Cure Autism Now (CAN) is pleased to name Isaac Pessah, Ph.D., as recipient of its first CAN Environmental Innovator Award. This award was designed to identify and support researchers who are studying how relevant exposures to toxins translate into altered biology, and how this is related to the deficits we see
in individuals with autism. The Environmental Innovator award is given to Dr. Pessah in recognition of his ongoing research into the biological impact of environmental exposures.
"I'm thrilled to be working with CAN to extend our studies in this area," says Dr. Pessah. "The goal of my research is to understand the genetic and environmental risk factors contributing to the incidence and severity of core symptoms and co-morbidity seen in childhood autism."
With a rising number of reported autism cases, there has been growing concern about the potential role environmental factors might play in the development of autism. Given this concern, it is crucial to put a greater effort into investigating the role environmental risk factors play in shaping the outcome of autism. This includes not only identifying those risk factors, but also understanding how an exposure to something in the external environment ultimately gets translated inside the body into a lasting change in biology. While the former is critical for preventing new cases of autism, the latter is crucial for being able to design effective treatments for those already affected.
Dr. Pessah is Professor of Toxicology at U.C. Davis and Director of the NIEHS Center for Children's Environmental Health and Disease Prevention, a collaborative research initiative focused primarily on examining how toxic chemicals may influence the development of autism in children. He is also a member of the Center for Neuroscience and the M.I.N.D. Institute. In his 18 years at U.C. Davis, Dr. Pessah has co-authored more than 110 peer-reviewed papers.
This past March, Dr. Pessah released a study connecting thimerosal, a mercury-based preservative that until recently was present in routine vaccines, with disruptions in antigen-presenting cells, known as dendritic cells, obtained from mice. The study provided the first evidence that dendritic cells (which help to protect us from external pathogens or harmful substances) can be damaged by thimerosal, potentially altering the immune system's ability to respond to external influences. In keeping with his desire to always work toward an understanding of relevance to human conditions, plans are now underway to follow up this work by drawing blood from children with autism participating in the CHARGE (Childhood Risk from Genes and the Environment) study to specifically look for evidence of changes in dendritic cell and natural killer (NK) cell functions and responses.
Dr. Pessah's work on dendritic cells suggested that thimerosal may be acting by affecting calcium (Ca2+) signaling processes. Ca2+ is a key molecule that regulates many different biological processes in the body. The Pessah lab is actively studying how dysfunctions of calcium channels, molecules that transmit Ca2+ signals, contribute to heritable diseases and susceptibility to environmental triggers.
Recognition from Cure Autism Now in the form of the Environmental Innovator Award is allowing Dr. Pessah to pursue his hypothesis that mutations in specific types of calcium channels may contribute to certain forms of autism and significantly increase susceptibility to adverse effects of environmental toxicants. This hypothesis is based on evidence from the Pessah lab that organic mercury and other persistent toxins -- such as polychlorinated biphenyls, flame retardants (PBDEs), and agents that cause oxidative damage -- can alter the intracellular Ca2+ signals generated by ryanodine receptors (RyR), one important type of calcium channel. Signals generated by these receptors inside cells are essential for normal development and function of both the immune and nervous systems. Dr. Pessah's lab has already found that mice possessing mutations in RyR channels have heightened susceptibility to chemically-induced adverse reactions of the immune and nervous systems.
Mice that contain mutations for calcium channels will be studied for abnormal social behavior and their possible heightened susceptibility to organic mercury compounds such as thimerosal. One mouse currently being developed possesses a mutation within a specific calcium channel (CaV1.2) that has been found to cause Timothy Syndrome (TS). Children with TS have a 60% rate of an autism diagnosis, with up to 80% of the children showing some signs of autism.
Two additional mouse models are currently being studied that possess a mutation within the type 1 or type 2 ryanodine receptor Ca2+ channels (RyR1 and RyR2, respectively). Together, the CaV1.2 and RyR2 receptors form a signaling unit in the heart, neurons and T lymphocytes. This project will investigate whether these three lines of mice, which all have different underlying genetic defects in Ca2+ signaling, will have increased behavioral and immunological problems when exposed to mercury. Dr. Pessah will also examine whether mercury directly affects the development of nerve cells from these animals.
Finally, the Pessah lab will determine whether children with autism have a higher frequency of CaV1.2 or RyR mutations or any particular polymorphic variations. Collectively these experiments will provide important new information on the possible contribution of CaV1.2 or RyR genetic variants to autism risk in humans, and launch studies of enhanced susceptibility of the developing nervous and immune systems to organic forms of mercury in mice carrying mutations relevant to autism.
With the Environmental Innovator Award, the Pessah lab is now able to compare, combine and interpret many different lines of their research to determine how the toxins they've been studying impact the function of proteins involved in Ca2+ signaling, which is crucial for regulation of the brain, heart and immune cells. This information may also allow us to begin to design interventions that can directly address the biological disruptions. "It's amazing that so many different lines of my research are coming together," explained Dr. Pessah. "With the recent discovery that calcium channel mutations can be linked to diseases characterized by autism, I started to put it all together. The CAN Innovator Award is allowing me to tie all these pieces of research into an important new project that I wouldn't otherwise have been able to move my lab into so quickly."
Cure Autism Now acknowledges Isaac Pessah, Ph.D. for his distinguished work in autism research and is proud to support his continued study through the first-ever CAN Environmental Innovator Award. The Environmental Innovator Award was made possible by a generous gift from Sallie and Tom Bernard.