Roger Rosenberg, M.D.

Professor

Endowed Title: The Abe (Brunky), Morris and William Zale Distinguished Chair in Neurology

Department: Neurology & Neurotherapeutics, Physiology

Biography

Development of a DNA Aβ42 Vaccine to Prevent Alzheimer’s Disease is my major scientific interest and effort in my laboratory. I have spent the past 30 years in research in neurodegenerative diseases and Alzheimer’s disease in particular. I have been at the University of Texas Southwestern Medical Center since 1973, hold the Abe (Brunky), Morris and William Zale Distinguished Chair, am Professor of Neurology and Neurotherapeutics and Physiology and have Chaired the Department of Neurology from 1973- 1991. I am the founding Director of the NIH funded Alzheimer’s Disease Center at UT Southwestern and it has been funded now through five consecutive competitive funding cycles since 1988 and will be funded through 2016 representing 28 years of continuous NIH Center funding.

My early amyloid related research in the UT Southwestern Alzheimer’s Disease Center is directed at determining amyloid precursor protein (APP) processing by neural cells in culture as a model system for the abnormal deposition of amyloid in the brain of Alzheimer’s disease patients. I have described  a platelet APP bio-marker that correlates in a linear manner with the severity of patient dementia . In 2006, I published that human platelets utilize beta and gamma secretase to produce Aβ42 and that platelets from Alzheimer’s disease patients synthesize more Aβ42  than control platelets due to an increased activity of beta-secretase. Platelet A β42 levels may be an important bio-marker for Alzheimer’s disease and a means to monitor effectiveness of drug effect in clinical trials.

In 2006, I published with colleagues in my laboratory that a DNA A β42 vaccine can reduce Abeta42 peptide levels in the brain of AD transgenic mice by 50%. Since 2003, we have shown a DNA A β42 vaccine with the gene gun produces in Alzheimer transgenic mice an anti-A β42 antibody of the IgG1/Th2 type which is known to be anti-inflammatory. More recently we have shown that this DNA vaccine induces CD4 non-inflammatory spleenocytes and not CD8 pro-inflammatory cells which are induced by  Aβ42 peptide vaccination. We have shown that A β42 peptide vaccination produces a Th1 and Th2 immune response that is 1:1( IgG1 ratio with IgG2a is 1:1) and thus brain inflammation with A β42  peptide vaccination is due to the induction of  a pro-inflammatory immune response not seen with DNA A β42 vaccination.  The DNA vaccine produces a highly predominant Th2 immune response  (Th2/Th1 is 10:1 ratio). A clinical trial with Alzheimer’s disease patients is being developed using this new DNA gene vaccination methodology. I received in 2009 a US Patent as the Inventor of “Amyloid Beta Gene Vaccines”.

My other major area of research has been the molecular and clinical study of genetic neurological diseases. In that regard, I have been most active in studying the inherited ataxias including Machado-Joseph disease which I described initially with William Nyhan, M.D. Ph.D, in 1976. Our collaborative group mapped the chromosomal location of this disease to 14q24.3, and determined the molecular mutation causal of the disease in patients throughout the world (United States, Portugal, Canada, Japan, Brazil, Spain, France, England, China) is an increase in CAG unstable DNA triplet repeats which represents a novel, new mechanism of disease. CAG repeat levels in the MJD gene is now a commercially available bio-marker which has been shown to be effective in reducing the prevalence of this dominantly inherited spinocerebellar degeneration in at risk persons in families known to have the disease.

Education

Medical School Northwestern University Medical School (1964)
Internship Beth Israel Deaconess Medical Center and Harvard Medical School (1965), Internal Medicine
Residency Columbia University Medical Center (1968), Neurology

Specialty Areas

Clinical Interests

  • Alzheimer's Disease
  • Dementia
  • Dementia with Lewy Bodies

Research Interests

  • Alzheimer's Disease
  • Clinical and Molecular Neurogenetics; genomics
  • Neurodegenerative Disorders

Publications

Featured Publications Legend

Featured Publications

DNA Immunization Against Amyloid beta 42 has High Potential as Safe Therapy for Alzheimer's Disease as it Diminishes Antigen-Specific Th1 and Th17 Cell Proliferation.

Lambracht-Washington D, Qu BX, Fu M, Anderson LD, Stüve O, Eagar TN, Rosenberg RN Cell. Mol. Neurobiol. 2011 Aug 31 6 867-74

The relationship of cardiovascular risk factors to Alzheimer disease in Choctaw Indians.

Weiner MF, Hynan LS, Rossetti H, Womack KB, Rosenberg RN, Gong YH, Qu BX Am J Geriatr Psychiatry 2011 May 19 5 423-9

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.

Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J, Gallins PJ, Buxbaum JD, Jarvik GP, Crane PK, Larson EB, Bird TD, Boeve BF, Graff-Radford NR, De Jager PL, Evans D, Schneider JA, Carrasquillo MM, Ertekin-Taner N, Younkin SG, Cruchaga C, Kauwe JS, Nowotny P, Kramer P, Hardy J, Huentelman MJ, Myers AJ, Barmada MM, Demirci FY, Baldwin CT, Green RC, Rogaeva E, St George-Hyslop P, Arnold SE, Barber R, Beach T, Bigio EH, Bowen JD, Boxer A, Burke JR, Cairns NJ, Carlson CS, Carney RM, Carroll SL, Chui HC, Clark DG, Corneveaux J, Cotman CW, Cummings JL, DeCarli C, DeKosky ST, Diaz-Arrastia R, Dick M, Dickson DW, Ellis WG, Faber KM, Fallon KB, Farlow MR, Ferris S, Frosch MP, Galasko DR, Ganguli M, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Gilman S, Giordani B, Glass JD, Growdon JH, Hamilton RL, Harrell LE, Head E, Honig LS, Hulette CM, Hyman BT, Jicha GA, Jin LW, Johnson N, Karlawish J, Karydas A, Kaye JA, Kim R, Koo EH, Kowall NW, Lah JJ, Levey AI, Lieberman AP, Lopez OL, Mack WJ, Marson DC, Martiniuk F, Mash DC, Masliah E, McCormick WC, McCurry SM, McDavid AN, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Parisi JE, Perl DP, Peskind E, Petersen RC, Poon WW, Quinn JF, Rajbhandary RA, Raskind M, Reisberg B, Ringman JM, Roberson ED, Rosenberg RN, Sano M, Schneider LS, Seeley W, Shelanski ML, Slifer MA, Smith CD, Sonnen JA, Spina S, Stern RA, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Williamson J, Woltjer RL, Cantwell LB, Dombroski BA, Beekly D, Lunetta KL, Martin ER, Kamboh MI, Saykin AJ, Reiman EM, Bennett DA, Morris JC, Montine TJ, Goate AM, Blacker D, Tsuang DW, Hakonarson H, Kukull WA, Foroud TM, Haines JL, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD Nat. Genet. 2011 May 43 5 436-41

Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes.

Jun G, Naj AC, Beecham GW, Wang LS, Buros J, Gallins PJ, Buxbaum JD, Ertekin-Taner N, Fallin MD, Friedland R, Inzelberg R, Kramer P, Rogaeva E, St George-Hyslop P, Cantwell LB, Dombroski BA, Saykin AJ, Reiman EM, Bennett DA, Morris JC, Lunetta KL, Martin ER, Montine TJ, Goate AM, Blacker D, Tsuang DW, Beekly D, Cupples LA, Hakonarson H, Kukull W, Foroud TM, Haines J, Mayeux R, Farrer LA, Pericak-Vance MA, Schellenberg GD Arch. Neurol. 2010 Dec 67 12 1473-84

Translational research in neurology and neuroscience 2010-2011.

Rosenberg RN Arch. Neurol. 2010 Oct 67 10 1176

Analysis of three plasmid systems for use in DNA A beta 42 immunization as therapy for Alzheimer's disease.

Qu BX, Lambracht-Washington D, Fu M, Eagar TN, Stüve O, Rosenberg RN Vaccine 2010 Jul 28 32 5280-7

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Honors/Awards

  • World Federation of Neurology
    1st Science Medal for Scientific Achievements in Neurology and Neuroscience; presented at the World Congress of Neurology in Bangkok, Thailand. (2009)
  • World Federation of Neurology Trustee
    2005-2009 (2009)
  • Honorary Member (Elected)
    American Neurological Association (2006)
  • Nancy R. McCune Research Award
    Alzheimer’s Association (AWARE) (2005)
  • American Medical Association
    Editor in Chief, Archives of Neurology (1997-present); Editorial Board JAMA (1997-present) (1997)
  • 1st Distinguished Neurology Alumnus Award of the Neurological Institute; Columbia University Medical Center
    (1994)
  • Elected Honorary Member, Spanish Neurological Society
    (1994)
  • American Academy of Neurology
    President (1991)
  • American Association for the Advancement of Science
    Elected Fellow (1991)
  • American Neurological Association
    1st Vice President (1988)
  • Northwestern University Alumni Association Merit Award
    (1986)
  • Chief Resident
    H. Houston Merritt Center for Neuromuscular and Mitochondrial Disorders (1968)

Professional Associations/Affiliations

  • American Academy of Neurology
  • American Neurological Association
  • Society for Neuroscience
  • Texas Neurological Society