Age: 18Evans, GA
Project Title: Exosomes in Amyloid Aggregates Promote Neuronal Damage: A Mechanism of Alzheimer’s Pathology
Miniscule nanovesicles called exosomes are released by most cells and have been observed to help form clusters of amyloid, a protein that plays a major role in Alzheimer’s Disease. However, this process is still unknown. Our research found a specific molecule in exosomes, ceramide, that binds to amyloid, contributing to its aggregation. Furthermore, I have shown for the first time that this combination of exosomes and amyloid is extremely toxic to brain cells. These findings suggest a novel treatment for Alzheimer’s Disease that includes using drugs that reduce ceramide levels in exosomes, slowing the formation of deadly amyloid aggregates and the accompanying onset of the disease.
Being named a Davidson Fellow is the most rewarding culmination of a year’s work for which anyone could ask. Just finishing the project and having something significant to submit was gratifying, but progressing this far is really an incredible honor that I had not expected to achieve. I am humbled to be included in this close group of extraordinary young people, and I hope our paths will cross again in the near future. Winning here is also a testimony to the careful mentorship and dedicated teaching that I have been fortunate to receive. My mentor, Dr. Bieberich, and Dr. Dinkins with whom I also worked closely helped get me to where I am today, and I am thankful for all that they have done for me. Back at Greenbrier High School in Evans, GA, my nominator, Mrs. Yarnell, gave me the knowledge necessary to succeed in my future lab work during my two classes with her and saw me progress all four years during my leadership in our Science Bowl teams.
Alzheimer’s Disease is a debilitating brain disease that causes confusion, loss of memory, and death. Affecting more than 5.4 million people in the United States alone, Alzheimer’s Disease damages and eventually kills brain cells, specifically neurons that transmit signals essential for memory. A small protein called β-amyloid (Aβ) has been found in aggregates (plaques) near dying cells and is known to play a central role in neuronal death, but the process surrounding the formation of plaques is still largely unknown. Recently, nanoparticles called exosomes have entered the Alzheimer’s research stage because they have been shown to be involved in plaque formation and contain a bioactive lipid called ceramide that causes cells to die. Using a technique to detect close protein interactions called a Proximity Ligation Assay, we developed a novel tool specialized for the visualization of protein-lipid interactions and found that exosomes enhance aggregation of Aβ by directly binding amyloid to ceramide, its specific target lipid in their membranes. After Aβ forms a complex with exosomes, we tested if this combination is more deadly to neurons than either Aβ or exosomes alone. Using microscopy to view neuronal health, I observed for the first time that many more neurons that were exposed to the combination of exosomes and Aβ were killed than in any other condition tested. These findings show how exosomes and Aβ contribute to the development of plaques in Alzheimer’s Disease. Knowing that ceramide in exosomes causes the creation of plaques, the formation of Aβ and exosome aggregates can be slowed and eliminated by reducing ceramide levels in exosomes. This illuminates the possibility of a novel treatment of Alzheimer’s Disease by employing agents that inhibit ceramide production to eliminate deadly ceramide-containing exosomes.
First of all, without Drs. Bieberich’s and Dinkins’s superb mentorship, I would never have been able to go this far. From working with them, I learned numerous lab techniques, but most importantly, they helped me understand the process of scientific inquiry. During work on my project, I learned that data analysis is a challenging aspect of science. Specifically, I needed to quantify neuronal damage in confocal images that I acquired. The obstacle of finding the best way to quantify my data was debilitating, but I persevered, finding the method I needed. Overwhelmed by many images, I was lost and spent a long time manually quantifying neuronal injury and death. After dismally scattered results, it was clear that I needed automatic methods that will indiscriminately analyze images. I perused literature and searched for the solution. Finally, I found a paper discussing a form of image analysis that helps assess neuronal damage. Invigorated, I immediately installed the recommended tools and was able to accurately analyze my images to reveal statistically significant neuronal injury from the combination of amyloid and exosomes, a finding that I included in my paper. I came up with the idea to apply the Difference-of-Gaussians filter to remove low-frequency fluctuations in intensity which prepared images for automatic segmentation using Otsu's method. My mentor now adopted my method as a standard procedure in his lab. Learning from this experience, if I want to pursue research, I must learn to cope with many obstacles in the way of scientific discovery and follow my goals with determination. Outside of the lab, I have had outstanding Biology teachers throughout my high school career. Mrs. Yarnell, the faculty sponsor for Science Bowl, taught me in 9th grade, and took her AP Environmental Science course as a senior. Junior year, AP Biology with Dr. Fowler was my favorite class. He shared with us his expertise in Molecular Biology, and I felt comfortable taking on cutting-edge research in Alzheimer’s Disease the following summer with my mentor, Dr. Bieberich.
I do not need to elaborate much on the horrors of Alzheimer’s Disease. An elderly person can be energetic, smart, and outgoing one year, but then, not more than five years later, lose all passion in life and not even remember his or her identity. From the caregiver’s perspective, a family member that you loved has been replaced with an empty shell. Alzheimer’s Disease is the fifth leading cause of death and affects 5.4 million Americans alone. While the three leading causes of death, heart disease, stroke, and prostate cancer, have decreased since 2000, deaths from Alzheimer’s Disease have increased by 71%. Indeed, the trend is expected to continue as deaths from Alzheimer’s Disease are predicted to increase by another 40% in the next decade. To this day, there is still no cure or viable treatment, only a few drugs providing inconsistent relief from some of its symptoms, namely deterioration in cognition. The primary cause of Alzheimer’s Disease is the aggregation of a misfolded protein, β-amyloid, into deadly plaques around brain cells. I hope that my work has pinpointed an essential “molecular switch” in the formation of these amyloid plaques. This switch has a known, non-toxic inhibitor that can be evaluated as drug candidate. I hope that our work will lay a foundation for future collaboration with Transitional Medicine to develop a novel treatment for Alzheimer’s Disease by blocking the formation of plaques before they can cause damage to the brain. In my opinion, I am optimistic that Alzheimer’s Disease can be cured in the nearest two decades.
I attended a public school in Columbia County, Georgia, Greenbrier High School. In my race to earning Valedictorian, I took the nearly all the AP class we offered in the STEM and Social Sciences fields. This fall, I will be attending Yale University to study Molecular Biophysics and Biochemistry, though I am still undecided about this major. I hope to pursue an MD/PhD program, and someday, I wish to become an independent investigator to help advance our well-being on the cutting-edge of Medicine and Biomedical Sciences.
I love sport, including tennis, skiing, and sailing. I played number 1 for my school’s varsity tennis team, and I volunteer at tennis camps at my school and tennis club to help teach rising players to enjoy the sport. I play tennis in USTA-sanctioned tournaments on the Southern level, and I am ranked in the top 15th percentile of our region of nine states. I was named the Most Valuable Player on my school’s varsity team. My biggest academic achievements are being named a 2017 Davidson Fellow and winning 3rd place in the US at the 2016 Siemens Competition National Finals in Math, Science, and Technology. I am also honored to have been able to give a talk at the 7th CaribeGLIA International Symposium on Molecular Mechanisms of Neuron-Glia Interactions In Vivo and In Vitro at the Universidad Central del Caribe. Our work was also presented as an abstract on which I am the third author at the 2017 American Society for Neurochemistry Meeting in Little Rock. I was the captain of my school’s Science Bowl teams for two years where my A-Team won two-time Runner-Up and B-Team won 3rd in the Regional Championships. I was also the captain of our Math Team and Varsity History Bowl Team since sophomore year where we qualified for the National Championships. I founded my school’s chapter of the “International Science Olympiads,” and we are the only school in my county that enables interested students to sit for the USA Biology Olympiad, US National Chemistry Olympiad, and USA Physics Olympiad entrance exams and their national levels free of cost, paid by our $2,000 Science Bowl wins. My junior year, I competed in the United States National Chemistry Olympiad as a top 9 regional qualifier from over 300 participants. I finished school as Valedictorian, and I am a Watson-Brown Foundation and Elks Foundation Scholar.
Do you collect anything?
I don't collect any materials, but collecting knowledge seems like a common trend here.
If you had a warning label, what would yours say?Don't play poker with me.
If you could have one super power, what would it be?
Flying, soaring above, that just feels optimistic and enlightening, to me at least.
In the News9/12/17 - The Society For Science & The Public: Ten Tips From Davidson Fellows on How to Be Successful in STEM
EVANS TEEN AWARDED $25,000 FOR ALZHEIMER’S RESEARCH
Alexander Kirov to be Named a 2017 Davidson Fellow
Click the links below to see hi-res photos of Alexander:
Started in 1999, the Davidson Institute for Talent Development is a 501(c)3 private operating foundation. Our mission is to recognize, nurture and support profoundly intelligent young people ages 18 and under, and to provide opportunities for them to develop their talents to make a positive difference.
Profoundly gifted students are those who score in the 99.9th percentile on IQ and achievement tests. Read more about this population in this article.