Giuseppe Pettinato, Ph.D.
Dr. Pettinato is an Instructor at Harvard Medical School and holds the position of Director of the Stem Cell and Organoid Research and Engineering Center at Beth Israel Deaconess Medical Center (BIDMC). His expertise spans the fields of developmental and cell biology, bioengineering, and regenerative medicine, with a specific focus on the differentiation of human pluripotent stem cells and the development of tissue-specific organoids. He has contributed to scientific advancements through the invention of a technique that enables the rapid and high-throughput formation of embryoid bodies derived from dissociated human induced pluripotent stem cells (hiPSCs). This innovative methodology utilizes microfabricated cell-repellent microwell arrays, facilitating the efficient generation of organoids for various applications and research endeavors.
The principal focus of his research centers on the generation of liver organoids using a specialized, proprietary protocol that he has not only developed but also patented. These liver organoids exhibit the primary characteristics inherent to human primary hepatocytes. Consequently, they represent a promising resource for multifaceted applications, including cell replacement therapy for instances of acute and chronic liver failure. Additionally, these organoids serve as invaluable models for studying liver diseases such as non-alcoholic steatohepatitis (NASH), and non-alcoholic fatty liver disease (NAFLD), and for elucidating drug targeting strategies for hepatitis B virus (HBV), among other potential applications.
Leveraging his profound expertise in the field of organoid bioengineering, he has successfully advanced the creation of pancreatic organoids from human induced pluripotent stem cells (hiPSCs). These pioneering pancreatic organoids encompass both endocrine and exocrine compartments within a single construct, thus offering a remarkable platform for in vitro investigations into the intricate interactions between endocrine and exocrine cell populations. Furthermore, these innovative constructs hold promise as a prospective source for whole-pancreas replacement therapies.
More recently, drawing on his existing expertise, he has successfully devised a cutting-edge methodology to derive free-floating intestinal and colonic organoids derived from hiPSCs. These advanced organoids have exhibited a remarkable capacity to elicit dynamic responses when exposed to diverse pro-inflammatory and pro-fibrotic stimuli, resulting in a significant upregulation of collagen I and III gene expression. This compelling finding underscores the robustness of the organoid system and its ability to faithfully replicate the intricate molecular processes underlying fibrogenesis. By harnessing this novel experimental platform, we can delve deeper into the mechanisms driving fibrotic pathogenesis in a controlled and precise manner, paving the way for a comprehensive understanding of fibrotic signaling cascades in the context of gastrointestinal disorders.
These newly derived organoids leverage the potential to comprehensively investigate the underlying molecular mechanisms driving fibrosis in inflammatory bowel diseases, including the complex and multifaceted Crohn's disease. By utilizing this in vitro model, we can gain invaluable insights into the molecular cues responsible for fibrotic progression, ultimately paving the way for the development of innovative therapeutic platforms at BIDMC.