News

We are thrilled to announce that Rachel Niederer as agreed to join us as a faculty member in Biological Chemistry, the Center for RNA Biomedicine, and the LSI.

About Dr. Rachel Niederer:
Dr. Niederer completed her undergraduate degree at the University of Maryland, College Park in Biochemistry and Cell Biology/Molecular Genetics where she worked with Dr. Jon Dinman to study the effect of RNA modifications on translational fidelity. She went on to obtain her Ph.D. from John Hopkins under the mentorship of Dr. David Zappula, where she defined shared structural and functional features in telomerase RNA and explored the transcriptional response to telomere loss and senescence. Dr. Niederer carried out postdoctoral studies first with Dr. Melissa Moore at the University of Massachusetts and then (when Dr. Moore moved to Moderna) with Dr. Wendy Gilbert at Yale studying mechanisms of translational control. Rachel developed a novel method to rapidly and quantitatively measure ribosome recruitment to thousands of 5’-UTR sequences to define features controlling translation initiation. This approach, termed Direct Analysis of Ribosome Targeting (DART), published this spring in Cell Systems, has uncovered hundreds of new, functional RNA elements in yeast that differ in their ability to recruit ribosomes and to act as sequence-specific translational repressors.

Future Scientific Plans:
Dr. Niederer’s laboratory will explore mechanisms of translational control. She will bring a new set of cutting-edge approaches for studying translation initiation to the Department of Biological Chemistry, the Center for RNA Biomedicine, and the broader UM community.

If you would like to reach out to welcome Rachel, you may contact her here: rachel.niederer@yale.edu and @roniederer

We are thrilled to announce that Jay Brito Querido as agreed to join us as a faculty member in Biological Chemistry, the Center for RNA Biomedicine, and the LSI.

About Dr. Brito Querido:
A native of Cape Verde, Dr. Querido received undergraduate and M.S. degrees at the University of Lisbon. For his Ph.D., Dr. Querido worked with Dr. Yaser Hashem in Strasbourg, France using cryo-EM to study parasite-specific ribosomal proteins. Dr. Querido then moved to Dr. Venki Ramakrishnan’s lab at the MRC Laboratory of Molecular Biology for post-doctoral work, where he has tackled longstanding questions surrounding translation initiation on eukaryotic mRNAs. Most prominently, Dr. Querido determined the structure of a 48S translation initiation complex and suggested a novel mechanism for ribosome recruitment and mRNA scanning (Brito Querido et al., Science 2020).

Future Scientific Plans:
Currently, Dr. Querido is exploring translation initiation on structured mRNAs and the role of the human tumor suppressor protein Pdcd4 in regulating translation. Dr. Querido has exciting plans to continue in this field, with a goal of understanding the many ways in which RNA helicases regulate gene expression in health and disease.

If you would like to reach out to welcome Jay, you may contact him here: jquerido@mrc-lmb.cam.ac.uk

By Justin P. Hicks | jhicks3@mlive.com

Empty syringes wait to be filled with the Pfizer-BioNTech COVID-19 vaccine at the Kalamazoo Expo Center (Joel Bissell | MLive.com)

Vaccines to protect against severe illness and death from COVID-19 started as the key to a return to normal, but they could wind up unlocking much more for the future of health care.

The mRNA vaccine technology used by Pfizer/BioNTech and Moderna for their respective coronavirus vaccines has been heavily touted by doctors and public health officials as a modern miracle of science and a means to revolutionize vaccine development.

“It’s hard to overestimate the impact this will have on human health,” said Nils Walter, a professor of biological chemistry at the University of Michigan who has studied mRNA for about 30 years. “It’s like introducing the iPhone when everyone had a flip phone.”

Beyond its uses for COVID-19, numerous mRNA vaccine candidates are being researched and undergoing clinical trials for the treatment of cancer, including pancreatic cancer, colorectal cancer and melanoma, as well as HIV, influenza, Ebola, Zika, and rabies.

“The same molecule from billions of years ago that gave us life is now coming back to what ails us today in life, which are viral infections and the terrible diseases like cancer,” Walter said. “It’s transformative.”

Vaccines using mRNA technology work by delivering instructions to the cells. In the case of COVID-19, those instructions are to create a protein that mimics the spike protein found in SARS-CoV-2, which triggers an immune response and the development of antibodies to defend against that virus.

Unlike previously used viral vector vaccines, mRNA vaccines don’t introduce live or dead virus into the body as a means of triggering antibody production.

The ingredients of the vaccine are broken down and discarded in a matter of days. The mRNA never enters the nucleus of the cell, and has no interaction with the cell’s DNA, health officials have repeatedly stated.

Dr. Liam Sullivan, an infectious disease specialist for Spectrum Health, expects mRNA technology to “revolutionize vaccine development.”

“This is just the beginning; we’re just scratching the surface here,” he said. “mRNA vaccine technology for treating diseases isn’t going anywhere. If anything, it’s going to get better and better and be used more widespread.”

Previous vaccines like the annual flu shot could take a year to develop, which made it challenging to predict which strains would be around by the next flu cycle. As a result, flu shot effectiveness has varied year to year.

With mRNA vaccines, that timeline can be cutdown 10-fold, Walter said.

“We can now operate at the same speed as the virus and therefore, viruses can no longer outmaneuver us and the vaccine can be made to specs in very, very short time,” he said. “It’s a totally different ball game.” [Read more…] about After COVID-19, mRNA vaccines could treat flu, HIV and even cancer

Renowned U-M researcher is recognized by Royal Swedish Academy of Sciences for pioneering prostate cancer discovery

Arul M. Chinnaiyan, MD, PhD

ANN ARBOR, Michigan — Arul M. Chinnaiyan, M.D., Ph.D., S.P. Hicks Professor of Pathology and Urology at Michigan Medicine, was awarded the 2022 Sjöberg Prize by the Royal Swedish Academy of Sciences, which also awards Nobel Prizes.

Chinnaiyan is being honored for the discovery of recurrent gene fusions in prostate cancer, a groundbreaking finding initially published in 2005 that has led to a better understanding of how prostate cancer develops and improved methods to detect the disease.

“It is a great honor to be selected for this award and to follow in the footsteps of the luminaries who have received this award in the past,” said Chinnaiyan, director of the Michigan Center for Translational Pathology and a member of the University of Michigan Health Rogel Cancer Center.

This is the sixth time the Sjöberg Prize has been awarded. It was established by businessman Bengt Sjöberg, who was diagnosed with cancer and donated two billion Swedish kronor to promote scientific research primarily focused on cancer, health and the environment. The Royal Swedish Academy selects the laureates and the Sjöberg Foundation provides the financing. Winners receive $1 million, which includes $100,000 personal prize and $900,000 to support their research.

Chinnaiyan’s lab found that a prostate-specific gene called TMPRSS2 fuses with the gene ERG, to drive prostate cancer development. This gene fusion, fueled by the hormone androgen, acts as an “on switch” to trigger prostate cancer. The fusion is an exquisitely specific biomarker of prostate cancer that can be detected in prostate needle biopsies and non-invasively in the urine of men with prostate cancer, which has led to improved methods for screening and diagnosing prostate cancer. It also represents a potential target for treatment, and research is ongoing to develop drugs against this genetic anomaly.

“The Sjöberg Prize is an incredibly well-deserved recognition for Dr. Chinnaiyan,” said Eric R. Fearon, M.D., Ph.D., director of the Rogel Cancer Center. “His gene fusion discovery provided unique insights into recurrent genetic defects fueling development of prostate cancers. The work also showed gene fusions could be at the heart of common cancer types. Moreover, he has translated his basic research findings into a screening test that has significantly improved how prostate cancer, especially aggressive prostate cancer, is detected. His discoveries are making a real difference for people with cancer.”

Former Sjöberg laureates include James P. Allison, Ph.D., who was awarded the Nobel Prize in Medicine in 2018.

An award ceremony will be held in Sweden on June 13, and Chinnaiyan will also deliver the Sjöberg Prize lecture then at the Karolinska Institute.

The scientific journey of Bambarendage (Pini) Perera, Ph.D., Research Assistant Professor of Environmental Health Sciences, School of Public Health

Diet, exercise, or environmental exposures have an impact on how our genes are activated or silenced. These factors do not permanently affect our DNA, but they can interfere with our gene expression by acting upon RNA regulation mechanisms. These phenomena comprise “epigenetics,” a field of research that fascinates Bambarendage Pinithi (Pini) Perera, Ph.D., Research Assistant Professor in the department of Environmental Health Sciences of the School of Public Health, and a new member of the Center for RNA Biomedicine. Through epigenetics research, she sees the opportunity to contribute to society, and to scientifically inform the public and stakeholders about the benefits and risks of environmental exposures.

Dr. Perera is particularly interested in embryonic development and the effect of environmental exposures during pregnancy. In this context, she studies the consequences of toxic exposures on imprinted genes—these are normal monoallelic genes, meaning that only one of the two parents’ genes is activated—and RNA regulation processes.

[Read more…] about Being and belonging: science and community

While most efforts involving CRISPR are focused on genome editing, the CRISPR machinery could also be used as a molecular weapon to slice up chromosomes of cancer cells. Research has shown that chromosomes may undergo a “catastrophic” event early in the process of carcinogenesis causing multiple breakages. While many cells die in such events, some of them repair the damaged chromosomes in ways that give them the power to multiply faster and to form tumors. Such chromosome rearrangements bring into close proximity pieces of chromosomes that are normally far apart. The formation of chromosome rearrangements is unique to cancer cells and is observed across all forms of cancer. “This is our Achilles’ heel, right there,” said Dr. Ljungman, Professor of Radiation Oncology and co-director of the Center for RNA Biomedicine, “and we could use CRISPR to specifically target these chromosome rearrangement junctions and cut tumor DNA strands similarly to what is done with radiation therapy, but without affecting normal cells.”

This article is reprinted from RNA Translated 2021. Photo: KLIPP team, Summer 2021. From left to right: Mats Ljungman, Radhika Suhas Hulbatte, Huibin Yang, Lauren Hertzer, and Natalie Gratsch. Photo: Elisabeth Paymal

[Read more…] about CRISPR to KLIPP cancer

Congratulations to Amanda Garner, Ph.D., for receiving the ACS Division of Medicinal Chemistry 2022 David W. Robertson Award for Excellence in Medicinal Chemistry!
The David W. Robertson Award for Excellence in Medicinal Chemistry, awarded in even-numbered years, is intended to recognize seminal contributions by young scientists to medicinal chemistry. The nominee must have had a primary role in the discovery of a novel therapeutic agent(s), target(s), theoretical concept(s) in medicinal chemistry or drug discovery, and/or made a significant scientific discovery that enhances the field of medicinal chemistry.

Amanda Garner is Associate Professor, Medicinal Chemistry, College of Pharmacy, and former Member of our Executive Committee.

Congratulations to Chase Weidmann, Ph.D., for receiving a K22 grant from NCI for “Unraveling the MALAT1 lncRNA-protein interaction networks that drive lung cancer metastasis”

This project’s goal is to integrate cutting-edge sequencing and quantitative proteomics technologies with cell-based functional approaches to understand how RNA-protein interaction networks of MALAT1 promote metastatic activity in human lung cancers.

Chase Weidmann is our second RNA Faculty Scholar hire and is an Assistant Professor in the department of Biological Chemistry at the Medical School.

Weidmann page
Read about Weidmann’s journey into science: “Exploring unknown territories”
Read his scientific feature
Watch his introduction video

An initiative to make the University of Michigan a world leader in RNA therapeutics,
spearheaded by the Center for RNA Biomedicine and the Biointerfaces Institute

Fueled by the COVID-19 mRNA vaccine success and the recent Nobel Prize in Chemistry for the discovery and elucidation of the bacterial CRISPR systems that can be harnessed for genome editing, RNA therapeutics has garnered considerable interest from academia, the pharmaceutical industry, and the public at large. To capitalize on this great momentum, the Center for RNA Biomedicine and the Biointerfaces Institute plan to leverage the strength of University of Michigan (U-M) research in RNA biomedicine and nanoparticle sciences to build a world-class resource that will convert U-M foundational research innovations into RNA-based clinical treatments.

Together, we envision establishing a pipeline of RNA therapeutics reaching from the research lab to the clinic in five to ten years. Our therapies will include mRNA for vaccines against a multitude of diseases, antisense oligonucleotides (ASOs) for the suppression of undesired genes, and CRISPR for genome editing of defective genes and for precision targeting of cancer cells. M-RNA Therapeutics will also offer these technologies for laboratory research such as gene knockouts and screens.

(Reprinted from RNA Translated 2021)

[Read more…] about M-RNA therapeutics at the University of Michigan

Introducing Chase Weidmann, Ph.D.,
Assistant Professor in the Department of Biological Chemistry
and RNA Scholar Faculty of the Center for RNA Biomedicine.

Chase Weidmann had three goals for a career: do something “cool,” improve the lives of other people, and, of course, be able to support himself.

Weidmann found the “cool” in high school science classes and he quickly realized that biology and `biotechnology offer vast uncharted territories to explore. One such uncharted area was the academic system itself, as he sometimes struggled to navigate his way through college. Still, he was very glad to find that stipends and resources would enable him to continue exploring in graduate school. He pursued his doctoral research at the University of Michigan (U-M) where now, a decade later, he is joining the RNA faculty community as an Assistant Professor in the Department of Biological Chemistry and as the second hired RNA Scholar Faculty of the Center for RNA Biomedicine.

[Read more…] about Exploring unknown territories

[Read more…] about Refer your colleagues to join the U-M Center for RNA Biomedicine.

Photo: Adrien Chauvier, Ph.D., in the Nils Walter’s lab (Credit: Laura Penabad-Peña)

Dr. Adrien Chauvier’s journey has taken him around the world, from the Amazon rainforest to Michigan snowy winters, and his passion for science has never left him. He is now a postdoctoral fellow in Nils Walter’s lab, in the Department of Chemistry of the University of Michigan.

Dr. Chauvier grew up in the equatorial forests of French Guiana, north of Brazil. French Guiana is an important biodiversity hotspot and is also the largest French territory outside the metropole.

His father owned a large plant nursery and he is the one who instilled a deep interest for the natural world into him. ” I always wanted to go outside with my dad. I was very curious. We would take care of the plants and the soil together. It was no surprise that growing-up, I wanted to pursue a career in Science and especially in the biological field (…),” he fondly recalled. [Read more…] about First step first: understanding normal processes before tackling pathologies