I was appointed in 2018, but I was unable to attend my induction ceremony. Then the pandemic hit in 2020, moving the meeting to a virtual format and postponing my induction again. Now, through virtual meetings, a 2022 workshop which I co-organized for the Vatican and finally this in-person September meeting, I’ve had the opportunity to witness how valuable and important this Academy is for the world of science, for bridging different disciplines and sharing different perspectives for positive outcome. I am so fortunate to be a part of this wonderful Academy and its mission.
In my own scientific career, I was initially trained as a physical chemist. As a graduate student at Princeton University, I then began working in carbohydrate chemistry. As I neared completion of my PhD studies, I heard a seminar by then the late Howard Green, who was able to take a piece of human skin and isolate from it cells that he could passage endlessly without their losing the ability to make skin. I soon joined his lab at MIT, where I began a career at the biomedical interface, bringing molecular biology to the fascinating problem of how cells within our body are able to make and repair tissues.
The cells that we were culturing from skin were the first tissue stem cells that were ever cultured in a lab. Howard Green went on to use that technology for the treatment of burn patients. It is still in place today. I was interested in how these adult stem cells worked, what gave them these properties to divide endlessly to be able to make tissue and repair tissue.
It turns out that every tissue of our body has reservoirs of tissue stem cells that are dedicated to be able to replace dying cells and repair damaged tissue. We’re losing 80 billion cells a day from our body, and the stem cells of our body repair and replace them.
As a young Professor, I elucidated the genetic basis of a group of different blistering skin disorders. Knowing the genetic bases for inherited childhood skin disorders has served as the platform for gene editing and gene replacement to correct defects in the skin of affected children, work that has been done by a colleague of mine, Michele de Luca. The pioneering technology of Green has also been used to culture corneal epithelial cells and restore corneal blindness. In the current decade, the field now has the ability to culture and study the properties of a many different tissue stem cells. Cell and organoid culture has revolutionized the field of stem cell biology as we know it today and the use of stem cells in a regenerative setting.
So, over my independent career beginning at the University of Chicago with the experience that I’ve described to you, but then also continuing at Rockefeller University for the last twenty years, I continue to work on how stem cells divide, how they make tissue, how they repair wounds. As we understand more and more about the process, it has allowed me to focus on how stem cells in tissues cope with the stresses of our environment. Our skin is exposed to not only wounds, but also mechanical stress, ultraviolet radiation, noxious agents, pathogens, infections and allergens. By understanding how the stem cells in the tissue respond, we can begin to understand how the stem cells go awry in disorders such as chronic inflammatory disorders and cancer. For instance, in the treatment of cancers, what often makes people sick is that the therapeutics harm our normal tissues as well as our cancer tissue. It’s our premise that if we can understand enough about the differences between normal stem cells and cancer stem cells we should be able to design therapeutics that will kill the cancer cells without harming the normal stem cells. So those are the kinds of experiments that my students and postdocs are doing now in the laboratory. With regards to inflammatory disorders, we discovered that stored within the DNA of its nucleus, a skin stem cell retains memories of its past experiences. ‘Epigenetic memory’ enables the cell to repair wounds faster the next time skin encounters an injury. It enables tissues to respond to pathogens it has never encountered before. But it also has downsides – heightened reactions to inflammation and possibly even increased susceptibility to cancer. We’re working on how we can erase the bad memories that stem cells have that contribute to chronic inflammatory disorders and still keep the good memories that stem cells have in terms of being able to repair wounds. These kinds of avenues continue to inspire me after four decades of research in tissue stem cell biology.