Published: Oct. 21, 2019

Maria LoMaria Lo

Blog post


I am very thankful to the Sie Foundation and the Linda Crnic Institute for the opportunity to perform research aimed at enhancing the lives of individuals with Down Syndrome, or Trisomy 21. The Sie Fellowship has provided me with the resources to apply my skillset to a very important area of research and allowed me to become part of a dynamic community highly motivated to tackling the many health challenges faced by individuals with Down Syndrome. I have been working as a postdoctoral fellow in Dr. Amy Palmer’s lab at the BioFrontiers Institute on understanding how an essential micronutrient, Zn2+, influences cell proliferation. In a forthcoming paper, I have described how Zn2+ deficiency influences human cell growth on a cell-by-cell basis. This work helped lay the groundwork for my studies in trisomy 21 cells.  

Interestingly, there are several reports in the literature where individuals with Down Syndrome had decreased levels of Zn2+. Importantly, Zn2+ deficiency can cause growth and developmental defects and, at the cellular level is known to reduce growth and proliferation.  However, how these Zn2+ deficiencies influence cell growth in trisomy 21 cells is not understood. I am exploring how potential Zn2+ deficiencies in individuals with Down Syndrome influences their cell growth. At a basic level, a series of steps called the cell cycle controls how cells grow and divide. Proper control of each step in the cell cycle is critical for tissue development and homeostasis. In humans, dysregulation of the cell cycle can give rise to diseases such as neurodegeneration, characterized by a loss in proliferation, or cancer, characterized by uncontrolled proliferation and an inability to respond to cues otherwise triggering controlled exit from the cell cycle. To understand why individuals with Down Syndrome have a different spectrum of these proliferative disorders, I wanted to determine how the cell cycle is different in cells from individuals with Down Syndrome compared to typical individuals. This is an area that has been touched upon by various scientists, but a comprehensive analysis of the cell cycle at a single-cell level is lacking. I found that a critical protein controlling normal progression of the cell cycle is misregulated in trisomy 21 cells, suggesting individuals with Down Syndrome have a defect in proper control of the cell cycle. I am exploring how this fundamental difference changes the response of cells to conditions of stress such as serum starvation and Zn2+ deficiency. With the remainder of my time as a Sie Fellow, I am working to further elucidate key changes in the cell cycle pathway that differ in individuals with Down Syndrome. I hope these analyses will help elucidate how cell cycle switches are impaired in trisomy 21 cells, and ultimately how these changes might contribute to the altered cancer and neurobiology profile inherent to Down Syndrome.