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Research at Mass General
Carla D'Avanzo, PhD, is a postdoctoral fellow in the laboratory of Doo Yeon Kim, PhD. She is part of a team that developed a gel matrix capable of reproducing the symptoms of Alzheimer's disease in a more lifelike 3D environment.
When I was a kid, if you asked me; "What do you want to be when you grow up?” I would always reply; “I want to be a lawyer!” But when I started high school, I fell in love with biology and chemistry.
I found it so interesting to study how human bodies work and I became passionate about understanding human diseases, their causes, and how to defeat them.
Carla D'Avanzo, PhD
Thus, when it was time to choose my university path, I decided to pursue a bachelor’s degree in Biotechnology of Health followed by a master’s degree in Pharmaceutical Biotechnology at the University of Naples, “Federico II” in Italy.
During those years at the University, I became fascinated by neuroscience. I found it exciting and challenging at the same time that so little was known about such a powerful human organ—the brain.
Those feelings led me to a PhD program in neuroscience in the same laboratory where I conducted my master’s thesis. It was at that time that I started working on Alzheimer’s disease (AD).
The choice of a research project focused on AD was not random. My grandpa developed Alzheimer’s disease when I was 10 years old, and that experience left a mark on me. It was so sad that he couldn’t remember my name anymore, even though I carry his same first name.
He also couldn’t take me out for nice walks like he used to because he would get lost on his way back home. I really wanted to understand what happened in my grandpa’s brain at that time, and try to help the millions of people worldwide who are also affected by this terrible disease.
I was so excited when in 2011 I had the opportunity to join the laboratory of Dora Kovacs, PhD, at Massachusetts General Hospital (MGH) as a visiting PhD student, and be part of an excellent group of neurobiologists in the Genetics and Aging Unit led by Rudolph Tanzi, PhD.
The following year, I decided to stay on as a postdoc in the same lab under the supervision of Doo Yeon Kim, PhD.
I’m so glad to be working with Dr. Kim, who is a great scientist and great mentor. After moving to his laboratory, I contributed to the development of a unique three-dimensional (3D) human cell model that is able to reproduce AD “in a dish."
AD patients’ brains are characterized by the presence of amyloid plaques and neurofibrillary tangles. The plaques are aggregates of a “sticky” protein called amyloid. In AD, they collect outside the cells and cause brain cell death.
The tangles are agglomerates of the protein tau, which in AD conditions aggregate in a thread-like form inside brain cells, also contributing to cell death.
One of the challenges in studying the progression of Alzheimer’s disease in the laboratory is that the brain exists in three-dimensions. A Petri dish is flat. Thus it has been difficult to replicate the disease solely by culturing neuronal stem cells and growing them in a dish.
Our novel cell culture model is made of a three-dimensional gel matrix that is capable of housing and supporting neuronal stem cells that have been genetically engineered to develop the same plaques and tangles found in the genetic form of Alzheimer’s disease.
The gel not only provides a more brain-like environment for the neurons, allowing them to create more connections, it also helps to retain the Alzheimer’s-linked proteins that are produced by the genetically engineered neuronal cells.
In two-dimensional models, the cells are kept in a liquid media that provides them with nourishment. When the media has to be switched out to provide the cells with a fresh supply of nutrients, many of the Alzheimer's-linked proteins released by the cells are lost in the liquid exchange. Thus we do not see the same buildup of proteins that happens in the brain over time.
The gel we developed is also kept in a liquid media, but it does a better job of retaining the proteins when the media is changed, allowing the plaques and tangles to form in a more natural and progressive fashion—like they do in the human brain.
This new model could represent a big step forward in Alzheimer’s research, as it will allow investigators to test thousands of chemical compounds against a more realistic model of the disease, which could speed development of new therapies.
Our 3D culture model was one of the “10 Breakthrough Technologies of 2015” by MIT Technology Review, and chosen for a 2015 Smithsonian American Ingenuity Award.
During my postdoctoral training, I have been actively involved with social activities in the Boston scientific community in addition to doing research. I have been co-chair of the Mass General Postdoc Association (MGPA) for two years, where I organized career development and networking events. My responsibilities included inviting relevant speakers, managing budgets, defining programs and moderating panel discussions.
I also presented on my research at science communication events along with postdocs from other Boston biomedical institutions, with the goal of making our science more accessible and comprehensible to the general public.
I strongly believe that building a postdoctoral and professional network (both within and outside of Mass General), is not only important for career development of junior researchers, but also for accelerating scientific discovery.”
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