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 (America/Detroit) | 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 Here, I will present new unpublished data describing 3D genome miswiring in a human neuron model with rare familial Alzheimer’s mutations as well as the functional link among loops and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
