Schedule of Program

Conference Schedule

Check in outside Kahn Auditorium.

Refreshments served in ABC Rooms.

Nils G. Walter, Ph.D., Francis S Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry 

Santa J. Ono, Ph.D., President, University of Michigan

Laurie K. McCauley, Ph.D., Provost and Executive Vice President for Academic Affairs, William K and Mary Anne Najjar Professor of Periodontics, Professor of Dentistry, Department of Periodontics and Oral Medicine, School of Dentistry, and Professor of Pathology, Medical School.

Abstract: Vaccines prevent 4-5 million deaths a year making them the principal tool of medical intervention worldwide. Nucleoside-modified mRNA was developed over 15 years ago and has become the darling of the COVID-19 pandemic with the first 2 FDA approved vaccines based on it. These vaccines show greater than 90% efficacy and outstanding safety in clinical use. The mechanism for the outstanding immune response induction are the prolonged production of antigen leading to continuous loading of germinal centers and the adjuvant effect of the LNPs, which selectively stimulate T follicular helper cells that drive germinal center responses. Vaccine against many pathogens, including HIV, HCV, HSV2, CMV, universal influenza, coronavirus variants, pancoronavirus, nipah, norovirus, malaria, TB, and many others are currently in development. Nucleoside-modified mRNA is also being developed for therapeutic protein delivery. Clinical trials with mRNA encoded monoclonal antibodies are underway and many other therapeutic or genetic deficient proteins are being developed. Finally, nucleoside-modified mRNA-LNPs are being developed and used for gene therapy. Cas9 knockout to treat transthyretin amyloidosis has shown success in phase 1 trials. We have developed the ability to target specific cells and organs, including lung, brain,
heart, CD4+ cells, all T cells, and bone marrow stem cells, with LNPs allowing specific delivery of gene editing and insertion systems to treat diseases such as sickle cell anemia, Nucleoside-modified mRNA will have an enormous potential in the development of new medical therapies.

Bio: Dr. Weissman, 2023 Nobel Laureate in Medicine, is the Roberts Family Professor in Vaccine Research at the Perelman School of Medicine, University of Pennsylvania and Director of the Penn Institute for RNA Innovations.  He received his B.A. and M.A. from Brandeis University in Waltham, Massachusetts in 1981 and his M.D./Ph.D. from Boston University in 1987 before completing his medical Residency at Beth Israel Hospital in Boston, Massachusetts in 1990. He completed his Fellowship in Immunology at the Lab of Immunoregulation in the National Institute of Allergy and Infectious Disease of the National Institutes of Health, serving in the lab of Dr. Anthony Fauci. Following his Fellowship, Dr. Weissman became an Assistant Professor in the Division of Infectious Disease at the University of Pennsylvania in 1997. In 2005, he was promoted to Associate Professor, and to full Professor in 2012.

His major contributions to the scientific field include the identification of the mechanism by which RNA activates the innate immune system, and that naturally occurring modified nucleosides were the mechanism used by the cell to distinguish foreign RNA from self RNA. Further, Dr. Weissman and his colleagues identified that nucleoside modified mRNA not only did not cause inflammation, but that it was also more stable and efficiently translated than conventional mRNA and went on to develop nucleoside modified mRNA as a delivery system for therapeutic proteins. Building on this work, Dr. Weissman and his colleagues began using nucleoside modified mRNA complexed to lipid nanoparticles to deliver therapeutic mRNA as a vaccine platform, resulting in high titers of neutralizing antibodies against many different pathogens with minimal doses. In addition, Dr. Weissman and his collaborators analyzed the mechanisms that HIV envelope uses to suppress the immune system and proceeded to alter the envelope immunogen to improve responses against it when used in an encoding vaccine.

Dr. Weissman’s work has resulted in the publication of more than 100 papers. He holds many patents, including the ones which detail the modifications required to make mRNA suitable for vaccines and other therapies. 

Bio: Dr. Cooke trained in Cardiovascular Medicine at the Mayo Clinic and obtained a Ph.D. in Physiology there.  Subsequently, he became a faculty member at Harvard Medical School, and then Stanford University where he was  Professor and Associate Director of the Stanford Cardiovascular Institute until his recruitment to the Houston Methodist Research Institute (HMRI) in July 2013. 

Dr. Cooke chairs the Department of Cardiovascular Science which generates fundamental insights that transform cardiovascular care.   The basic science effort in angiogenesis, atherosclerosis, vascular regeneration, and cardiomyocyte function are carried out by nine faculty using a range of molecular, cellular, physiological, bioinformatics tools and technologies.  In addition, the Department of Cardiovascular Sciences provides the infrastructure for about 200 industry-sponsored and investigator initiated trials in cardiovascular diseases.

Dr. Cooke also directs the Center for RNA Therapeutics.  Dr. Cooke’s team developed  methods for the synthesis, purification, validation, lyophilization, and delivery of mRNA, and makes RNA constructs for investigators world-wide.  Dr. Cooke has explored the use of mRNA encoding human telomerase to reverse senescence and to improve cell therapies.  His regenerative medicine research is funded by the NIH, NASA, BARDA, AHA, CPRIT and industry. Dr. Cooke has published > 500 research papers, reviews and patents (>35,000 citations; h index = 104; Scopus  4-11-23).  He was named an Outstanding Inventor of 2015 by the Office of Technology Transfer at Stanford University, and elected to the National Academy of Inventors in 2019; and received the Mayo Clinic Distinguished Alumni Award in 2020.   His Center for RNA Therapeutics received the 2021 Innovation Award from the Houston Business Journal; the 2021 Best Academic Team Research, Vaccine Industry Excellence Award, at the 2021 World Vaccine Congress;  the 2022 Fire Award, Houston Business Journal, Top Health Care and Life Science Innovators; and was chosen in 2023 to provide a novel RNA vaccine platform for the global vaccine effort of the Coalition for Epidemic Preparedness Initiative.

A preview of the day’s poster session, hear from junior researchers on their topics of study during these rapid-fire presentations.

Refreshments served in the ABC Rooms.

Abstract: In retroviruses, reverse transcription is initiated from an intermolecular duplex primer formed by nucleocapsid-driven annealing of the U5-primer binding site (U5-PBS) region of the genome with a host tRNA. I will present data that redefines our basic understanding of this complex by assigning RT an additional structural remodeler role, separate from its enzymatic function, and then discuss a unique mechanism that contributes to the control of start of DNA synthesis in virions. I will also highlight the potential importance of organization of the initiation complex in a dimeric genome context, and the role of nucleocapsid during initiation and extension.

Bio: My research focuses on the biochemical and structural analysis of RNAs and their interaction with proteins; both with a focus on those involved in viral biology (example, HIV, SARS and MLV), and those involved in cellular systems that have a virus-like approach to function. To elaborate, I have been involved in studying the mechanistic details of many RNA-mediated processes that drive viral replications; including regulation of reverse transcription (U5-PBS:tRNA complexes), transcription (Tat-TAR), translation (ribosomal readthrough, frameshifting and IRES-mediated), and genome packaging. From the cellular angle, we are interested in understanding specialized ribosomal readthrough that occurs in VEGF and headcase mRNA, and IRES regulation in neuronal transcripts such as CamK2a, and trafficking of Oskar mRNA during drosophila oogenesis. My lab uses a multidisciplinary approach to understanding the structure-function relationship, including, in vitro and cellular assays, high-resolution structure determination by Nuclear Magnetic Resonance (NMR) and more recently x-ray and cryo-EM; biophysical analysis by Small Angle X-ray Scattering (SAXS) and Isothermal Calorimetry (ITC); and functional analysis by cell culture and virological assays.

I have also been actively involved in graduate training and mentoring. I am the co-director of the Molecules, Cells and Organelles (MCO) graduate program at the Cambridge campus at Harvard. In addition, I am involved in graduate training in the Program in Virology at the Harvard Medical School. I am a strong advocate of promoting inclusive and supportive research training environments. I have initiated numerous programs have led to an increase in the number of URMs applying and being admitted in the program (from three percent a decade ago to an average of sixteen percent in the last three years), which I believe is a direct result of these initiatives.

A preview of the day’s poster session, hear from junior researchers on their topics of study during these rapid-fire presentations.

Abstract: There are over 3 million Short Tandem Repeats in the human genome. Expansion in a small subset (~50) of these repeats are currently linked to human neurological diseases such as Autism, ALS, and FTD, although recent findings suggest more disease-causing repeats await discovery. Our group studies the mechanisms by which repeat expansions cause disease, with a specific focus on toxic RNA gain-of-function mechanisms and the unconventional translation of repeats in the absence of an AUG start codon (“RAN translation”). In this presentation, I will discuss recent data on the mechanisms by which RAN translation occurs and its role in disease pathogenesis in Fragile X-associated disorders. I will also discuss how repeats have important native functions in neurobiology. Our thesis is that emerging disease mechanisms can inform a broader understanding of the native roles of short tandem repeats in neuronal function and that aberrations in these native processes provide clues to novel therapeutic strategies for these currently untreatable disorders.

Bio: Peter K. Todd, M.D., Ph.D. is the Chester and Anne Sackett Endowed Professor of Neurology and Human Genetics and associate chair for research in the department of Neurology. Dr. Todd earned his Bachelor degree in Biology from the University of California, San Diego. He obtained his Medical Degree and completed his Doctorate in Neuroscience at the University of Wisconsin, where he studied the molecular mechanisms underlying Fragile X Syndrome with Dr. Jim Malter and Dr. Ken Mack. During neurology residency at the University of Pennsylvania, he worked with Dr. J. Paul Taylor using Drosophila models of neurodegeneration. He then completed clinical and research fellowships in movement disorders and neurogenetics at the University of Michigan with Dr. Hank Paulson.

As a physician scientist, Dr. Todd’s lab studies the mechanisms by which nucleotide repeat expansions cause neurological disorders with a long-term goal of developing novel therapeutics for currently untreatable conditions. His lab has published extensively on Fragile X-associated disorders, such as Fragile X Syndrome and Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) as well as C9orf72 repeat expansions that cause ALS and frontotemporal dementia. More recent studies explore roles for repeat expansions in more common neurological conditions.

As a clinician, Dr. Todd sees patients at both the University of Michigan and at the VA medical Center in Ann Arbor. He directs both the UM Ataxia and Fragile X Clinics where he sees patients with inherited and sporadic neurologic disorders. He also serves as founding director of the Neurogenomic Medicine program at Michigan and as clinical director of the RNA therapeutics Initiative within the Center for RNA biology at Michigan. Both of these programs aim to improve research and precision healthcare for patients with inherited disorders.

Dr. Todd has given over 100 invited presentations across the world and published over 70 papers on his research. His lab has been continuously funded by the NIH and VA since its inception. He has received numerous awards including the Michigan Medical School Dean’s Award for basic science research, the American Academy of Neurology’s S. Weir Mitchell Alliance Award, and the American Neurological Association’s Derek Denny Brown Award.

Peruse the great work of our junior researchers during the poster session.

A selection of boxed lunches will be available in the ABC Rooms.

Mats Ljungman, Ph.D., Professor of Radiation Oncology, Medical School and Professor of Environmental Health Sciences, School of Public Health

Steve Kunkel, Ph.D., Endowed Professor of Pathology Research, Peter A. Ward Distinguished University Professor, Executive Vice Dean for Research, U-M Medical School, Chief Scientific Officer, Michigan Medicine

Abstract: The objective of the ENCORE (Encyclopedia of RNA Elements) project is to develop a foundational, functional map of protein-RNA interactions of RNA binding proteins (RBPs) encoded in the human genome, and the RNA elements they bind to across the transcriptome. These RNA elements, when expressed, form the basis of co- and post-transcriptional regulation of human genes. Our strategy consists of developing and integrating a physical map of hundreds of RBPs in two different human cell lines with transcriptome-wide measurements of the effects of depleting these RBPs. These efforts will culminate in a comprehensive map of the functional RNA elements recognized by essentially all RBPs expressed in two human cell lines, representing approximately half of the known complement of human RBPs. These data will enable a more systematic and comprehensive understanding of the role of RBPs and RNA biology in the contribution to human biology and disease.

Bio: Brenton Graveley joined UConn Health as an Assistant Professor in the Department of Genetics and Developmental Biology in 1999. He is currently Chair of the Department of Genetics and Genome Sciences, the Health Net, Inc. Chair in Genetics and Developmental Biology, and Associate Director of the Institute for Systems Genomics. Brent has studied RNA biology throughout his entire career and is a recognized leader in the field of alternative splicing. He performed his undergraduate studies at the University of Colorado, Boulder with David Prescott, his graduate studies at the University of Vermont with Greg Gilmartin, and his postdoctoral studies at Harvard University with Tom Maniatis. Brent has been a lead investigator of the ENCODE and modENCODE projects. Brent was a member of the Board of Directors of the RNA Society, Editor of the journal RNA, the National Advisory Council for Human Genome Research, and is an elected member of the Connecticut Academy of Science and Engineering.

Abstract: Over 60% of the human protein-coding genes are regulated by microRNAs (miRNAs), underscoring their critical role in many, if not most, biological processes. MiRNAs are ~ 22-nucleotide non-coding RNAs that are processed from hairpin-containing primary transcripts (pri-miRNAs) by the Microprocessor (MP), a heterotrimeric nuclear complex containing Drosha, an RNase III endonuclease, and two copies of its essential co-factor, DGCR8. MP-mediated pri-miRNA processing (M2P2) produces a shorter hairpin precursor (pre)-miRNA with a 2-nucleotide 3’ overhang and, in some cases, a 1-nucleotide 3’ overhang. Pri-miRNAs are characterized by a ~ 35 ± 1 base pair double-stranded stem, single-stranded flanking regions, and a ≥ 10-nucleotide apical loop. They also contain several conserved sequence motifs, including a 5’ UG dinucleotide motif, a 5’ UGUG motif at the base of the apical loop, a 3’ CNNC motif, and a GHG mismatch (mGHG) motif in the lower stem. These motifs impact M2P2 fidelity. Nonetheless, the structural and sequence diversity of these MP substrates is considerable. We performed a single-particle cryo-EM structural study combined with biochemical analyses of pri-miRNA belonging to a particular family, the let-7 family, important in development, to understand how the MP accommodates this wide array of pri-miRNAs and how some of the known motifs assist in M2P2.  We found that the MP itself has an innate structural plasticity to respond to pri-miRNAs with sequence and structural variation. We defined structural features associated with two conserved sequence motifs commonly used in pri-miRNA classification.

Bio: Leemor Joshua-Tor, Ph.D. is a Howard Hughes Medical Institute Investigator and W.M. Keck Professor of Structural Biology at Cold Spring Harbor Laboratory. She is also the Chair of the Cancer and Molecular Biology Program. She was trained at Tel-Aviv University, where she earned a B.Sc. in chemistry, and at the Weizmann Institute of Science in Rehovot, where she earned a Ph.D. in chemistry. She was a Jane Coffin Childs postdoctoral fellow at the California Institute of Technology (Caltech) prior to joining the CSHL faculty. At CSHL, she was the Director of the Undergraduate Summer Research Program and then the Dean of the School of Biological Sciences, CSHL’s graduate school. She is the recipient of the Mildred Cohn Award in Biological Chemistry from the ASBMB, the Dorothy Crowfoot Hodgkin Award from the Protein Society, a Beckman Young Investigator Award and is a Fellow of the Biophysical Society. She is an elected member of the National Academy of Sciences, a member of the American Academy of Arts and Sciences and a Fellow of the American Association for the Advancement of Science. She served on several advisory committees at the National Institutes of Health and serves on the editorial boards of a number of international scientific journals.

Leemor Joshua-Tor’s laboratory studies the molecular basis of nucleic acid regulatory processes, RNA interference (RNAi) and DNA replication in particular. She is perhaps best known for her work revealing the inner workings of components of the gene-silencing mechanisms of RNA interference. She discovered the role of an enigmatic protein called Argonaute at the heart of the RNAi machinery. Argonaute, also known as Slicer, is a programmable protein that effects gene silencing. In addition to basic mechanisms of gene silencing, they have been studying the regulation of the miRNA let-7, important in embryonic development and differentiation. She is also known for her studies of E1, a key factor in the replication of papillomavirus, a virus that causes cervical cancer. Dr. Joshua-Tor discovered how E1 moves along DNA, which has had implications to molecular motors in many fields of biology. More recently, they have been examining the eukaryotic replication machinery with the human Origin Recognition Complex (ORC) as the centerpiece of these studies.

Refreshments served in ABC Rooms.

Join the full lineup of guest speakers for a roundtable discussion on unmasking the power of RNA.

Moderated by Michelle Hastings, Ph.D. & John Cooke, M.D., Ph.D.

Center for RNA Biomedicine Leadership Team