RNA Innovation Seminar: Susan Gottesman, NIH/NCI
2023-10-23 16:00 - 17:00 (America/Detroit)
“Bacterial Small RNAs: Regulatory Circuits, On & Off Switches, & Quality Control”
Susan Gottesman, Ph.D.
Chief, Laboratory of Molecular Biology
NIH/NCI Distinguished Investigator

In-person: BSRB, ABC Seminar Rooms / hybrid link
Abstract: Bacteria use small regulatory RNAs (sRNAs) and the RNA chaperone Hfq to regulate mRNA translation and stability, akin to miRNAs and the RISC complex in eukaryotes. The approaches to defining bacterial sRNAs and their targets have dramatically improved since the screens that first identified many of them over 20 years ago. Current tools provide a global view of Hfq-binding RNAs that suggests increasingly interwoven regulatory networks, helping cell respond appropriately to stress and host interactions. On-switches for sRNAs are primarily at the level of transcription; when transcription ceases, most of the sRNAs are used stoichiometrically, being degraded as they are used, providing an effective Off-switch for sRNA regulation. We have used genetic screens to identify novel regulators of both Hfq and the sRNAs. One of these, HqbA, binds directly to the distal face of Hfq, and competes with weakly binding RNAs for association with Hfq, suggesting it is a new quality control regulator for Hfq. Data suggests that this is a bifunctional protein, directly regulating Hfq by protein-protein interaction and regulating other processes independently of Hfq. HqbA, along with other factors, help to ensure appropriate hierarchy of sRNA function.
Keywords: mRNA translation; RNAse E; Escherichia coli.

RNA Innovation Seminar: Irina Artsimovitch, Ohio State University
2023-11-06 16:00 - 17:00
“Locking Rho up”
Irina Artsimovitch, Ph.D.
Arts & Sciences Distinguished Professor
Department of Microbiology
The Ohio State University
In-person: BSRB, ABC seminar rooms / hybrid link
Abstract: Bacterial termination factor Rho co-transcriptionally surveils the nascent RNA and releases damaged and junk transcripts from RNA polymerase. During rapid growth, Rho maintains the transcriptome health, but how is Rho activity modulated during dormancy or stress, conditions prevalent in natural habitats? Rho is a hexameric RNA helicase that adopts active closed-ring and inactive open-ring states, and the interconversion between these states is thought to be a key checkpoint in Rho control. I will discuss two mechanisms by which ligands that bind at Rho subunit interfaces restrain ring dynamics. The Sm-like Rof protein binds at the extended RNA-binding site of Rho, occluding its RNA- and RNA polymerase-binding sites and locking the hexamer open. The stress alarmone (p)ppGpp binds to the ATP-binding site and stabilizes the open ring, triggering phase separation into inactive higher-order oligomers and extended filaments. These and other anti-termination mechanisms are expected to silence Rho under conditions when unrestrained termination would be lethal.
Keywords: transcription; termination; Rho helicase; stress response; phase separation

RNA Innovation Seminar: George Lisi, Brown University
2023-11-20 16:00 - 17:00
“The Invisible Dance of CRISPR-Cas9 through Molecular Space and Time”
George Lisi, Ph.D.
Thomas J. & Alice M. Tisch Assistant Professor
Department of Molecular Biology, Cell Biology & Biochemistry
Brown University

In-person: BSRB, ABC seminar rooms / hybrid link
Abstract: This talk will focus on long-range signaling in CRISPR-Cas9, a cutting-edge genome editing tool. The transformative potential of Cas9 as a precision therapeutic cannot be realized without an understanding of its interdomain communication and the mitigation of deleterious off-target cleavage, which is being characterized at the atomic level in the group. A series of vignettes will highlight NMR studies of Cas9 through a “divide-and-conquer” approach using engineered protein constructs and first demonstrate that multi-timescale motions in the catalytic nuclease of Cas9 propagates chemical information that regulates cleavage of double-stranded DNA. The talk will also highlight specificity-enhancing mutations in Cas9 that rewire its regulatory mechanism and RNA interactions at the molecular level to mitigate off-target DNA cleavage. Critical energetics of the mechanism will be discussed, including the importance of metal ions and the protonation state of the catalytic histidine, studied via catalytic pocket mutations that limit conformational sampling of the Cas9 active state. Lastly, insight from canonical Cas9s will be expanded to highly stable thermophiles that are more promising for genome engineering and offer tunable high-temperature DNA editing and RNA binding. The underlying chemistry and atomic level dynamics of Cas9 will be linked to its nucleic acid interactions and biological outcomes, hopefully opening new avenues for intuitive manipulation of its function and precision therapeutic properties.

RNA Innovation Seminar: Andy Berglund, University at Albany
2023-12-04 16:00 - 17:00
“Mis-splicing in repeat expansion diseases and development of potential therapeutics”
Andy Berglund, Ph.D.
Empire Professor of Innovation
Director of the RNA Institute
University at Albany

In-person: BSRB, ABC Seminar Rooms / hybrid link
Abstract: Repeat or microsatellite expansions are responsible for more than 50 human diseases. Myotonic dystrophy (DM), amyotrophic lateral sclerosis (ALS), and spinocerebellar ataxias (SCAs) are a few examples of repeat expansion diseases. RNA processing (pre-mRNA splicing) pathways are negatively impacted in these diseases with specific changes in pre-mRNA splicing proposed to lead to symptoms observed in affected individuals. Many of the projects in the lab combine biochemical, molecular, and genomic approaches with cellular and other model systems to understand the mechanisms through which these diseases alter pre-mRNA splicing. Through screening approaches, small molecules have been identified that reduce the levels of the repeat expansion RNAs and rescue mis-splicing in DM and SCA cell and animal models.
Keywords: Myotonic Dystrophy, Spinocerebellar Ataxias, Alternative Splicing and RNA Binding Proteins

RNA Innovation Seminar: Anthony Rosenzweig, University of Michigan
2024-01-22 16:00 - 17:00
“Noncoding RNA Targets in Heart Failure”
Anthony Rosenzweig, M.D.
Professor of Internal Medicine
Director of the MM Institute of Heart & Brain Health
University of Michigan

In-person: BSRB, ABC seminar rooms / hybrid link
Abstract: TBA

RNA Innovation Seminar: Sarah Woodson, Johns Hopkins University
2024-02-05 16:00 - 17:00
“How chaperones help RNAs choose the right partner”
Sarah Woodson, Ph.D.
T.C. Jenkins Professor of Biophysics
Johns Hopkins University

In-person: BSRB, ABC seminar rooms / hybrid link
Abstract: Non-coding RNAs must fold into specific structures to create the machinery for protein synthesis or to control gene expression. As nascent transcripts can form different base pairing interactions, finding the right partner can take time. RNA chaperone proteins increase the RNA dynamics, enabling the kinetic selection of optimal RNA interactions. How a DEAD-box helicase improves the fidelity of ribosome assembly and how Hfq increases the selectivity of small RNA regulation will be discussed.

RNA Innovation Seminar: Joan Steitz, Yale University
2024-02-19 16:00 - 17:00
“RNA-RNA Base Pairing: Key to unlocking the functions of many noncoding RNAs”
Joan Steitz, Ph.D.
Sterling Professor of Molecular Biophysics and Biochemistry
Yale University

In-person: BSRB, ABC seminar rooms / hybrid link
Abstract: Dr. Steitz’s talk will be primarily historical, with many examples of discoveries of RNA-RNA base pairing over her 50-year+ career being reviewed. At the end, she will mention her latest unpublished finding: how RNA-RNA-based pairing prevents neuronal death under stress conditions.

8th Annual RNA Symposium
2024-03-08 08:30 - 17:00
“Unmasking the Power of RNA: From Structure to Medicine”
Friday, March 8, 2024, 8:30 am – 5:00 pm
A. Alfred Taubman Biomedical Science Research Bldg, Kahn Auditorium
109 Zina Pitcher Pl, Ann Arbor, Michigan
For More Information and to Register, Click Here.

RNA Innovation Seminar: Evgeny Nudler, New York University
2024-03-18 16:00 - 17:00
“Transcription-driven DNA Repair”
Evgeny Nudler, Ph.D.
Julie Wilson Anderson Professor of Biochemistry
Investigator, Howard Hughes Medical Institute
Department of Biochemistry & Molecular Pharmacology
NYU Grossman School of Medicine

In-person: BSRB, ABC seminar rooms / hybrid link
Abstract: Using E. coli as a model system, we have developed new approaches to study damage recognition and processing in vivo for three major DNA repair pathways, nucleotide excision repair (NER), ribonucleotide excision repair (RER), and base excision repair (BER). Our recent findings let us to formulate a conceptually new model of global transcription-driven repair (TDR), in which RNA polymerase serves as the indispensable genome-wide DNA damage sensor and also delivery vehicle and platform for the assembly of specialized repair complexes in living cells. The model provides a framework for better understanding genotoxic stress response and genome instability in bacteria and beyond.
Keywords: DNA repair, transcription elongation, RNA polymerase, ppGpp, NER, BER, RER

RNA Innovation Seminar: Shuying Sun, Johns Hopkins University
2024-04-01 16:00 - 17:00
“RNA Metabolism in C9ORF72-linked neurodegenerative diseases ALS and FTD”
Shuying Sun, Ph.D.
Associate Professor, Department of Physiology
Brain Science Institute
Johns Hopkins University School of Medicine

In-person: BSRB, ABC seminar rooms / hybrid link
Abstract: We have a long-standing interest in RNA metabolism dysfunction and RNA-targeting therapy in neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The hexanucleotide GGGGCC repeat expansion in C9ORF72 is the most frequent genetic cause of both ALS and FTD. RNA-mediated gain of toxicity is critical for the pathogenesis. We employ multiple molecular approaches to understand the regulation of the repeat RNA processing, uncover genetic modifiers, and elucidate the influence on global RNA metabolism. We aim to understand the disease mechanisms and identify potential therapeutic targets for C9ORF72-ALS/FTD.

**CANCELED** RNA Innovation Seminar: Catherine Kaczorowski, University of Michigan
2024-05-06 16:00 - 17:00
**CANCELED**
Due to unforeseen circumstances, today’s RNA Innovation seminar featuring Dr. Catherine Kaczorowski has been canceled. Please be on the lookout for rescheduling information in the coming days
“Using Complex Genetics in Mice to Unlock the Secrets of Cognitive Resilience”
Catherine Kaczorowski, Ph.D.
Elinor Levine Professor of Dementia Research
Professor of Neurology
University of Michigan, Medical School
In-person: BSRB, ABC Seminar Room / hybrid link
Abstract: Alzheimer’s Disease, Systems Genetics, Resilience

RNA Innovation Seminar: Alexandra Piotrowski-Daspit, Internal Medicine
2024-06-03 16:00 - 17:00
“RNA: the delivery perspective”
Alexandra Piotrowski-Daspit, Ph.D.
Assistant Professor, Biomedical Engineering
Assistant Professor, Internal Medicine – Pulmonary & Critical Care Medicine Division
University of Michigan

In-person: BSRB, Kahn Auditorium / hybrid link
Abstract: The primary barrier for clinical translation of RNA therapeutics remains delivery to target tissues in vivo. Upon entering the body, delivery vehicles encounter extracellular and intracellular barriers. It is also unclear how carrier design features impact physiological interactions with biological systems, highlighting the need for studies that elucidate these structure-function relationships. In this seminar, I will describe our work on developing polymeric nanoparticles (NPs) to deliver therapeutic RNAs to a variety of tissues following local and systemic IV administration. We find that gene therapy can be significantly enhanced using a new class of polymeric vehicles consisting of poly(amine-co-ester) (PACE) polymers that are designed for safe and effective nucleic acid delivery. We have also developed tools to study nanomaterial-biology interactions in animal models, including a high-throughput quantitative microscopy-based platform to measure circulation half-life and biodistribution in vivo. This tool, alongside the development of novel polymeric carriers, can be used to study the structure-function relationships that guide the physiological fate of NPs in order to rationally design more effective delivery vehicles for RNA delivery.
Keywords: RNA therapeutics, in vivo delivery, polymeric nanoparticles (NPs), nanomaterial-biology interactions

David R. Walt, Ph.D. — Special Lecture and Open House Breakfast
2024-09-12 09:00 - 12:30 | Michigan League, 911 N University, Ann Arbor, MI, 48109, United States
The Center for RNA Biomedicine presents microwell array pioneer, David R. Walt, PH.D.

On Thursday, September 12, the Center for RNA Biomedicine will host life sciences industry expert David R. Walt, Ph.D. for a special lecture titled, “Why sensitivity matters for clinical diagnosis (see abstract below).”
Following the lecture, there will be an open house breakfast with opportunities to socialize with peers and connect with Dr. Walt.
Schedule — Thursday, September 12 | 9 a.m. – 12:30 p.m.
9 a.m. – 10:15 a.m. | David Walt, Ph.D. Lecture — Koessler Room, 3rd Floor, Michigan League
10:30 a.m. – 12:30 p.m. | Open House Breakfast with Dr. Walt — Henderson Room (directly across from Koessler), 3rd Floor, Michigan League
**A hybrid option is being offered via Zoom — click here to register.**
Whether in person or virtual, we hope you’ll join us for learning, coffee, and socializing with one of the top minds in fields of bio-inspired engineering, RNA-based clinical diagnosis, and life sciences startups.
Abstract and Speaker Info
Abstract:
A major challenge for many clinical diagnostic applications is the quantification of low-abundance proteins and other biomolecules in biological fluids. For example, traditional techniques, such as enzyme-linked immunosorbent assay (ELISA), can only measure several hundred proteins in human blood, which is limiting because there are thousands of proteins present at low concentrations that are of potential diagnostic utility. Single-molecule technologies allow for digital counting of individual protein molecules and have enabled 1000-fold increases in sensitivity over conventional protein detection methods. We have pioneered the development of these technologies that provide for multiplexed measurements with femtomolar sensitivities or below. I will discuss the technologies and describe their application to neurodegenerative disease, cancer, and infectious diseases.
About David R. Walt, Ph.D.:
David R. Walt is the Hansjörg Wyss Professor of Bioinspired Engineering at Harvard Medical School, Professor of Pathology at Brigham and Women’s Hospital and Harvard Medical School, Core Faculty Member of the Wyss Institute at Harvard University, Associate Member at the Broad Institute, and is a Howard Hughes Medical Institute Professor. His lab’s research focuses on creating and using novel technologies to solve unmet clinical diagnostics problems. Walt is the Scientific Founder of Illumina Inc., Quanterix Corp., and has co-founded multiple other life sciences startups including Ultivue, Inc., Arbor Biotechnologies, Sherlock Biosciences, Vizgen, Inc., and Protillion Biosciences. He has received numerous national and international awards and honors for his fundamental and applied work in the field of optical microwell arrays and single molecules including the 2023 National Academy of Engineering’s Fritz J. and Dolores H. Russ Prize and the 2021 Kabiller Prize in Nanoscience and Nanomedicine. He is a member of the U.S. National Academy of Engineering, the U.S. National Academy of Medicine, a Member of the American Philosophical Society, a Fellow of the American Academy of Arts and Sciences, a Fellow of the American Institute for Medical and Biological Engineering, a Fellow of the American Association for the Advancement of Science, a Fellow of the National Academy of Inventors, and is inducted in the US National Inventors Hall of Fame.

RNA Innovation Seminar: Gregor Neuert, Ph.D. — Vanderbilt University
2024-09-23 16:00 - 17:00 | BSRB – ABC Seminar rooms, 109 Zina Pitcher Pl, Ann Arbor, MI, 48109, United States
The University of Michigan Center for RNA Biomedicine Seminar Series is excited to host Gregor Neuert, Ph.D., for the first talk of the 2024 – 2025 RNA Innovation Seminar Series.

Gregor Neuert, Ph.D.
Associate Professor,
Molecular Physiology and Biophysics
Biomedical Engineering,
Pharmacology
Vanderbilt University

Date and Time: Monday, September 23 | 4 p.m.
In-person: Kahn Auditorium, BSRB
Virtual: The seminar will be available via Zoom for those unable to attend in person. Click here to register for the Zoom.
Talk Title: “Transcriptional stochasticity reveals multiple mechanisms of long non-coding RNA regulation”

Abstract:
Long noncoding RNAs (LncRNAs) are increasingly recognized as being involved in human physiology and diseases, but there is a lack of mechanistic understanding for the majority of lncRNAs. We comparatively tested proposed mechanisms of antisense lncRNA regulation at the X-chromosome Inactivation (XCI) locus. Our single-cell analyses argue against mechanisms that require the Xist or Tsix transcript to bind to each other. Intriguingly, we find that due to stochasticity in transcription, different mechanisms based on the act of transcription regulate Xist and Tsix at different levels of nascent transcription. At medium levels, RNA polymerases transcribe Xist and Tsix on each strand at the same transcription site and deposit significant amounts of the histone mark H3K36me3, which inhibits Xist. At high levels of nascent transcription, many RNA polymerases transcribe Xist or Tsix resulting in transcriptional interference. Therefore, lncRNA expression variability is not just a quirk of transcription but an important aspect of regulation that allows multiple mechanisms to be employed by the same gene locus within the same cell population.
Please visit the Neuert Lab for Quantitative Systems Biology website to learn more about Dr. Neuert and his work.

RNA Innovation Seminar: Joseph Yesselman, Ph.D. — University of Nebraska
2024-10-07 16:00 - 17:00 | BSRB – Kahn Auditorium
The University of Michigan Center for RNA Biomedicine Seminar Series will host Joseph Yesselman, Ph.D., as part of the 2024 – 2025 RNA Innovation Seminar Series.
Joseph Yesselman, Ph.D.
Assistant Professor, Chemistry
University of Nebraska

Date and Time: Monday, October 7 | 4 p.m.
In-person: Kahn Auditorium, BSRB
Hybrid Option: Click here to join the Zoom.

Talk Title: “High-throughput determination of RNA tertiary contact thermodynamics by quantitative DMS chemical mapping”
Abstract:
Structured RNAs often contain long-range tertiary contacts that are critical to their function. Despite the importance of tertiary contacts, methods to measure their thermodynamics are low throughput or require specialized instruments. Here, we introduce a new quantitative chemical mapping method (qMaPseq) to measure Mg2+-induced formation of tertiary contact thermodynamics in a high-throughput manner using standard biochemistry equipment. With qMaPseq, we measured the ΔG of 98 unique tetraloop/tetraloop receptor (TL/TLR) variants in a one-pot reaction. These results agree well with measurements from specialized instruments (R2=0.64). Furthermore, the DMS reactivity of the TL directly correlates to the stability of the contact (R2=0.68), the first direct evidence that a single DMS reactivity measurement reports on thermodynamics. Combined with structure prediction, DMS reactivity allowed the development of experimentally accurate 3D models of TLR mutants. These results demonstrate that qMaPseq is broadly accessible, high-throughput, and directly links DMS reactivity to thermodynamics.
Please visit the Yesselman Lab website to learn more about Dr. Yesselman and his work.

RNA Innovation Seminar: Laura Scott, Ph.D., University of Michigan School of Public Health
2024-10-21 16:00 - 17:00 | BSRB – Kahn Auditorium
“Regulation of RNA levels in muscle and adipose tissues by sex and genetic variants”
Laura Scott, Ph.D.
Research Professor, Biostatistics
University of Michigan School of Public Health
Research interests:
Dr. Scott uses a combination of bulk and single nucleus omic data – RNA expression, chromatin accessibility, metabolites and DNA methylation – to understand the cellular genetic regulatory landscape and to infer biological connections between genetic variation and disease risk.
Click here to read more about Dr. Scott and her work in a 2020 Faculty Spotlight article.
In-person: BSRB, Kahn Auditorium / hybrid link

Abstract:
Gene expression is regulated by multiple factors including genetic variation, sex, and cell type. I will describe differences by sex in human skeletal muscle cell type composition, cell type-level gene expression and chromatin accessibility, and bulk miRNA expression in 287 people. I will describe regulation of subcutaneous adipose gene expression by genetic variants in a meta-analysis of >2,200 people. These studies help to better understand transcription and post-transcriptional regulation of gene expression by sex and genetic regulation of gene expression.

RNA Innovation Seminar: Nils G. Walter, Ph.D., Co-Director, U-M Center for RNA Biomedicine
2024-11-04 16:00 - 17:00 | BSRB – Kahn Auditorium
“Single molecules come into focus: From bacterial riboswitches to mammalian cellular phase separation”
Nils G. Walter, Ph.D.
Co-Director,
U-M Center for RNA Biomedicine
Francis S Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry,
U-M LSA

Abstract:
At least 75% of the 3 billion base pairs of the human genome are transcribed into RNA, but the vast majority of these transcripts do not code for proteins but rather for “non-coding” RNAs (ncRNAs), many of which remain uncharacterized in terms of their structure and function. Currently, more than 80,000 unique ncRNAs have been identified in human cells alone, suggesting that for a long time we have underestimated the intricacies involved in human genome maintenance, processing, and regulation by neglecting this far-reaching “RNA World.” Nature and modern nanotechnology likewise employ nanoscale RNA machines that self-assemble into structures of complex architecture and functionality. Fluorescence microscopy offers a non-invasive tool to probe, dissect and ultimately control these nanoassemblies in real-time. In particular, single molecule fluorescence resonance energy transfer (smFRET) allows us to measure distances at the 2-8 nm scale, whereas complementary super-resolution localization techniques based on Gaussian fitting of imaged point spread functions (PSFs) measure distances in the 10 nm and longer range. Encapsulating the power of these recent technical advances, we have combined single-molecule and biochemical approaches to show that a central, adaptable RNA helix in the widespread manganese-sensing riboswitch functions analogous to a molecular fulcrum to integrate disparate signals for finely balanced bacterial gene expression control. We posit that many more examples of such intimate structural and kinetic coupling between RNA folding and gene expression remain to be discovered, leading to the exquisite regulatory control and kinetic proofreading enabling all life processes. On the more applied side, we are developing tools to study the liquid-liquid phase separation of RNA-protein granules involved in human pathologies.
Biography:
Nils G. Walter (photo by Michigan Photography) is currently the Francis S. Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry in the College of Literature, Science and the Arts of the University of Michigan in Ann Arbor, Michigan. He cofounded and currently co-directs the Center for RNA Biomedicine at Michigan, now developing a thrust in RNA Therapeutics. His research interests focus on gene regulation by noncoding RNAs through the lens of single molecule techniques and applications in drug discovery.
In-person: BSRB, Kahn Auditorium / hybrid link

Links to learn more about Nils Walter and his work:
Nils Walter’s Faculty Page
Nils Walter’s Lab Page
Nils Walter’s Wikipedia Page

RNA Innovation Seminar: Jennifer E. Phillips-Cremins, Ph.D., Associate Professor and Dean's Faculty Fellow, Biomedical Engineering and Human Genetics, Penn Epigenetic Institute
2024-11-18 16:00 - 17:00 | BSRB – Kahn Auditorium
“The Science of Connections: Bridging chromatin folding, synaptic plasticity, and neurophysiology”
Jennifer E. Phillips-Cremins, Ph.D.
Associate Professor and Dean’s Faculty Fellow,
Bioengineering and Genetics,
Penn Epigenetics — University of Pennsylvania
In-person: Kahn Auditorium, BSRB | Hybrid link
Abstract:
The Cremins Laboratory works at the spatial biology-technology interface to investigate the structure-function relationship of connections in the brain across the scales of chromatin, synapses, and circuits in normal neurophysiology and in neurological disorders. We have thus far focused in the nucleus on creating kilobase-resolution maps of higher-order folding of the chromatin fiber and understanding how classic epigenetic modifications work through long-range connections to govern genome function in neurodevelopment. We have developed and applied new molecular and computational technologies to elucidate chromatin folding patterns at kilobase-resolution genome-wide, thus discovering that long-range looping interactions in cis and inter-chromosomal interactions in trans change substantially during neural lineage commitment, somatic cell reprogramming, activation of post-mitotic neural circuits, and in neurological disorders. We have demonstrated that cohesin-mediated loops are necessary for the establishment of new gene expression programs in post-mitotic neurons, including the upregulation of genes encoding axon guidance, dendritic spine morphology, and synaptic plasticity during neuron maturation in vivo as well as activity-dependent transcription during neural stimulation in vitro. We have also identified cohesin-mediated loops anchored by divergently-oriented CTCF binding sites that are necessary and sufficient for the firing efficiency and localization of human replication origins during S phase re-entry after mitosis. Using fragile X syndrome as a natural perturbation, we have uncovered BREACHes (Beacons of Repeat Expansion Anchored by Contacting Heterochromatin) – rare inter-chromosomal interactions connecting heterochromatinized synaptic genes susceptible to repeat instability, thus providing early insight into the genome’s structure-function relationship. Here, I will present new unpublished data describing 3D genome miswiring in a human neuron model with rare familial Alzheimer’s mutations as well as the functional link among loops and activity-dependent gene expression during neural circuit activation in vitro and in vivo. The long-term goal of the Cremins lab is to elucidate how the genome’s structure-function relationship influences synaptic plasticity and neurophysiology during memory encoding and consolidation and how this goes awry in intractable neurological disorders.
Bio:
Jennifer Phillips-Cremins, Ph.D. is an Associate Professor and Deans’ Faculty Fellow in Engineering and Medicine at the University of Pennsylvania with primary appointments in the Departments of Genetics and Bioengineering. Dr. Cremins obtained her Ph.D. in Biomedical Engineering from the Georgia Institute of Technology in the laboratory of Andres Garcia. She conducted a multi-disciplinary postdoc in the laboratories of Job Dekker and Victor Corces. Dr. Cremins runs the Laboratory of Chromatin and Spatial Neurobiology at UPenn. Her primary research interests lie in understanding the long-range chromatin architecture mechanisms that govern neural specification and synaptic plasticity in healthy neurons and how chromatin-synapse communication is dysregulated in neurodevelopmental and neurodegenerative diseases. She has been selected as a 2014 New York Stem Cell Foundation Robertson Investigator, a 2015 Albert P. Sloan Foundation Fellow, a 2016 and 2018 Kavli Frontiers of Science Fellow, 2015 NIH Director’s New Innovator Awardee, 2020 NSF CAREER Awardee, a 2020 CZI Neurodegenerative Disease Pairs Awardee, the 2022 ISSCR Susan B. Lim Outstanding New Investigator Award, and as a recipient of the 2021 NIH Pioneer Award.

RNA Innovation Seminar: Sundeep Kalantry, Ph.D., Professor of Human Genetics, U-M Medical School
2025-02-17 16:00
“Evolution of Mammalian Dosage Compensation”
Sundeep Kalantry, Ph.D.
Professor,
Human Genetics,
University of Michigan Medical School

In-person: Kahn Auditorium, BSRB | Hybrid link
Abstract:
The sex chromosomes pose an inequality between XX females and XY males. In therian mammals, the Y chromosome contains few unique genes, whereas the X chromosome harbors ~1000 protein-coding genes and many more noncoding loci. Excessive expression of X-linked genes in females can cause abnormal development and lethality. To equalize X-linked gene expression to that of males, females evolved X-chromosome inactivation as a dosage compensation mechanism. X-inactivation results in the silencing of most genes on one of the two Xs in females. In eutherian (‘placental’) mammals, X-inactivation requires the Xist long noncoding RNA that is expressed from and accumulates on the inactive X chromosome. Xist RNA recruits proteins that silence genes on the inactive-X. That dosage compensation requires X-inactivation and that X-inactivation requires the Xist RNA are tenets of mammalian sex chromosome biology.
Despite much work, however, whether dosage compensation requires Xist RNA and X-inactivation remains unclear. Dosage compensation is believed to have originated in therian mammals when the Y chromosome differentiated from the X chromosome. To prevent loss of genes that favored male sexual differentiation, discrete segments of the Y chromosome are thought to have undergone a series of inversions to suppress recombination with the X chromosome. Suppression of recombination is believed to have led to degeneration of genes on the Y chromosome. Due to the loss of Y-linked genes in males, females are believed to have ultimately evolved X-inactivation as a dosage compensation mechanism. Since the Y chromosome lost its gene content gradually, the need to dosage compensate X-linked genes is likely to also have arisen in a piecemeal manner. The step-wise differentiation of the X and Y chromosomes, therefore, is incompatible with chromosome-wide dosage compensation by Xist RNA and X-inactivation.
How dosage compensation can occur in the absence of Xist and X-inactivation is not known. The first Y chromosome segment to undergo differentiation from the X chromosome preceded the divergence of eutherian from metatherian mammals. Yet, Xist evolved later and only in eutherians and not in metatherians. Dosage compensation of genes in this ancestral segment of the X chromosome, therefore, is likely to have occurred prior to the advent of Xist. The ancestral form of dosage compensation is unknown but we hypothesize is still functional. We further hypothesize that this ancestral mechanism of dosage compensation was subsequently co-opted to regulate Xist when Xist arose for chromosome-wide dosage compensation through X-inactivation.
In testing the above hypotheses, we find that dosage compensation can occur in the absence of Xist and X- inactivation. We further identify an ancestral X-linked gene in the Xist- and X inactivation-independent dosage compensation mechanism. Together, our data provide insights into the origins of sex differences, mechanistically define the evolution of mammalian dosage compensation, and broadly inform how cells balance gene expression despite changes in chromosome copy number.

Bio:
Our long-standing focus is to understand mechanisms that underlie mammalian X chromosome dosage compensation, including X chromosome inactivation. X-inactivation ensures similar levels of X-linked gene expression between female and male mammals by silencing genes on one of the two X chromosomes in females. Notably, X-inactivation is also a model of sexually dimorphic epigenetic regulation, since two identical X chromosomes in female cells become transcriptionally divergent. The study of dosage compensation promises to elucidate the origins of sex differences and inform how cells balance gene expression despite changes in chromosome copy number
Links:
Kalantry Lab

2025 RNA Symposium
2025-03-06 11:00 - 2025-03-08 13:00 | BSRB – Kahn Auditorium
The Center for RNA Biomedicine at the University of Michigan, in partnership with the Society for RNA Therapeutics, proudly invites you to the 2025 RNA Symposium. Taking place from Thursday, March 6 to Saturday, March 8, 2025, this premier event will convene thought leaders and pioneering researchers in the field of RNA science and biomedicine.
Scheduled Speakers:
Jeff Coller,
Johns Hopkins Medicine
Beverly L. Davidson, University of Pennsylvania
Adrian R. Krainer,
Cold Springs Harbor Laboratory
Mats Ljungman,
University of Michigan Center for RNA Biomedicine
Muthiah Manoharan, Alnylam Pharmaceuticals
Anna Marie Pyle,
Yale School of Medicine

Dates: March 6 – 8, 2025
Location: University of Michigan Ann Arbor Campus
IMPORTANT DEADLINES!
January 26, 2025 – final date to submit an abstract
February 27, 2025 – final date to register

RNA Collaborative Seminar Series
2025-04-09 16:00 - 17:00 | Virtual
The next RNA Collaborative Seminar will be held virtually on Wednesday, April 9th at 4 pm ET (Eastern, US/Canada), hosted by the University of Rochester Center for RNA Biology & University of Michigan Center for RNA Biomedicine. Please see below for more details and the Zoom webinar registration link, and share widely with your communities and networks.
Wednesday, April 9th at 4 pm ET
Hosted by: University of Rochester Center for RNA Biology & University of Michigan Center for RNA Biomedicine
Zoom Registration: https://us02web.zoom.us/webinar/register/WN_QYg_EA_uSkK2CB987gltVA
“Discovery and Therapeutic Applications of RNA ‘Stitching’”
Doug Anderson, PhD
Assistant Professor of Medicine, Cardiovascular Research Institute (CVRI)
Member, University of Rochester Center for RNA Biology: From Genome to Therapeutics
“High-Throughput Identification of Small Molecule Inhibitors Targeting OncoMiR-181a for Cancer Therapy”
Grace McIntyre, PhD Student
PhD Candidate, Department of Pathology, University of Michigan
“Real-time Monitoring of Ligand Recognition by a Riboswitch during Transcription”
Adrien Chauvier, PhD. Research Lab Specialist
Nils Walter Laboratory – Department of Chemistry, University of Michigan
RNA Center for Biomedicine
Moderators:
Eric J. Wagner, Ph.D.
Professor, Department of Biochemistry and Biophysics
Associate Director, Center for RNA Biology
Wilmot Cancer Institute
University of Rochester School of Medicine and Dentistry
and
Nils G. Walter, Ph.D.
Director, Center for RNA Biomedicine; Francis S. Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry, University of Michigan
RNA Collaborative Seminars are sponsored by the RNA Society (@RNASociety)
For more information on the RNA CSS, please visit: https://www.rnasociety.org/rna-collaborative-seminar-series
RNA Collaborative YouTube: https://www.youtube.com/channel/UC7QawzQsUqhgIqjKGTny41A

RNA Innovation Seminar: Connie Wu, Ph.D., Research Assistant Professor, Life Sciences Institute; Assistant Professor, Biomedical Engineering and Pharmaceutical Sciences, University of Michigan
2025-04-28 16:00 - 17:00 | BSRB – ABC Seminar rooms, 109 Zina Pitcher Pl, Ann Arbor, MI, 48109, United States
“Programming and probing the body: from RNA therapeutics to single-molecule detection”
Connie Wu, Ph.D.
Research Assistant Professor,
Life Sciences Institute,
Assistant Professor,
Biomedical Engineering and Pharmaceutical Sciences,
University of Michigan, U-M Medical School
In-person: ABC Seminar Rooms, BSRB | Hybrid link
Abstract:
Our lab integrates biomolecular engineering and bioanalytical chemistry approaches to develop next-generation diagnostic and therapeutic platforms. I will first discuss our work in developing multifunctional RNA systems for cancer immunotherapy applications. Leveraging RNA as a programmable scaffold, we engineer RNA nanostructures to activate multiple innate immune pathways and present additional immunomodulators. In parallel, we develop ultrasensitive single-molecule detection platforms for diagnostic applications. While ultrasensitive digital ELISA methods have unlocked a broader spectrum of disease biomarkers, achieving attomolar (10 -18 M) detection limits, the simultaneous detection of many proteins and biomolecule types with high analytical sensitivities and throughput remains a critical challenge in biomarker signature discovery. Our ongoing efforts aim to expand the ultrasensitive single-molecule detection toolkit to enable accurate high-order multiplexing and multiparametric profiling of diverse biomarker types.
Bio:
Connie Wu obtained her B.S. in chemical engineering from Yale University, where she worked with Paul Van Tassel, Ph.D., in designing porous layer-by-layer polymer films for tissue engineering applications. She pursued her Ph.D. in chemical engineering at MIT in the lab of Paula Hammond, Ph.D., where she engineered a highly potent small interfering RNA (siRNA) nanoparticle delivery system via nucleic acid engineering and polymer chemistry approaches.
Following her graduate studies, Wu transitioned to the diagnostics field for her postdoctoral research in the lab of David Walt, Ph.D., at Brigham and Women’s Hospital and the Wyss Institute at Harvard University, where she pioneered ultrasensitive single-molecule detection methods that can measure attomolar protein concentrations with versatile multiplexing capabilities. In parallel, she developed ultrasensitive digital assays for detecting the long interspersed element-1 (LINE-1) retrotransposon-encoded protein ORF1p in blood as a highly specific multi-cancer biomarker.
Wu was the recipient of multiple fellowships during her graduate and postdoctoral training, including a National Science Foundation Graduate Research Fellowship, MIT Presidential Fellowship and NIH Ruth L. Kirschstein F32 Postdoctoral Fellowship.
As part of the U-M Life Sciences Institute and the Department of Biomedical Engineering at the University of Michigan, Wu’s lab develops technologies for biomarker signature discovery and RNA therapeutic delivery, with applications across cancer and other diseases.
Links:
Connie Wu Lab – Life Sciences Institute
Biomedical Engineering
College of Pharmacy
University of Michigan Medical School

RNA Translated 2025 Feature Article

RNA Innovation Seminar: Lydia Freddolino, Ph.D., Associate Professor of Biological Chemistry, Computational Medicine and Bioinformatics, U-M Medical School
2025-05-19 16:00 - 17:00 | BSRB – Kahn Auditorium
“Transcriptional control by heterochromatin-like regions is a conserved feature across the bacterial kingdom”
Lydia Freddolino, Ph.D.
Associate Professor
Biological Chemistry
Computational Medicine and Bioinformatics
University of Michigan Medical School

In-person: Kahn Auditorium, BSRB | Hybrid link
Abstract:
Despite decades of dogma indicating that bacterial chromosomes are universally accessible to transcription, more recent evidence has emerged indicating that bacteria in fact contain densely protein occupied, transcriptionally silent regions in their genomes. We have observed such silent regions across every bacterial species so far tested using appropriate methods, despite substantial differences in the molecular implementation in each case. Furthermore, these regions can be partitioned roughly into constitutive and condition-dependent regions of silencing, drawing clear functional analogies to constitutive vs. facultative heterochromatin in eukaryotes. I will present an overview of recent findings on the molecular architecture and functional roles played by bacterial heterochromatin-like regions, along with an outlook of how these regions may interact with epigenetic phenomena and evolution.
Biography:
Lydia Freddolino obtained her B.S. with Honors in Biology at the California Institute of Technology, followed by Ph.D. work in the laboratory of Prof. Klaus Schulten at the University of Illinois at Urbana-Champaign, focusing on large-scale molecular dynamics simulations of protein folding and assembly. She then pivoted to pursue postdoctoral training in bacterial systems biology under the guidance of Prof. Saeed Tavazoie, first at Princeton University and later at Columbia University. Since joining the faculty at the University of Michigan in 2015, Lydia has built her research program around two main pillars, one centered on the transcriptional regulatory roles of bacterial chromatin, and one focused on developing and applying new computational methods for predicting protein structure and function.

Links:
Freddolino Lab

RNA Innovation Seminar: John Lueck, Ph.D., Associate Professor, Pharmacology and Physiology; Neurology, University of Rochester Medical Center
2025-06-16 16:00 - 17:00 | BSRB – ABC Seminar rooms, 109 Zina Pitcher Pl, Ann Arbor, MI, 48109, United States
“Development of ACE-tRNAs as a platform therapeutic for nonsense-associated diseases”
John D. Lueck, Ph.D.
Associate Professor
Pharmacology and Physiology
Neurology
University of Rochester Medical Center

In-person: ABC Seminar Rooms, BSRB | Hybrid link
Co-hosted by the Cystic Fibrosis at UM Initiative

Abstract:
We have generated a library of AntiCodon Edited (ACE) -tRNAs that are capable of suppressing disease-causing nonsense mutations and rescuing WT protein function. However, to advance ACE-tRNAs as a therapeutic, we set out to determine how well they function as a platform therapeutic, where one ACE-tRNA sequence encoding one amino acid can be used to restore significant function of the target protein with nonsense to missense mutations. This maneuver would significantly reduce the burden of advancing several ACE-tRNA sequences through clinical trials and FDA approval. Further, we are working to determine modalities for viral and non-viral delivery of ACE-tRNAs to different tissues. In doing so, we have taken advantage of the diminutive size of the ACE-tRNA expression cassette to generate small DNA vectors for efficient cell delivery and nuclear targeting.
Biography:
The focus of my research is to evaluate the therapeutic promise of suppressor tRNA for treatment of cystic fibrosis. In my graduate training I studied myotonia in myotonic dystrophy type 1 (DM1) in Dr. Robert Dirksen’s laboratory and in collaboration with Dr. Charles Thornton. I used both molecular biology/genetics and electrophysiology approaches to determine how the DM1-associated problems with alternative splicing affect function of ClC-1 chloride channel and muscle excitability. I showed that chloride conductance is rapidly rescued if ClC-1 splicing is corrected or if sequestration of splicing factors is released. I also investigated the effects of splicing misregulation on function of RyR1. These studies resulted in 10 publications and cemented my interest in doing translational research. Following my graduate work, I joined Dr. Kevin Campbell’s laboratory. There I learned membrane protein biochemistry, antibody generation and testing mouse skeletal muscle physiology testing and gene therapy approaches, in studies focused on muscular dystrophy. This experience makes me well suited to conduct independent research using a breadth of techniques focused disease pathogenesis. My research took a turn as I became interested in the field of genetic code expansion and its use as a therapeutic for cystic fibrosis (CF) that result from nonsense mutations. I quickly published 5 studies in 3 years with Dr. Chris Ahern that propelled me to my current independent position, where I have been able to extend my research in determining the therapeutic promise of our suppressor tRNA technologies for CF. In my next steps, I will use my extensive training in mouse genetics, molecular biology, membrane biophysics and protein biochemistry to investigate the impact on cellular and tissue processes following stop codon suppression in vivo and generate new CF therapeutic deliverables that can be translated into other nonsense associated diseases. More broadly, I’m interested in applying membrane biophysics and molecular and cellular biology approaches to elucidate the molecular underpinning of genetic diseases, and then using mechanistic insights to develop new treatments.
Research interests:
My research focuses on the molecular genetics and experimental treatment of diseases resulting from nonsense mutations. I am investigating the use of engineered tRNAs for suppression of nonsense mutations in cystic fibrosis transmembrane conductance regulator (CFTR) transcripts as therapeutic intervention for cystic fibrosis. Additionally, I am interested in the molecular genetics and experimental treatment of the trinucleotide repeat disorder myotonic dystrophy (DM1). Moving forward, I intend to study pre-mRNA splicing defects in DM1 to determine the causes of muscle weakness and wasting, and develop and test new therapeutic strategies to target the genetic misstep and reverse symptoms. More broadly, I’m interested in applying membrane biophysics, molecular and cellular biology approaches to understand the molecular underpinning of genetic diseases and develop therapeutic interventions.
Links:
John D. Lueck, Ph.D. | University of Rochester Medical Center Faculty Page
Lueck Lab
John D. Lueck | Google Scholar

Cracking the Code: Phil Sharp and the Biotech Revolution - Film Screening and Post-Film Panel Discussion
2025-10-23 19:00 - 21:30 | Michigan Theater, 603 E Liberty St, Ann Arbor, MI, 48104, United States
﻿

Thursday, October 23 at 7:00 PM
Michigan Theater
603 E Liberty St
Ann Arbor, MI 48104.
To purchase tickets, please visit the Marquee Arts Website
Special offer for current U-M students!
Use the promo code UMRNA to unlock the Complimentary Ticket option. Good for one ticket, while supplies last. Must show current U-M Student ID for entry.

Film | Documentary | NR | 1h 36m | 2025

Cracking the Code, narrated by Mark Ruffalo, is an inspiring story of vision, perseverance, and the power of science to change the world. Phil Sharp’s journey from a Kentucky farm boy to Nobel laureate embodies the American Dream and the triumph of entrepreneurial spirit. His 1977 groundbreaking discovery of RNA splicing rewrote the rules of molecular biology and ignited a life-saving scientific revolution, laying the foundation for an industry that has become a cornerstone of global innovation and economic growth – and transformed the health of billions of patients worldwide.

Featuring a post-film Q&A with a panel co-presented by the University of Michigan Center for RNA Biomedicine and U-M Innovation Partnerships. Panelists include (subject to change):
Dr. Amanda Garner – Charles Walgreen Jr Professor, Professor of Medicinal Chemistry and Director, Interdepartmental Program in Medicinal Chemistry, College of Pharmacy
Dr. Muneesh Tewari – Ray and Ruth Anderson-Laurence M Sprague Memorial Research Professor, Professor of Internal Medicine, Associate Division Chief, Basic Research, Medical School and Professor of Biomedical Engineering, Medical School and College of Engineering
Dr. Nils Walter – Director, U-M Center for RNA Biomedicine, Francis S Collins Collegiate Professor of Chemistry, Biophysics and Biological Chemistry, Professor of Chemistry, Professor of Biophysics, College of Literature, Science, and the Arts, Program Associate, Office of Graduate and Postdoctoral Studies and Professor of Biological Chemistry, Medical School
Kate Remus, Senior Associate Director & Business Development Group Lead, University of Michigan Innovation Partnerships
Additional panelists TBD

Download the official flyer HERE.
To purchase tickets, please visit the Marquee Arts Website
Special offer for current U-M students! Use the promo code UMRNA to unlock the Complimentary Ticket option. Good for one ticket, while supplies last. Must show current U-M Student ID for entry.

2026 RNA Symposium
2026-03-06 - 2026-03-07 | BSRB – Kahn Auditorium
RNA Frontiers: From Mechanisms to Medicine
This year’s symposium explores the dynamic world of RNA, highlighting how fundamental mechanisms and molecular machines are shaping both our understanding of cellular processes and the development of next-generation medical innovations. Through cutting-edge scientific talks and a patient advocacy panel discussion, we will explore a wide range of topics spanning epigenetics, genome editing, RNA structure, and translational research, and discover together how RNA is propelling biological discovery from molecular intricacy to real-world impact in medicine and beyond.

Early bird registration is now open!

Click here to register!

The Center for RNA Biomedicine at the University of Michigan proudly invites you to the 2026 RNA Symposium. Taking place from Friday, March 6 to Saturday, March 7, 2026, this premier event will convene thought leaders and pioneering researchers in the field of RNA science and biomedicine.
Scheduled Speakers:
Shelley Berger, Ph.D.
University of Pennsylvania
Karla Neugebauer, Ph.D.
Yale School of Medicine
Madeleine Oudin, Ph.D.
Tufts University
Erik Sontheimer, Ph.D.
UMass Chan Medical School
Nils Walter, Ph.D.
University of Michigan
Sarah Woodson, Ph.D.
Johns Hopkins University

Dates: March 6 – 7, 2026
Kahn Auditorium
BIOMEDICAL SCIENCE RESEARCH BUILDING
109 ZINA PITCHER PLACE
ANN ARBOR, MICHIGAN 48109
University of Michigan Ann Arbor Campus
