Primary Research Focus
The Warnhoff Lab studies the biology of the molybdenum cofactor, a 520-dalton prosthetic group that is essential for animal development. Despite its requirement for life, the biology of the molybdenum cofactor remains understudied (~1,300 Pubmed papers) when compared to other essential cofactors such as vitamin B12 (~33,000 Pubmed papers) or heme (~57,000 Pubmed papers). We use the powerful genetic model organism Caenorhabditis elegans to identify genes and pathways that maintain metabolic homeostasis during health and disease
The Warnhoff Lab has two major goals:
- Identify the protein network that facilitates molybdenum cofactor transport between cells, tissues and organisms.
- Discover and characterize genetic pathways that modify molybdenum cofactor-mediated metabolism.
To achieve these goals, we will employ an interdisciplinary approach using unbiased genetic strategies in the model organism C. elegans in combination with functional genomics, biochemistry, and cellular biology. The discoveries made in this fast, powerful, and cost-effective model system will continue to suggest novel therapeutic approaches for treatment of disease where molybdenum cofactor biology is altered (i.e. molybdenum cofactor deficiency (MoCD), a rare and devastating genetic disorder).
About the Warnhoff Lab
Lab Projects and News
Mechanisms of molybdenum cofactor transport
The molybdenum cofactor (Moco) is a prosthetic group that is essential in animals; humans with mutations in genes that encode Moco-biosynthetic enzymes display lethal neurological and developmental defects. Moco supplementation seems a logical therapy, however free/unbound Moco is too fragile to be purified and administered therapeutically. Surprisingly, we have discovered that the nematode C. elegans efficiently takes up Moco from its bacterial diet and distributes it throughout its body via an unknown mechanism. A major goal of the lab is to identify and characterize the proteins that facilitate the stable transport of Moco. A deep understanding of these proteins/pathways will inform novel therapeutic strategies for the treatment of diseases where Moco homeostasis is disturbed.
Genetic pathways that modify molybdenum cofactor-mediated metabolism
Molybdenum cofactor deficiency (MoCD) is a rare inborn error of metabolism caused by loss-of-function mutations in the enzymes that synthesize Moco. Moco deficiency causes severe neurological dysfunction and neonatal lethality in humans. The pathophysiology underlying this genetic disorder remains incompletely understood. Our genetic analyses of MoCD in C. elegans demonstrates that cysteine catabolism is the major metabolic liability for cells deficient in Moco. Cysteine metabolism yields sulfite, a toxin that accumulates to catastrophic levels when Moco is deficient due to inactivity of sulfite oxidase (a Moco-requiring enzyme). Limiting the metabolic production of sulfite would be predicted to alleviate the symptoms caused by MoCD. Using genetic approaches, we will discover and characterize new genes/pathways that control cysteine metabolism and sulfite production. These pathways will suggest novel therapeutic targets for the treatment of disease where Moco homeostasis is defective.
Meet the Warnhoff Team
Jennifer Snoozy completed her bachelor’s degree in biology with a minor in chemistry from the University of Sioux Falls in 2021. Previously, she worked in the Lee Lab for three years as an undergraduate intern. With the Warnhoff Lab, Jennifer is working on defining new genetic pathways that modify molybdenum cofactor biology.
Robin Fettig, BA
Robin Fettig completed her bachelor’s degree in Biology and Psychology with a minor in Chemistry from Concordia College in Moorhead, MN in 2018. In 2017, she spent a summer as a SPUR intern in the Vermeer Lab where she conducted research on HPV-related Head and Neck cancer. Before joining the Warnhoff Lab, Robin was an Associate Scientist at a clinical research company where she utilized HPLC and LC/MS systems to ensure generic pharmaceuticals met FDA standards before reaching the market. She began pursuing her PhD in the Basic Biomedical Sciences program through the University of South Dakota in 2021 and joined the Warnhoff Lab in 2022. In the Warnhoff Lab, she is working on defining genes involved in molybdenum cofactor homeostasis and molybdate transport within C. elegans.
Sushila Bhattacharya, PhD joined the lab in September 2022. She aims to “Identify and characterize regulators of Moco-mediated metabolism using C. elegans as a model system”. Sushila holds PhD in Biochemistry from C.S.J.M.U Kanpur, India. She worked as DST- Women Scientist in CSIR-CDRI, Lucknow, India before moving to United States for her Postdoctoral training at UMASS Chan Medical School (Department of Systems Biology), Massachusetts.