Ambros honored for discovery of microRNA and its role in post-transcriptional gene regulation
UMass Chan Medical School researcher Victor R. Ambros, PhD, will share the 2024 Nobel Prize in Physiology or Medicine for his co-discovery of microRNA, the very short, single-stranded RNA molecules that are now understood to play a critical role in post-transcriptional gene regulation. The announcement was made this morning at Karolinska Institute in Stockholm, Sweden. It is the second time that a UMass Chan scientist has been recognized by the Nobel Assembly. UMass Chan Distinguished Professor Craig C. Mello, PhD, was co-recipient of the 2006 Nobel Prize in Physiology or Medicine for his discovery of RNA interference or RNAi.
A central figure in ribonucleic acid (RNA) biology, Dr. Ambros, the Silverman Chair in Natural Sciences and professor of molecular medicine at UMass Chan, will share the award with his longtime collaborator Gary B. Ruvkun, PhD, of Massachusetts General Hospital and Harvard Medical School.
“Victor has had a profound impact on our world-leading RNA community,” said UMass Chan Medical School Chancellor Michael F. Collins. “He is an integral member of a remarkable group of RNA researchers here who together are advancing the world’s understanding of biological mechanisms and furthering the field of biomedical sciences. The Nobel Prize confirms what the UMass Chan community already knows of Victor’s contributions to scientific discovery and innovation.”
“On behalf of the University of Massachusetts, I applaud Dr. Ambros and Dr. Ruvkun as they receive this distinguished honor,” said University of Massachusetts President Marty Meehan. “UMass Chan is truly at the epicenter of a revolution in biomedical research. For the second time, our distinguished faculty has been recognized by the Nobel Assembly for breakthroughs that have changed the world’s understanding of a foundational biological process and have the potential to provide new avenues for the treatment of a variety of human diseases.”
When Ambros and his lab discovered microRNA, also known as miRNA, in the nematode C. elegans in 1993, its broad implications for human biology weren’t immediately apparent. However, scientists now know the ability of these tiny RNA molecules to regulate or silence gene expression has a profound and far-reaching impact on most biological processes governing health and disease, including development, aging, cancer, diabetes, heart disease, Alzheimer’s disease, schizophrenia and many others.
Surprisingly abundant in human cells, these molecules escaped notice by scientists because of their small size (approximately 22 nucleotides-long compared to protein coding genes that contain thousands of nucleotides). Researchers have now identified more than 1,000 unique human miRNAs that are responsible for regulating more than half of all human genes.
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Ambros and his lab discovered the first miRNA while investigating the genetics of C. elegans. Looking to explain developmental abnormalities in worms caused by a mutation to the lin-4 gene, Ambros knew from his previous work that this gene somehow controlled the output of the lin-14 protein. Worms with mutant lin-4 had persistently high levels of lin-14, which affected their development, causing them to remain stuck in a juvenile state.
Expecting to find that the lin-4 gene coded for a regulatory protein that would stop production of the lin-14 protein, Ambros and colleagues found something altogether different. Instead, lin-4 encoded for a very short, single-stranded RNA molecule that scientists now know is miRNA. This miRNA was responsible for putting the brakes on the machinery necessary for creating the lin-14 protein. As a result, worms with a mutated lin-4 gene were unable to produce the miRNA necessary for shutting off the lin-14 gene that would allow the worm to mature normally.
The discovery, however, seemed more an oddity than a breakthrough at the time, in part because the lin-4 gene existed only in the worm. In 2000, Dr. Ruvkun discovered a second miRNA in C. elegans and reported evidence that miRNAs are evolutionarily ancient. By 2001, Ambros and other scientists had identified multiple miRNAs in worms, flies and humans.
Today, the discovery of miRNA is recognized as a pioneering step toward understanding that a host of different, and previously unknown, RNA molecules play a critical role in the complex regulation of genes. Scientists have gone on to show that disruption of these miRNA regulators can have a profound impact on or cause many diseases, including many types of cancers. The new field of miRNA profiling—determining the specific miRNA related to a particular cancer—is already being used in developing treatments for people with chronic lymphocytic leukemia.
Likewise, misregulation of miRNA has been associated with biological functions involving cardiac cells and the nervous system. Several research studies have found that miRNAs play a key role in the development of cardiac muscle, and that the amount of miRNA changes in hearts damaged by heart attack. Translational studies to determine if miRNA could be used as an early diagnostic tool for detecting cardiac arrhythmias such as atrial fibrillation or heart attacks are underway.
“For all of us on the University of Massachusetts Board of Trustees, I want to offer our congratulations to Dr. Ambros and Dr. Ruvkun,” said Stephen R. Karam, chairman of the University of Massachusetts Board of Trustees. “Receiving a Nobel Prize is a defining moment in a research scientist’s life and in a university’s life as well. In this case, the Nobel committee is recognizing research and scholarship that is poised to have a tremendous impact on both science and humanity.”
In 2006, Dr. Mello received the Nobel Prize in Physiology or Medicine with colleague Andrew Z. Fire, PhD, of Stanford University, for their work in discovering RNAi and demonstrating that a particular form of RNA—the cellular material responsible for the transmission of genetic information—can silence targeted genes. Mello completed his PhD research in Ambros’ lab in the 1980s.
Ambros completed his undergraduate and graduate degrees, as well as his postdoctoral research, at the Massachusetts Institute of Technology. During graduate school, he worked with David Baltimore, PhD, a co-recipient of the 1975 Nobel Prize in Physiology or Medicine for discoveries related to the interaction between tumor viruses and genetic material of the cell. In Dr. Baltimore’s lab, Ambros studied the poliovirus genome structure and replication. In 1979, he began his postdoctoral research in the lab of H. Robert Horvitz, PhD, who shared the 2002 Nobel Prize in Physiology or Medicine for his research related to genetic regulation of organ development and programmed cell death. Working as a postdoctoral fellow in Dr. Horvitz’s lab—where he met Ruvkun—Ambros focused on genetic pathways that control developmental timing in C. elegans. After completing his postdoctoral fellowship, Ambros joined the faculty at Harvard in 1984 and remained there until 1992, when he accepted a faculty position at Dartmouth. He arrived at UMass Chan in 2007. Ambros has maintained a very close collaborative relationship with Ruvkun through the years, though the two have not worked in the same laboratory since the early 1980s.
At UMass Chan, Ambros continues his research on microRNA function and gene regulation during development and is focused on understanding the genetic and molecular mechanisms that control cell division, differentiation and morphogenesis in animals. He came to UMass Chan eager to expand his work in a thriving RNA research community.
The Nobel Prize award ceremony will take place in Stockholm, Sweden, on Dec. 10, the anniversary of the death of Alfred Nobel, founder of the Nobel Prize. Established in1901, the Nobel Prize is awarded for achievements in physics, chemistry, physiology or medicine, literature and peace.
About UMass Chan Medical School
UMass Chan Medical School, one of five campuses of the University of Massachusetts system, comprises the T.H. Chan School of Medicine; the Morningside Graduate School of Biomedical Sciences; the Tan Chingfen Graduate School of Nursing; ForHealth Consulting at UMass Chan Medical School, a public service health care consulting division; and MassBiologics, the only nonprofit, FDA-licensed manufacturer of vaccines, biologics and viral vector gene therapies in the United States. At UMass Chan, we are advancing together to improve the health and wellness of our diverse communities throughout Massachusetts and across the world by leading and innovating in education, research, health care delivery and public service. UMass Chan has built a reputation as a world-class destination for biomedical research, with more than $300 million in annual funding and more than 500 active clinical trials. It is ranked among the best medical schools in the nation for primary care education and biomedical research by U.S, News and World Report. In 2021, the Medical School received a $175 million gift from The Morningside Foundation and was renamed UMass Chan Medical School. Learn more at www.umassmed.edu.
For more information:
UMass Chan Medical School and Ambros: www.umassmed.edu.
Ambros Lab: http://www.umassmed.edu/ambroslab/
Nobel Foundation: www.nobelprize.org
Ruvkun: Massachusetts General Hospital: www.massgeneral.org