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Lynne Maquat spoke with WXXI: 'A wave of the future': local biologist explores what's next for mRNA technology

Wednesday, September 8, 2021

The recent approval of Pfizer and BioNTech’s COVID-19 vaccine by the U.S. Food and Drug Administration, has scientists enthusiastic about the future of the messenger RNA, or mRNA, technology used to produce the vaccine. For RNA biologists, in particular, the pandemic has become a catalyst for modern medicine. “It's a big step forward for mRNA-based therapeutics,” said UR Medicine’s director for centers for RNA biology, Dr. Lynne Maquat. “We've had a worldwide need. And the need has been met.” 

Maquat defines mRNA as the messenger molecule between our DNA, and the proteins that our cells need to perform their duties. She says the COVID-19 vaccine produces a piece of the spike protein that surrounds the coronavirus and raises an immune response to it. 

“Our immune system will attack the virus, because the spike protein is on the outside of the virus,” said Maquat.

She says the success of the Pfizer and Moderna vaccines is causing scientists to look at other illnesses that could benefit from the mRNA technology like dengue.

“There's lots of infectious diseases, especially in Third World countries that need to be addressed,” Maquat said.

UR Medicine infectious disease specialist Dr. Edward Walsh says existing vaccines can also benefit from messenger RNA.

“If an mRNA vaccine for the influenza vaccine could reach the kind of efficacy data, especially over a six-month period, we really only need to get protection for about six months through the flu season each year,” Walsh said.

He said the flu vaccine is roughly 60% effective, but mRNA technology could increase that...

“If we could get that very high degree of efficacy, it could really do a lot of public health good,” said Walsh.

Maquat said she and her team are already looking at how some cancers could be treated with messenger RNA technology

“Let's say you have a pancreatic cancer,” said Maquat, “you could have your tumor removed, and you can have it characterized for new proteins.”

The new discovered proteins in the tumor would allow scientists to develop an mRNA treatment to combat that protein.

“It's a type of personalized medicine,” said Maquat. "This is a wave of the future"

Read More: Lynne Maquat spoke with WXXI: 'A wave of the future': local biologist explores what's next for mRNA technology

That's the Rochester Effect: Featuring Dr. Lynne Maquat. PhD

Friday, July 2, 2021

Graduate Women in Science Receives 2021 Best of Rochester Award

Tuesday, May 4, 2021

Graduate Women in Science has been selected for the 2021 Best of Rochester Award in the University category by the Rochester Award Program.

Each year, the Rochester Award Program identifies companies that we believe have achieved exceptional marketing success in their local community and business category. These are local companies that enhance the positive image of small business through service to their customers and our community. These exceptional companies help make the Rochester area a great place to live, work and play.

Various sources of information were gathered and analyzed to choose the winners in each category. The 2021 Rochester Award Program focuses on quality, not quantity. Winners are determined based on the information gathered both internally by the Rochester Award Program and data provided by third parties.

About Rochester Award Program

The Rochester Award Program is an annual awards program honoring the achievements and accomplishments of local businesses throughout the Rochester area. Recognition is given to those companies that have shown the ability to use their best practices and implemented programs to generate competitive advantages and long-term value.

The Rochester Award Program was established to recognize the best of local businesses in our community. Our organization works exclusively with local business owners, trade groups, professional associations and other business advertising and marketing groups. Our mission is to recognize the small business community's contributions to the U.S. economy.

Lynne Maquat Wins Warren Alpert Foundation Prize

Monday, May 3, 2021

Lynne Maquat, Ph.D., the founding director of the Center for RNA Biology at the University of Rochester, has been awarded the Warren Alpert Foundation Prize for her pivotal discoveries in the field of RNA biology. She shares the prize with fellow RNA biologist Joan Steitz, Ph.D., Sterling Professor of Molecular Biophysics and Biochemistry at Yale School of Medicine.

The award is given by the Warren Alpert Foundation in recognition of work that has improved the understanding, prevention, treatment or cure of human disease. The prize is administered by Harvard Medical School, and since its inception in 1987, 12 honorees have gone on to receive Nobel prizes.

George Q. Daley, dean of Harvard Medical School, said of Maquat and Steitz: "The discoveries made by the two award winners are stunning in their elegance and scope." Earlier this year, the pair won the 2021 Wolf Prize in Medicine for their work. They shared the Wolf Prize with a third RNA biologist, Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory.

RNA Makes its Mark

Maquat has studied RNA since she started her own laboratory in 1982. But until the development and approval of multiple mRNA COVID-19 vaccines in 2020, RNA wasn't on the public radar. Decades of research by Maquat and Steitz on how RNAs work and how they are involved in human disease helped set the stage for the rapid development of these vaccines, which are key to bringing the COVID pandemic under control.

Many are familiar with DNA, which contains the genetic instructions that make us who we are. But RNA is equally important in the process of gene expression:

  • DNA lives in the nucleus of a cell and makes many types of RNA, including mRNA (messenger RNA).
  • mRNA takes genetic instructions from DNA, travels out of the nucleus and delivers them to factories in our cells called ribosomes.
  • Ribosomes use the instructions to create proteins.
  • Proteins carry out myriad functions throughout the body, including ferrying nutrients around, helping with chemical reactions and protecting us from disease.

Many disorders result from problems with our DNA, but over the past several decades Maquat, Steitz and other scientists revealed that mRNA plays a role in a multitude of diseases, too. Cystic fibrosis, fragile X syndrome, Duchene muscular dystrophy and a long list of other inherited and acquired diseases result from defective mRNAs.

"Scientists used to think that gene regulation was all about DNA, and that RNA didn't influence gene expression, the production of proteins or the development of disease," said Maquat, the J. Lowell Orbison Endowed Chair and Professor of Biochemistry and Biophysics, Oncology and Pediatrics at the University of Rochester School of Medicine and Dentistry. "We now know that a very complicated network exists in our cells to regulate how, when and where our mRNAs are produced. This knowledge has opened the door to using RNA as both a treatment target and a tool to develop new therapies."

Read More: Lynne Maquat Wins Warren Alpert Foundation Prize

Lynne Maquat Awarded 2021 Wolf Prize in Medicine

Tuesday, February 9, 2021

Lynne Maquat

Lynne E. Maquat, Ph.D., the founding director of the Center for RNA Biology at the University of Rochester, was honored with the 2021 Wolf Prize in Medicine. The acclaimed international award is given to outstanding scientists from around the world for achievements that benefit mankind.

Maquat was selected for "fundamental discoveries in RNA biology that have the potential to better human lives." She has spent her career deciphering the many roles that RNA plays in sickness and in health, and is well known for her discovery of nonsense-mediated mRNA decay or NMD. One of the major surveillance systems in the body, NMD protects against mistakes in gene expression that lead to disease. Maquat's lab also revealed that NMD helps our cells adjust to changes in development and in their environment, and more rapidly respond to certain stimuli.

Maquat shares the award with Joan Steitz, Ph.D., Sterling Professor of Molecular Biophysics and Biochemistry at Yale School of Medicine and Adrian Krainer, Ph.D., St. Giles Foundation Professor and Cancer Center Deputy Director of Research at Cold Spring Harbor Laboratory. Steitz and Krainer were also honored for discoveries in RNA biology.

The Wolf Foundation, which celebrates exceptional achievements in the sciences and the arts, is based in Israel, where Maquat's quest to unravel the intricacies of NMD began. In 1980 she traveled to Jerusalem to retrieve bone marrow samples from four children suffering from thalassemia major, the most severe form of the inherited blood disorder thalassemia. Maquat wanted to learn why the children's marrow contained no beta-globin protein, which is necessary for the oxygen-carrying function of red blood cells. Her 1981 breakthrough manuscript, "Unstable beta-globin mRNA in mRNA-deficient beta0 thalassemia," published in Cell, was the first to reveal the role of NMD in human cells and how it can lead to disease.

"Lynne's work on nonsense-mediated mRNA decay is the bedrock of an ever-growing body of research on how mRNAs are monitored and regulated," said Mark B. Taubman, M.D., dean of the University of Rochester School of Medicine and Dentistry. "Her dedication to her science and to the field of RNA biology has opened the door to the development of RNA-based therapeutics for a wide range of disorders that you can't reach with conventional drugs. We're thrilled that her contributions are being recognized with this prestigious award."

RNA secured its place in the public eye in 2020 with the development and approval of multiple mRNA COVID-19 vaccines. Years of research by Maquat, Steitz and Krainer helped set the stage for the rapid development of these vaccines.

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 is the recipient of several other significant honors, including:

Winners of the Wolf Prize are selected annually by an international jury committee of the Wolf Foundation; prizes are awarded regardless of religion, gender, race, geographical region, or political view. The official announcement of this year's prize by the President of the State of Israel, Reuven Rivlin, was made on February 9, 2021.

Read More: Lynne Maquat Awarded 2021 Wolf Prize in Medicine

UR Center for RNA Biology RNA Presentation Contest Results

Tuesday, February 2, 2021

Thank you to those who participated in and/or viewed the UR Center for RNA Biology's RNA Presentations on Jan 6th, 13th, and 27th, sponsored by the RNA Society and Lexogen. The judging committee was impressed with the quality of the presentations given on all three dates, making final decisions difficult.

All nine of the graduate student, postdoc, and technician presenters, chosen based on their quality of their abstract, will be receiving a one-year membership to the RNA Society. Of these, four who were chosen based on the quality of their presentation will be awarded $375 each to be used toward the attendance of an RNA-centric meeting, in person or virtually.

The four to be awarded a one-year membership in the RNA Society and $375, in alphabetical order, are:

Kamel Awayda (presented Jan 6th )

Technician, Mitch O'Connell Lab

"Characterization of THUMP Domain-Containing Protein 1, and Putative Modulator of RNA Modification"

Chen Bao (presented Jan 13th)

Biochemistry Grad Student, Dmitri Ermolenko Lab

"mRNA Stem-Loops Can Induce Translational Pause through Two Pathways"

Xavier Rambout, PhD (presented Jan 27th)

Postdoc, Lynne Maquat Lab

"Transcriptional Coactivator PGC-1α Contains a Novel CBP80-Binding Motif that Orchestrates Efficient Target-Gene Expression"

Arica VanderWal (presented Jan 13th)

Biochemistry Grad Student, Mitch O'Connell Lab

"The Role of Csx28 in CRISPR-Cas13b Anti-Bacteriophage Defense"

The remaining to be awarded a one-year membership in the RNA Society, in alphabetical order, are:

Lily Cisco (presented Jan 6th )

Pharm-Phys Grad Student, John Lueck Lab

"Testing Therapeutic Intervention for Myotonic Dystrophy Type 1 in a Novel Mouse Model"

Xueyang He (presented Jan 6th )

Biophysics Grad Student, Paul Boutz Lab

"A Novel Method to Capture and Sequence Intron Lariats"

Shon Koren (presented Jan 6th )

Technician, Gail Johnson Lab

"Tau-Ribosome-tRNA Associations Underlie Common Features of Dys sincening Protein Synthesis in Dementia"

Sean Lindley (presented Jan 13th )

Biology Grad Student, Doug Anderson Lab

"StitchR: Ribozyme-Mediated RNA Trans-Splicing and Expression in Mammalian Cells"

Debanjana Maji (presented Jan 27th )

Biophysics Grad Student, Clara Kielkopf Lab

"Representative Cancer-Relevant U2AF2 Mutations Alter RNA Interactions and Splicing"

Beneath the Surface of Fragile X Syndrome: Study Sheds Light on What’s Happening in Nerve Cells

Monday, January 25, 2021

A new study shows that many abnormalities in fragile X syndrome cells are related to glitches with one of the body's major quality control systems. Published in Nature Cell Biology, the research provides fresh insight into the molecular mechanisms of the disorder and a pathway to search for potential treatments.

Fragile X syndrome occurs when individuals don't make the fragile X protein known as FMRP, which is needed for normal brain development. Currently, little is known about how the loss of this crucial protein leads to the intellectual disability and severe learning problems characteristic of the disease.

Rochester researchers found that many irregularities in cells that lack FMRP are due to misregulated nonsense-mediated mRNA decay, or NMD. Discovered by RNA biologist Lynne E. Maquat, Ph.D., NMD is like a molecular guide that helps our cells make smart decisions that (in most cases) improve cellular function and contribute to good health. For example, NMD helps our cells adjust to changes in development and in their environment, and more rapidly respond to certain stimuli.

Through a series of cellular analyses, Maquat's team discovered that NMD influences a wide range of genes throughout the brain, including genes that govern motor control and cognitive processes related to attention, learning and language. They also found that when FMRP is absent from cells, as it is in people with fragile X syndrome, nonsense-mediated mRNA decay shifts into overdrive.

Read More: Beneath the Surface of Fragile X Syndrome: Study Sheds Light on What’s Happening in Nerve Cells

New Research Funding Initiative to Support Young Investigators

Friday, January 15, 2021

Thanks to a partnership between pediatric researchers and the GCH Advancement division, a new funding initiative will seek to provide $25,000 -- matched with grant funds -- to support individual young investigators who are undertaking pediatric research.

These young investigators would be tenure-track assistant professors or post-doctoral fellows who already have a PhD degree and are on the path to obtain a tenure track position. This type of "seed" funding will be critical for fostering the careers of young researchers at URMC and could potentially pay dividends for institutional growth in the long-term, according Tom Mariani, PhD, professor of Neonatology and director of research for the Department of Pediatrics.

"In addition to funding discovery and innovation which could potentially save millions of lives, the career development of one investigator can be leveraged many times over to merit additional external funding, creation of new labs, and stimulate economic growth in the Rochester community."

Alan Wood, owner of the Realty company RE/Max Plus and supporter of GCH, and Lynne Maquat, PhD, endowed chair and professor in the Departments of Biochemistry and Biophysics, Oncology, and Pediatrics, developing this funding idea after Wood and his children visited Maquat's Fragile X Syndrome lab this Fall. Fragile X Syndrome is the most common single-gene cause of autism and intellectual disability, and Wood's family got a thorough education on the scope of Maquat's work, which is examining disease-causing mutations in children, and what those mutations do to gene expression via RNA production.

"My children loved getting first-hand experience touring the lab and seeing real-world visualizations of the work Maquat and her team are doing. Wearing lab coats and gloves, they isolated genetic material from bananas, which turn out to have more genetic material than us humans," said Wood.

Wood will be leading the effort to develop the program and secure funding. Donors who sponsor a young investigator will be able to establish a relationship to learn more about their research as it evolves.

"We have several talented young researchers in the Department of Pediatrics," said Maquat, "providing early support for their career is a long-term goal. The results won't be immediate, but over time, this support will build the foundation for discovery that will improve kids' lives."

Read More: New Research Funding Initiative to Support Young Investigators