DOCSLIB.ORG

Nucleosome Maps of the Human Cytomegalovirus Genome Reveal a Temporal Switch in Chromatin Organization Linked to a Major IE Protein

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Nucleosome Maps of the Human Cytomegalovirus Genome Reveal a Temporal Switch in Chromatin Organization Linked to a Major IE Protein Nucleosome maps of the human cytomegalovirus genome reveal a temporal switch in chromatin organization linked to a major IE protein Einat Zalckvara,b, Christina Paulusc, Desiree Tilloa,b, Alexandra Asbach-Nitzschec, Yaniv Lublinga, Carla Winterlingc,1, Nicholas Striederc,2, Katrin Mückec, Felicia Goodrumd, Eran Segala,b,3, and Michael Nevelsc,3 Departments of aComputer Science and Applied Mathematics and bMolecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel; cInstitute for Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany; and dDepartment of Immunobiology, BIO5 Institute, University of Arizona, Tucson, AZ 65721 Edited* by Thomas Shenk, Princeton University, Princeton, NJ, and approved June 27, 2013 (received for review March 25, 2013) Human CMV (hCMV) establishes lifelong infections in most of us, Human CMV (hCMV), one of eight human herpesviruses, causing developmental defects in human embryos and life-threat- establishes lifelong infections in most people worldwide. The ening disease in immunocompromised individuals. During produc- virus is best known for causing developmental defects in human tive infection, the viral >230,000-bp dsDNA genome is expressed embryos and major disease or death in immunocompromised widely and in a temporal cascade. The hCMV genome does not individuals, including AIDS, cancer, and transplant patients carry histones when encapsidated but has been proposed to form (14, 15). hCMV is among the largest and most complex viruses presently known. During productive infection of human cells, the nucleosomes after release into the host cell nucleus. Here, we ∼ present hCMV genome-wide nucleosome occupancy and nascent viral 235,000-bp dsDNA genome is expressed extensively and in transcript maps during infection of permissive human primary a temporal cascade of immediate-early (IE), early, and late transcription. The most abundant gene products in the IE phase cells. We show that nucleosomes occupy nuclear viral DNA in of hCMV infection are expressed from the viral major IE tran- a nonrandom and highly predictable fashion. At early times of scription unit. The predominant major IE protein species are the infection, nucleosomes associate with the hCMV genome largely nuclear phosphoproteins IE1-72kDa (also known as IE72, pUL123, according to their intrinsic DNA sequence preferences, indicating or IE1) and IE2-86kDa (also known as IE86, pUL122, or IE2). that initial nucleosome formation is genetically encoded in the These viral proteins are key transcriptional regulators that are virus. However, as infection proceeds to the late phase, nucleo- well-known for activating viral gene expression to facilitate somes redistribute extensively to establish patterns mostly deter- productive infection (14, 16, 17). Notably, IE1 engages in host mined by nongenetic factors. We propose that these factors nuclear interactions with both the interchromatin and chromatin include key regulators of viral gene expression encoded at the compartments (18), including human proteins involved in his- hCMV major immediate-early (IE) locus. Indeed, mutant virus tone modification (19) and nucleosome assembly (20). genomes deficient for IE1 expression exhibit globally increased The genomes of hCMV and other herpesviruses do not carry nucleosome loads and reduced nucleosome dynamics compared histones when encapsidated (21–23). However, on release from with WT genomes. The temporal nucleosome occupancy differen- virus capsids into cell nuclei, hCMV DNA associates with host- ces between IE1-deficient and WT viruses correlate inversely with derived histones likely forming nucleosomes (24). Progression changes in the pattern of viral nascent and total transcript accu- through the viral transcriptional program concurs with changes mulation. These results provide a framework of spatial and tem- in posttranslational histone modifications as analyzed at indi- – poral nucleosome organization across the genome of a major vidual viral genomic sites (25 29). However, information on the human pathogen and suggest that an hCMV major IE protein gov- nucleosomal organization and function of hCMV chromatin erns overall viral chromatin structure and function. during infection is limited, in part because no genome-wide studies are available. For instance, it is not known whether the hCMV genome has evolved to contain nucleosome favorable herpesvirus | functional genomics | epigenetic regulation | ChIP-chip and disfavorable sequences, if the viral DNA forms nucleosomes in an organized fashion, how the virus may control its nucleo- uclear DNA is typically organized and maneuvered through some organization, and how nucleosome occupancy may regu- Nnucleosomes that individually assemble ∼147 bp of DNA in late the cascade of viral transcription. 1.65 superhelical turns around a core histone octamer composed To address these questions, we generated high-resolution of a central H3-H4 tetramer flanked by two H2A-H2B dimers spatial and temporal maps of nucleosome occupancy and (na- (1, 2). Additionally, linker histone H1 binds to the nucleosome at scent) transcription across entire hCMV genomes after infection the DNA entry–exit points outside the octamer. Nucleosomes have higher intrinsic affinity for particular DNA sequences, reflecting the ability of the sequence to bend sharply (3, 4). We Author contributions: F.G., E.S., and M.N. designed research; C.P., A.A.-N., C.W., N.S., and have previously shown that these sequence preferences are not K.M. performed experiments; E.Z., D.T., Y.L., F.G., E.S., and M.N. analyzed data; E.Z., D.T., only relevant in vitro but also predictive of nucleosome occu- F.G., E.S., and M.N. interpreted data; and E.Z., C.P., D.T., F.G., E.S., and M.N. wrote the paper. fl pancy across eukaryotic genomes in vivo (5–9). Nucleosome The authors declare no con ict of interest. occupancy and positioning is also controlled by remodeling ma- *This Direct Submission article had a prearranged editor. chines, which may read out DNA sequence features to establish Data deposition: The data reported in this paper are available at http://genie.weizmann. specific nucleosome patterns (10), and structural alterations to ac.il/pubs/hcmv2013. 1 the histone octamer, including histone variant exchange and Present address: Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany. posttranslational modifications. These alterations can directly 2Present address: Institute for Biochemistry I, University of Regensburg, 93053 affect nucleosome properties and/or may serve to recruit chro- Regensburg, Germany. – matin-modifying proteins (11 13). The dynamic regulation of 3To whom correspondence may be addressed. E-mail: [email protected] or genome accessibility through nucleosomes is thought to affect [email protected]. transcription and most other DNA-based nuclear processes in This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. only partly resolved ways. 1073/pnas.1305548110/-/DCSupplemental. 13126–13131 | PNAS | August 6, 2013 | vol. 110 | no. 32 www.pnas.org/cgi/doi/10.1073/pnas.1305548110 of permissive human primary cells with WT or IE1-deficient (dlIE1) 48, or 96 h. Subsequently, we either performed ChIP using an viruses. Our results suggest that, despite not carrying histones when antibody directed against the H3 histone fold domain or pre- encapsidated, hCMV genomes undergo organized nucleosome pared mononucleosomes by MNase digestion. The resulting in- formation and encode nucleosome reorganizing mechanisms to put and output (for ChIP-chip) or sonicated and nucleosomal function properly within the chromatin environment of their host. (for MNase-chip) DNA sample pairs were subjected to dual- color labeling and cohybridized to custom-designed tiling arrays Results covering most of the hCMV genome at ∼7-bp resolution. By Nucleosomes Initially Occupy hCMV Genomes According to Their DNA using tiling arrays, we selectively measured the viral (but not Sequence Preferences but Undergo Massive Reorganization as Infection human) DNA sequences associated with H3 or nucleosomes. Proceeds. Our work has suggested that hCMV DNA forms Subsequently, we determined the average nucleosome occupancy nucleosomes in the nuclei of productively infected human cells per base pair. Data were obtained from two to six independent (24). This view is supported by the fact that hCMV genomes infections per each virus and time point. There was high corre- associate with all four classes of human core histones (H2A, lation between replicate results (Fig. S2A), and signal intensities H2B, H3, and H4) as well as the human linker histone (H1) as were not generally guanosine-cytidine (GC)-biased (Fig. S2C). determined by ChIP analysis (Fig. S1A). Although the histone We found that the nucleosome patterns derived from ChIP- content of hCMV chromatin is generally lower compared with chip and MNase-chip analyses were highly similar, at least at the bulk cellular chromatin (Fig. S1A) (24), core histones associate 8 h time point (ρ = 0.8 at 8 h and 0.41 at 48 h postinfection) (Fig. with nuclear viral DNA at a ratio equaling the histone ratio of 1B). The modest differences observed at 48 h might be caused by chromatinized cellular genomic sites (H2A:H2B:H3:H4 ∼ 1:1:1:1) detection of slightly dissimilar nucleosome populations by meth- (Fig. S1A). Accordingly, hCMV nuclear DNA is at least partially ods involving fixed (ChIP-chip) or nonfixed (MNase-chip) chro- present
Load more

Recommended publications
  • ASM Journals Eliminate Impact Factor Information from Journal Websites
    ASM Journals Eliminate Impact Factor Information from Journal Websites The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Casadevall, A., S. Bertuzzi, M. J. Buchmeier, R. J. Davis, H. Drake, F. C. Fang, J. Gilbert, et al. 2016. “ASM Journals Eliminate Impact Factor Information from Journal Websites.” mSphere 1 (4): e00184-16. doi:10.1128/mSphere.00184-16. http:// dx.doi.org/10.1128/mSphere.00184-16. Published Version doi:10.1128/mSphere.00184-16 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:27822275 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA EDITORIAL crossmark ASM Journals Eliminate Impact Factor Information from Journal Websites Arturo Casadevall,a Editor in Chief, mBio®, Stefano Bertuzzi,b Chief Executive Officer, ASM, Michael J. Buchmeier,c Editor in Chief, Microbiology and Molecular Biology Reviews®, Roger J. Davis,d Editor in Chief, Molecular and Cellular Biology®, Harold Drake,e Editor in Chief, Applied and Environmental Microbiology®, Ferric C. Fang,f Editor in Chief, Infection and Immunity®, Jack Gilbert,g Editor in Chief, mSystems™, Barbara M. Goldman,b Director, Journals, ASM, Michael J. Imperiale,h Editor in Chief, mSphere™, Philip Matsumura,i Editor, Genome Announcements™, Alexander J. McAdam,j Editor in Chief, Journal of Clinical Microbiology®, Marcela F. Pasetti,k Editor in Chief, Clinical and Vaccine Immunology®, Rozanne M.
    [Show full text]
  • Holmes Washington 0250E 22
    ©Copyright 2020 Daniel Holmes Identification of Targetable Vulnerabilities During Latent KSHV Infection Daniel Holmes A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2020 Reading Committee: Michael Lagunoff, Chair Adam Philip Geballe Jason G Smith Program Authorized to Offer Degree: Department of Microbiology University of Washington Abstract Identification of Targetable Vulnerabilities During Latent KSHV Infection Daniel Holmes Chair of the Supervisory Committee: Professor Michael Lagunoff Department of Microbiology Viruses are defined as obligate intracellular parasites that require host processes to repli- cate. Latent virus life cycles are no exception to this definition, as viruses are still reliant on host machinery for continued proliferation and maintenance of viral genomes, even in the absence of lytic replication. In this thesis, I used essentiality screening to identify host factors on which Kaposi's Sarcoma Associated Herpesvirus (KSHV) relies for the proliferation and survival of latently infected cells. KSHV is the etiological agent of Kaposi's Sarcoma (KS), an endothelial cell-based tumor where more than 90% of the endothelial cells in the tumor are latently infected with KSHV. While traditional therapies for herpesviruses target lytic replication, the prevalence of latency in KS necessitates exploration of options for intervening in this stage of the viral life cycle. I performed CRISPR/Cas9 screening using lentiviral vec- tors encoding a library of single guide RNAs (sgRNAs) targeting every protein coding gene in the human genome. I compared mock infected and KSHV infected endothelial cells eight days post infection to identify genes essential to latent KSHV infection.
    [Show full text]
  • Editors' Statement on Considerations of Biodefence and Biosecurity
    EDITORIAL Editors’ statement on considerations of biodefence and biosecurity The threat of bioterrorism requires active consideration by scientists. On 9 January 2003, the US National Academy of Sciences held a discussion on the balance between scientific openness and security. The next day, a group of editors met to discuss the issues with specific reference to the scientific publication process. The following statement has emerged from that meeting. The principles dis- cussed will be considered and followed through by Nature Medicine The process of scientific publication, is a view, shared by nearly all, that there is FOURTH: We recognize that on occasions through which new findings are reviewed information that, although we cannot an editor may conclude that the potential for quality and then presented to the rest now capture it with lists or definitions, harm of publication outweighs the poten- of the scientific community and the pub- presents enough risk of use by terrorists tial societal benefits. Under such circum- lic, is a vital element in our national life. that it should not be published. How and stances, the paper should be modified, or New discoveries reported in research pa- by what processes it might be identified not be published. Scientific information is pers have helped improve the human con- will continue to challenge us, because – as also communicated by other means: semi- dition in myriad ways: protecting public all present acknowledged — it is also true nars, meetings, electronic posting, etc. health, multiplying agricultural yields, that open publication brings benefits not Journals and scientific societies can play fostering technological development and only to public health but also in efforts to an important role in encouraging investi- economic growth, and enhancing global combat terrorism.
    [Show full text]
  • Table of Contents (PDF)
    December 30, 2014 u vol. 111 u no. 52 u 18401–18800 Cover image: Pictured are Konik horses, a semiferal breed, at a nature reserve in Oostvaar- dersplassen, Holland. Mikkel Schubert et al. sequenced the DNA from ancient horse bones and compared it to the genomes of five modern domesticated breeds and the only living wild horse species, Przewalski’s horse. Phylogenetic analysis revealed that domesticated breeds likely derived at least partially from the ancient populations. In addition, genes involved in muscle, limb, joint, and cardiac system development, and in social behavior, learning capa- bilities, fear response, and agreeableness were favored during domestication, indicating adaptations that may have resulted from human use and taming. See the article by Schubert et al. on pages E5661–E5669. Image courtesy of Ruben Smit (photographer). From the Cover E5661 Genetics of horse domestication 18460 Dating mastodon extinction 18524 Ethnic diversity and price bubbles 18530 Gulf of Mexico hypoxic zone 18709 Plague bacteria and flea hosts Contents REVIEWER ACKNOWLEDGMENT (ONLINE ONLY) E5724 Acknowledgment of Reviewers, 2014 THIS WEEK IN PNAS SCIENCE AND CULTURE—How science intersects with culture 18401 In This Issue 18403 Science and Culture: Q&A with Roger Malina Maggie McKee LETTERS (ONLINE ONLY) COMMENTARIES E5602 Incorrect representation of Barrier Canyon rock art site’s history and other factors invalidate reported dates Nancy Simon and Richard Reed 18405 The curious case of the Arctic mastodons Duane Froese E5604 Reply to Simon and Reed: Independent and converging See companion article on page 18460 results rule out historic disturbance and confirm age constraints for Barrier Canyon rock art 18407 Downsides of social capital Joel L.
    [Show full text]
  • Uncensored Exchange of Scientific Results
    Correction EDITORIAL Correction for “Uncensored exchange of scientific results,” by Journal Editors and Authors Group, which appeared in issue 4, February 18, 2003, of Proc Natl Acad Sci USA (100:1464; first published February 15, 2003; 10.1073/pnas.0630491100). Due to a printer’s error, the author name “Steven Salzburg” should instead appear as “Steven Salzberg.” Additionally, the affiliation for Steven Salzberg should instead appear as “The Institute for Genomic Research.” The corrected group author footnote appears below. The online version has been corrected. *Group members: Ronald Atlas, President, ASM, and Editor, CRC Critical Reviews in Mi- crobiology; Philip Campbell, Editor, Nature; Nicholas R. Cozzarelli, Editor, PNAS; Greg Curfman, Deputy Editor, New England Journal of Medicine; Lynn Enquist, Editor, Journal of Virology; Gerald Fink, Massachusetts Institute of Technology; Annette Flanagin, Man- aging Senior Editor, Journal of the American Medical Association, and President, Council of Science Editors; Jacqueline Fletcher, President, American Phytopathological Society; Elizabeth George, Program Manager, National Nuclear Security Administration, Depart- ment of Energy; Gordon Hammes, Editor, Biochemistry; David Heyman, Senior Fellow and Director of Science and Security Initiatives, Center for Strategic and International Studies; Thomas Inglesby, Editor, Biosecurity and Bioterrorism; Samuel Kaplan, Chair, ASM Pub- lications Board; Donald Kennedy, Editor, Science; Judith Krug, Director, Office for Intel- lectual Freedom, American Library
    [Show full text]
  • 20.2 Leader 771
    editorials Statement on the consideration of biodefence and biosecurity As discussed in a Commentary by Tony Fauci on page 787, the threat of bioterrorism requires active consideration by scientists. On 9 January 2003, the US National Academy of Sciences held a discussion meeting on the balance between scientific openness and security (see Nature 421, 197; 2003). The next day, a group of editors met to discuss the issues with specific reference to the scientific publication process. The following statement has emerged from that meeting. The statement was conceived in a US context, but the principles discussed will be considered and followed through by Nature and its related journals in their international arenas. he process of scientific publication, through which new find- information, but also recognize that research in the very same ings are reviewed for quality and then presented to the rest fields will be critical to society in meeting the challenges of Tof the scientific community and the public, is a vital element defence. We are committed to dealing responsibly and effectively in our national life. New discoveries reported in research papers with safety and security issues that may be raised by papers have helped improve the human condition in myriad ways: protect- submitted for publication, and to increasing our capacity to ing public health, multiplying agricultural yields, fostering techno- identify such issues as they arise. logical development and economic growth, and enhancing global Third: Scientists and their journals should consider the appropriate stability and security. level and design of processes to accomplish effective review of But new science, as we know, may sometimes have costs as well as papers that raise such security issues.
    [Show full text]
  • Activation of the JC Virus Tat- Response Transcriptional Control
    Corrections Proc. Natl. Acad. Sci. USA 94 (1997) 9511 Microbiology. In the article “Activation of the JC virus Tat- Physiology. In the article “Activation of heteromeric G pro- response transcriptional control element by association of the tein-gated inward rectifier K1 channels overexpressed by Tat protein of human immunodeficiency virus 1 with cellular adenovirus gene transfer inhibits the excitability of hippocam- protein Pura” by Chavdar P. Krachmarov, Lara G. Chepenik, pal neurons” by Markus U. Ehrengruber, Craig A. Doupnik, Sharon Barr-Vagell, Kamel Khalili, and Edward M. Johnson, Youfeng Xu, Justine Garvey, Mark C. Jasek, Henry A. Lester, which appeared in number 24, November 26, 1996, of Proc. and Norman Davidson, which appeared in number 13, June 24, Natl. Acad. Sci. USA (93, 14112–14117), the authors wish to 1997, of Proc. Natl. Acad. Sci. USA (94, 7070–7075), the note that the sequences of two deletion mutants were incor- authors wish to correct the institutional affiliation of Dr. D. E. rectly described. In the left column on page 14116, lines 13–16 Clapham, which was printed incorrectly on page 7070 as should read: “We have tested the effect of two additional Pura McMaster University. Dr. Clapham’s correct affiliation is mutants on transactivation of the JVC late promoter in vivo. Harvard University Medical School. One mutant, Pura 1-215, is illustrated in Fig. 3. The other mutant was PuraD72-216.” The last three sentences of this paragraph should be deleted. Please note that the experiments mentioned in this correction were not included in any of the figures or tables and were not mentioned elsewhere in the text.
    [Show full text]
  • The Host Exosome Pathway Underpins Biogenesis of the Human
    RESEARCH ARTICLE The host exosome pathway underpins biogenesis of the human cytomegalovirus virion Declan L Turner1, Denis V Korneev2, John G Purdy3, Alex de Marco4,5,6, Rommel A Mathias1,4* 1Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Victoria, Australia; 2School of Biological Sciences, Monash University, Victoria, Australia; 3Department of Immunobiology and BIO5 Institute, University of Arizona, Tucson, United States; 4Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia; 5ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Victoria, Australia; 6University of Warwick, Coventry, United Kingdom Abstract Human Cytomegalovirus (HCMV) infects over half the world’s population, is a leading cause of congenital birth defects, and poses serious risks for immuno-compromised individuals. To expand the molecular knowledge governing virion maturation, we analysed HCMV virions using proteomics, and identified a significant proportion of host exosome constituents. To validate this acquisition, we characterized exosomes released from uninfected cells, and demonstrated that over 99% of the protein cargo was subsequently incorporated into HCMV virions during infection. This suggested a common membrane origin, and utilization of host exosome machinery for virion assembly and egress. Thus, we selected a panel of exosome proteins for knock down, and confirmed that loss of 7/9 caused significantly less HCMV production. Saliently, we report that *For correspondence: VAMP3 is essential for viral trafficking and release of infectious progeny, in various HCMV strains [email protected] and cell types. Therefore, we establish that the host exosome pathway is intrinsic for HCMV Competing interests: The maturation, and reveal new host regulators involved in viral trafficking, virion envelopment, and authors declare that no release.
    [Show full text]
  • Journal of Virology
    JOURNAL OF VIROLOGY VOLUME 36 0 NUMBER 3 0 DECEMBER 1980 EDITORIAL BOARD Robert R. Wagner, Editor-in-Chief (1982) University of Virginia School ofMedicine, Charlottesville Dwight L. Anderson, Editor (1983) Harold S. Ginsberg, Editor (1984) School of Dentistry, Columbia University University ofMinnesota, New York, N. Y. Minneapolis David T. Denhardt, Editor (1982) Edward M. Scolnick, Editor (1982) University of Western Ontario National Cancer Institute London, Ontario, Canada Bethesda, Md. David Baltimore (1981) Nancy Hopkins (1980) Fred Rapp (1981) Amiya K. Baaerjee (1982) Calderon Howe (1982) Dan S. Ray (1980) jeaneth 1. Berns (1982) Alice S. Huang (1981) M. E. Reicn (1982) IH. L Bishop (1982) D. C. Kelly (1982) Bernard E. Reilly (1980) DavlW9otstein (1982) Tlomas J. Kelly, Jr. (1982) Willham S. Robinson (1980) Michael A. Bratt (1980) George Khoury (1981) Benard Ro (1982) Dennis T. Brown (1981) Jonathan A. King (1981) Roland R. Rueckert (1982) Ahmad 1. Bukhari (1981) David W. Kingsbury (1982) Norman P. Salman (1981) Purnell Choppin (1980) Lloyd M. Kozloff (1982) Joseph Sambook (1982) John M. Coffin (1980) Robert M. Knig (1980) Priscila A. Schaffer (1981) Richard W. Compans (1982) Robert A. L i 1981) Sondra S ger (1980) Geoffrey M. Cooper (1981) Richard A. Lerner (1981) Phlp A. Sharp (1982) Nicbolas R. Cozzarelli (1980) Myron Levine (1982) Aaron J. Shatkln (1982) Clive Dickson (1981) Tomas Lindahl (1981) Saul J. Silverstein (1982) Walter Doerfier (1980) David M. Livingston (1980) Lee D. Simon (1981) Harrison Echols (1981) Ronald B. Luftig (1981) Kai Simn (1981) Elvera Ebrenfeld (1980) Robert MartiDn (1981) Alan E. Smith (1980) Robert N.
    [Show full text]
  • February 2010
    Updated 06.21.2021 CURRICULUM VITAE Gary S. Francis, M.D., F.A.C.C., F.A.H.A., F.A.C.P., F.H.F.S.A. U.S. Citizen Office Physical Address: Office Mailing Current Position: University of Minnesota Address: Professor Emeritus Variety Club Research 420 Delaware Street, University of Minnesota Center SE Cardiovascular Division MMC 508 401 East River Road Minneapolis, MN Minneapolis, MN 55455 55455 Direct Phone: (612) 626- 4895 Office Phone: (612) 624- 8970 FAX: (612) 626-4411 E-mail: [email protected] Exec.Administrator, Kitty Tincher Education: Degree Institution Date Degree Granted None University of Minnesota (1963-1965) None Honors Course MD Creighton University School of Medicine 1969 (early entry, 2 scholarships, AOA) Internship Creighton University School of Medicine 1969-1970 and Affiliated Hospitals Residency in Internal Medicine U.S. Navy 1970-1972 CV Disease Fellowship Naval Regional Medical Center 1972-1974 San Diego, California National Awards Master Teacher Award – University of Miami – May 26, 1996 Master Teacher Award – University of Miami – May 25, 2002 Annual Laennec Clinician Educator Award – American Heart Association – November 2006 Distinguished Teacher Award – American College of Cardiology – March 21, 2014 Lifetime Achievement Award – Heart Failure Society of America – September 15, 2014 Scholarly Overview Total publications – 560 (about 14-15 papers per year) h-index – 88, 83, 84 (various services) Total citations – 50,946 Views on internet – 382,539 (Mendeley) First/last author citations – 7740 Top 1% of scientists world-wide, as noted by Heart Failure Society of America using SCOPUS 2019 Academic Appointments: Professor Emeritus – University of Minnesota January 1, 2021 Gary S.
    [Show full text]
  • Macdonald CV 2020-02-06
    Curriculum vitae CLINTON C. MACDONALD, PH. D. ADDRESS Department of Cell Biology & Biochemistry Texas Tech University Health Sciences Center 3601 4th Street Lubbock, TX 79430-6540 CONTACT +1-806-743-2524 [email protected] PERSONAL Born April 18, 1958, Memphis, Tennessee, USA EDUCATION Ph. D., Molecular Biology and Biochemistry, State University of New York at Stony Brook, Stony Brook, NY, 1990 B. A., Biology, Middlebury College, Middlebury, VT, 1980 PROFESSIONAL EXPERIENCE 2012–present Professor with tenure, Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center 2015–2019 Associate Chair, Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center 2002–2012 Associate Professor with tenure, Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center 2003–present Associate Professor, Program in Biotechnology, Texas Tech University Health Sciences Center 2000–2009 Director, Summer Undergraduate Biomedical Research (SABR) Program 1997–2002 Assistant Professor, Southwest Cancer Center, Texas Tech University Health Sciences Center 1995–2002 Assistant Professor, Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center 1993–1995 Associate, Howard Hughes Medical Institute, Princeton University 1990–1993 American Cancer Society Postdoctoral Fellow, Dr. Thomas Shenk, Department of Molecular Biology, Princeton University 1983–1989 Graduate Research Assistant, Dr. David L. Williams, Molecular Biology Graduate Program, State
    [Show full text]
  • DEPARTMENT of MEDICINE 2016 Annual Report DIVISIONS and INSTITUTES
    DEPARTMENT OF MEDICINE 2016 Annual Report DIVISIONS AND INSTITUTES The Divisions » Allergy John Ohman, MD » Cardiology James Udelson, MD » Clinical Decision Making» John Wong, MD » Clinical Nutrition Edward Saltzman, MD »» »Endocrinology Ron Lechan, MD » Gastroenterology Joel Weinstock, MD » Geographic Medicine and Infectious Disease David Snydman, MD » Hematology/Oncology Andrew Evens, DO » Internal Medicine and Adult Primary Care Deborah Blazey-Martin, MD » Nephrology Andrew Levey, MD » Pulmonary, Critical Care and Sleep Medicine Nicholas Hill, MD » Rheumatology Timothy McAlindon, MD The Institutes » Institute for Clinical Research and Health Policy Studies Harry Selker, MD » Molecular Cardiology Research Institute Richard Karas, MD, PhD » Molecular Oncology Research Institute Philip Tsichlis, MD Photography by Martha Stewart Photography. Design and production by Mark Vincent Communications, Inc. — www.markvincent.net. TABLE OF CONTENTS The Department of Medicine Chairman’s Message 4 Departmental Leadership 6 Departmental Organization Chart 7 Clinical Activity 11 Research Activity 13 Internal Medicine Training Program 15 The Divisions Allergy 18 Cardiology 20 Clinical Care Research 36 Clinical Decision Making 38 Clinical Nutrition 42 Endocrinology, Diabetes and Metabolism 46 Gastroenterology 54 Geographic Medicine and Infectious Diseases 60 Hematology/Oncology 72 Internal Medicine and Adult Primary Care 88 Geriatrics 96 William B. Schwartz Division of Nephrology 98 Pulmonary, Critical Care and Sleep Medicine 106 Rheumatology 114 The Institutes Institute for Clinical Research and Health Policy Studies 124 Molecular Cardiology Research Institute (MCRI) 138 Molecular Oncology Research Institute (MORI) 148 Publications 152 3 CHAIRMAN’S MESSAGE It is with pleasure that I offer the Annual Report for the Department of Medicine for 2016, a year that ended with a major strategic accomplishment for Tufts Medical Center.
    [Show full text]