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Litwack Lecture Distinguished Speakers

Lynne Elizabeth Maquat, Ph.D. – 2018 FASEB Excellence in Science Award and the Wiley Prize in Biomedical Sciences

Dr Maquat was awarded the 2018 FASEB Excellence in Science Award and the Wiley Prize in Biomedical Sciences Research in Dr. Maquat’s lab focuses on RNA decay pathways. One pathway, called nonsense-mediated mRNA decay (NMD) or mRNA surveillance, surveys all newly synthesized mRNAs during what we call a “pioneer” round of translation. This round of translation involves mRNA that is associated with the cap-binding heterodimer CBP80 and CBP20. It is distinct from the type of translation that supports the bulk of cellular protein synthesis and involves a different cap-binding protein, eukaryotic initiation factor (eIF) 4E. Generally, if translation terminates more than 50-55 nt upstream of an exon-exon junction that is marked by the NMD factors Upf3 or Upf3X, Upf2 and ultimately Upf1, then the mRNA will be subject to NMD. By the time CBP80 and CBP20 have been replaced by eIF4E, the Upf mark has been removed so that mRNA is largely immune to NMD.

Studies in progress will significantly advance our understanding of the mRNP proteins, translation factors and nucleases that trigger NMD. Results will be useful when designing therapies that aim to abrogate NMD in order to abrogate the severity of nonsense-generated diseases. Dr. Maquat’s lab is also interested in further characterizing the pioneer translation initiation complex and requirements for its remodeling to the steady-state initiation complex that involves eIF4E. Additionally, we are interested in the cycle of posttranslational modifications that typify at least some of the NMD factors, including phosphorylation of Upf1 that is mediated by the PI 3-kinase-related protein kinase Smg1.

Over the past 15 years, their discovery and subsequent work on the mechanism of Staufen (Stau)-mediated mRNA decay (SMD) has uncovered new roles for cytoplasmic long non-coding RNAs (lncRNAs) and retrotransposon-derived short interspersed elements (SINEs) in post-transcriptional gene regulation. These SINEs include human Alu elements and mouse B1, B2, B4 and ID elements. We have shown that NMD and SMD are competitive pathways in ways that contribute to cellular homeostasis and also differentiation. Dr. Maquat’s lab continues to define new cellular roles for SINEs as sites for nucleating intermolecular base-pairing between different mRNAs, between mRNAs and lncRNAs, and between different lncRNAs. The lab is additionally extending their studies of inverted-repeat Alu elements (IRAlus) and how competitive binding among the many nuclear and cytoplasmic double-stranded RNA binding proteins influence nuclear and cytoplasmic IRAlus-containing RNA metabolism.

Most recently, Dr. Maquat’s lab has discovered a new microRNA decay pathway that is mediated by Tudor-SN. This pathway, which they call TumiD, promotes G1-to-S phase transition by degrading microRNAs that degrade mRNAs encoding proteins that promote this transition. They are currently working on how TumiD is regulated.

Maquat Lab

Don W. Cleveland, PhD – 2018 Life Sciences Breakthrough Prize Laureate

Life Sciences Breakthrough Prize Laureate recipient Dr. Don W. Cleveland won the 2018 Prize for elucidating the molecular pathogenesis of a type of inherited ALS, including the role of glia in neurodegeneration, and for establishing antisense oligonucleotide therapy in animal models of ALS and Huntington’s disease.

For pioneering discoveries of the mechanisms of chromosome movement and cell-cycle control during normal cellular division, as well as of the principles of neuronal cell growth during mammalian development – defects that lead to inherited human neurodegenerative disease.

Dr. Cleveland holds joint appointments in the Departments of Medicine and Cellular and Molecular Medicine. In addition, he heads the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research, where he pursues two lines of scientific investigation: deciphering the mechanisms of chromosome movement during mitosis and identifying the mechanisms that mediate the very large change in axonal volume post-synapse formation. The latter is a feature that is essential for nerves to achieve their proper signal conduction velocities.

While his research spans several basic science and clinical disciplines, it is important to note that he was the first to clone tubulin genes and to purify tau protein, the major constituent of neurofibrillary tangles in Alzheimer’s disease.
Dr. Cleveland’s formal teaching in Neurosciences includes the Molecular and Cellular Neurobiology course. Additionally, he serves on the thesis committees of graduate students in Neurosciences.

His neuroscience-related service activities include membership in the Charcot Prize Panel, Motor Neuron Disease Association, and Scientific Advisory Board of Neurogenics, Inc. He often attends the monthly Neurosciences faculty meetings and actively participates in the annual academic review meetings. He also serves as needed on Neurosciences recruitment committees.
Dr. Cleveland regularly serves as a reviewer for a number of first-tier journals such as Science, Nature, Neuron, Nature Neuroscience, and Journal of Neuroscience. He is a sought-after lecturer and is on the “who’s who” list of invited speakers at national and international symposia, including the Gordon Conference, Cold Spring Harbor Meeting, International Meeting on Neurodegeneration, and American Association of Neurology Meeting.

2017 Life Sciences Breakthrough Prize Laureate

Dr. Roeland Nusse won the 2017 Prize for pioneering research on the Wnt pathway, one of the crucial intercellular signaling systems in development, cancer and stem cell biology.

Dr. Nusse’s laboratory is interested in the growth, development and integrity of animal tissues. They study multiple different organs, trying to identify common principles, and they extend these investigations to cancer and injury repair. In most organs, different cell types are generated by stem cells – cells that also make copies of themselves and thereby maintain the tissue. An optimal balance between the number of stem and differentiated cells is essential for the proper function of the organs. Locally-acting signals are important to maintain this balance in a spatially-organized manner and these signals are key to understanding the regulation of growth.

A common theme linking their work together are Wnt signals. Work from many laboratories, including their own, has shown that Wnt proteins are essential for the control over stem cells. How this is achieved is far from clear and is the subject of studies in the lab, both in vivo and in cell culture. In vivo, a particular question they address is how physiological changes, such as those occurring during hormonal stimuli, injury or programmed tissue degeneration have an impact on the self-renewal signals and on stem cell biology.

In their most recent work, Dr. Nusse’s lab has designed cell fate tracking experiments to study stem cells in vivo. They identified Wnt-responsive stem cells by their expression of Axin2 (a common Wnt target gene) and generated a mouse strain with the CreERT2 recombination signal inserted into the Axin2 locus, Axin2-Cre. By clonal labeling, they showed that single stem cells differentiate into different cell types of the tissues of interest. Unexpectedly, in the liver, they found that hepatocytes that reside in the pericentral domain of the liver demonstrate stem cell behavior. Although these cells are functional hepatocytes, they are diploid and thus differ from the mostly polyploid mature hepatocyte population. They are active in homeostatic cell replacement. Adjacent central vein endothelial cells provide the essential source of Wnt signals for the hepatocyte stem cells and thereby constitute the liver stem cell niche.

2016 Life Sciences Breakthrough Prize Laureate

Dr. Boyden won the 2016 Prize for the development and implementation of optogenetics — the programming of neurons to express light-activated ion channels and pumps, so that their electrical activity can be controlled by light.

Ed Boyden is a professor of Biological Engineering and Brain and Cognitive Sciences at the MIT Media Lab and the MIT McGovern Institute. He leads the Synthetic Neurobiology Group, which develops tools for analyzing and repairing complex biological systems such as the brain, and applies them systematically to reveal ground truth principles of biological function as well as to repair these systems. These technologies, created often in interdisciplinary collaborations, include expansion microscopy, which enables complex biological systems to be imaged with nanoscale precision, optogenetic tools, which enable the activation and silencing of neural activity with light, and optical, nanofabricated, and robotic interfaces that enable recording and control of neural dynamics. He has launched an award-winning series of classes at MIT that teach principles of neuroengineering, starting with basic principles of how to control and observe neural functions, and culminating with strategies for launching companies in the nascent neurotechnology space. He also co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress.

Amongst other recognitions, he has received the Breakthrough Prize in Life Sciences (2016), the BBVA Foundation Frontiers of Knowledge Award (2015), the Society for Neuroscience Young Investigator Award (2015), the Carnegie Prize in Mind and Brain Sciences (2015), the Jacob Heskel Gabbay Award (2013), the Grete Lundbeck Brain Prize (2013), the NIH Director’s Pioneer Award (2013), the NIH Director’s Transformative Research Award (twice, 2012 and 2013), and the Perl/UNC Neuroscience Prize (2011). He was also named to the World Economic Forum Young Scientist list (2013), the Technology Review World’s “Top 35 Innovators under Age 35” list (2006), and his work was included in Nature Methods “Method of the Year” in 2010.

His group has hosted hundreds of visitors to learn how to use new biotechnologies, and he also regularly teaches at summer courses and workshops in neuroscience, and delivers lectures to the broader public (e.g., TED (2011); World Economic Forum (2012, 2013, 2016)). Ed received his Ph.D. in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before that, he received three degrees in electrical engineering, computer science, and physics from MIT. He has contributed to over 300 peer-reviewed papers, current or pending patents, and articles, and has given over 300 invited talks on his group’s work.

2005 Nobel Prize in Physiology for Medicine

Nobel Prize winner Dr. John Robin Warren won the 2005 Prize in Physiology for Medicine, which was was awarded jointly to Dr. Warren and Barry J. Marshall  “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.

Dr. Warren was born in Adelaide in 1937. Despite an equal love for photography Warren entered medical school at the University of Adelaide, graduating with an MB and BS in 1961. A chance turn of fate led Warren to pathology and after training at the Royal Melbourne Hospital in 1967 he was admitted to the Royal College of Pathologists of Australasia. Warren then moved to Perth to take up a position as staff specialist in pathology at the Royal Perth Hospital (1968–98). It was during this time that Warren first observed bacteria in stomach sections associated with peptic ulcers (1979). Warren began to work with Barry Marshall in 1981 and together they were able to demonstrate that the bacteria Warren observed (now called Helicobacter pylori) was the causative agent in peptic ulcers. This revolutionary discovery was at first rejected by the medical fraternity but finally led to a cure for peptic ulcers.

1998 Nobel Laureate in Physiology or Medicine

Dr. Louis J. Ignarro, a distinguished molecular and medical pharmacologist and 1998 Nobel Laureate in Physiology or Medicine, is currently Distinguished Professor of Pharmacology at UCLA, USA, and an Honorary Professor of Medicine at CUHK. Professor Ignarro discovered that nitric oxide causes vasodilation, inhibits thrombosis, and is produced in arteries as the endothelium-derived relaxing factor. His discoveries have greatly encouraged research in the protective mechanism of the cardiovascular system against pathological conditions and in vascular complications, bearing significant impact on medical development. The University will confer upon Professor Ignarro the degree of Doctor of Science, honoris causa, in recognition of his valuable advice and support to CUHK in its research and development in medicine and science.