Rudolph E. Tanzi

Dr. Rudolph E. Tanzi

Rudolph Tanzi (also Rudy Tanzi) is the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University, and Vice-Chair of Neurology, Director of the Genetics and Aging Research Unit, and Co-Director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital (MGH).[1] Tanzi has been investigating the genetics of neurological disease since a student in the 1980s when he participated in the first study that used genetic markers to find a disease gene (Huntington's disease). Tanzi co-discovered all three familial early-onset Alzheimer's disease (FAD) genes and several other neurological disease genes including that responsible for Wilson’s disease. As the leader of the Cure Alzheimer's Fund Alzheimer’s Genome Project, Tanzi has carried out multiple genome wide association studies of thousands of Alzheimer’s families leading to the identification of novel AD candidate genes, including CD33 and the first two rare mutations causing late-onset AD in the ADAM10 gene. His research on the role of zinc and copper in AD has led to clinical trials at Prana Biotechnology. He is also working on gamma secretase modulators (together with Steve Wagner, UCSD) for the prevention and treatment of Alzheimer's. He also serves as Chair of the Cure Alzheimer's Fund Research Leadership Group and Director the Cure Alzheimer’s Fund Alzheimer’s Genome Project™. Dr. Tanzi and his team have used Alzheimer’s genes and human stem cells to create “Alzheimer’s-in-a-Dish” - a three-dimensional human stem cell-derived neural culture system that was the first to recapitulate both pathological hallmarks of Alzheimer’s disease: plaques and tangles. This model has made drug screening for Alzheimer’s disease considerably faster and more effective. Using this system, Dr. Tanzi has developed several novel therapies for AD including gamma secretase modulators aimed at plaque pathology. These promising drugs are now heading into clinical trials in Alzheimer’s disease. Most recently, Dr. Tanzi and his team have discovered that beta-amyloid, the main component of senile plaques, may play a role in the innate immune system of the brain operating as an anti-microbial peptide, suggesting a possible role for infection in the etiology and pathogenesis of AD. Most recently, Dr. Tanzi showed a link between herpes viruses and plaque production in Alzheimer's disease, proposing the hypothesis that brain plaques causing Alzheimer's disease may form as a defense mechanism to protect the brain against viruses, bacteria and other microbes.

Publications

Dr. Tanzi has published over 500 scientific papers including the top three most cited papers in the field of Alzheimer's disease research. Dr. Tanzi also co-authored the books "Decoding Darkness: The Search the Genetic Causes of Alzheimer's Disease, the New York Times Best Seller book “Super Brain: Unleashing the Explosive Power of Your Mind to Maximize Health, Happiness, and Spiritual Well-Being" Paperback – October 22, 2013” and "Super Genes: Unlock the Astonishing Power of Your DNA for Optimum Health and Well-Being", "The Healing Self: A Revolutionary New Plan to Supercharge Your Immunity and Stay Well for Life" with Deepak Chopra.[2] Tanzi has made numerous television appearances on shows such as CBS This Morning and Dr. Oz. He also hosts the shows "Super Brain with Dr. Rudy Tanzi" "Super Genes with Dr. Rudy Tanzi" and "The Brain Body Mind Connection with Dr. Rudy Tanzi and Dr. Deepak Chopra" on PBS television.

Education

Tanzi received his B.S. in microbiology and B.A.in history from the University of Rochester in 1980. In 1990, he received his Ph.D. in neurobiology at Harvard Medical School, where his doctoral thesis was on the discovery and isolation of the first Alzheimer's disease gene - the amyloid precursor protein (APP), published in 1987 in Science.

Research work and awards

Tanzi discovered (with others) the other two early-onset familial Alzheimer's genes known as the presenilins 1 and 2, in 1995.[3]

Tanzi serves on dozens of editorial and scientific advisory boards, and as Chair of the Cure Alzheimer’s Fund Research Consortium. He has received numerous awards, including the two highest awards for Alzheimer's disease research: The Metropolitan Life Award and The Potamkin Prize. He was included on the list of the "Harvard 100 Most Influential Alumni", and was chosen by the Geoffrey Beene Foundation as a “Rock Star of Science”. In 2015, he was named by TIME magazine to the TIME100 Most Influential People in the World list. For his invention of "Alzheimer's-in-a-Dish with Dr. Doo Yeon Kim, in 2015, he and Kim received the Smithsonian American Ingenuity Award, the nation's highest award for invention and innovation. He also received the Silver Innovator Award.

Tanzi was awarded an honorary doctorate from The University of Rhode Island on May 17, 2015.[4]

Dr. Tanzi and his team have used Alzheimer’s genes and human stem cells to create “Alzheimer’s-in-a-Dish” - a three-dimensional human stem cell-derived neural culture system that was the first to recapitulate both pathological hallmarks of Alzheimer’s disease: plaques and tangles. This model has made drug screening for Alzheimer’s disease considerably faster and more effective. Using this system, Dr. Tanzi has developed several novel therapies for AD including gamma secretase modulators aimed at plaque pathology. These promising drugs are now heading into clinical trials in Alzheimer’s disease. Most recently, Dr. Tanzi and his team have discovered that beta-amyloid, the main component of senile plaques, may play a role in the innate immune system of the brain operating as an anti-microbial peptide, suggesting a possible role for infection in the etiology and pathogenesis of AD. Most recently, Dr. Tanzi showed a link between herpes viruses and plaque production in Alzheimer's disease, proposing the hypothesis that brain plaques causing Alzheimer's disease may form as a defense mechanism to protect the brain against viruses, bacteria and other microbes.

Other works:

  • 1983: Helped localize the Huntington’s disease gene via genetic linkage (with James F. Gusella and Anne Young).
  • 1984-1988: Was among first to clone the amyloid precursor protein (APP) gene and map it to chromosome 21, for which he produced the first map.
  • 1993: Carried out chromosome 21 physical mapping leading to first familial ALS gene-SOD1.
  • 1993: Discovered the Wilson’s disease gene.
  • 1994: Showed zinc/copper drives A? aggregation and neurotoxicity.
  • 1995: Cloned and discovered first mutations in AD gene presenilin 2; collaborated on the cloning of presenilin 1.
  • 2005: Showed auto-antibodies to oligomeric A? protect against AD – acknowledged by Biogen to significantly influence the promising AD immunotherapy, Aducanumab.
  • 2007: Established widely used gene databases: AlzGene, PDGene and SZGene
  • 2008: Employed family-based GWAS to discover the AD gene, CD33, now a major drug target for neuroinflammation in AD.
  • 2008: Showed first evidence that isoflurane (a general anesthetic) induces Abeta generation and neurodegeneration, leading to a dramatic reduction in its clinical use.
  • 2010: Discovered the first non-NSAID gamma secretase modulators (GSM), which selectively lower production of A42 without off-target effects of gamma secretase inhibitors. A clinical candidate is slated for phase I clinical trials in 2019.
  • 2010-2013: Discovered and validated the first highly penetrant late-onset AD mutations in ADAM10, the main ?-secretase that precludes A?? production in brain.
  • 2012: With Dr. Lee Goldstein, first showed that the “bobble head” effect of head injury/concussion causes tangle and gliosis pathology leading to chronic traumatic encephalopathy.
  • 2014: Invented a 3D human stem cell-derived neural culture AD model that recapitulated for the first time, plaques and tangles in vitro. This was the first model to definitively show that ??amyloid plaques and induce bona fide neurofibrillary tangles from endogenous tau.
  • 2016: Demonstrated A?? to be a potent antimicrobial peptide in the brain; showed for the first time in mice and 3D models that microbes can rapidly (overnight) seed deposition of ?-amyloid as a defense mechanism of the brain’s innate immune system.
  • 2018: Invented a new 3D human stem cell-derived mixed neural-astrocyte-microglial microfluidic AD model, which showed neuronal A? deposition/tangle formation induces microglial activation and synaptic pruning/axotomy beginning with astrocytic release of MCP1.

Music

In musical pursuits, Tanzi professionally plays keyboards, most recently with Joe Perry and Aerosmith.[1] He also co-wrote the song tribute to Alzheimer's patients called "Remember Me", performed by singer Chris Mann.[5][6] He plays keyboards on the albums: Aerosmith: Music from Another Dimension, and Joe Perry: Switzerland Manifesto.

Bibliography

Books

  • Decoding Darkness: The Search for the Genetic Causes of Alzheimer’s Disease. Rudolph E. Tanzi and Ann B, Parson, Perseus Publishing, N.Y. 2000.[7]
  • Super Brain: Unleashing the Explosive Power of Your Mind to Maximize Health, Happiness, and Spiritual Well-Being. Deepak Chopra and Rudolph E. Tanzi, Harmony Books, Random House, 2012.[8]
  • Super Genes: Unlock the Astonishing Power of Your DNA for Optimum Health and Well-Being. Deepak Chopra and Rudolph E. Tanzi, Rider, Ebury Publishing, London 2015.[9]
  • The Healing Self: A Revolutionary New Plan to Supercharge Your Immunity and Stay Well for Life. Deepak Chopra and Rudolph E. Tanzi, Harmony, Random House, N.Y. 2018.[10]

Key journal articles

  • Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX, et al. "Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis."
  • Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY, Young AB, Shoulson I, Bonilla E, Martin JB. "A polymorphic DNA marker genetically linked to Huntington's Disease." Nature 1983; 306: 234-238.
  • Tanzi, RE, Gusella JF, Watkins PC, Bruns GAP, St. George-Hyslop PH, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL. "The amyloid beta protein gene: cDNA cloning, mRNA distribution, and genetic linkage near the Alzheimer locus." Science 1987; 235: 880-884.
  • Tanzi RE, McClatchey AI, Lamperti ED, V-Komaroff L, Gusella JF, Neve R. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature, 1988; 331: 528-530.
  • Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, Romano DM, Brzustowicz LM, Devoto M, Peppercorn J, Bush AI, Sternlieb I, Pirastu M, Gusella JF, Evgrafov O, Penchaszadeh GK, Honig B, Edelman IS, Soares MB, Scheinberg IH and Gilliam TC. Identification of the Wilson's disease gene: A copper transporting ATPase with homology to the Menke's disease gene. Nature Genetics, 1993; 5: 344-350.
  • Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima Jm Pettingell WH, Yu C, Jondro PD, Schmidt SD, Wang K, Crowley AC, Fu Y-H, Guenette SY, Galas D, Nemens E, Wijsman EM, Bird TD, Schellenberg GD, Tanzi RE. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science, 1995; 269: 973-977.
  • Bertram L, Blacker D, Mullin K, Keeney D, Jones J, Basu S, Yhu S, McInnis M, Go R, Vekrellis K, Selkoe D, Saunders A, Tanzi RE. Evidence for genetic linkage of Alzheimer’s disease to chromosome 10q. Science 2000; 290: 2302-2303.
  • Bertram L, Hiltunen M, Parkinson M, Ingelsson M, Lange C, Ramasamy K, Mullin K, Menon R, Sampson AJ, Hsiao MY, Elliott KJ, Moscarillo T, Hyman BT, Wagner SL, Becker KD, Blacker D, Tanzi RE. Family-based association between Alzheimer’s disease and variants in UBQLN1. New Engl. J. Med., 2005 352: 884-894.
  • Bertram, L, McQueen MB, Mullin K, Blacker D, Tanzi RE. Systematic Meta-Analyses of Alzheimer’s Disease Genetic Association Studies: The AlzGene Database. Nature Genetics, 2007; 39:17-23.
  • Griciuc A, Serrano-Pozo A, Parrado AR, Lesinski AN, Asselin CN, Mullin K, Hooli B, Choi SH, Hyman BT, Tanzi RE. Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta, Neuron, 2013 78(4):631-43.
  • Suh J, Choi SH, Romano DM, Gannon MA, Lesinski AN, Kim DY, Tanzi RE. ADAM10 Missense Mutations Potentiate -Amyloid Accumulation by Impairing Prodomain Chaperone Function. Neuron 2013 80(2): 385-401.
  • Choi SH, Kim YH, Hebisch M, Sliwinski C, Lee S, D'Avanzo C, Chen J, Hooli B, Asselin C, Muffat J, Klee JB, Zhang C, Wainger BJ, Peitz M, Kovacs DM, Woolf CJ, Wagner SL, Tanzi RE, Kim DY. (2014) A three-dimensional human neural cell culture model of Alzheimer's disease. Nature 2014 13:515(7526):274-8.
  • Kumar D, Choi SH, Washicosky KJ, Eimer WA, Tucker S, Ghofrani J, Lefkowitz A, McColl G, Goldstein LE, Tanzi RE, Moir RD. Amyloid-BetaPeptide Protects Against Microbial Infection In Mouse and Worm Models of Alzheimer’s Disease. Science Transl. Med., 2016, 8(340):340ra72.
  • Park J, Wetzel I, Marriott I, Dréau D, D’Avanzo C, Kim D-Y, Tanzi RE, Cho H. Neuron-Glia Interactions Recapitulated in a 3D Organotypic Human Alzheimer’s Disease Brain Model. Nature Neuroscience 2018,(7):941-951.
  • Eimer WA, Kumar D, Kumar N, Breakefield XO, Tanzi RE, Moir RD. Alzheimer’s Disease-Associated b-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection. Neuron, 2018 99, 1-9.


References

  1. 1 2 Fletcher, Bevin (26 Jun 2015). "Alzheimer's Expert Jams with Aerosmith". Drug Discovery & Development.
  2. ↑ Nanos, Janelle (2017-10-13). "Forging a better connection between the brain and the mind". The Boston Globe. Retrieved 2017-10-16.
  3. ↑ Tanzi, R.E.; Zhang, C; Browne, A; Kim, D.Y. (Feb 2010). "Familial Alzheimer's Disease Mutations in Presenilin 1 Do Not Alter Levels of the Secreted Amyloid-β Protein Precursor Generated by β-Secretase Cleavage". Current Alzheimer Research. 7 (1): 21–26. PMC 3260056. PMID 3260056.
  4. ↑ Staff. "Brain scientist "rock star" to address class of 2015". University of Rhode Island. Archived from the original on 11 April 2015. Retrieved 26 Jun 2015.
  5. ↑ Chris Mann (2015-01-22). "Chris Mann - Remember Me (An Anthem for Alzheimer's Disease)". YouTube. Retrieved 2017-10-16.
  6. ↑ Tanzi, Rudy; Mann, Chris (2017-03-03). "Curing Alzheimer's with Science and Song". TEDxNatick. Retrieved 2017-10-16.
  7. ↑ "Decoding darkness : the search for the genetic causes of Alzheimer's disease (Book, 2000)". WorldCat. Retrieved 26 Jun 2015.
  8. ↑ "Super brain : unleashing the explosive power of your mind to maximize health, happiness, and spiritual well-being (Book, 2012)". WorldCat. Retrieved 26 Jun 2015.
  9. ↑ Chopra, Deepak; Tanzi, Rudolph (2015). "Super Genes: The hidden key to total well-being". worldcat.org. Retrieved 2017-10-16.
  10. ↑ "The Healing Self: A Revolutionary New Plan to Supercharge Your Immunity and Stay Well for Life (Book, 2018)". WorldCat. Retrieved 3 May 2018.
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