School of Medicine
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Clinical Instructor, Pediatrics - Immunology and Allergy
Current Research and Scholarly Interests Schimke Immuno-Osseous Dysplasia (SIOD) is a rare disease that is inherited when children receive two mutated copies of the gene SMARCAL1, one from each parent. SIOD begins in early childhood and causes significant disease, including kidney failure leading to a need for kidney transplantation, stokes, growth delay, cartilage and bone malformations, and recurrent infections due to defects in their immune system. There is currently no cure for children with SIOD. Current therapies only treat the symptoms of the disease; they are not curative and they may not slow or prevent worsening of SIOD. While we know the gene that causes this disease, there are significant knowledge gaps about exactly how mutations in the SMARCAL1 gene lead to problems in so many organs including the kidneys, bones/cartilage, immune system, and vascular system.
As an immunologist, my research lies in better understanding how mutations in SMARCAL1 lead to changes in all of these organs and organ systems, with the ultimate goal of improving treatment options for children with SIOD. T-cell development and function in these children is particularly impaired. In fact, a vast majority of these children develop clinically significant immune deficiency and suffer from recurrent infections by the time they reach mid-childhood. By examining the structure of the SMARCAL1 gene, the protein produced by the SMARCAL1 gene, and the network of other proteins that it interacts with in the t cells of these children, we can better understand the mechanism of disease. These insights into t-cell development and protein expression in patients with SIOD may also enhance our understanding of other t-cell immunodeficiency diseases.
Telomeres are segments of DNA at the end of chromosomes that act as a protective ?cap? against degradation. Each time the cell divides, the telomere sequence is not completely copied, leading to shorter telomere segments with each round of DNA replication. Abnormally shortened telomeres have been associated with aging, cancer, and many other chronic diseases such as diabetes mellitus. This research investigates telomere length maintenance in a disease called Schimke Immuno-Osseous Dysplasia (SIOD). If patients with SIOD have impaired telomere maintenance, then potential therapies targeted at enhancing telomere length/maintenance could be explored. This would open up a whole new area of potential therapy. Additionally, defining the role of SMARCAL1 in telomere maintenance may have general implications for other diseases in which telomere instability has been described, including cancer and diabetes.