Center for RNA Biomedicine

RNA Innovation Seminar: Joseph Yesselman, Ph.D. — University of Nebraska
2024-10-07 16:00 - 17:00 (America/Detroit) | 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: 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

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
