David Ginsburg
University of Michigan, MI·Genetics
Blood has to clot at a wound but stay liquid everywhere else, and the molecular machinery that balances those two demands fails in both directions in human disease: excessive bleeding on one side, dangerous clots on the other. This program studies the genes and proteins that set that balance, taking its cues from patients with inherited bleeding and clotting disorders and then dissecting the underlying biology in mice, cells and purified proteins.
- Fields
Genetics
Biochemistry
Medicine & Clinical Research
- Topics
hemostasis
thrombosis
von Willebrand factor
- Grants
- 1 known grant, through Feb 2031
What they work on
- Map endothelial cell gene expression across diverse vascular beds in live mice at single-cell resolution, in models of thrombotic thrombocytopenic purpura and other vascular disorders, to explain organ-specific disease.
- Identify and characterize a novel mouse modifier gene that alters susceptibility to thrombotic thrombocytopenic purpura, testing its relevance to the variable severity of the human disease.
- Generate deep mutational scanning datasets covering every possible single amino acid substitution in PAI-1, a brake on clot breakdown, and selected domains of von Willebrand factor, to guide interpretation of clinical genome sequences.
- Use directed molecular evolution to engineer serine protease inhibitors (SERPINs) with new target specificities, probing what determines which protease PAI-1 and related proteins inhibit.
- Define the complete cargo repertoires of the LMAN1/MCFD2 receptor, required for secreting coagulation factors V and VIII, and of SURF4, the receptor for the cholesterol regulator PCSK9.
- Search for cargo receptors with overlapping specificity and probe unconventional protein secretion routes relevant to disorders of hemostasis and lipid metabolism.
More about the research
Four lines of work run in parallel.
Why it matters
Inherited variation in clotting genes shapes how severely patients bleed or clot, yet clinical genome sequencing often returns variants of unknown meaning. Complete maps of every amino acid substitution in PAI-1 and von Willebrand factor could let clinicians interpret those variants and diagnose patients more confidently. Engineered SERPIN inhibitors and a clearer picture of the LMAN1 and SURF4 secretion receptors could also point toward new treatments for bleeding, thrombosis and cholesterol disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yohei Hisada
University of North Carolina at Chapel Hill, NC·Medicine & Clinical Research
Test whether podoplanin on leukemia blast cells drives platelet loss in acute promyelocytic leukemia by activating platelets through their CLEC-2 receptor, using xenograft and allograft mouse models that reproduce patient clotting abnormalities.
Rafal Pawlinski
University of North Carolina at Chapel Hill, NC·Medicine & Clinical Research
Identify the disease-specific triggers that activate Factor XII, a protein that starts blood clotting, in sickle cell disease, using blood samples from patients and a mouse model of the disease.
Anne-Marie Krachler
University of Texas Health Science Center at Houston, TX·Microbiology & Immunology
Test whether host fecal proteins bound to the EHEC surface, including serpins such as alpha-1 antitrypsin and serpinE2, raise infectivity, by adding individual and combined proteins in controlled exposure and challenge experiments in zebrafish larvae.
The school
University of Michigan: 124 labs on PI Pages, $2.1B a year on research, 963 research doctorates a year.
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