Charles V. Vorhees, PhD

I am a neuroscientist investigating how changes in brain development affect behavior using animal models of pediatric neurological disorders. I focus on the causes of neurodevelopmental disorders, learning disabilities, attention deficit hyperactivity disorder (ADHD), manganese and pyrethroid neurotoxicity, and the long-term effects of proton radiotherapy.

Dr. Michael Williams and I merged labs to enhance progress by leveraging different scientific backgrounds to work on shared goals. Our lab studies egocentric/procedural/habit learning which is striatally-mediated. We developed a test to better assess this ability, the Cincinnati water maze (CWM). Reducing dopamine in the dorsal medial or dorsal lateral striatum causes CWM deficits while sparing spatial learning in the Morris water maze (MWM). However, reducing dopamine in both striatal regions impairs both tests. The basis of this is unknown and is under investigation.

We also created an Animal Behavior Core (ABC). The ABC was developed to collaborate with investigators throughout Cincinnati Children’s and the University of Cincinnati (UC) on behavioral phenotyping. The core runs the tests, analyzes the data and writes the findings for grant applications and publications.

Some of the notable projects of the Vorhees/Williams lab include the development of the first latrophilin-3 (Lphn3) constitutive and conditional knockout (KO) rats, the first Slc30a10 conditional KO rat, the first phosphodiesterase-1b (Pde1b) KO mouse, and the first creatine transporter KO mouse (since transferred to Dr. Skelton), and for ways to improve proton radiotherapy. Some specific findings include:

• Lphn3: This protein is an adhesion G protein-coupled receptor important in synapse formation and maintenance, variants of which are linked to ADHD. The lab uses Lphn3 KO and conditional Lphn3/TH-Cre rats to investigate the function of Lphn3 on the brain and behavior.
• Slc30a10: This is an intracellular manganese transporter. When mutated, it causes a rare form of developmental manganese neurotoxicity similar to that seen in children who are environmentally exposed to manganese. We hypothesize that Slc30a10 dysregulation is a mechanism that contributes to manganese neurotoxicity.
• Pesticides: Pyrethroids are widely used pesticides. Several epidemiological studies report increased rates of ADHD and reduced IQ in exposed children. We tested deltamethrin (a prototypical pyrethroid) during development in rats and found learning, memory and dopamine deficit. The lab is testing the hypothesis that pyrethroids are more deleterious to those with ADHD or those genetically predisposed to ADHD.
• Protons: The lab is investigating ways to reduce the adverse cognitive effects of radiotherapy in children after treatment for brain tumors. We are testing the Flash hypothesis, i.e., that high dose/high dose-rate short exposures are safer than low dose/low dose-rate conventional exposures.

My research has been supported and funded by the National Institutes of Health (NIH) and with grants from the National Science Foundation (NSF), Food and Drug Administration (FDA), Department of Defense Biomedical Research Program, foundations and industry. I am currently serving or have served on scientific advisory panels for the FDA, Environmental Protection Agency (EPA), California Environmental Protection Agency (CalEPA) and the National Academy of Science.

Some of my other activities and positions include:

• Former director of the Molecular and Developmental Biology (MDB) graduate program
• Former director of Graduate Studies of the Neuroscience graduate program and current member of the admissions committee
• Founding member of the Developmental Neurotoxicology Society and twice elected president
• National Institutes of Health grant recipient and reviewer
• Editorial Board: Brain, Behavior & Immunity and Neurotoxicology
• Former editor-in-chief of Neurotoxicology and Teratology