Genetic Insults/Ataxia Telangiectasia (AT)
As an example of a genetic insult that affects brain development, we study Ataxia-telangiectasia (A-T), which is a rare, systemic disease characterized by immunodeficiency, increased incidence of cancer, and progressive cerebellar neurodegeneration resulting in loss of gross motor control and death. Individuals with A-T harbor homozygous recessive mutations in the Atm gene, resulting in truncation, inactivation, or loss of ATM protein.
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Nutritional Insults During Gestation/Gestational Iron Deficiency
The majority of data that support this novel hypothesis come from our studies that are focused on iron deficiency, one of the world most prevalent nutritional deficiencies. In this paradigm we have shown for the first time that embryonic CNS tissue is not protected from iron deficiency during pregnancy, as commonly thought, and that early glial precursor cell populations are highly sensitive to changes in tissue iron concentrations.
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Inflammation and Viral Insults/Infection with Human Herpes Virus 6 (HHV6)
This project is focused on determining the effect of the human herpesvirus 6 (HHV-6) on oligodendrocyte progenitor cells (OPCs). Uniquely among the human herpesviruses, new data show that HHV6 maintains or establishes its latency state via chromosomal integration into the host genome. Importantly, chromosomal integration of both HHV-6A and B strains occurs in 1% of live births and has been associated with a number of pathologies ranging from chronic fatigues syndrome to impairment of mental functioning. The mechanisms underlying these defects are not known.
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Exposure to Environmental Toxicants/Environmental Lead (Pb) Exposure
Lead (Pb) exposure is a widespread public health problem that continues to affect women and children. Interestingly, iron deficiency (ID) and exposure to Pb produces similar neurotoxic effects on the developing CNS and humans exposed to Pb are often also iron deficient. Although studies of these insults singularly suggest the potential for enhanced neurotoxicity in their combination, previous work has failed to address the impact of a combined exposure in relevant animal models.
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Glial Progenitor Populations in the Brain
This project is an ongoing collaboration with the Proschel/ Noble laboratory where we define and characterize progenitor cells in the brain. Through the work in the Chris Proschel laboratory it became increasingly clear that Astrocytes generated from embryonic glial restrict progenitor cells (GRP cells) can display both positive as well as negative functions depending the signaling molecules that were used to induce their differentiation.
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