Introducing Saul J. Karpen, MD, PhD, the 77th President of AASLD

It is our honor and distinct pleasure to introduce Saul J. Karpen, MD, PhD, as the 77th president of the American Association for the Study of Liver Diseases (AASLD), and notably the 5th pediatrician to serve as president. Saul’s impact in the field of hepatology has been enormous and includes contributions to clinical practice, basic science research, translational research, national service, and, in his role, as a mentor. As colleagues who have worked with Saul and/or trained under Saul’s guidance, we are grateful for the opportunity to share a personal side of our society’s next president. BACKGROUND, EDUCATION, AND TRAINING Saul was born in Norwood, New Jersey, on August 11, 1960. His father, Seymour (“Sy”) Karpen, was born in the Bronx, joined the army in 1943 at age 17 in lieu of going to college, fought and was wounded in the Battle of the Bulge, and then returned home with a Bronze Star and Purple Heart. He married Saul’s mother, Leah, a librarian and NYU graduate, and moved to the small New Jersey town of Norwood (pop 4000) to help raise a family and run a small local company—“Karpen’s Roofing and Sheet Metal.” This is where Saul spent his formative years, growing up with an older sister (who became an astrophysicist and now heads the Space Weather Lab at the NASA Goddard Space Flight Center in Maryland) and brother (who became a molecular biologist and is now a prominent genetic researcher at UC Berkley). Sy Karpen’s army stories ingrained in Saul the importance of service and a desire to make a difference, whereas working alongside his father introduced Saul to the world of technology and engineering. Saul remembers a childhood of making construction designs, running heavy machinery, cutting sheet metal, and “fixing things.” It was these experiences and a “fixing-of-problems” mentality that led him to apply to engineering schools, ultimately choosing the University of Pennsylvania’s biomedical engineering program. At Penn, Saul discovered the biology classes were as much fun (and easier) than his engineering courses. He jumped at the opportunity to do undergraduate research in orthopedics and material sciences, applying his sheet metal skills to design better artificial joints. Perhaps as important for his future path, he and his friends would frequent a McDonald’s at the nearby Children’s Hospital of Philadelphia, where Saul was introduced to pediatric physicians. Although not yet differentiated (adult vs. pediatric medicine), Saul became hooked on applying engineering to medicine and looked to Medical Scientist Training Programs to pursue that path. Saul joined the MD-PhD program at Mt. Sinai in 1982, where his interests quickly turned to the exciting and rapidly developing field of molecular biology. Saul dabbled in aspects of liver regeneration in his rotations but finally found his PhD home in hepatology with George Acs, MD, PhD. Acs’s lab was the first to culture HBV in any cell line, and Saul undertook an engineer’s approach to the ambitious project of trying to understand how HBV gene expression was controlled. Saul’s work ultimately identified 2 upstream sites for transcription factors (one was HNF1α, whereas the other site bound a transcription factor that would become a focus of many years of future investigation in the nuclear receptor field). Notably, his research in Acs's lab was reported in the first of many papers that Saul would publish in Hepatology. Saul also took advantage of the opportunity to learn from the remarkable concentration of prominent hepatologists at Mt Sinai, which included Hans Popper, MD (14th President of AASLD), Fenton Schaffner, MD (28th President of AASLD), and Paul Berk, MD, FAASLD (40th President of AASLD). For those of us who have worked with Saul, we know from his own recollections that the interactions with Hans Popper, the undisputed father of modern hepatology, were fortunate and the most meaningful as a medical and graduate student. Saul remembers being inspired by Dr Popper, who, in the late stages of his career, would sit in the front row of a seminar on the most up-to-date aspects of molecular biology and ask the best questions. In fact, one of the most treasured publications for Saul is not in a high-impact journal paper indexed by PubMed. Rather, it is an article in the proceedings of a Falk Symposium titled “Regulation of hepatitis B virus in liver cells and culture", in which Saul was a co-author with Hans Popper. CLINICAL AND SCIENTIFIC CAREER Saul officially began his academic career in hepatology at Yale, first as a pediatric resident, followed by a fellowship and then a faculty appointment in 1994. Saul intentionally chose to focus on children because of the relative dearth of research on childhood diseases. These were vibrant years in another epicenter of leaders in the field. Saul was drawn by the array of talent in liver research at Yale, principally to the lab of Fred Suchy (54th President of AASLD), who was chief of the Pediatric GI/Liver division. For his research, Saul applied his molecular biology skills to identify regulatory sequences and transcription factors (including a nuclear receptor) controlling expression of the bile acid transporter NTCP. At Yale, Saul also had the benefit of mentorship and collaborations with other Yale hepatology luminaries in addition to Fred Suchy, including James Boyer (31st President of AASLD), Roberto J. Groszmann (recipient of the 2002 Distinguished Achievement Award for the AASLD), and Michael Nathanson (former editor of Hepatology). The friendships Saul made during these critical early-career years have been the closest and most enduring to date. Benjamin Shneider, MD (a major thought leader in pediatric hepatology) and Sundararajah Thevananther, PhD (who would later co-build Saul’s research program in Houston) were training at Yale, as were Michael Trauner, MD, Marco Arese, MD, and Emmanuel Gonzales, MD. Saul’s groundbreaking work on transcriptional regulation of NTCP soon attracted the attention of younger talent and postdoctoral fellows from other research groups and became the center of collaborative efforts across labs at Yale at that time. The quality of Saul’s mentorship was already apparent at this early stage of his career, as he promoted the careers of younger colleagues by selflessly offering his support and sharing his ideas. Saul, Michael Trauner, and Marco Arrese engaged in close research collaborations concerning the transcriptional regulation of NTCP in inflammation-induced cholestasis, which later laid the foundation for many other seminal papers from Saul’s lab on this central aspect in the pathogenesis of sepsis and TPN-associated cholestasis. Through this early work, Saul, Michael, and Marco developed an enduring friendship, reflected in subsequent collaborative endeavors and periodic inter-institutional visits. Each time they meet, a photograph is taken, documenting their shared history over the last 30 years (Figure 1). Apart from his passion for science, there is always time for enlightening discussions about history and contemporary literature, where Saul shares his wonderful sense of humor which is greatly appreciated by colleagues across the globe.FIGURE 1: Saul Karpen, Marco Arrese, and Michael Trauner in pictures over the years, capturing the evolution of friendships and collaborations planted in hepatology and blossoming through AASLD. (A) 1997 in New Haven, Saul is left; (B) 2011 in Vienna, Saul is left; and (C) 2024 in San Diego at The Liver Meeting, Saul is middle.In 1999, Saul made a life-changing trip to Texas Children’s Hospital in Houston, by invitation from the leading pediatrician at the time, Ralph Feigin, MD. Unbeknownst to Saul, Ralph Feigin was always one to aggressively pursue talent when he saw it. This visit, where Saul gave a talk on nuclear receptors and cholestasis, was followed by a series of invitations from Ralph Feigin. Ultimately, Saul was convinced to move and start anew in a large but often academically-overlooked city and build a liver program for the nation’s largest children’s hospital. From 2000 to 2011, Saul teamed up with a new group of colleagues in Houston that spanned clinical and research expertise, including John Goss, MD (transplant surgeon), Milton Finegold, MD (pediatric liver pathologist), John Vierling, MD (57th President of AASLD), Mary Brandt, MD (pediatric surgeon), Blaine Hollinger, MD (hepatitis B expert), and David Moore, PhD and Bert O’Malley, PhD (nuclear receptor biologists). In this environment, Saul’s clinical and research programs accelerated. He helped build the largest pediatric liver transplant center in the country, which to this day still consistently ranks #1 or #2 in pediatric transplant volume in the United States. Saul’s group was also instrumental in identifying plant sterols in TPN as the inciting agent in TPN-associated cholestasis, leading to seminars given around the world, which have since changed daily NICU practice and led to dramatic reductions in morbidity and mortality in premature infants. In Houston, Saul also began his work on the serious liver disease biliary atresia. He started by securing Baylor’s spot in the ChiLDReN Network, an NIH-sponsored consortium led by Ronald Sokol, MD (69th President of AASLD), to study cholestatic liver diseases. In this setting, Saul helped increase enrollment in the landmark randomized-controlled trial for steroids, a study led by Jorge Bezerra, MD (71st President of AASLD). Saul also examined the large number of patients at Texas Children’s Hospital to make important clinical observations about biliary atresia that had not been appreciated. Saul helped establish that biliary atresia starts in utero, rather than after birth, which had been previously thought. Saul also helped to identify the cardiac effects of high bile acids in biliary atresia and other forms of cholestasis, which he and his colleagues were the first to term “cholecardia.” In 2011, Saul accepted the position as Professor, Division Chief of Pediatric Gastroenterology, Hepatology and Nutrition, and Raymond F. Schinazi Distinguished Biomedical Chair at the Emory School of Medicine. In 2014, he partnered with Paul Dawson, PhD, a world expert in bile acid transport and metabolism, to form a joint laboratory. The goal of the “Saul-Paul Lab” was to understand how changes in bile acid homeostasis contribute to hepatic and metabolic diseases and to exploit those insights to develop new preventative measures and therapies. This work highlighted the role of retained bile acids in liver disease pathology and the mechanism of action of ileal bile acid transport inhibitors, which are now in clinical use in pediatric patients with Progressive Familial Intrahepatic Cholestasis and Alagille Syndrome. Saul also immediately capitalized on Emory’s strong genetics program. He created the now ubiquitous “EGL Emory Genetics Panel,” which industry has since adopted and provided free of charge for any baby with cholestasis. The service has transformed care and catapulted the field of neonatal cholestasis into the ever-expanding world of genetic diagnoses. Saul’s group also identified a potential genetic cause of biliary atresia—a mutation in the ciliopathy gene PKD1L1—and created a corresponding mouse model, which was recently lauded as a breakthrough in a recent NIDDK report. Finally, during his time at Emory, Saul partnered with industry to lead a worldwide trial for ileal bile acid transporter inhibitors in biliary atresia. Though the results of the trial are still not known, these efforts will undoubtedly serve as a model for how to collaborate with pharmaceutical companies to test therapies for biliary atresia in the future. Saul’s drive to contribute and serve now continues at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University (VCU; Arun Sanyal, Director, 61st President of the AASLD), where he recently accepted the position of Chief Scientific Officer. To VCU, Saul brings a wealth of knowledge and experience guiding highly successful collaborations, now with the added goal of advancing both pediatric and adult hepatology. He also brings invaluable insights gained from his scientific contributions supported by continuous support from the NIH in the form of K08, R01, R21, and U01 grants and disseminated in >200 publications and multiple textbook chapters, which include transcription control of NTCP, nuclear receptor involvement in cholestasis diseases, prevention of TPN-associated cholestasis, identification of an early onset for biliary atresia, characterization of bile acid effects on the heart, therapeutic targeting of bile acid transporters for liver disease, evaluating cholestatic infants through genetic testing, and creating a genetic mouse model for biliary atresia. He also brings many of the other contributions through collaborations with academic societies such as AASLD, NASPGHAN, AAP/SPR, AGA, the Cystic Fibrosis Foundation, and Transplant Societies, which have involved giving and/or organizing talks that have guided clinicians caring for countless numbers of children afflicted by liver disease. PERSONAL LIFE AND FAMILY Throughout his journey through hepatology, Saul has been joined by some very faithful fellow-travelers. Saul’s daughter Emily was born in 1999 in New Haven, and his son Matthew was born in 2002 in Houston. Saul could be found just as often at their swim meets as at lab or in clinic in the 2000s. Emily is now off to a successful career start as a lawyer in Los Angeles, while Matthew plans to follow in his father’s footsteps in medicine. In 2022, Saul and Binita Kamath, MBBChir, married in London. Binita is the division chief of Pediatric Gastroenterology, Hepatology, and Nutrition at the Children’s Hospital of Philadelphia, the same place a college-aged Saul would visit for fast food and to learn about medicine. Binita’s clinical and research focus is on Alagille Syndrome, a disease that in many ways is complementary to biliary atresia (bile ducts are missing inside the liver in Alagille Syndrome, and bile ducts are missing outside the liver in biliary atresia). Both have dynamic personalities, and given that Binita and Saul are leaders in the study of their respective diseases, many younger pediatric hepatologists have fondly and informally dubbed Binita and Saul as the current “Queen and King” of pediatric hepatology. VISION FOR THE AASLD Saul assumes the Presidency in 2026 as one of only 5 pediatricians in the Society’s 70+ year history. He credits AASLD for being a home during his formative years, starting with interactions with Hans Popper as a budding MD/PhD student. Saul sees the presidency as an incredible honor, is in awe of the current membership, and recognizes the enormous responsibility to influence the next generation of hepatologists. Saul’s vision is to help AALSD equip members now and in the future with the best information possible, to fill scientific gaps and provide the best possible care to those suffering from liver diseases.