Harvard University Program in Neuroscience
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Neuregulin Induces the Expression of Transcription Factors and Myosin Heavy Chains Typical of Muscle Spindles in Cultured Human Muscle
Neuregulin induces the expression of transcription factors and myosin heavy chains typical of muscle spindles in cultured human muscle Christian Jacobson*, David Duggan†, and Gerald Fischbach‡§ *Microarray Unit, Genetics and Genomics Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892; †Translational Genomics Research Institute (TGen), Phoenix, AZ 85004; and ‡Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032 Contributed by Gerald Fischbach, June 29, 2004 Neuregulin (NRG) (also known as ARIA, GGF, and other names) is (DRG) (28), proprioceptive sensory neurons in particular, ex- a heparin sulfate proteoglycan secreted into the neuromuscular press NRG early in development (14, 29, 30). While these junction by innervating motor and sensory neurons. An integral experiments were ongoing, reports appeared implicating NRG in part of synapse formation, we have analyzed NRG-induced the development of muscle spindles. Hippenmeyer et al. (14) changes in gene expression over 48 h in primary human myotubes. showed that NRG induces the expression of early growth We show that in addition to increasing the expression of acetyl- response 3 (Egr3), a transcription factor that is critical to the choline receptors on the myotube surface, NRG treatment results differentiation of muscle spindle fibers (31). Evidence for NRG’s in a transient increase of several members of the early growth role in spindle formation is re-enforced by the phenotypic response (Egr) family of transcription factors. Three Egrs, Egr1, -2, similarities between conditional Erb2 knockout animals and and -3, are induced within the first hour of NRG treatment, with Egr3 null mice (13, 15, 24). -
Neurosurgery Residency Training Program Massachusetts General Hospital Harvard Medical School Boston, Massachusetts OVERVIEW
Neurosurgery Residency Training Program Massachusetts General Hospital Harvard Medical School Boston, Massachusetts OVERVIEW The goal of the residency training program at the Massachusetts General Hospital (MGH) is to train neurosurgeons who will become leaders in academic neurosurgery. The program has a long and proud tradi- tion of training surgeons who have made major clinical and scientific contributions to the field of neurosurgery. More recently, the program has undergone a significant expansion with appointment of new faculty members and the planned move into new operative suites and patient units in the Building for the Third Century (B3C), with a doubling of the department’s laboratory space. The program is dynamic, growing, and strongly positioned to continue this tradition of leadership into the 21st century. The philosophy of the program is to expose residents to a large number of high-quality cases spanning the entire range of neurosurgery. The Massachusetts Robert L. Martuza, M.D. General Hospital is a tertiary referral center for the entire New England area as well as for many parts of the United States and the world. Accordingly, the program benefits from access to an excellent variety and quantity of cases. As train- ing progresses, residents gain more responsibility in perform- ing surgery and in managing cases. This process reaches its ‘We aim to culmination when the trainee becomes a full attending of the produce excellent North service at the MGH for a six-month period at the end of the program. During this period the North attending has full ad- clinical surgeons mitting and operating privileges and runs his or her own service with a passion for with the support of the faculty. -
Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System
International Journal of Molecular Sciences Review Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System Shenglong Zou and Ujendra Kumar * Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-604-827-3660; Fax: +1-604-822-3035 Received: 9 February 2018; Accepted: 11 March 2018; Published: 13 March 2018 Abstract: The biological effects of cannabinoids, the major constituents of the ancient medicinal plant Cannabis sativa (marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids. Keywords: cannabinoid; endocannabinoid; receptor; signaling; central nervous system 1. Introduction The plant Cannabis sativa, better known as marijuana, has long been used for medical purpose throughout human history. -
Neuroscience in Brief
Neuroscience in Brief On the Move from Academia to Industry: Established Neuroscientists Who Have Made the Transition from Academia to Industry Are Finding Different Rewards in a New Environment Contributed by Laura Bonetta In 1997, neuroscientist Frank Walsh was Wyeth Research in Pennsylvania, as exec- asked by Peter Goodfellow whether he utive vice president for discovery research would be interested in leading the neuro- worldwide. At Wyeth, a company that has science division at SmithKline Beecham several blockbuster drugs in the market, in- Pharmaceuticals (now GlaxoSmithKline) in cluding the antidepressant Effexor XR (ven- Harlow, UK. Goodfellow, a well known ge- lafaxine), drug discovery depended mostly neticist, had joined the company from the University of Cambridge a few years earlier. on a large chemistry effort and on broad in- Although Walsh, then research dean at teractions with colleagues. “As a biologist, it Guy’s Hospital in London, and head of a is typically difficult to gain access to chemis- well-funded research lab, was not looking to try. It is very pleasing to have chemists to move, he started thinking about the oppor- work with on projects,” says Walsh. tunities created by working in an industrial environment. “I was working in a large Looking for change medical school on diseases. But I had a lim- Unlike Walsh, when Richard Scheller left ited ability to impact on human health. That academia, he was actively seeking a is just the nature of how an academic insti- change. He had been a professor at Stan- tution is set up,” he says. In addition, Smith- ford University School of Medicine in Kline was “a very academically oriented “One of the main differences is the availability of resources company. -
GSK3 Signalling Regulates Mammalian Axon Regeneration by Inducing the Expression of Smad1
ARTICLE Received 28 Mar 2013 | Accepted 27 Sep 2013 | Published 28 Oct 2013 DOI: 10.1038/ncomms3690 PI3K–GSK3 signalling regulates mammalian axon regeneration by inducing the expression of Smad1 Saijilafu1,*, Eun-Mi Hur1,2,*, Chang-Mei Liu1, Zhongxian Jiao1, Wen-Lin Xu1 & Feng-Quan Zhou1,3 In contrast to neurons in the central nervous system, mature neurons in the mammalian peripheral nervous system (PNS) can regenerate axons after injury, in part, by enhancing intrinsic growth competence. However, the signalling pathways that enhance the growth potential and induce spontaneous axon regeneration remain poorly understood. Here we reveal that phosphatidylinositol 3-kinase (PI3K) signalling is activated in response to peripheral axotomy and that PI3K pathway is required for sensory axon regeneration. Moreover, we show that glycogen synthase kinase 3 (GSK3), rather than mammalian target of rapamycin, mediates PI3K-dependent augmentation of the growth potential in the PNS. Furthermore, we show that PI3K–GSK3 signal is conveyed by the induction of a transcription factor Smad1 and that acute depletion of Smad1 in adult mice prevents axon regeneration in vivo. Together, these results suggest PI3K–GSK3–Smad1 signalling as a central module for promoting sensory axon regeneration in the mammalian nervous system. 1 Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. 2 Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea. 3 The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. * These authors contributed equally to this work. -
LHX2 Interacts with the Nurd Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11
194 • The Journal of Neuroscience, January 4, 2017 • 37(1):194–203 Development/Plasticity/Repair LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11 X Bhavana Muralidharan,1 Zeba Khatri,1 Upasana Maheshwari,1 Ritika Gupta,1 Basabdatta Roy,1 Saurabh J. Pradhan,2,3 Krishanpal Karmodiya,2 XHari Padmanabhan,1,4,5 XAshwin S. Shetty,1,4 Chinthapalli Balaji,1 X Ullas Kolthur-Seetharam,1 XJeffrey D. Macklis,4,5 Sanjeev Galande,2 and XShubha Tole1 1Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India, 2Indian Institute of Science, Education, and Research, Pune 411008, India, 3Symbiosis School of Biomedical Sciences, Symbiosis International University, Lavale, Pune, 4Department of Stem Cell and Regenerative Biology and 5Center for Brain Science, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138 In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to dif- ferentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. When LHX2 is absent, active histone marks at the Fezf2 and Sox11 loci are increased. Loss of LHX2 produces an increase, and overexpression of LHX2 causes a decrease, in layer 5 Fezf2 and CTIP2-expressing neurons. -
Synapse – Autumn 2005 Page 1
Synapse – Autumn 2005 Page 1 Table of Contents pages Event Reports 2 SP Foundation 2-8 Caregiving 12 Living with PLS/HSP 13-19 Medical Updates 8-12 Event Photos 20 TeamWalks - 2005 National - Ohio October 2 Northeast September 11 Northwest October 8 Oklahoma September 17 Autumn 2005 Serving the Primary Lateral Sclerosis Community since 1997 Welcoming the SP Foundation since 2003 and Carrol Doolen at the Red Lobster. We when a cure is found, I will be roller blading had a great meal and visit. Marlene was one right along side of her, holding her hand. of the founding board members of the SPF Norman Regional Hospital brought out lunch and it was indeed a pleasure to meet her. for us to enjoy after the walk. They also sent On Saturday, it was very nice to be able to Chaplin, Mike Bumgarner to lead us in a place faces with e-mail contacts and also to very informative discussion about visit with old friends at the same time. After depression. His discussion was based on visiting a while, we walked and rolled along our comments to him about depression the beautiful Legacy Trail. My daughter led related to a variety of situations including the walk wearing her roller blades because, loss of jobs due to disability, losing the ability to do things we used to do and being annual Austin Patient Connection was held dependent on someone else. His main pointtoday. "We are the Experts" was the theme. was to find a sounding board, an impartial After a tasty lunch, we held a round table person you can talk with about how you feel discussion about a variety of subjects and what you are going through. -
Profile of Gary Ruvkun
PROFILE Profile of Gary Ruvkun wash in the faint glow of a fluo- Brush with Molecular Biology rescent lamp, a pair of serpentine The story of Ruvkun’s metamorphosis Anematode worms lie on a Petri from a keen undergraduate into a leading plate, their see-through bodies light in his field of study begins at Har- magnified 100-fold by one of several vard University, where he enrolled in microscopes arrayed in a darkened bay in a Ph.D. program in 1976 upon returning National Academy of Sciences member to the United States. Like many other Gary Ruvkun’s laboratory at Massachu- scientific institutions across the world in setts General Hospital. While one of the the mid-1970s, Harvard was astir with the worms wiggles its way around the plate, promise of recombinant DNA technol- the other shows no signs of life, ogy, and Ruvkun wasted no time em- its midsection ruptured and its innards bracing its tools. “My undergraduate strewn asunder. A filter slides into place, education had not prepared me at all for and the worms are bathed in a dull recombinant DNA, but I immersed my- green haze. The wiggling worm has a bea- self into its culture at Harvard, much of con of nerve cells in its head, the ganglia which was James Watson’s creation from lit up by a genetic trick that has rescued a decade earlier,” Ruvkun says. Propelled the worm from death; its neighbor wears Gary Ruvkun. by a desire to be a part of the culture of no such beacon. The worms were deprived basic molecular biology, all while per- of a tiny RNA molecule, called a micro- forming science with the potential to im- RNA, which helps shepherd them through not 5-year-old children. -
NGF-Dependent Retrograde Signaling: Survival Versus Death
Cell Research (2009) 19:525-526. npg © 2009 IBCB, SIBS, CAS All rights reserved 1001-0602/09 $ 30.00 RESEARCH HIGHLIGHT www.nature.com/cr NGF-dependent retrograde signaling: survival versus death Yang Zhou1, Ting-Jia Lu1, Zhi-Qi Xiong1 1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China Cell Research (2009) 19:525-526. doi: 10.1038/cr.2009.47; published online 4 May 2009 Nerve growth factor (NGF) was which could also provide as the ret- nisms underlying NGF-dependent first discovered more than 5 decades rograde signals [7]. These hypotheses retrograde signaling. Previous studies ago as a molecule that promotes the are not mutually exclusive, and mul- from Campenot’s laboratory demon- survival and maturation of develop- tiple retrograde signals may exist. strated that NGF applied to distal ax- ing neurons in the peripheral nervous In this issue, Mok and colleagues ons of sympathetic neurons supports system [1]. NGF released from target describe a fundamentally different neuronal survival without transport of cells activates tropomyosin-related retrograde mechanism in which NGF NGF towards the cell bodies or TrkA kinase A (TrkA) on axon terminals and suppresses an apoptotic signal in distal phosphorylation in the cell bodies, triggers activation of PI3K/Akt, MEK/ axons [8]. Campenot’s group devel- suggesting that NGF binding to TrkA ERK, and PLCg signaling pathways. oped compartmentalized cultures of in distal axons triggers its downstream The signal then travels retrogradely sympathetic neurons which could seg- signaling cascades locally; afterwards along axon to cell body to promote regate the distal axons from cell bod- the signals travel retrogradely to the neuronal survival [2]. -
2008 Harvard / Paul F
The 2008 Harvard / Paul F. Glenn Symposium on Aging June 23, 2008 Paul F. Glenn Laboratories for the Biological Mechanisms of Aging Welcome to the 3rd Annual Harvard/Paul F. Glenn Symposium on Aging. Each year, the Paul F. Glenn Laboratories host the Harvard Symposium on Aging with a mission to educate the wider research community about advancements in this fast-paced field and to stimulate collaborative research in this area. We have been fortunate to have many of the leaders in the aging field speak at these symposia. As a result, attendees come not only from the Harvard research community but from across the nation and from overseas for this one day event. We are glad you could join us here today. The reasons for accelerating research molecular biology of aging are clear. First and foremost, the number of aged individuals in developed countries is growing rapidly, which is going to place an unprecedented burden on the families and the economies of those nations. Because chronic illness in the elderly is a major medical cost, enormous savings would be achieved if mortality and morbidity could be compressed within a shorter duration of time at the end of life. A study by the RAND Corporation in 2006 concluded that advances in medicine arising from aging research would be 10-100 times more cost-effective than any other medical breakthrough. Advances in aging research have shown that it is possible to extend the healthy lifespan of laboratory animals through genetic and pharmacological means. Many leaders in the aging field predict that significant strides will be made in understanding how human health and lifespan are regulated, leading to novel medicines to forestall and treat diseases of aging such as diabetes, cancer, Alzheimer’s and heart disease. -
Untangling Schizophrenia the Genetics of Mental Illness
Poetic Voices • Commencement • Liberal-Arts MakeoverMakeover JULY-AUGUST 2017 • $4.95 Untangling Schizophrenia The genetics of mental illness Reprinted from Harvard Magazine. For more information, contact Harvard Magazine, Inc. at 617-495-5746 S:7” S:9.25” MERCK INVENTS TO KEEP JOY ALIVE So today, on Claudia’s wedding day, her grandfather Eduardo is there for the milestone event. Creating another special memory for the both of them. For more than a century, Merck has been inventing medicines and vaccines for many of the world’s most challenging diseases. Today, we’re exploring entirely new approaches in our search to prevent Alzheimer’s. So people remain healthy and present, able to share every precious moment with the ones they love. Learn more at Merck.com/InventingForLife Keep Joy Alive Copyright ©2017 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA. All Rights Reserved. CORP-1210605-0005 06/17 Reprinted from Harvard Magazine. For more information, contact Harvard Magazine, Inc. at 617-495-5746 170701_Merck.indd 1 5/17/17 3:31 PM JULY-AUGUST 2017, VOLUME 119, NUMBER 6 FEATURES 32 Poetry, Voiced | by Sophia Nguyen Preserving the treasures of the Woodberry Poetry Room 38 Vita: Blanche Ames | by Laura J. Snyder Brief life of an intrepid botanical illustrator: 1878-1969 p. 32 40 Probing Psychoses | by Courtney Humphries Genetic and genomic clues to understanding schizophrenia p. 15 47 An Educated Core | by John S. Rosenberg Three bold attempts to redesign the liberal arts JOHN HARVARD’S JOURNAL 14 Abdi, Biden…Zuckerberg: the 366th Commencement, animated, academic—and political. -
Pin Faculty Directory
Harvard University Program in Neuroscience Faculty Directory 2019—2020 April 22, 2020 Disclaimer Please note that in the following descripons of faculty members, only students from the Program in Neuroscience are listed. You cannot assume that if no students are listed, it is a small or inacve lab. Many faculty members are very acve in other programs such as Biological and Biomedical Sciences, Molecular and Cellular Biology, etc. If you find you are interested in the descripon of a lab’s research, you should contact the faculty member (or go to the lab’s website) to find out how big the lab is, how many graduate students are doing there thesis work there, etc. Program in Neuroscience Faculty Albers, Mark (MGH-East)) De Bivort, Benjamin (Harvard/OEB) Kaplan, Joshua (MGH/HMS/Neurobio) Rosenberg, Paul (BCH/Neurology) Andermann, Mark (BIDMC) Dettmer, Ulf (BWH) Karmacharya, Rakesh (MGH) Rotenberg, Alex (BCH/Neurology) Anderson, Matthew (BIDMC) Do, Michael (BCH—Neurobio) Khurana, Vikram (BWH) Sabatini, Bernardo (HMS/Neurobio) Anthony, Todd (BCH/Neurobio) Dong, Min (BCH) Kim, Kwang-Soo (McLean) Sahay, Amar (MGH) Arlotta, Paola (Harvard/SCRB) Drugowitsch, Jan (HMS/Neurobio) Kocsis, Bernat (BIDMC) Sahin, Mustafa (BCH/Neurobio) Assad, John (HMS/Neurobio) Dulac, Catherine (Harvard/MCB) Kreiman, Gabriel (BCH/Neurobio) Samuel, Aravi (Harvard/ Physics) Bacskai, Brian (MGH/East) Dymecki, Susan(HMS/Genetics) LaVoie, Matthew (BWH) Sanes, Joshua (Harvard/MCB) Baker, Justin (McLean) Engert, Florian (Harvard/MCB) Lee, Wei-Chung (BCH/Neurobio) Saper, Clifford