Presentation of the AGA William Beaumont Prize in Gastroenterology to Anil K. Rustgi, MD

We are pleased to report that the American Gastroenterological Association (AGA) has elected to honor our colleague and friend, Dr Anil Rustgi, as the recipient of the 2023 William Beaumont Prize in Gastroenterology. The prize was initially given every 3 years and has been awarded annually since 2015; it “recognizes an individual who has made a major contribution that has significantly advanced the care of patients with digestive diseases through clinical or translational research.”1American Gastroenterological Association. William Beaumont Prize in Gastroenterology.https://gastro.org/membership/recognition-awards/william-beaumont-prize-in-gastroenterology/Google Scholar Dr Rustgi’s research track record and accomplishments are reflected perfectly by the prize selection criteria, as he has been a world class investigator and gastroenterology leader for more than 3 decades. Through discoveries in the laboratory and the clinic, as well as through his mentoring and leadership, he has had a lasting impact on the field of digestive diseases. We begin with a brief historical perspective to highlight the significance of the Beaumont Prize. The Prize was created in 1976,2Kern F. Presentation of the first Beaumont Prize to Roderic A. Gregory and Viktor Mutt.Gastroenterology. 1976; 71: 542-551Abstract Full Text PDF Scopus (1) Google Scholar as described in its first presentation published in Gastroenterology (Photo 1, left panel). As described in the write-up by Dr Fred Kern Jr, past AGA president,2Kern F. Presentation of the first Beaumont Prize to Roderic A. Gregory and Viktor Mutt.Gastroenterology. 1976; 71: 542-551Abstract Full Text PDF Scopus (1) Google Scholar Dr William Beaumont was a US Army physician stationed at Fort Mackinac, Michigan. In 1822, Dr Beaumont was called to a nearby fur trading post to treat Alexis St Martin, who was wounded by an accidental gun discharge. The wound resulted in a permanent fistula from the stomach to the abdominal wall. After discharge from the Army hospital, Dr Beaumont took Mr St Martin into his home and nurtured him back to health. Several years later, after full recovery, Dr Beaumont recognized the opportunity that the gastric–cutaneous fistula provided for research on gastric physiology. With fully informed consent that would be approved today by any stringent Human Subjects Review Committee, Dr Beaumont began a historic series of 238 experiments spanning 8 years, while being stationed at 5 different army posts. The results of these carefully conducted and recorded experiments were published in 1833 in a classic book (Photo 1, right panel) that formed the basis of current gastric physiology. Fast forward 47 years from the first presentation of the AGA William Beaumont Prize in Gastroenterology,2Kern F. Presentation of the first Beaumont Prize to Roderic A. Gregory and Viktor Mutt.Gastroenterology. 1976; 71: 542-551Abstract Full Text PDF Scopus (1) Google Scholar we are humbled to introduce you to Dr Anil Rustgi. Anil was born in New Haven, Connecticut, the son of Moti L. and Kamla Rustgi, who had both emigrated from Delhi, India. While his mother was the backbone of the family, his father was a Professor of Physics who spent most of his career at the University of Buffalo. Their devotion to the education and scholarly success of Anil and his brother Vinod (a renowned hepatologist, currently Director of Hepatology and Distinguished University Professor at Rutgers University’s Robert Wood Johnson Medical School) and many others, led Anil and Vinod to establish the AGA International Travel Award in honor of their parents. Anil met his wife, Poonam Sehgal, a physician, during his gastroenterology fellowship at Massachusetts General Hospital (MGH). They have a son, Naryan, and a daughter, Sabrina. Anil attributes so much to his wife and children for their enduring support and love. Anil spent his early years (ages 2–6 years) in India (attending Happy School!) then returned to the United States for all of his formal education, developing a passion for history and literature, along with sports trivia. He attended college at Yale University, graduating summa cum laude with a Bachelor of Science degree in molecular physics and biochemistry, then attended Duke University Medical School, where he was elected to the Alpha Omega Alpha Honor Medical Society and received several prizes. He then completed his residency at Beth Israel Hospital in Boston, followed by a fellowship in gastroenterology at MGH under the tutelage of the late Dr Kurt J. Isselbacher and Dr Daniel K. Podolsky (currently President of UT Southwestern Medical Center). It was there, under the early mentorship of Dr René Bernards in the MGH Cancer Center, that Anil developed an interest and a passion for cancer research, and recognized the opportunity to make an impact on what was an underdeveloped field of gastrointestinal cancers. After his fellowship, Anil established an independent laboratory in the MGH gastroenterology unit in 1992, and quickly rose to the rank of Associate Professor by 1998. That same year, the University of Pennsylvania Medical School (Penn) recognized Anil as a rising superstar and recruited him as their Division Chief of Gastroenterology and the T. Grier Miller Professor of Medicine. During his 20-year tenure at Penn, Anil increased the number of faculty, expanded the gastroenterology fellowship and subspecialty fellowship programs, grew the National Institutes of Health and clinical research portfolio, expanded the regionalized clinical gastroenterology practices, and evolved Penn gastroenterology into arguably the best in the country at that time. In early 2019, Anil was recruited to the Columbia University Irving Medical Center as Director of the Herbert Irving Comprehensive Cancer Center, Herbert and Florence Irving Professor of Medicine, Associate Dean of Oncology at the Vagelos College of Physicians and Surgeons, and Chief of Cancer Services at New York Presbyterian Hospital (Columbia University Irving Medical Center campus). He stepped quickly into this leadership role, while continuing to oversee a highly productive laboratory (Photo 2), renewing the National Cancer Institute P30 Cancer Center Support Grant, and recruiting numerous established faculty and rising stars in the cancer field. In June 2020, Anil was asked by Columbia University’s President, in the midst of the outbreak of the COVID-19 pandemic in New York City, to serve as Interim Executive Vice President and Dean of the Faculties of Health Science and Medicine at Columbia University. In this role, he guided the Heath Science and Medicine campus through a most difficult period, which he did until February 2022 and then returned to his aforementioned roles. Anil has been a highly productive and innovative investigator. He has studied and elucidated fundamental aspects of gastrointestinal epithelial biology, spanning the esophagus, pancreas, and colon. Driven by a desire to unravel common and divergent mechanisms, Anil studied tissue metaplasia, the continuum from normal epithelial homeostasis to precancer to cancer. Furthermore, his research delved into the tumor microenvironment and tumor metastasis. Anil developed various genetic and nongenetic models of esophageal biology and cancers therein. This included the first robust model of esophageal squamous cell carcinoma through conditional deletion of p120-catenin (Cancer Cell 2011;19:470–483). These mouse models suggested the critical importance of the tumor microenvironment (EMBO Rep 2021;22:e48351) and further studies elucidated the importance of hepatocyte growth factor, interleukin 6, CCL5, and CD38+ myeloid-derived suppressor cells (Proc Natl Acad Sci U S A 2010;107:11026–11031; Cancer Res 2015;75:4074–4085; Cancer Res 2018;78:4957–4970; JCI Insight 2018;3:e97022). More recently, the Rustgi laboratory has begun to unravel the mechanisms underlying esophageal squamous cell carcinoma metastasis, specifically, the roles of p53 and Survivin (Genes Dev 2021;35:528–541). Some of this work has been translated into upcoming phase 1 clinical trials. Simultaneously, Anil became interested in basic aspects of esophageal epithelial biology, His group was the first to identify a subpopulation of basal cells as stem cells and show that they were heterogeneous (J Clin Invest 2008;118:3860–3869; J Clin Invest 2017;127:2378–2391; Cell Stem Cell 2021;28:1343–1361). He identified unique markers for these cells, and then developed protocols for the differentiation of human-induced pluripotent stem cells into esophageal squamous epithelial cells. In addition, the Rustgi laboratory was a pioneer in the development of 3-dimensional (3D) organotypic cultures of esophageal epithelial cells (Genes Dev 2007;21:2788–803; Proc Natl Acad Sci U S A 2010;107:11026–11031; Nat Protoc 2012;7:235–246), and 3D organoid development from mouse and human tissues (Curr Protoc Stem Cell Biol 2020;53:e109; Sci Rep 2021;11:21304). The strength of this work, now done in collaboration with Drs Hiro Nakagawa (himself a pioneer in the field) and Joel Gabre, both faculty at Columbia University, has been that patient-derived organoids can maintain the in vivo histology and disease behavior, thereby mimicking the continuum from normal to preneoplasia to neoplasia, and allowing for the testing of precision-based therapeutics. Anil’s work has also involved the investigation of Barrett’s esophagus and esophageal adenocarcinoma. As part of the Barrett’s Esophageal Translational Research Network (supported by the National Cancer Institute), he studied in detail the role of the microenvironment (eg, proinflammatory cytokines and fibroblasts) and characterized several 3D organoid systems. He collaborated on novel mouse models of Barrett’s esophagus (Cancer Cell 2012;21:36–51), and his work on Barrett’s esophagus and esophageal cancer led to his collaborative 2022 multi–principal investigators R01 grant award (with Drs James Wells, Marcia Cruz-Correa, and Joel Gabre) to study the role of gastric metaplasia as part of the new National Cancer Institute Program on the Origins of Gastroesophageal Cancers. Furthermore, Anil has, throughout his career, achieved equally impactful accomplishments in research focused on the pancreas and colon, areas funded further by the National Institutes of Health. In the context of the pancreas, he has studied mechanisms underlying acinar–ductal metaplasia, as well as pancreatic carcinogenesis. He identified a central role for the Prrx1 homeodomain transcription factor (Genes Dev 2013;27:288–300) and the ETS transcription factor ETV1 (Gastroenterology 2016;151:540–553.e14). He has revealed how primary pancreatic cancer cells metastasize through a continuum of epithelial-to-mesenchymal transition (to the lung) to mesenchymal-to-epithelial transition (to the liver) (Dev Cell 2018;45:696–711.e8). Most recently, his laboratory found that the parathyroid hormone–related protein is frequently amplified as part of the KRAS amplicon in pancreatic cancer, and this amplification drives both primary and metastatic tumors (Cancer Discov 2021;11:1774–1791). His laboratory has made similar fundamental contributions to colorectal cancer pathogenesis and biology, with recent discoveries of key roles for the LIN28B messenger RNA binding protein (Genes Dev 2013;27:2233–2245; PLoS Genet 2015;11:e1005408; JCI Insight 2021;6:e140382), which, in part, suppresses the Let-7 microRNAs. He has used 3D organoids in both pancreatic and colon research to permit him to dissect fundamental mechanistic pathways. Dr Rustgi has been elected to the American Society of Clinical Investigation, the Association of American Physicians (he presently serves on its Council), American Association for the Advancement of Science, and National Academy of Medicine, and was selected as an American Cancer Society Research Professor. He is former President of the AGA,3Wu G.D. Yang V.W. Omary M.B. Our New President—Anil K. Rustgi, MD.Gastroenterology. 2013; 144: 1129-1135Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Editor-in-Chief of Gastroenterology, President of the International Society of Gastroenterological Carcinogenesis, and President of the American Pancreatic Association. He is past recipient of the AGA Julius Friedenwald Medal,4Falk G.W. Ginsberg G.G. Katzka D.A. et al.Presentation of the Julius M. Friedenwald Medal to Anil K. Rustgi.Gastroenterology. 2017; 152: 2063-2067Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar the AGA Distinguished Mentor Award, and the AGA Research Mentor Award (Gastrointestinal Oncology Council Section). He has received several mentorship awards for faculty, postdoctoral fellowship, and MD, PhD training. More than 45 postdoctoral fellows (many of whom have faculty and leadership positions) and more than 40 students have worked in his laboratory, a point of pride for him. In closing, we are honored to present to the readership of Gastroenterology, Dr Anil K. Rustgi, the 2023 recipient of the prestigious AGA William Beaumont Prize in Gastroenterology. Given Anil’s outstanding and remarkable research discoveries, research mentoring, service and leadership contributions, and dedication for more than 30 years, it is hard to imagine someone more deserving of this recognition. As written by Dr Fred Kern 47 years ago in his inauguration note of the prize, “We hope that this Award . . . will be perceived as the Nobel Prize of Gastroenterology”—we wholeheartedly agree! Indeed, as Dr Kern noted about this prize’s recipients “. . . like Beaumont, they recognized an opportunity to make a contribution to medical science. Like Beaumont, they devoted years of single-minded labor to pursuing that opportunity without any assurance that their efforts would be successful. And, like Beaumont, their genius produced work that changed the course of medical science.” The authors are grateful to Alison Kim and Nick Tomeo from the AGA who provided key information related to the history of the Beaumont Prize. We also thank our colleagues who have co-signed Dr Rustgi's nomination letter: Drs Rick Blumberg, Hans Clevers, Gail Hecht, Peter Kahrilas, Anna Lok, Chung Owyang, Norman Sharpless, Jerry Turner, Gay Wu, and Vincent Yang.