SURF

Ted Daniel Llera

Establishing The Mechanisms of AGS MANF in Neuroprotection and Regulated Cell Death Using CRISPR-Engineered AGS and Mouse Neural Cells

My goal is to identify the mechanisms of innate metabolic resilience and discover targets with translational potential for neuroprotection by characterizing the function of protein variants that make Arctic ground squirrels (AGS) resistant to cerebral ischemia. Studies show that cellular resistance to metabolic stressors is an intrinsic property of neural cells generated from AGS. Through functional genomic screens and computational analysis, they identified novel cytoprotective protein variants with amino acid substitutions that are unique to AGS but otherwise conserved in mammals. Among the identified proteins with the most striking metabolic resilience phenotypes, mesencephalic astrocyte-derived neurotrophic factor (MANF) demonstrates enhanced cytoprotective effects specific to the AGS variant. I hypothesize that this key AGS MANF variant promotes ischemia resilience and neuronal survival by enhancing sulfatide binding, ER stress response, and mitochondrial function while reducing cell death under metabolic stress conditions. I will characterize the neuroprotective potential of this AGS cytoprotective variant, which can potentially create a cure or treatment for diseases like stroke.

Message to Sponsor

Thank you Pergo Fund for supporting my research project last summer, which gave me the opportunity to learn, grow, and even further love my passion for helping society through the power of science. Your support has helped me grow as a scholar and as an individual by enabling and harnessing my critical-thinking, organizational, and wet-lab hands-on skills while conducting my research. I realized that my research does not only benefit myself but potentially others as well due to the possibility of utilizing my research in creating cures or regenerative therapy for ischemic injuries, such as strokes or heart attacks. Thus, through my experience as a SURF fellow and your support, my passion for science and helping others have been amplified to which I enjoy and hope to continue my career as a translational researcher. Even with the challenges I faced during this summer, I have become stronger and confident that I can inspire others, especially people of color, to walk on the same path as I did of becoming a research scientist. Thank you again for your generosity, and for enabling my interest and passion to turn to reality.
  • Major: Molecular and Cell Biology: Immunology and Pathogenesis
  • Sponsor: Pergo Fund
  • Mentor: Neel Singhal