News

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."

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:

• Wiley Prize in Biomedical Sciences (2018)
• Vanderbilt Prize in Biomedical Science (2017)
• Canada Gairdner International Award (2015)
• RNA Society's Lifetime Achievement Awards in Service (2010) and in Science (2017)
• Election to the National Academy of Medicine (2017), the National Academies of Sciences (2011) and the American Academy of Arts and Sciences (2006) More about Nonsense-Mediated mRNA Decay

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.

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 6^th )

Technician, Mitch O'Connell Lab

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

Chen Bao (presented Jan 13^th)

Biochemistry Grad Student, Dmitri Ermolenko Lab

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

Xavier Rambout, PhD (presented Jan 27^th)

Postdoc, Lynne Maquat Lab

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

Arica VanderWal (presented Jan 13^th)

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 6^th )

Pharm-Phys Grad Student, John Lueck Lab

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

Xueyang He (presented Jan 6^th )

Biophysics Grad Student, Paul Boutz Lab

"A Novel Method to Capture and Sequence Intron Lariats"

Shon Koren (presented Jan 6^th )

Technician, Gail Johnson Lab

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

Sean Lindley (presented Jan 13^th )

Biology Grad Student, Doug Anderson Lab

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

Debanjana Maji (presented Jan 27^th )

Biophysics Grad Student, Clara Kielkopf Lab

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

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.

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."

John Lueck

Joanne Ladolcetta, a freelance writer based out of San Francisco, wanted to put together information to help address circulating fears and misconceptions about the recently FDA approved COVID-19 mRNA vaccines. She reached out to friends Bryant Johnson (Cartoonist) and John Lueck (Researcher at the University of Rochester Medical Center) to tackle some of the most common vaccine questions. The collaboration resulted in an approachable informative write-up with creative illustrations and helpful links to provide readers the ability to do a deeper dive into the generation and application of the novel COVID-19 mRNA vaccines.

Courtesy of Bryant Johnson

Read More: Blog: Are the new mRNA vaccines safe?

RNA Presentations by UR Grad Students, Postdocs, and Techs!

Sponsored by the RNA Society, Lexogen, and the UR Center for RNA Biology

Virtual presentations will be on Wednesdays at 2pm EST on January 6th, 13th, & 27th during the usual Department of Biochemistry & Biophysics Seminar. There will be 3-4 presentations on each date (~20-min slots). Winners will be determined by the anonymous panel of judges based on the quality of their lay and research presentations and their ability to address questions during the Q&A session.

Register Here

JANUARY 2021 PRESENTATION SCHEDULE

Day 1: Wed, Jan 6th

2:00 -- 3:20pm

Day 2: Wed, Jan 13th

2:00 -- 3:00pm

Day 3: Wed, Jan 27th

2:00 -- 3:00pm

Contestants for oral presentations were selected based on the scientific merit of their abstract submissions, in December, by an anonymous panel of six faculty judges and two graduate student judges. Competitors will present a 2-min lay talk without slides followed by a 12-min slide presentation of their research, i.e. the topic of their abstract, and a 3-min Q&A session.

The US Food and Drug Administration recently approved emergency use authorization for a COVID-19 vaccine developed by Pfizer and the German pharmaceutical company BioNTech.

The vaccine made history not only because it reported a 95 percent efficacy rate at preventing COVID-19 in clinical trials, but because it is the first vaccine ever approved by the FDA for human use that is based on RNA technology.

"The development of RNA vaccines is a great boon to the future of treating infectious diseases," says Lynne Maquat, the J. Lowell Orbison Distinguished Service Alumni Professor in biochemistry and biophysics, oncology, and pediatrics at Rochester and the director of Rochester's Center for RNA Biology.

COVID-19, short for "coronavirus disease 2019," is caused by the novel coronavirus SARS-CoV-2. Like many other viruses, SARS-CoV-2 is an RNA virus. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in ribonucleic acid (RNA). The viral RNA is sneaky: its features cause the protein synthesis machinery in humans to mistake it for RNA produced by our own DNA.

For that reason, several of the leading COVID-19 vaccines and treatments are based on RNA technology.

A contingent of researchers at the University of Rochester study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. This RNA research provides an important foundation for developing vaccines and other drugs and therapeutics to disrupt the virus and stop infections.

"Understanding RNA structure and function helps us understand how to throw a therapeutic wrench into what the COVID-19 RNA does—make new virus that can infect more of our cells and also the cells of other human beings," Maquat says.

In the past few decades, as scientists came to realize that genetic material is largely regulated by the RNA it encodes, that most of our DNA produces RNA, and that RNA is not only a target but also a tool for disease therapies, "the RNA research world has exploded," Maquat says. "The University of Rochester understood this."

In 2007, Maquat founded The Center for RNA Biology as a means of conducting interdisciplinary research in the function, structure, and processing of RNAs. The Center involves researchers from both the River Campus and the Medical Center, combining expertise in biology, chemistry, engineering, neurology, and pharmacology.

Clara Kielkopf, Ph.D., left, and Laura Calvi, M.D., stand by the University's new cryo-microscope

With the recent acquisition of Nobel Prize-winning technology and two new grants, Wilmot Cancer Institute researchers are streamlining their investigations into a malignant blood disease known as MDS, working toward discovering targeted therapies.

Laura Calvi, M.D., and Clara Kielkopf, Ph.D., are leading collaborative teams that will be using a device at the University of Rochester Medical Center — a cryo-electron microscope — that has ushered in a new era in biochemistry. The microscope allows scientists to see 3D snapshots and more details of living molecules than ever before, down to near-atomic resolution, to understand disease and uncover new ways to design drugs. The developers of the technology were awarded the Nobel Prize in Chemistry 2017.

Calvi and Kielkopf each received Edward P. Evans Foundation awards totaling $1.2 million for this project. Evans grants go to scientists seeking a cure for myelodysplastic syndromes (MDS), which originates in the bone marrow and disrupts healthy blood cell formation. MDS often leads to leukemia.

The Kielkopf lab will use the cryo-electron microscope to obtain 3D views of recurrent MDS mutations as guides for targeting molecular therapies. The modern microscope is the first of its kind in the Rochester region, Kielkopf said, and will be accessible to all UR researchers through the Electron Microscopy Shared Resource Laboratory. She is a professor of Biochemistry and Biophysics in the Center for RNA Biology.

We are thrilled to announce that Professor David Mathews, MD, PhD, was honored at this year's School of Medicine Opening Convocation by being installed as the first Lynne Maquat Distinguished Professor in RNA Biology in the School of Medicine and Dentistry. The professorship was awarded by Dr. Mark Taubman, Dean of the School of Medicine and CEO of the University of Rochester Medical Center. The Convocation was held virtually this year and can be viewed at the link below.

Congratulations to Professor Mathews!

The UR Center for RNA Biology offered an exercise during the time when COVID-19 became a sufficient threat to largely shut-down our research enterprise. We're pleased to announce the winners of the UR's Center for RNA Biology Essay Contest on "The role of RNA research in community health". These awards are sponsored by a grant from the RNA Society & Lexogen to the UR Center for RNA Biology, and funds from UR RNA Structure & Function Cluster.

Our Gold prize (~$1,000 value) award goes to Sydney Simpson, an Immunology, Microbiology & Virology graduate student in Steve Dewhurst's lab in the Department of Microbiology & Immunology, for her essay: "Nucleoside Analog Inhibitors: Timeless & Timely Beacons of Hope".

The Silver Prize (~$250 value) award goes to Omar Hedaya, a Biochemistry & Molecular Biology graduate student in Peng Yao's lab in the Department of Medicine/Department of Biochemistry & Biophysics, for his essay: "Know the Fundamentals when Seeking the Future".

Omar Hedaya

Sydney Simpson

Both awardees have become members of the RNA Society and will use their winnings toward technology needs for the upcoming semester.

The RNA Society now features our contest results, including the winning essays, in its latest RNA Salon update: https://www.rnasociety.org/featured-salons, see bullet #3.

We would like to acknowledge Honorable Mentions for the following applicants:

• Sai Shashank Chavali -- Graduate student; Biophysics, Structural & Computational Biology; Wedekind Lab
• Lily Cisco -- Graduate student; Cellular and Molecular Pharmacology & Physiology; Lueck Lab
• Gabrielle Kosoy -- Graduate student; Biophysics, Structural & Computational Biology; Miller Lab
• Ashwin Kumar -- Graduate student; Biophysics, Structural & Computational Biology; Topham Lab
• Li Xie -- Graduate student; Genetics, Development & Stem Cells; Pröschel Lab

We thank all who participated -- and our judges, too!

Prof. Clara Kielkopf has been awarded an EvansMDS research grant to use the new, state-of-the-art cryo-electron microscope at the U of R Medical Center EM facility. The Kielkopf group will use this revolutionary technique to study 3D structures of mutant U2AF1-splicing complexes in human malignancies. The title of the EvansMDS grant is: "Cryo-Electron Microscopy Structures of Mutant U2AF1-Containing Ribonucleoproteins Associated with Myelodysplastic Syndromes". This grant was made possible by our new Talos cryo-EM.

This week's URMC Research Heroes featured the Maquat lab's Tatsuaki Kurosaki, PhD, and Shuhei Mitsutomi, MS, who were recognized today for their work on SARS-CoV-2.

https://www.instagram.com/p/CA-QN7oAl07/

Both Tatsuaki and Shuhei have worked as members of the Maquat Lab (Center for RNA Biology and the Department of Biochemistry & Biophysics) during the sequestration on SARS-CoV-2, collaborating with a lab at Harvard to determine the mechanism by which the virus inhibits human-cell nonsense-mediated mRNA decay (NMD) so as to express and replicate its RNA efficiency.

From Tatsuaki: "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 19 (COVID-19) pandemic, is a novel enveloped RNA virus carrying a large (~30 kb) positive-sense single-stranded RNA genome. Although human cells innately have an RNA surveillance pathway called nonsense-mediated mRNA decay (NMD) that generally protects cells from infection by many different types of viruses, little is known about how SARS-CoV-2 inhibits NMD to proliferate in human cells. We hope that our research helps to elucidate the molecular mechanisms of SARS-CoV-2 proliferation in human cells, eventually contributing toward the development of therapeutic strategies to combat COVID-19."

Sponsored by the RNA Society & Lexogen, UR RNA Structure & Function Cluster, and UR Center for RNA Biology

Who is eligible: Any University of Rochester graduate student or post-doc with an interest in RNA biology

Entry rules: Essays should be no more than two pages, single-spaced (excluding references, which should be present), 11-point Arial font, with half-inch margins all around.

Prizes: Two prizes will be given out. Gold (valued at ~$1000), and Silver (valued at ~$250). Additionally, winning essays along with photos of the winning authors will be posted on the Center for RNA Biology webpage and featured on the RNA Society's RNA Salon page, offering international exposure.

Details

The UR's Center for RNA Biology is running an essay contest, sponsored by the RNA Society & Lexogen, and UR's RNA Structure & Function Cluster, on "The role of RNA research in community health". This contest, which is open to all UR graduate students and post-docs, aims to promote creative yet data-driven thinking about the importance of RNA in the "big picture".

Considering that reliable technology is required for research in an increasingly virtual world, prizes will consist of a PC or Mac laptop for Gold winners (~$1000), and software licenses or peripherals (e.g., second monitor or laptop dock) for Silver winners (~$250), subject to the needs of each recipient.

Submissions must be emailed to Liz by Monday, July 13th, 2020.

Winners will be announced in the beginning of August.

Links

The RNA Society: https://www.rnasociety.org/

RNA Structure & Function Cluster: http://www.rochester.edu/ucis/rnastructure.html

Center for RNA Biology: https://www.urmc.rochester.edu/rna-biology.aspx

Viruses like the coronavirus that causes COVID-19 are able to unleash their fury because of a devious weapon: ribonucleic acid, also known as RNA.

A contingent of researchers at the University of Rochester study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. As COVID-19 continues to spread around the globe, RNA research provides an important foundation for developing antiviral drugs, vaccines, and other therapeutics to disrupt the virus and stop infections.

"Understanding RNA structure and function helps us understand how to throw a therapeutic wrench into what the COVID-19 RNA does—make new virus that can infect more of our cells and also the cells of other human beings," says Lynne Maquat, professor of biochemistry and biophysics at the University of Rochester Medical Center and the director of Rochester's Center for RNA Biology.

In the past few decades, as scientists came to realize that genetic material is largely regulated by the RNA it encodes, that most of our DNA produces RNA, and that RNA is not only a target but also a tool for disease therapies, "the RNA research world has exploded," Maquat says. "The University of Rochester understood this."

In 2007, Maquat founded the Center for RNA Biology as a means of conducting interdisciplinary research in the function, structure, and processing of RNAs. The center involves researchers from both the River Campus and the Medical Center, combining expertise in biology, chemistry, engineering, neurology, and pharmacology.

While much of the research across the University has been put on pause, labs that are involved in coronavirus research remain active.

"Our strength as a university is our diversity of research expertise, combined with our highly collaborative nature," says Dragony Fu, an assistant professor of biology on the River Campus and a member of the Center for RNA Biology. "We are surrounded by outstanding researchers who enhance our understanding of RNA biology, and a medical center that provides a translational aspect where the knowledge gained from RNA biology can be applied for therapeutics."

Lynne Maquat, Ph.D., the J. Lowell Orbison Endowed Chair and Professor in the Department of Biochemistry and Biophysics, was honored with the International Union of Biochemistry and Molecular Biology (IUBMB) Jubilee Lectureship in September. The IUBMB unites biochemists and molecular biologists in 75 countries and is devoted to promoting research and education in biochemistry and molecular biology, giving particular attention to areas where the subject is still in its early development.

The IUBMB Jubilee Lectureship was established to commemorate the 50th anniversary of the First International Congress of Biochemistry that was held in Cambridge, England in 1949, at which the initial steps were taken that led to the formation of IUBMB. Maquat gave the keynote lecture at the IUBMB Molecular Biosystems Conference in Puerto Varas, Chile on September 30 and was presented with a medal in recognition of the event.

The founding director of the University of Rochester's Center for RNA Biology, Maquat has spent her career deciphering the many roles that RNA plays in sickness and in health. She's an international leader in the field and is credited with several major discoveries that are informing a new generation of therapies for a wide range of genetic disorders.

Her lecture, titled "Nonsense-mediated mRNA Decay in Human Health and Disease," described her discovery of nonsense-mediated mRNA decay or NMD and how this important surveillance system protects against mistakes in gene expression that lead to disease. She also discussed ongoing work on how misregulation of NMD in Fragile X Syndrome, the most common single gene cause of intellectual disability and autism, results in neuronal defects that typify this disorder.

Thank you, from the Center of RNA Biology members, to Dianne Edgar, MD and Terry Platt, PhD for their generous gifts to the Center over the years.

Dr. Edgar is a Clinical Professor in the Department of Obstetrics and Gynecology at the URMC, and a Pediatrician at Parkwest Women's Health. Dr. Platt is a Professor Emeritus of the Department of Biochemistry and Biophysics at the URMC.

The Center will use the gift toward an RNA-centric seminar in their names, a testament to their generosity. Thank you, Dr. Edgar and Dr. Platt!

Emily's Entourage (EE) is incredibly honored to have a group of scientists dedicated to accelerating research and drug development for nonsense mutations of Cystic Fibrosis (CF). In the next year, 90% of the CF population could see the benefits of a life-saving drug on the market (currently pending FDA review and approval), but those in the final 10%, including those with nonsense mutations, will not benefit from these new breakthrough drugs.

And in fact, the commitment of the scientists run so deep that it is not merely limited to their "day job" at the lab advancing critical research. Rather, at times, it permeates many aspects of their lives. There is no better example of that than University of Rochester's John Lueck, PhD, who has decided not only to do research to speed breakthroughs and a cure for the final 10%, but also to raise the funds that will drive the critical research.

Over the last few months, Dr. Lueck has trained to climb The Matterhorn in the Swiss Alps, a mountain he tackled on August 22 that reaches almost 15,000 feet high. As a two-time EE grantee through the Catalyst for a Cure Campaign, he flipped the script and committed to raise funds for EE throughout the entire training process!

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.”

The magazine's new issue, now in an interactive, flip-book format, highlights the investigative work of the J. Lowell Orbison Endowed Chair, as well as the impressive efforts of our medical students, alumni and faculty—past and present.

Lynne Maquat, PhD, received the 2018 Federation of American Societies for Experimental Biology (FASEB) Excellence in Science Award during the Experimental Biology 2018 meeting in San Diego, hosted by the American Society for Biochemistry and Molecular Biology (ASBMB). The award recognizes women whose outstanding career achievements in biological science have contributed significantly to the understanding of a particular discipline through scientific achievements, training of students and postdoctoral fellows, and contributions to the broader scientific community. Maquat is best known for unraveling RNA's role in sickness and in health and for advocating for young women in the sciences. View Dr. Maquat's award interview on ASBMB's interviews page.

Read more: Maquat celebrated for her service and scientific achievements
Read more: Unraveling RNA and Stereotypes: Q&A with award-Winning Scientist Lynne Maquat

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.

Other avenues

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 Fernandez

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."

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 12^th 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."

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.

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.

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.

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.

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

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.

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.

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."

Current Postdoctoral Berkeley Fellow, Mitchell O'Connell, Ph.D. is set to open his new lab in April 2017, in the department of Biochemistry & Biophysics, at URMC. Currently Mitch is working in Jennifer Doudna's lab and his research aims to understand the mechanisms of RNA-mediated gene regulation through the development of new RNA-targeting tools based on CRISPR/Cas technology.

Welcome Mitch!

Challenging a long-held convention, University researchers have shown they can inhibit the influenza A virus by targeting its genomic RNA with “antisense” compounds.

Their findings, highlighted on the cover of Nucleic Acid Therapeutics, offer scientists a new way to attack an increasingly drug-resistant pathogen that causes an estimated 250,000 to 500,000 deaths a year.

“Antisense” compounds are synthesized with nucleotides, the building blocks of nucleic acid, often shown as various combinations of A, U, G and C. When the compounds – called antisense oligonucleotides (ASOs) – bind to the targeted genomic RNA, they block its ability to replicate.

The collaboration, involving the labs of Douglas Turner, professor of chemistry; Luis Martinez-Sobrido, associate professor of microbiology and immunology; and two researchers in Poland, reported that “antisense” compounds targeting one of the virus’ eight genomic RNA segments caused a five- to 25-fold reduction of influenza A virus in cell cultures.

“That’s a big difference,” Martinez-Sobrido says. “When mice are infected with 10,000 viruses, they all die. However, with 25 times less virus, all animals can survive infection and they don’t even develop symptoms.”

Collins' first stop was lunch with 15 graduate students and postdocs who came prepared with a wide range of questions. The discussion covered the importance of communicating science to the public and policymakers, increasing diversity in biomedical research and new mechanisms to support young scientists at the start of their careers. Postdoctoral fellow Sarah Latchney and Ph.D. graduate student Solomon Abiola attended the lunch with Collins and describe the experience here.

Members of the Center for RNA Biology highlighted their most promising work for Collins and Center director Lynne E. Maquat, Ph.D., gave Collins a tour of her lab, where he met more trainees and junior researchers (admittedly, Collins' favorite part of visits like these).

In his keynote address at the end of the day, Collins delivered an uplifting message to a packed house in the Class of '62 auditorium: it is an extremely exciting time to be in biomedical research, and after many lean years we are turning a corner, with the NIH budget finally increasing in real terms. He detailed several of the NIH's new programs, like the Human Microbiome Project, Big Data to Knowledge (BD2K), the Precision Medicine Initiative and the Cancer Moonshot.

He applauded URMC on the renewal of the CTSI funding and cited the translational research conducted by Arthur J. Moss, M.D., which has led to new treatments for patients with Long QT syndrome (LQTS), and John J. Treanor, M.D., which is helping scientists in pursuit of a universal flu vaccine. Collins outlined several new funding initiatives, including the NIH Director's Early Independence Award, which is helping assistant professor Elaine L. Hill, Ph.D., study the impact of fracking on infant and child health.

Collins affirmed that the U.S. is the strongest biomedical research country in the world thanks to institutions like URMC. You can view his keynote, "Exceptional Opportunities in Biomedical Research," here.

Dr. Harold Smith, Professor at The University of Rochester, has been selected to join the Education Board at the American Health Council. Dr. Smith will be sharing his knowledge and expertise in the field of molecular biology, molecular virology, RNA biology, and drug discovery.

Dr. Harold Smith became involved in research after beginning his career as a professor in the Department of Biochemistry at The University of Rochester. As a biophysics professor, he utilized his knowledge and expertise in the areas of research and innovation of RNA, protein molecular biology, cell regulation, and drug discovery. Furthermore, Dr. Smith develops curriculum, teaches and mentors students from high school to postgraduate.

Dr. Harold Smith is also the Founder, President, and CEO of OyaGen, Inc. The objective of OyaGen, Inc. is to induce transient and beneficial changes in the protein expression and function in human tissues by involving the editing enzymes in targeting biomedically relevant pathways.

Dr. Harold Smith is a member of The American Heart Association, The Council on Atherosclerosis, The RNA Society, The American Society for Biochemistry and Molecular Biology and a fellow in the The Royal Society of Biology. In addition, Dr. Smith serves on the Scientific Advisor Board of Cannabis Sciences, Inc., IgxBio, Inc. and Trovita Health Sciences as well as the Editorial Board of the International Journal of Virology and AIDS, Frontiers in Microbiology, The Journal of Biological Chemistry, and The Journal of BioDiscovery.

J. Lowell Orbison Chair of Biochemistry and Biophysics, and of Oncology, Lynne Maquat, PhD, was a featured speaker at The Creativity Spark: a creativity workshop for scientists, a workshop put on by Cornell University, July 25.

The creativity workshop featured award winning scientists and scholars, including two Nobel Laureates, as they discussed the Creativity Spark and its role in science exploration.

Beth Grayhack, Ph.D., with lab
members and grad students
Christina Brule and Jiyu Wang

Scientists for years have known that the genetic code found in all living things contains many layers of complexity. But new research from the University of Rochester cracks the code more deeply, clarifying for example why some genes are inefficiently translated into proteins.

In a study published in the journal Cell, the researchers, co-led by Beth Grayhack, Ph.D., of the UR School of Medicine and Dentistry, discovered the existence and identity of 17 pairs of inefficient codons (DNA nucleotides or bases) within the genetic code.

Scientists have generally considered each piece of the genetic code (or codon) as a single “word” in a language. But the new data suggests some codon combinations act as compound words or phrases whose order and pairing has a significant impact on the translation of genes into proteins.

“Consider the words ‘pancake’ versus ‘cake pan,’ “ said Grayhack, an associate professor of Biochemistry and Biophysics, Pediatrics, and Cancer, in the Center for RNA Biology, at the UR Medical Center.

A new gene editing technology called CRISPR-Cas9 has taken the scientific world by storm. It allows researchers to quickly and easily make changes to the DNA of humans, animals and plants. The hope is that CRISPR-Cas9 may be used in the future to eliminate or correct faulty genes that cause disease.

In a recent issue of the journal Cell, Lynne E. Maquat, Ph.D. and Maximilian W. Popp, Ph.D. of the University of Rochester Center for RNA Biology describe how scientists can make this technology more efficient. Understanding the principles of nonsense-mediated mRNA decay (NMD), a cellular mechanism that Maquat discovered early in her career, will help anyone employing the technology achieve a better result -- namely, a more complete knock out or deletion of a desired gene.

Biochemistry & Biophysics Associate Professor, Clara Kielkopf's project, entitled, Structural mechanisms and targeting of MOS-relevant pre-mRNA splicing factors has been selected by EvansMDS for funding for 2016. This year EvansMDS requested 12 full DRG proposals and were able to fund 6 of them. Their hope is that these findings will translate into improvements in therapy that can be delivered to MDS patients.

The Kielkopf lab investigates splicing defects in hematologic malignancies; roles of human pre-mRNA splicing factors in HIV-1 infectivity; development of engineered splicing factors for correction of splicing defects and splice sites and their associated proteins as therapeutic targets.

Epigenetics is a popular, yet still mysterious concept in health and medicine. It’s the study of a variety of biological processes that alter the expression of our genes. Sometimes this involves modifying the structure of our chromosomes to mask or unmask genes, and other times the actual genetic code is changed in certain cells. Harold C. Smith, Ph.D., a longtime professor of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry has studied epigenetics in a research focus known as RNA and DNA editing since it was introduced two decades ago. He was invited to write a commentary on the progress and future of this research, published today in Trends in Biochemical Sciences, and answers a few questions about the subject.

Dr. Harold Smith, Professor of Biochemistry & Biophysics has been inducted into the Royal Society of Biology.

A long time member of the department, Dr. Smith's primary interest is understanding the composition, regulation and structure of macromolecular complexes involved in regulating gene expression at the level of messenger RNA expression and processing. The lab's focus is on a platform of enzymes that change the genetic code at the DNA or RNA level by deaminating cytidine to form uridine. Current data suggest that this family of cytidine deaminase function with other proteins (auxiliary proteins) as holoenzymes complexes which we refer to as editosomes (for RNA) or mutasomes (for DNA). RNA editing or DNA mutational activity by these enzymes affect the protein coding capacity of mRNAs and thereby can diversify the proteins that are expressed by cells (the proteome). Please visit the Smith Lab for more information. Dr. Smith has a 30 year track record of teaching and mentoring graduate students, medical students and undergraduates at the University of Rochester and has lead curriculum design and reform for these programs.

The Royal Society of Biology (RSB), previously called the Society of Biology, is a learned society in the United Kingdom created to advance the interests of biology in academia, industry, education, and research. Formed in 2009 by the merger of the Biosciences Federation and the Institute of Biology, the society has around 16,000 individual members, and over 100 member organizations. In addition to engaging the public on matters related to the life sciences, the society seeks to develop the profession and to guide the development of related policies.

The Clinical Science and Drug Discovery Conference had its inaugural meeting in 2015 in Baltimore, MD where Dr. Smith was asked to serve as a Keynote Speaker (and judge for poster sessions). The organizers of that meeting nominated him to organize this years meeting in Dundee, Scotland along with Drs. Ian Catchpole from GlaxoSmithKline in the UK and Nikolai Zhelev, professor at Abertay University, the hosting institution. The meeting will be held July 27-29. Dr. Smith will also deliver a keynote lecture at this meeting and chair a special topics session that he is bringing together on 'Host Cell Factors as Therapeutic Targets'. For more information, please visit the Drug Discovery Summit site, see also the CSDD Brochure.

OyaGen, a small medical research firm off Jefferson Road in Henrietta, has used federal grants for its HIV drug discovery programs with the goal of finding a cure. Dr. Harold Smith, Professor of Biochemistry & Biophysics at the University of Rochester, and the company's founder, president and CEO got his start as a molecular biologist studying heart disease.

"It became clear to me that the things we were doing to study heart disease and find out why things were happening translated directly into the HIV research arena," Smith said.

By 2010, things kicked into high gear. Advanced robotics were added allowing scientists to work with advanced chemistries. They've now identified a weak point in the HIV virus that's never been exploited before. Vif is a viral defense HIV releases into cells it infects. It destroys the body's natural defense against infections. OyaGen discovered a way to defeat HIV by disabling Vif.

"If we can proceed along track, we will be looking at entering clinical trials within a completely different way of approaching the virus and the disease within three years," Smith said.

Former Biochemistry graduate student and current Chair of Biology, Dr. Gloria Culver, will be formally installed as dean of the School of Arts & Sciences during an investiture ceremony at 4 p.m. today in the Interfaith Chapel on the River Campus.

University Trustee Ani Gabrellian ’84 will provide opening remarks, followed by words from Provost Peter Lennie, the Robert L. and Mary L. Sproull Dean of the Faculty of Arts, Sciences & Engineering. Mariette Westermann, vice president of the Andrew W. Mellon Foundation, and Jon Lorsch, director of the National Institute of General Medical Sciences, will serve as guest speakers. Following the ceremony, a reception will be held in the Hawkins-Carlson Room of Rush Rhees Library.

On October 29, Dr. Lynne E. Maquat received a 2015 Canada Gairdner International Award, for her work discovering and elucidating the mechanism of mRNA decay pathways. Dr. Maquat was accompanied during presentation of the award by University of Rochester President Joel Seligman, Dean Mark Taubman, and the US Ambassador to Canada, Bruce Heyman (see photo). The sold out annual black tie gala took place at the Royal Ontario Museum in Toronto, Canada and was attended by members of the health care, academic, private and public sectors. Among the attendees were Nobel Laureate Dr. Phillip Sharp, His Excellency the Right Honourable David Johnston, Governor General of Canada, and the Swiss and Japanese Ambassadors to Canada, who accompanied recipients of the Canada Gairdner International Award from those countries.

Leading up to this event, Dr. Maquat visited four local universities where she spoke to high school students about her personal story of how she became interested in research and what she hopes to achieve through her work. She also met with post-docs and graduate students at each university as well as speaking to faculty members about their research. Following the gala, Dr. Maquat attended and spoke at a 2015 Gairdner Symposium RNA and The New Genetics at the University of Toronto, which she helped coordinate. Her last event occurred at the University of New Brunswick, Fredericton where she once again spoke to high school students On being a Scientist: Uncovering the mysteries of life and met with post-docs and graduate students about their research. Dr. Maquat took every opportunity to be part of the National Program, where the goal of these programs is to contribute to Canadian science culture and innovation, and to be part of the Student Outreach Programs where she helped realize one of the Gairdner Foundation's missions to inspire young people to consider a career in science, and to increase their awareness of the value of scientific research.

A local reception was also held to honor Dr. Maquat; pictures available here.

Lynne Maquat, the J. Lowell Orbison Distinguished Service Alumni Professor in the Department of Biochemistry and Biophysics, and Research Assistant Professor, Tatsuaki Kurosaki, Ph.D. have been awarded FRAXA Postdoctoral Fellowship for their application entitled, Re-purposing clinically approved drugs to dampen hyperactive nonsense-mediated mRNA decay in fragile X syndrome.

The FRAXA Research Foundation was extremely impressed with their proposed research, and delighted to support this exciting work. Funding of 45,000 has been authorized for the period from May 1, 2015 to April 30, 2016.

Congrats to both Lynne and Tatsuaki!

Gloria Culver, former Biochemistry graduate student in the Phizicky Lab, has been appointed dean of the School of Arts & Sciences, effective immediately. Culver is currently a professor of Biology and Biochemistry & Biophysics. Peter Lennie, the Robert L. and Mary L. Sproull Dean of the Faculty of Arts, Sciences & Engineering, made the announcement following a yearlong national search. Culver has been serving as interim dean since July 1, 2014.

Biochemistry & Biophysics Professor, Harold Smith, PhD has been awarded a Drug Development Pilot Award for his project, Development of an Assay for High Throughput Screening for Antagonists of the Ebola VP40 Protein Function. The project was externally reviewed by leading drug development researchers and received a meritorious score. To learn about Dr. Smith's research please visit the Smith lab site.

Congrats Harold!

A University of Rochester team found a way to make chemotherapy more effective, by stopping a cellular quality-control mechanism, according to a study published today in Nature Communications.

The mechanism is known as NMD (nonsense-mediated mRNA decay), and scientists found that exposing breast cancer cells to a molecule that inhibits NMD prior to treatment with doxorubicin, a drug used to treat leukemia, breast, bone, lung and other cancers, hastens cell death.

The research team, led by Lynne E. Maquat, Ph.D., director of the Center for RNA Biology at the University of Rochester, acknowledges that the work is in the early stages and a long way from being applied in humans. But, they believe their data provide insights that could lead to new treatment strategies for cancer patients in the future.