A Hidden Promise in the Language Cells Use to Communicate
Tuesday, May 8, 2018
Scientists have begun to implicate extracellular vesicles and exosomes in everything from cancer to viral infections to basic neural functioning. To Lynne Maquat, the J. Lowell Orbison Distinguished Service Alumni Professor in the Department of Biochemistry and Biophysics, the process shows how parts of the genome we used to think of as junk actually have important functions. “You could say that the host domesticated a viral sequence for its own purposes,” Maquat says. “That’s the beauty of our complexity—[these elements] allow tinkering or fine-tuning of genes.”Read More: A Hidden Promise in the Language Cells Use to Communicate
Looking to RNA for Answers
Friday, March 23, 2018
Cancer is a group of diseases in which the body’s cells divide uncontrollably and invade nearby tissues. Scientists at Wilmot Cancer Institute and the University of Rochester’s Center for RNA Biology are working to understand more about how and why this happens.
One piece of the puzzle they’re studying is ribonucleic acid, or RNA, which is found in all cells. RNA is made in the nucleus of a cell from our DNA, which holds the instruction manual for life. RNA puts those instructions into action.
RNA comes in many forms. One form, called messenger RNA (mRNA), carries those instructions out of the nucleus to the ribosomes, where proteins are made. These proteins are essential for functions ranging from digestion to protecting us from disease. If the mRNA has a bad copy of instructions, then either a faulty protein or no protein is created, leading to diseases like cancer.
Understanding the quality-control system
Lynne E. Maquat, Ph.D., director of the Center for RNA Biology, studies a quality control process that blocks cells from making faulty proteins. Called nonsense-mediated mRNA decay (NMD), this process comes into play when mRNA has a set of instructions with a mistake that will lead to short or incomplete proteins. NMD acts like a set of factory inspectors that find and destroy this mRNA before the faulty proteins can be made.
Sometimes, though, NMD doesn’t catch the mistakes and harmful proteins are made. This process plays a part in one-third of all inherited diseases, such as cystic fibrosis and muscular dystrophy, and one-third of all acquired diseases, including a number of cancers.
One reason is that tumors can influence how these inspectors work. Maquat and her team are looking for ways to stop tumors from interfering with NMD with the goal of finding new ways to treat cancer.
Slowing cancer’s growth
A team from Maquat’s lab has also identified a protein called Tudor-SN that is important as cells prepare to divide. This protein controls many microRNAs, molecules that are very small RNAs that control the expression of tens of thousands of genes.
The scientists found that when Tudor-SN is removed from human cells, levels of hundreds of microRNAs go up, putting the brakes on genes that encourage cell growth. This slows down the process of cell division known as the cell cycle, which goes awry in cancer.
Maquat and Reyad A. Elbarbary, Ph.D., a former post-doctoral fellow in Maquat’s lab, have filed a patent application for methods that target Tudor-SN for the treatment and prevention of cancer. They continue to study how Tudor-SN works in concert with other molecules and proteins so that scientists can identify the most appropriate drugs to target it.
Scientists at the Center for RNA Biology are also looking at RNA’s other roles in cancer to find new treatment strategies. For example, Mitchell O’Connell, Ph.D., is studying how microRNAs can interfere with the way genes are expressed and lead to cancer. He and his team are using the gene-editing technology known as CRISPR, which he has adapted to edit RNA, to learn more about the proteins involved in this process.
Yi-Tao Yu, Ph.D., and his team are studying various ways to modify mRNA so that it can override mistakes in genetic instructions. Sometimes there’s a premature stop signal that orders a cell to stop reading the genetic instructions in mRNA partway through the process, resulting in an incomplete protein. The Yu lab is working to alter mRNA in ways that turn “stop” signals into “go” signals, creating full length proteins and preventing diseases like cancer.
The study of RNA biology is allowing scientists and physicians to explore entirely new treatment strategies for cancer and a wide range of other genetic and acquired disorders.
Learn more about the work being done at the Center for RNA Biology.
By Lydia FernandezRead More: Looking to RNA for Answers
Maquat Wins 17th Annual Wiley Prize in Biomedical Sciences
Tuesday, February 20, 2018
The Wiley Foundation today announced the 17th annual Wiley Prize in Biomedical Sciences will be awarded to Lynne E. Maquat for elucidating the mechanism of nonsense-mediated messenger RNA decay, a fundamental process whereby cells remove defective transcripts that can encode toxic proteins.
Dr. Maquat is a Professor at the Department of Biochemistry & Biophysics in the School of Medicine and Dentistry, the Founding Director of the Center for RNA Biology: From Genome to Therapeutics, the Founding Chair of the University of Rochester Graduate Women in Science, and the J. Lowell Orbison Endowed Chair at the University of Rochester in Rochester, New York.
“The 2018 Wiley Prize honors Dr. Maquat, whose work illuminated how our cells prevent production of toxic proteins by removing defective messenger RNAs," said Dr. Titia de Lange, chairperson of the awards jury for the Wiley Prize at the Rockefeller University in New York City.
“The Wiley Foundation honors research that champions novel approaches and challenges accepted thinking in the biomedical sciences. The work of the 2018 Wiley Prize recipient Lynne Maquat truly upholds this mission,” said Deborah Wiley, Chair of the Wiley Foundation. “We are pleased to highlight the impact that her research on messenger RNA decay pathways has had in advancing our knowledge of the cellular cause of many human diseases.”Read More: Maquat Wins 17th Annual Wiley Prize in Biomedical Sciences
Lynne Maquat Wins Vanderbilt Prize in Biomedical Science
Tuesday, November 28, 2017
Lynne E. Maquat, Ph.D., the J. Lowell Orbison Endowed Chair and Professor in the Department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry is the recipient of the 2017 Vanderbilt Prize in Biomedical Science. Established by Vanderbilt University School of Medicine in 2006, the competitive prize honors women scientists with a “stellar record” of research accomplishments who have made significant contributions to mentoring other women in science.
Maquat is internationally known for a huge body of research that describes what goes wrong in our cells during disease. The founding director of the University of Rochester’s Center for RNA Biology, she has spent her career deciphering the many roles that RNA plays in sickness and in health.
She’s dedicated a great deal of time to helping women advance in scientific careers and in 2003 established the University of Rochester Graduate Women in Science program. Through monthly round-table discussions with high-profile speakers who are using advanced degrees in traditional and non-traditional ways, the program seeks to broaden awareness of what women can do with a Ph.D. Program members can apply for travel awards to attend conferences, seminars or other external events that will help them advance their careers.
Maquat, also a professor in the Wilmot Cancer Institute, is the recipient of other prestigious honors, including the Canada Gairdner International Award; the International RNA Society’s Lifetime Achievement Awards in Service and in Science; the Federation of American Societies for Experimental Biology (FASEB) Excellence in Science Award; the Rochester ATHENA Award®; and election to the National Academy of Medicine, the National Academy of Sciences and the American Academy of Arts and Sciences.
Maquat is the 12th recipient of the Vanderbilt Prize in Biomedical Science and will receive the prize on November 29, 2018, when she is scheduled to give a Flexner Discovery Lecture. She will also meet with Vanderbilt faculty and mentor Vanderbilt Prize Scholars, women who are pursuing graduate studies in the biomedical sciences in the School of Medicine.
“We are thrilled that Dr. Maquat is being recognized for her pioneering work in RNA biology, which has catalyzed innovative areas of research and provided insight to the role of RNA regulation in human disease,” said Jennifer Pietenpol, Ph.D., Vanderbilt University Medical Center Executive Vice President for Research and director of the Vanderbilt-Ingram Cancer Center. “She is a world-renowned scientist and an exceptional mentor, a role model for us all.”Read More: Lynne Maquat Wins Vanderbilt Prize in Biomedical Science
Lynne Maquat Delivers Harvey Society Lecture at Rockefeller University
Tuesday, November 7, 2017
Lynne E. Maquat, Ph.D., the J. Lowell Orbison Endowed Chair and Professor in the Department of Biochemistry and Biophysics and Director of the Center for RNA Biology gave a Harvey Society Lecture on October 19 at The Rockefeller University in New York City. The lecture series is one of the most prestigious in the country and the lecturers, who are selected by the Harvey Society's leadership council, are leading biomedical researchers from around the world.
Maquat discussed her career path and the discovery of nonsense-mediated mRNA decay (NMD), which she first described for humans in 1981. NMD is a cellular quality control mechanism that derails the production of unwanted proteins in the body that can disrupt normal processes and initiate disease. Maquat is known around the world for her work on NMD, which is critically important in both normal and disease states. UR President Joel Seligman and URMC CEO and SMD Dean Mark Taubman attended the lecture.
Founded in 1905, the Harvey Society sponsors seven lectures annually that are open to the public and are attended by hundreds of scientists from New York City and the surrounding areas. The Harvey Lectures are one of the great traditions in New York science and they are a place where scientists from different institutions meet regularly.
URMC Scientist Lynne Maquat Elected to National Academy of Medicine
Monday, October 16, 2017
Lynne E. Maquat, Ph.D., an internationally recognized researcher who studies what happens in our cells during disease, has been elected to the National Academy of Medicine. The honor is akin to an actor receiving an Emmy for an outstanding performance; current members of the Academy elected Maquat for her exceptional research in the field of RNA biology. The accolade places her amongst an elite group of scientists and physicians who have made significant contributions to health and medicine.
In studying RNA, a close cousin to DNA, Maquat has discovered intricate cellular processes that influence normal genes, as well as genes involved in a wide range of diseases. Her findings are leading to the development of new treatment approaches for everything from cancer and heart disease, to intellectual and developmental disabilities and other neurologic disorders.
“Lynne is at the forefront of a movement to transform our increasing understanding of RNA biology into promising therapies for virtually all disease processes,” said Mark B. Taubman, M.D., CEO of the University of Rochester Medical Center and Dean of the University of Rochester School of Medicine and Dentistry. “She is an incredible asset to the University and will undoubtedly bring a wealth of valuable experience and knowledge to the National Academy of Medicine.”
Formerly called the Institute of Medicine, the National Academy of Medicine is an independent organization of professionals from diverse fields that advises the nation and the international community on issues in health, medicine and related policy. For example, in 2016 the Academy released a report calling for more and better research into ovarian cancer, one of the deadliest cancers, and recently issued a report detailing how physicians can help combat America’s opioid crisis.
The J. Lowell Orbison Endowed Chair and Professor of Biochemistry & Biophysics and of Oncology at the University of Rochester School of Medicine and Dentistry, Maquat is also an elected member of the National Academy of Sciences and the American Academy of Sciences. She was the first individual from upstate New York to receive the prestigious Canada International Gairdner Award, the country’s top award for excellence in biomedical research, which she won in 2015.
The National Institutes of Health has continuously funded Maquat’s research for the past 34 years and she’s published more than 150 papers and reviews. She is the founding director of the University of Rochester Center for RNA Biology and founding chair of the Graduate Women in Science program. She’s committed countless hours to mentoring the next generation of researchers and advocating for young women in the sciences.
When she is formally inducted into the National Academy of Medicine in October 2018, Maquat will join four other active Rochester faculty members: Seymour I. Schwartz in the Department of Surgery: Elizabeth R. McAnarney in Pediatrics; Paul S. Frame in Family Medicine; and Robert C. Griggs in Neurology.Read More: URMC Scientist Lynne Maquat Elected to National Academy of Medicine
Protein identified in post-chemo cell death puzzle
Monday, September 11, 2017
Because anticancer drugs are designed to kill growing cells, they also affect normal, fast-growing cells—blood cells forming in the bone marrow, for example, and digestive, reproductive, and hair follicle cells. Chemotherapy may also affect cells in vital organs, such as the heart, kidney, bladder, lungs, and nervous system.
Researchers at the University of Rochester, collaborating with colleagues at MIT, Harvard, and the University of Oslo, have identified a protein that is required for cell death after undergoing chemotherapy—at least, it appears, in male mice.
“That was the unexpected part,” says Dragony Fu, an assistant professor of biology at Rochester and corresponding author of the study, regarding the sex-specific nature of the experimental results.Read More: Protein identified in post-chemo cell death puzzle
Maquat Honored with FASEB Award, Featured on People Behind the Science Podcast
Friday, August 25, 2017
Dr. Lynne Maquat, J. Lowell Orbison Endowed Chair and Professor of Biochemistry and Biophysics in the School of Medicine and Dentistry, Director of the Center for RNA Biology, and Chair of Graduate Women in Science at the University of Rochester was recently featured on the podcast, People Behind the Science.
Lynne discusses her mentors and career milestones, and offers advice to junior scientists. Maquat recently received the Federation of American Societies for Experimental Biology's Excellence in Science Award, which recognizes women who have made outstanding contributions to science through research discoveries and by training the next generation of scientists.
The entire interview can be listened to for free on iTunes.Read More: Maquat Honored with FASEB Award, Featured on People Behind the Science Podcast
Payea and Mishra are Inaugural Recipients of the Sayeeda Zain Travel Award
Friday, July 14, 2017
The department of Biochemistry and Biophysics recently presented to the inaugural Sayeeda Zain Travel Award to Mathew Payea and Laxmi Narayan Mishra.
Matthew Payea is a 6th year graduate student in the Biochemistry Ph.D. program studying tRNA biology in laboratory of Eric Phizicky. Matthew received his Bachelors in Science from Eastern Illinois University, majoring in Biochemistry. Matthew used the funding provided by the Sayeeda Zain Travel Award to attend the 22nd annual meeting of the RNA Society in Prague, Czech Republic this past June. There, he gave a talk on his research defining an RNA decay pathway in yeast that destroys mutant tRNAs.
Laxmi Narayan Mishra is a postdoctoral associate working in Dr. Jeffrey J Hayes’ Lab in the Department of Biochemistry and Biophysics, University of Rochester Medical Center. He has a Masters degree from University of North Bengal, Darjeeling, India and a Ph.D. in Biochemistry from Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India. His research is focused on how epigenetic modifications alter chromosome structure to facilitate gene expression. His Dr. Mishra will use the Sayeeda Zain Travel Award to attend and present his research findings at the international EMBO conference on “The Nucleosomes: From Atoms to Genomes” at Heidelberg, Germany, in August 2017.
The Sayeeda Zain Travel Award is given semi-annually to one or more graduate students and postdoctoral fellows in the Department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry. The award honors the life and achievements of Professor Sayeed Zain, Ph.D., a longtime faculty member in the Department of Biochemistry and Biophysics. Learn more about the award and Dr. Zain.
Matthew Payea (left) with Dr. Jeffrey Hayes
Laxmi Narayan Mishra (left) with Dr. Jeffrey Hayes
Study: A New Way to Slow Cancer Cell Growth
Friday, May 26, 2017
Cells grow and divide during the cell cycle
Cancer is an extremely complex disease, but its definition is quite simple: the abnormal and uncontrollable growth of cells. Researchers from the University of Rochester’s Center for RNA Biology have identified a new way to potentially slow the fast-growing cells that characterize all types of cancer. The findings, reported today in the journal Science and funded by the National Institutes of Health, were made in kidney and cervical cancer cells in the laboratory and are a long way from being applied in people. But, they could be the basis of a treatment option in the future, the authors said.
Cancer: The Cell Cycle Gone Wrong
All cells go through the “cell cycle,” a series of events that culminate in orderly cell growth and division. In cancer, the cell cycle is out of whack; cells divide without stopping and invade surrounding tissues.
Lynne Maquat, Ph.D.
Researchers identified a protein called Tudor-SN that is important in the “preparatory” phase of the cell cycle – the period when the cell gets ready to divide. When scientists eliminated this protein from cells, using the gene editing technology CRISPR-Cas9, cells took longer to gear up for division. The loss of Tudor-SN slowed the cell cycle.
“We know that Tudor-SN is more abundant in cancer cells than healthy cells, and our study suggests that targeting this protein could inhibit fast-growing cancer cells,” said Reyad A. Elbarbary, Ph.D., lead study author and research assistant professor in the Center for RNA Biology and the department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry.
Elbarbary, who works in the laboratory of senior study author Lynne E. Maquat, Ph.D., a world-renowned expert in RNA biology, adds that there are existing compounds that block Tudor-SN that could be good candidates for a possible therapy.
Putting the Brakes on Cell Growth
Maquat’s team discovered that Tudor-SN influences the cell cycle by controlling microRNAs, molecules that fine tune the expression of thousands of human genes.
When Tudor-SN is removed from human cells, the levels of dozens of microRNAs go up. Boosting the presence of microRNAs puts the brakes on genes that encourage cell growth. With these genes in the “off” position, the cell moves more slowly from the preparatory phase to the cell division phase.
“Because cancer cells have a faulty cell cycle, pursuing factors involved in the cell cycle is a promising avenue for cancer treatment,” noted Maquat, director of the Center for RNA Biology and the J. Lowell Orbison Endowed Chair and professor of Biochemistry and Biophysics.
Maquat, who also holds an appointment in the Wilmot Cancer Institute, and Elbarbary have filed a patent application for methods targeting Tudor-SN for the treatment and prevention of cancer. Research next steps include understanding how Tudor-SN works in concert with other molecules and proteins so that scientists can identify the most appropriate drugs to target it.
Keita Miyoshi, Ph.D., staff scientist in Maquat’s lab, served as lead study author with Elbarbary. Jason R. Myers and John M. Ashton, Ph.D. from the UR Genomics Research Center played an instrumental role in the study analysis.Read More: Study: A New Way to Slow Cancer Cell Growth
Using rooster testes to learn how the body fights viruses
Thursday, April 27, 2017
Researchers from the University of Rochester Center for RNA Biology: From Genome to Therapeutics examined the role of piRNA in safeguarding the integrity of the genetic information in germ cells. It's known that piRNA -- a type of ribonucleic acid (RNA) that's found most readily in the testes and ovaries -- shields germ cells by silencing the genetic sequences of viral intruders. It's also known that defects or mutations in piRNA lead to infertility in humans and other animals. What's not known is how piRNAs are generated in the first place.
A team led by Xin Li, Ph.D., assistant professor in the departments of Biochemistry and Biophysics and Urology at the University of Rochester School of Medicine and Dentistry, analyzed rooster testes to find out.Read More: Using rooster testes to learn how the body fights viruses
Maquat Receives Lifetime Achievement Award in Science from International RNA Society
Tuesday, February 7, 2017
Lynne E. Maquat, Ph.D. has spent her career unraveling what happens in our cells during disease, making seminal contributions to our understanding of RNA’s role in sickness and in health. She’s also committed countless hours to mentoring the next generation of researchers and advocating for young women in the sciences. For these exceptional efforts, she’s receiving the 2017 Lifetime Achievement Award in Science from the international RNA Society.
The J. Lowell Orbison Endowed Chair and Professor in the Department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry, Maquat began her professional career studying inherited anemias. She discovered a quality control process that blocks the creation of toxic proteins that cause disease. Known as nonsense-mediated mRNA decay or NMD, this process plays a part in one third of all inherited diseases, such as cystic fibrosis and muscular dystrophy, and one third of all acquired diseases, including a number of cancers.
“This award recognizes Lynne’s pioneering contributions to understanding the mechanisms of RNA, as well as her outstanding leadership, support and commitment to our field, including her role as a model for new generations of scientists,” said Juan Valcarcel Juarez, current president of the RNA Society, who works at the Centre for Genomic Regulation in Barcelona, Spain.
James McSwiggen, CEO of the RNA Society, added, “I can’t imagine a more appropriate choice of awardee.”Read More: Maquat Receives Lifetime Achievement Award in Science from International RNA Society