W Todd Lowther
Wake Forest University, NC·Biochemistry
Primary hyperoxaluria (PH) is a group of inherited diseases in which the body makes too much oxalate. Oxalate forms kidney stones and damages the kidneys.
- Fields
Biochemistry
Pharmacology
Chemistry
- Topics
primary hyperoxaluria
oxalate
glyoxylate
- Grants
- 1 known grant, through Jun 2029
What they work on
- Design and synthesize new compounds based on screening hits to explore the structure–activity relationships of hydroxyproline dehydrogenase (HYPDH) inhibitor scaffolds, improving potency, selectivity and drug-like properties.
- Determine the biochemical and cellular properties of HYPDH inhibitors, measuring how strongly they block the enzyme that starts hydroxyproline breakdown into oxalate.
- Use computational modeling and structural biology to determine how inhibitors bind HYPDH, feeding the binding information back into compound design.
- Test whether optimized HYPDH inhibitors lower glyoxylate and oxalate levels in several mouse models of primary hyperoxaluria.
More about the research
Patients with types 2 and 3 have no available therapies. Part of the extra oxalate comes from breaking down hydroxyproline, an amino acid found in the body's collagen and in meat. The team has shown that hydroxyproline is a large source of oxalate in both healthy people and PH patients. It is the largest known contribution to oxalate from any metabolite studied so far. The project aims to build a drug that blocks this pathway at its first step.
Why it matters
People with primary hyperoxaluria, especially types 2 and 3, have no approved therapies and suffer kidney stones and kidney damage. An optimized HYPDH-blocking drug could lower oxalate production from collagen and dietary meat breakdown. This approach may help prevent stones and kidney injury in these patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Zhaomin Yang
Virginia Polytechnic Institute and State University, VA·Microbiology & Immunology
Improve the potency and selectivity of a novel small-molecule inhibitor of the bacterial type IV pilus through structure–activity relationship studies that systematically vary its chemical structure.
Vardan Karamyan
Oakland University, MI·Pharmacology
Optimize two chemical families of small-molecule activators of neurolysin (Nln), a brain-protective enzyme, to improve potency, selectivity and drug-like properties through medicinal chemistry.
Wesley Van Voorhis
University of Washington, WA·Microbiology & Immunology
Develop bumped-kinase inhibitors that block the Toxoplasma enzyme CDPK1 and reach high levels in the brain and fetus while staying safe in pregnancy, using computer predictions and repeated chemistry and testing cycles.
The school
Wake Forest University: 27 labs on PI Pages, $345M a year on research, 54 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.