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David Ornitz received his BS degree from the University of California, Davis in 1981 and his MD and PhD from the University of Washington, Seattle in 1987. Graduate training at the University of Washington was with Dr. Richard Palmiter, in the Department of Biochemistry. As a graduate student, Dr. Ornitz was at the forefront of developing transgenic mouse technology for in vivo models of cancer and as tools to identify tissue-specific transcriptional regulatory elements. Postdoctoral training was in the laboratory of Dr. Philip Leder in the Department of Genetics at Harvard Medical School. As a postdoctoral fellow, Dr. Ornitz developed a binary genetic system to model cancer and other lethal diseases in mice. He also discovered that heparan sulfate proteoglycans are necessary cofactors for Fibroblast Growth Factor (FGF) signaling. This discovery linked cell-surface and extracellular matrix molecules to growth factor signaling pathways. Dr. Ornitz joined the faculty at Washington University in St. Louis School of Medicine in 1991 and is now an Alumni Endowed Professor in the Department of Developmental Biology. He is also an elected fellow of both the American Association of Anatomy (AAA) and the American Association for the Advancement of Science (AAAS). Dr. Ornitz is currently serving as an associate editor for the journal, Developmental Dynamics. Dr. Ornitz's main interests have related to the function of genes in mouse development and physiology and the generation and analysis of mouse models for human disease. Over the past 33 years, his research has focused on the in vivo function of FGFs in development, physiology, response to injury, and cancer, and he has made significant contributions to cardiovascular, inner ear, pulmonary, and skeletal system biology. Current research focuses on the functions of FGF signaling in lung, cardiovascular, and skeletal biology. Dr. Ornitz's interest in lung development initiated with the discovery that Fibroblast Growth Factor 9 (Fgf9) has a unique expression pattern in developing lung epithelium and mesothelium. By engineering a mouse that inactivates the Fgf9 gene, the Ornitz lab discovered that FGF9 has a major role in the regulation of lung mesenchyme development. Important milestones in lung development included the identification of a feed-forward regulatory network that involves mesenchymal FGFR and Wnt/β-catenin signaling, and the discovery that FGF9 also regulates lung epithelial development. Current studies have shifted to alveologenesis, the final stage of lung development. Fgf18 expression is markedly induced during alveologenesis. The Ornitz lab engineered genetic tools to target the Fgf18 gene, allowing them to study unique cell populations that contribute to alveologenesis and probe the function of FGF18 during this process. Cardiovascular projects are investigating the role of FGF signaling in hypoxia induced pulmonary hypertension and in vascular remodeling in a mouse model of heart failure with preserved ejection fraction. In the skeletal system, the Ornitz lab discovered that the mutation in FGF receptor 3 (FGFR3) that causes Achondroplasia activates receptor signaling. His laboratory created the first transgenic mouse model for Achondroplasia and showed that activation of FGFR3 decreased the proliferation of growth plate chondrocytes. This mouse model has been instrumental in demonstrating the potential efficacy of drugs that are now being used to treat this disease. Stemming from these early studies on FGFR3 signaling in the growth plate, the Ornitz lab has more recently pursued studies directed at understanding the function of FGF ligands and receptors in skeletal development, in the osteoblast and osteocyte lineages, and how FGFR-expressing osteoprogenitor cells interact with growth plate chondrocytes to regulate bone growth and homeostasis. As a child, I was always curious about how things worked—sometimes experimenting with homemade fireworks in the driveway and tinkering with things in the garage. My high school biology teacher was a true inspiration, with a classroom filled with plants and animals. My first research experience was during high school where I worked in a laboratory at UCLA, where I grew up. Later, I attended UC Davis, where I majored in biochemistry, worked in a research lab under the mentorship of Dr. Irwin Segel, studying enzyme kinetics, and published my first paper. Inspired by two of my undergraduate professors, whom I still keep in touch with, I decided to pursue an MD-PhD program at the University of Washington in Seattle, where I did my graduate work in Dr. Richard Palmiter's lab. This was during the early days of developing transgenic mouse technology. I published a paper demonstrating that a tissue-specific gene regulatory element could be used to target a transgene to a specific cell type. Initially, we targeted pancreatic acinar cells, and later hepatocytes. Building on that, we showed that we could drive expression of an oncogene and create mouse models for various types of cancer, which proved to be quite useful. I then went on to do a postdoc at Harvard Medical School with Dr. Philip Leder. There, I developed a binary transgenic mouse system that required combining two genes to activate gene expression—a precursor to the Cre-lox system we use today, though at the time it was based on GAL4, which is still in use. I also became involved in a cancer project studying a gene called Int2, also known as fibroblast growth factor 3 (Fgf3), which had been implicated in mammary cancer in mice. I created transgenic mouse models to study this gene and became interested in identifying its receptors. This was before FGF receptors had been cloned, but during that period, the first FGF receptor was identified, and I used that information to find other FGF receptors through homology. With that background, I moved to Washington University in St. Louis (distinct from the University of Washington in Seattle) to start my own lab. One of the FGF receptors I had identified as a postdoc was FGF receptor 3. I began studying its expression patterns and conducting functional assays to understand why FGF receptor 3 differed from other FGF receptors. About a year into my junior faculty position, a couple of papers were published identifying a mutation in FGF receptor 3 as the cause of achondroplasia, the most common form of dwarfism in humans. This discovery essentially turned my lab into a bone biology lab overnight. We had the FGF receptor 3 cDNA in hand, so we were able to introduce the achondroplasia mutation into our cDNA and demonstrate that this mutation activated FGF receptor 3 signaling. At the time, it was a surprising and counterintuitive finding that activating a growth factor receptor could cause dwarfism. Later, we and others showed that FGF receptor 3 inhibits the proliferation and differentiation of chondrocytes. This discovery was fascinating and led me to pursue studying the functions of FGF signaling in skeletal biology, which I continue to work on today. My current focus is on different FGF receptors, particularly in osteoblasts and osteocytes, the cell lineages found in mature bone. As more FGF ligands were discovered over the years, I examined their expression patterns and noticed that Fgf9 had a particularly interesting profile. We decided to create a knockout mouse for Fgf9, which resulted in a striking phenotype affecting lung development. This finding prompted us to begin studying lung development, an area I am still actively involved in. Inspired by interesting expression patterns, we also generated knockout models for Fgf18 and Fgf20. Fgf20 especially caught my attention due to its prominent expression in the inner ear. In our original knockout of FGF receptor 3, we observed that the animals exhibited not only skeletal abnormalities but also hearing loss. This made FGF20 a strong candidate ligand for FGF receptor 3, and we spent several years studying inner ear development, although that is not my current focus. Fgf18 also showed interesting expression patterns in developing bone and lung, and our targeted alleles for Fgf18 have been very useful tools to study bone and lung development. To bring things up to date, my lab is now working on projects related to skeletal homeostasis and development, as well as postnatal lung development—a process known as alveologenesis. Additionally, we have ongoing cardiovascular projects. For example, we study pulmonary hypertension by exposing mice to hypoxia, which leads to vascular remodeling in the lung. We also have a heart failure project, where we induce heart failure with angiotensin II, resulting in vascular defects in the coronary arteries and systemic vasculature. The future of developmental biology is a fascinating topic, and there is still so much we do not know. One area that is becoming increasingly important is the relationship between developmental biology and regenerative medicine. Understanding developmental mechanisms will greatly enhance our ability to understand regenerative biology, so that is certainly one direction the field is heading. There is also a significant push to identify disease-causing genes, as many birth defects remain unsolved. For example, I'm part of a consortium at Washington University focused on identifying genes of unknown significance that have been found in patients in our clinics. We have a pipeline to analyze mutations discovered through sequencing, determine their functions, and use developmental biology approaches to understand how these novel genes contribute to birth defects. These are just two examples of how developmental biology will continue to play a crucial role in the future. If I were to give advice to my younger self as a researcher, I would say that I may have missed some opportunities along the way. For example, when I was studying achondroplasia, I handed that project off to the postdoc who was working on it and chose not to pursue it myself. Looking back, I think that if I had stayed involved, I might have contributed more to the therapeutic aspects of achondroplasia, which has since become a significant area for many pharmaceutical companies. So, perhaps that was a missed opportunity, but not focusing on achondroplasia freed up time to pursue other projects, several of which turned out to be quite interesting and successful. Ultimately, if I had chosen a different path, I might not have achieved success in other areas. It is hard to say what would have been best. My main advice is to follow the science—let your curiosity guide you. For me, anticipated, and importantly, unanticipated phenotypes in knockout mice have often led to new projects and many more questions. I think that is the most important lesson: don't get siloed into one frame of mind; let the science and the biology lead the way. When I'm not researching, I try to stay active. When the weather is good, I enjoy biking or running outdoors, or hiking in nearby state parks. If the weather is not great, I will go spinning indoors or hit the gym. I really enjoy being outdoors whenever possible, and over the years, I have taken many hiking trips in various mountains. Seattle was fantastic for outdoor activities. Here in Saint Louis, the mountains are farther away, so we have to travel a bit more to find good hiking spots. We often go to the Rockies, and we have done a lot of hiking in the Alps in Europe as well. That is what I enjoy doing most in my free time. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.