUEQyMTcyOQ&PresenterID=1720424&rnd=0.8077798&mode=presenterinfo)
| Key fact | Detail |
|---|---|
| Position | Professor Emeritus, Department of Biology, University of North Carolina at Chapel Hill[1](https://bio.unc.edu/faculty-profile/stafford/) |
| Career span | At UNC Chapel Hill since 1965[2](https://endeavors.unc.edu/thick_and_thin) |
| Signature work | "Identification of the gene for vitamin K epoxide reductase", *Nature*, 2004, [doi:10.1038/nature02254](https://doi.org/10.1038/nature02254)[3](https://www.ovid.com/journals/natr/fulltext/00006056-200402050-00047~identification-of-the-gene-for-vitamin-k-epoxide-reductase) |
| Other landmark work | Cloning and expression of the cDNA for human gamma-glutamyl carboxylase, *Science*, 1991, [doi:10.1126/science.1749935](https://doi.org/10.1126/science.1749935)[4](https://wfhcongress2024.eventscribe.net/fsPopup.asp?efp=V1hPU09CUEQyMTcyOQ&PresenterID=1720424&rnd=0.8077798&mode=presenterinfo) |
| Major funding | NIH National Heart, Lung, and Blood Institute R01 HL048318, "Structure and Function of Gamma-Glutamyl Carboxylase", 1992 to 1997[5](https://grantome.com/grant/NIH/R01-HL048318-01) |
| Honors | North Carolina Award for Science, 2007; ISTH Distinguished Career Award, 2007[2](https://endeavors.unc.edu/thick_and_thin) • [6](https://www.ibiblio.org/carrborocitizen/main/2007/11/29/carrboro-scientist-presented-north-carolina-award/) |
| Recent activity | Papers through December 2025, including a *Journal of Thrombosis and Haemostasis* study of novel GGCX mutations[7](https://www.sciencedirect.com/author/7102888824/darrel-w-stafford) |
## Career and honors
Stafford came to the University of North Carolina at Chapel Hill in 1965 as a professor of biology in the College of Arts and Sciences.[2](https://endeavors.unc.edu/thick_and_thin) The university's biology department now lists him as Professor Emeritus with an office at 442 Wilson Hall,[1](https://bio.unc.edu/faculty-profile/stafford/) although a 2024 congress presenter profile still styles him Professor of Biology.[4](https://wfhcongress2024.eventscribe.net/fsPopup.asp?efp=V1hPU09CUEQyMTcyOQ&PresenterID=1720424&rnd=0.8077798&mode=presenterinfo) According to the NIH grant record, from 1992 to 1997 he held [National Heart, Lung, and Blood Institute](https://www.edgepedia.org/national-heart-lung-and-blood-institute) grant R01 HL048318, "Structure and Function of Gamma-Glutamyl Carboxylase", at Chapel Hill.[5](https://grantome.com/grant/NIH/R01-HL048318-01)
Two career awards came in 2007: the Distinguished Career Award at the XXIst Congress of the International Society on [Thrombosis](https://www.edgepedia.org/thrombosis) and [Hemostasis](https://www.edgepedia.org/hemostasis) in Geneva, Switzerland, in July,[6](https://www.ibiblio.org/carrborocitizen/main/2007/11/29/carrboro-scientist-presented-north-carolina-award/) and the North Carolina Award for Science.[2](https://endeavors.unc.edu/thick_and_thin)
## Early work: genes and chromatin
Before the advent of molecular cloning, Stafford's laboratory isolated a pure gene from sea urchins, the ribosomal rRNA gene, and purified to near homogeneity a gene for one of the sea urchin histones prior to cloning.[1](https://bio.unc.edu/faculty-profile/stafford/) A paper Stafford co-authored was the first to demonstrate nucleosome phasing, the arrangement of nucleosomes at fixed positions along DNA.[1](https://bio.unc.edu/faculty-profile/stafford/)
## Representative work
The 2004 *Nature* paper "Identification of the gene for vitamin K epoxide reductase" ([doi:10.1038/nature02254](https://doi.org/10.1038/nature02254)) reported the gene for the enzyme that recycles vitamin K and is the target of warfarin, the most widely prescribed anticoagulant for thromboembolic disorders.[3](https://www.ovid.com/journals/natr/fulltext/00006056-200402050-00047~identification-of-the-gene-for-vitamin-k-epoxide-reductase) Although the enzyme's warfarin sensitivity had been known since the 1970s, no one had purified it or identified its gene.[3](https://www.ovid.com/journals/natr/fulltext/00006056-200402050-00047~identification-of-the-gene-for-vitamin-k-epoxide-reductase) The discovery made the cover of *Nature*.[2](https://endeavors.unc.edu/thick_and_thin)
## Identifying the vitamin K epoxide reductase (2004)
Warfarin inhibits vitamin K epoxide reductase (VKOR), discovered in 1978 to block proper vitamin K metabolism, but the gene had never been isolated.[2](https://endeavors.unc.edu/thick_and_thin) Stafford's team took a positional-cloning route. Localization placed VKOR among 190 genes within human chromosome 16p12-q21, narrowing the search to 13 genes encoding candidate transmembrane proteins; the team then used pools of short interfering RNA (siRNA) against individual genes to test which one inhibited VKOR activity in human cells.[3](https://www.ovid.com/journals/natr/fulltext/00006056-200402050-00047~identification-of-the-gene-for-vitamin-k-epoxide-reductase) A graduate student narrowed the candidate list, and Stafford made siRNA for each gene.[2](https://endeavors.unc.edu/thick_and_thin) This was the first time siRNA had been used as a screening technique to isolate a gene.[2](https://endeavors.unc.edu/thick_and_thin)
The identified gene, MGC11276, encodes an enzyme 163 amino acids long with at least one transmembrane domain; activity was confirmed by expression in insect cells, with the expected sensitivity to warfarin.[3](https://www.ovid.com/journals/natr/fulltext/00006056-200402050-00047~identification-of-the-gene-for-vitamin-k-epoxide-reductase) A parallel *Nature* paper the same month identified the same gene, named [VKORC1](https://www.edgepedia.org/vkorc1), by using linkage information from three species, and showed that missense mutations in VKORC1 cause both warfarin resistance and multiple coagulation factor deficiency type 2.[8](https://www.nature.com/articles/nature02214) Until those 2004 papers, researchers had thought VKOR was a large multiprotein complex; the two groups reached the same single protein by different routes.[9](https://hum-molgen.org/NewsGen/02-2004/000014.html) Later work purified recombinant human VKORC1 and concluded that a single VKORC1 peptide performs both reduction steps, so VKOR is not a multisubunit enzyme.[10](https://mirror.omim.org/entry/608547)
## Recent developments
Stafford's laboratory has remained active. In February 2023, a genome-wide CRISPR-Cas9 knockout screen published in *Nature Communications* identified Fsp1 as the warfarin-resistant vitamin K reductase, the laboratory having earlier identified the gene and protein for an antidotal enzyme for vitamin K reduction in warfarin poisoning.[4](https://wfhcongress2024.eventscribe.net/fsPopup.asp?efp=V1hPU09CUEQyMTcyOQ&PresenterID=1720424&rnd=0.8077798&mode=presenterinfo) In 2024 the group published a *Methods in Enzymology* chapter, "Assessment of gamma-glutamyl carboxylase activity in its native milieu", and contributed to a *Haemophilia* review, "Unresolved hemostasis issues in haemophilia".[7](https://www.sciencedirect.com/author/7102888824/darrel-w-stafford) In December 2025, a *Journal of Thrombosis and Haemostasis* paper by Darrel W. Stafford, "Molecular insights into the comorbidity of vitamin K-dependent clotting factor deficiency and chondrodysplasia punctata", characterized novel GGCX mutations identified in a patient with vitamin K-dependent clotting factor deficiency.[7](https://www.sciencedirect.com/author/7102888824/darrel-w-stafford) The laboratory's current approach uses molecular modeling to suggest mutations and in vitro mutagenesis to characterize interactions among blood coagulation proteins.[1](https://bio.unc.edu/faculty-profile/stafford/)
## References
1. [Stafford, Darrel W. – UNC Department of Biology](https://bio.unc.edu/faculty-profile/stafford/)
2. [Thick and Thin – UNC Endeavors](https://endeavors.unc.edu/thick_and_thin)
3. [Identification of the gene for vitamin K epoxide reductase – Nature 427:541–544](https://www.ovid.com/journals/natr/fulltext/00006056-200402050-00047~identification-of-the-gene-for-vitamin-k-epoxide-reductase)
4. [Darrel W. Stafford, PhD – WFH Congress 2024 presenter profile](https://wfhcongress2024.eventscribe.net/fsPopup.asp?efp=V1hPU09CUEQyMTcyOQ&PresenterID=1720424&rnd=0.8077798&mode=presenterinfo)
5. [Structure and Function of Gamma-Glutamyl Carboxylase – NIH R01 HL048318](https://grantome.com/grant/NIH/R01-HL048318-01)
6. [Carrboro scientist presented North Carolina Award – The Carrboro Citizen](https://www.ibiblio.org/carrborocitizen/main/2007/11/29/carrboro-scientist-presented-north-carolina-award/)
7. [Darrel W. Stafford – ScienceDirect author page](https://www.sciencedirect.com/author/7102888824/darrel-w-stafford)
8. [Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2 – Nature](https://www.nature.com/articles/nature02214)
9. [Understanding Vitamin K – HUM-MOLGEN, February 2004](https://hum-molgen.org/NewsGen/02-2004/000014.html)
10. [OMIM 608547: Vitamin K epoxide reductase complex, subunit 1; VKORC1](https://mirror.omim.org/entry/608547)
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*Topic: Encyclopedia › Life and health › Life and health scientists › Medical and health researchers › Hematology and blood disorder researchers › Coagulation and fibrinolysis researchers › Surnames Ky to W*
*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026; Sep 30, 2026 · Edited: Sep 25, 2026; Sep 30, 2026; Oct 11, 2026; Oct 15, 2026 · Last review: Sep 30, 2026*
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