Presentation Information
[III-PL-1]Great minds think alike:Heart development research shaped by people along the way
Hiroyuki Yamagishi (Tokyo Metropolitan Children’s Medical Center)
My research has been shaped by many meaningful encounters. Early in my career as a pediatric cardiologist, I cared for an infant with complex congenital heart disease (CHD). This encounter became the origin of my lifelong quest to uncover its essence through developmental biology and genetics. In 1993, I was deeply inspired by the late Professor Atsuyoshi Takao’s lecture entitled “The molecular basis of cardiac malformations and pathogenesis” that led me to join his laboratory. There, I encountered the late Professor Rumiko Matsuoka, and I was trained to diagnose the infant I had cared for with 22q11.2 deletion syndrome. This experience was the starting point of my lifelong research journey.
In 1996, I joined the laboratory of Professor Deepak Srivastava in the United States as his first postdoctoral fellow and immersed myself in the forefront of heart development research. As a fellow pediatric cardiologist sharing the same passion for understanding the causes of CHD, my encounter with Professor Srivastava not only supported me throughout my research and life abroad but also greatly expanded my perspective as a scientist. Through him, I came to appreciate the meaning of the phrase, “Great minds think alike”—the power of encountering others who share the same vision across borders. After returning to Japan in 2002, I pursued the establishment of “clinical cardiac developmental biology” together with colleagues who shared the same passion for research, including Dr. Jun Maeda, Dr. Keiko Uchida and Dr. Kazuki Kodo. Through these efforts, we demonstrated that TBX1, the responsible gene for 22q11.2 deletion syndrome, is expressed not in neural crest cells but in cardiac progenitor cells derived from the second heart field, and elucidated its molecular regulatory mechanisms. These findings proposed a new concept for understanding the pathogenesis of CHD. Furthermore, we identified GATA6 as a novel disease gene causing CHD and demonstrated that molecular pathways involving GATA6 and TBX1 regulate the proliferation, migration, differentiation, and interaction of cardiac progenitor cells during cardiac morphogenesis. More recently, in Japanese patients with persistent truncus arteriosus, we identified a pathogenic TMEM260 variant (c.1617delG; designated the Keio-Tohoku variant) at a high frequency, revealing a previously unrecognized autosomal recessive inheritance pattern and providing a new perspective for genetic counseling in CHD.
Looking back, patients provided me with fundamental questions, Prof. Takao showed me the path forward, Prof. Srivastava broadened my horizons, and many colleagues of Keio Pediatric Cardiology (now directed by Dr. Takayuki Oyanagi), JSPCCS and others shared the same vision into discoveries. Each of these encounters has nurtured my journey in heart development research. I am deeply grateful for every one of them and will continue to pursue my path as a physician-scientist, advancing the philosophy of “Academic for Social”.
In 1996, I joined the laboratory of Professor Deepak Srivastava in the United States as his first postdoctoral fellow and immersed myself in the forefront of heart development research. As a fellow pediatric cardiologist sharing the same passion for understanding the causes of CHD, my encounter with Professor Srivastava not only supported me throughout my research and life abroad but also greatly expanded my perspective as a scientist. Through him, I came to appreciate the meaning of the phrase, “Great minds think alike”—the power of encountering others who share the same vision across borders. After returning to Japan in 2002, I pursued the establishment of “clinical cardiac developmental biology” together with colleagues who shared the same passion for research, including Dr. Jun Maeda, Dr. Keiko Uchida and Dr. Kazuki Kodo. Through these efforts, we demonstrated that TBX1, the responsible gene for 22q11.2 deletion syndrome, is expressed not in neural crest cells but in cardiac progenitor cells derived from the second heart field, and elucidated its molecular regulatory mechanisms. These findings proposed a new concept for understanding the pathogenesis of CHD. Furthermore, we identified GATA6 as a novel disease gene causing CHD and demonstrated that molecular pathways involving GATA6 and TBX1 regulate the proliferation, migration, differentiation, and interaction of cardiac progenitor cells during cardiac morphogenesis. More recently, in Japanese patients with persistent truncus arteriosus, we identified a pathogenic TMEM260 variant (c.1617delG; designated the Keio-Tohoku variant) at a high frequency, revealing a previously unrecognized autosomal recessive inheritance pattern and providing a new perspective for genetic counseling in CHD.
Looking back, patients provided me with fundamental questions, Prof. Takao showed me the path forward, Prof. Srivastava broadened my horizons, and many colleagues of Keio Pediatric Cardiology (now directed by Dr. Takayuki Oyanagi), JSPCCS and others shared the same vision into discoveries. Each of these encounters has nurtured my journey in heart development research. I am deeply grateful for every one of them and will continue to pursue my path as a physician-scientist, advancing the philosophy of “Academic for Social”.