Graduate Spotlight: Phillip Callihan
Expected Graduation: Spring 2012
Degree Objective: Ph.D. in Pharmaceutical and Biomedical Sciences
Other Degrees: B.S. in Biology
Phillip Callihan chose the University of Georgia’s Department of Pharmaceutical and Biomedical Sciences for its broad, interdisciplinary approach to research and drug development. Allowed to explore the diverse department and collaborate with wide range of faculty, Callihan has honed his understanding to focus on the intricate, complex nature behind cellular development.
“Development is composed of so many cellular processes,” said Callihan, a pharmaceutical and biomedical sciences doctoral candidate. “I am interested in the relationship between development and cancer, but my research led me in other directions as well.”
Working with Dr. Shelley Hooks, Callihan identifies how environmental toxins disrupt the development of the nervous system in embryos and can cause certain cancers. Callihan and Hooks detail the molecular mechanisms of G-protein coupled receptors to understand the complicated interactions among molecules, cells and toxins.
GPCRs are involved in all types of cellular processes, from the sense of sight and smell to regulation of the immune system. Embedded within the cell membrane, these receptors allow cells to respond to the external environment. Molecules trigger changes inside the cell by attaching to GPCRs.
“GPCRs are extremely important in human physiology,” said Callihan. “They are active from the beginning of development throughout your life.”
Callihan and Hooks are researching how a fungal toxin, called Fumonisin B1, alters GPCR functioning and disrupts cellular communication. People come into contact with Fumonisin B1 through contaminated food crops, such as corn or wheat.
According to Callihan, previous studies in Central America and Texas have shown a relationship between human exposure to Fumonisin B1 and increased rates of neural tube defects in infants. However, the exact cause remains unclear.
“We’re studying the molecular mechanism for how that’s happening,” said Callihan.
Fumonisin B1 can disrupt the synthesis of sphingolipids, which are vital molecules in the development of embryonic neural tissue. Some sphingolipids bind to GPCRs, thereby activating cellular responses. When a toxin interferes with the communication between cells and sphingolipids, the molecular breakdown may cause neural tube defects.
“Neural tube defects result from failure of neural tube closure,” said Callihan. “They are not only a problem in the United States but have been shown to affect up to two out of every 1,000 pregnancies worldwide.”
As an embryo’s nervous system develops, the neural tube encapsulates the brain and spinal cord. In a neural tube disorder, the tube fails to close completely during the third or fourth week of pregnancy. The defect exposes the nervous system to the outside environment and often has dramatic repercussions.
“Neural tube defects cause severe malformations,” said Callihan. “Many neural tube defects are lethal to embryos, and infants born with neural tube defects are at an increased risk of death and often suffer from serious neurological defects throughout life.”
Examples of neural tube defects include spina bifida and anencephaly. Spina bifida causes a section of the spinal cord to protrude through an opening in the vertebrae, potentially paralyzing an infant. Anencephaly can result in the absence of parts of the skull and brain when the head end of the neural tube fails to close completely.
By understanding the root causes of neural tube defects, Callihan is helping build the knowledge to prevent and treat these disorders.
“A better understanding of the factors leading to neural tube defect formation is imperative in developing effective therapies for preventing these birth defects,” said Callihan.
Callihan’s research with GPCRs and cell signaling has applications for cancer researchers as well. In particular, the lipid growth factors Callihan studies in neural development are implicated in ovarian and breast cancer.
“Interestingly, many of the pathways that are important in normal embryonic development – but which are inactive in normal adult tissue – are pathologically reactivated during the development of many cancers,” he said.
After graduation, Callihan plans to pursue a M.D. and a career in academic medicine.
“During my career I hope to make a positive contribution to the prevention and treatment of birth defects and cancer,” said Callihan.
Story & photography by Ben Benson
