the multidimensional mind part 1: creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 -...

9
THE MULTIDIMENSIONAL MIND PART 1: Creative Brains: Music, Art and Emotion Bruce L. Miller, MD BIOGRAPHY: Dr. Miller is Professor of Neurology at the University of California, San Francisco (UCSF) where he holds the A.W. & Mary Margaret Clausen Distinguished Chair. Dr. Miller directs the busy UCSF dementia center where patients in the San Francisco Bay Area receive comprehensive clinical evaluations. His goal is the delivery of model care to all of the patients who enter the clinical and research programs at the UCSF Memory and Aging Center. Dr. Miller teaches extensively and runs the Behavioral Neurology Fellowship at UCSF. Dr. Miller is a behavioral neurologist focused in dementia with special interests in brain and behavior relationships as well as the genetic and molecular underpinnings of disease. His work in frontotemporal dementia (FTD) emphasizes both the behavioral and emotional deficits that characterize these patients, while simultaneously noting the visual creativity that can emerge in the setting of FTD. He is the principal investigator of the NIHsponsored Alzheimer’s Disease Research Center (ADRC) and an NIHfunded program project on FTD called Frontotemporal Dementia: Genes, Imaging and Emotions. He oversees a healthy aging program supported through the Larry H. Hillblom Foundation and the Hellman Center, which includes an artist in residence program. In addition, he helps lead two philanthropyfunded research consortia, the Tau Consortium and Consortium for Frontotemporal Research, focused around developing treatments for tau and progranulin disorders respectively. Dr. Miller has received many awards including the Potamkin Award from the American Academy of Neurology, the Raymond Adams Lecture at the American Neurological Association, the Elliot Royer Award from the San Francisco Neurological community, the UCSF Annual Faculty Research Lectureship in Clinical Science, the UCSF Academic Senate Distinction in Mentoring Award, and the Gene D. Cohen Research Award in Creativity and Aging from the National Center for Creative Aging. He has authored The Human Frontal Lobes, The Behavioral Neurology of Dementia and extensive publications regarding dementia. He has been featured in Fortune Magazine, Charlie Rose Show, The PBS NewsHour, The New York Times, and other media. For nearly three decades, Dr. Miller has been the scientific director for the philanthropic organization The John Douglas French Alzheimer’s Foundation, a private philanthropic organization that funds basic science research in Alzheimer’s disease. BIBLIOGRAPHY: 1. Liu A, Werner K, Roy S, Trojanowski JQ, MorganKane U, Miller BL, Rankin KP. A case study of an emerging visual artist with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Neurocase. 2009 Jun;15(3):23547. 2. Cummings JL, Miller BL, Christensen DD, Cherry D. Creativity and dementia: emerging diagnostic and treatment methods for Alzheimer’s disease. CNS Spectr. 2008;13:120; quiz 22.

Upload: vanlien

Post on 28-Jun-2018

230 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: THE MULTIDIMENSIONAL MIND PART 1: Creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 - Creative Brains... · THE MULTIDIMENSIONAL MIND PART 1: Creative ... His goal is

THE MULTIDIMENSIONAL MIND 

 

PART 1: Creative Brains: Music, Art and Emotion 

Bruce L. Miller, MD 

BIOGRAPHY: 

Dr. Miller is Professor of Neurology at the University of California, San Francisco (UCSF) where he holds the A.W. & Mary Margaret Clausen Distinguished Chair. Dr. Miller directs the busy UCSF dementia center where patients in the San Francisco Bay Area receive comprehensive clinical evaluations. His goal is the delivery of model care to all of the patients who enter the clinical and research programs at the UCSF Memory and Aging Center. Dr. Miller teaches extensively and runs the Behavioral Neurology Fellowship at UCSF. 

Dr. Miller is a behavioral neurologist focused in dementia with special interests in brain and behavior relationships as well as the genetic and molecular underpinnings of disease. His work in frontotemporal dementia (FTD) emphasizes both the behavioral and emotional deficits that characterize these patients, while simultaneously noting the visual creativity that can emerge in the setting of FTD. He is the principal investigator of the NIH‐sponsored Alzheimer’s Disease Research Center (ADRC) and an NIH‐funded program project on FTD called Frontotemporal Dementia: Genes, Imaging and Emotions. He oversees a healthy aging program supported through the Larry H. Hillblom Foundation and the Hellman Center, which includes an artist in residence program. In addition, he helps lead two philanthropy‐funded research consortia, the Tau Consortium and Consortium for Frontotemporal Research, focused around developing treatments for tau and progranulin disorders respectively. 

Dr. Miller has received many awards including the Potamkin Award from the American Academy of Neurology, the Raymond Adams Lecture at the American Neurological Association, the Elliot Royer Award from the San Francisco Neurological community, the UCSF Annual Faculty Research Lectureship in Clinical Science, the UCSF Academic Senate Distinction in Mentoring Award, and the Gene D. Cohen Research Award in Creativity and Aging from the National Center for Creative Aging. He has authored The Human Frontal Lobes, The Behavioral Neurology of Dementia and extensive publications regarding dementia. He has been featured in Fortune Magazine, Charlie Rose Show, The PBS NewsHour, The New York Times, and other media. For nearly three decades, Dr. Miller has been the scientific director for the philanthropic organization The John Douglas French Alzheimer’s Foundation, a private philanthropic organization that funds basic science research in Alzheimer’s disease. 

BIBLIOGRAPHY: 

1. Liu A, Werner K, Roy S, Trojanowski JQ, Morgan‐Kane U, Miller BL, Rankin KP. A case study of an emerging visual artist with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Neurocase. 2009 Jun;15(3):235‐47. 

2. Cummings JL, Miller BL, Christensen DD, Cherry D. Creativity and dementia: emerging diagnostic and treatment methods for Alzheimer’s disease. CNS Spectr. 2008;13:1‐20; quiz 22. 

Page 2: THE MULTIDIMENSIONAL MIND PART 1: Creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 - Creative Brains... · THE MULTIDIMENSIONAL MIND PART 1: Creative ... His goal is

3. Seeley WW, Matthews BR, Crawford RK, Gorno‐Tempini ML, Foti D, Mackenzie IR, Miller BL. Unravelling Boléro: progressive aphasia, transmodal creativity and the right posterior neocortex. Brain. 2008;131:39‐49. 

4. Rankin KP, Liu AA, Howard S, Slama H, Hou CE, Shuster K, Miller BL. A case‐controlled study of altered visual art production in Alzheimer's and FTLD. Cogn Behav Neurol. 2007;20:48‐61. 

5. Miller BL, Hou CE. Portraits of artists: emergence of visual creativity in dementia. Arch Neurol. 2004;61:842‐4. 

   PART 2: Mouse Models, Jellyfish and Stem Cells: Mechanisms for Disease 

 Keith Vossel, MD, MSc 

 BIOGRAPHY: Keith Vossel, MD, MSc is a Staff Scientist in the Gladstone Institute of Neurological Disease and Assistant Professor of Neurology  in the UCSF Memory and Aging Center.   Dr. Vossel received a BS in engineering science and mechanics and MSc in biomedical engineering at the University of Tennessee.  He  received  an MD  at  the University  of  Tennessee  and  subsequently  completed residency  training  in neurology at Massachusetts General Hospital and Brigham and Women’s Hospital, where he served his final year as a chief resident. In addition to caring for patients, Dr. Vossel  investigates  mechanisms  and  novel  treatment  approaches  for  neural  network dysfunction  in  Alzheimer's  disease.  His  laboratory  investigation  focuses  on  the microtubule‐associated  protein  tau  and  regulation  of  axonal  transport  and  his  clinical  study  investigates seizures and epileptiform activity in Alzheimer’s disease and related dementias.  BIBLIOGRAPHY: 1. Vossel KA, Zhang K, Brodbeck J, et al. Tau reduction prevents Abeta‐induced defects in 

axonal transport. Science 2010;330:198.  

2. Vossel KA, Miller BL. New approaches to treatment of frontotemporal lobar degeneration. Current Opinion in Neurology 2008, 21(6):708–716.  PMCID2744321 

 3. Morris M, Maeda S, Vossel K, Mucke L. The many faces of tau. Neuron. 2011, 70:410‐26.    4. Sanchez PE, Zhu L, Verret L, Vossel KA, Orr AG, Cirrito JR, Devidze N, Yu G, Palop JJ, 

Mucke L. Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in Alzheimer's disease mouse model. Proceedings of the National Academy of Sciences U.S.A. Epub 2012 Aug 6.  

 5. Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol 

2009;66:435‐440.  

6. Miyawaki A. Green Fluorescent Protein Glows Gold. Cell 135;987‐990.  

7. Lindvall L and Kokaia K. Stem cells in human neurodegenerative disorders — time for clinical translation? J Clinical Invest 2010;120:29‐40.  

Page 3: THE MULTIDIMENSIONAL MIND PART 1: Creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 - Creative Brains... · THE MULTIDIMENSIONAL MIND PART 1: Creative ... His goal is

FINANCIAL STRENGTH

Grants from the National Institutes of Health (NIH) and other federal agencies are Gladstone’s major source of support. Foundations and private donors contri- bute other significant funding—which is critical towards advancing our mission to overcome some of the world’s most devastating diseases.

2011 SOURCES OF FUNDING

External Grants(including NIH) $60 MillionPhilanthropy 6 MillionOther revenues 6 Million

Revenue $72 Million

EMPLOYEESAt the beginning of 2012, we had approximately 400 employees.

UCSF AFFILIATION

Gladstone has a vibrant partnership with the University of California, San Francisco (UCSF), one of the nation’s premier medical schools. All of Gladstone’s principal investigators are seamlessly integrated faculty members at UCSF, where they regularly teach and mentor UCSF graduate students.

GLADSTONE HISTORY

Established in 1971 from the estate of J. David Gladstone, the Gladstone Trust is a 501(c)(3) tax-exempt charity. Valued at about $8 million at the time of Mr. Gladstone’s death, this original bequest has since multiplied more than 20-times its original value—while also supporting more than three decades of biomedical research and training.

Mr. Gladstone was a real estate devel- oper who made his fortune as the first developer to create enclosed shopping malls (such as the Northridge Fashion Center mall) in Southern California. His accidental death in 1971 left an estate dedicated to supporting medical students interested in research.

The Gladstone Trust was used to launch The J. David Gladstone Institutes in 1979, under the leadership of Robert W. Mahley, MD, PhD. Through an affiliation agreement with UCSF, Gladstone was founded as a research and training facility at San Francisco General Hospital. Initially focused on cardiovascular research, Gladstone added expertise in virology and immunology in 1991 and in neurological disease in 1998.

In 2004, the Gladstone Institutes moved to a new and dedicated facility in San Francisco’s Mission Bay, ushering in a renewed sense of collaboration among Gladstone’s growing scientific staff. In 2010, after three decades of leading Gladstone, Dr. Mahley stepped down in order to return to more active research.

That same year, R. Sanders “Sandy” Williams, MD, left Duke University, where he had been Dean of the School of Medicine—as well as Senior Vice Chancellor and Senior Advisor for International Strategy—to become Gladstone’s new president. The following year, the independent and philanthropic Gladstone Foundation formed with the mission of expanding the financial resources available to drive Gladstone’s mission.

ABOUT US

Gladstone is a nimble and independent nonprofit biomedical-research organiza-tion dedicated to rigorous, cutting-edge science—our mission is to unravel the basics of biology in order to better understand, prevent, treat and cure cardiovascular, viral and neurological conditions such as heart failure, HIV/AIDS and Alzheimer’s disease.

OUR SCIENCE

Gladstone combines the best of basic science with expertise in cardiovascular, viral and neurological diseases. Our scientists are at the forefront of stem cell biology research, using induced pluri- potent stem cell (see graphic) and other cellular reprogramming technologies in their research. We have a robust trans- lational research effort to transform our basic discoveries into solutions for patients. Another key component of our work at Gladstone is training tomorrow’s physicians and researchers. We are passionate about science and determined in our goal of preventing, treating and curing some of the world’s most relentless illnesses.

LEADERSHIP

Gladstone’s president, three research directors and three trustees strategically guide the organization to foster and enrich innovation, talent, entrepreneur-ship and financial strength.

R. Sanders Williams, MDPresident, Gladstone Institutes

Deepak Srivastava, MDDirector, Cardiovascular Research

Warner C. Greene, MD, PhDDirector, Immunology and Virology Research

Lennart Mucke, MDDirector, Neurological Research

TRUSTEES

Richard D. Jones, JDAlbert A. DormanAndrew S. Garb, JD

DERIVED FROM ADULT SKIN CELLS, THESEINDUCED PLURIPOTENT STEM CELLS— WHICH ACT VERY MUCH LIKE EMBRYONIC STEM CELLS—ARE DIFFERENTIATING INTO HEART AND NERVE CELLS.

| BACKGROUNDER

SCIENCE OVERCOMING DISEASE

Contact Press Relations: email: [email protected] | phone:

1650 Owens Street | San Francisco | California 94158 | www.gladstoneinstitutes.org

Page 4: THE MULTIDIMENSIONAL MIND PART 1: Creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 - Creative Brains... · THE MULTIDIMENSIONAL MIND PART 1: Creative ... His goal is

10/31/2012

1

Part II: Mouse Models, Jellyfish and Stem Cells: Mechanisms for Disease

Creative Brains: Music, Art and Emotion

Keith A. Vossel, MD, MScAssistant Professor of Neurology, UCSF

Staff Scientist, Gladstone Institute of Neurological Disease Research Scientists

Physician Scientists

Overview

Part II: Mouse Models, Jellyfish and Stem Cells: Mechanisms for Disease

• Mouse models of Alzheimer’s disease

• Jellyfish proteins illuminate inner workings of cells

• Transforming skin cells into stem cells

Alzheimer’s Disease

• 5.4 million Americanshave Alzheimer’s

• 6th leading causeof death in US

• Impending public health crisis

www.alz.org

Today

Page 5: THE MULTIDIMENSIONAL MIND PART 1: Creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 - Creative Brains... · THE MULTIDIMENSIONAL MIND PART 1: Creative ... His goal is

10/31/2012

2

Alzheimer’s Disease

Normal Brain Alzheimer’s Patient Brain

Alzheimer’s Disease: Multiple Factors

Why study mice?

• Short life span (30 months)

• Entire genome mapped

• Transgenic models isolate effects of single genes

• Relevant functional measures

• Biomarkers validated in humans

Tanzi R, N Engl J Med (1995) 332:1512–3

AD Brain

hAPP TransgenicMouse Brain

Amyloid Plaques

Transgenic Mouse Models of AD

hAPPFADhAPPFAD

Dystrophic Neurites

AD Brain

Page 6: THE MULTIDIMENSIONAL MIND PART 1: Creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 - Creative Brains... · THE MULTIDIMENSIONAL MIND PART 1: Creative ... His goal is

10/31/2012

3

Morris Water Maze: hAPP Mice Show Learning and Memory Deficits

Nontransgenic (Normal) hAPP (Alzheimer’s)

What hAPP Mice Have Taught Us

Biomarkers

Cell andMolecularChanges

Cognitive/Behavioral Deficits Seizures

Therapies

hAPP Mice

Overview

Part II: Mouse Models, Jellyfish and Stem Cells: Mechanisms for Disease

• Mouse models of Alzheimer’s disease

• Jellyfish proteins illuminate inner workings of cells

• Transforming skin cells into stem cells

2008 Nobel laureates from Miyawaki Cell 2008; Mouse cortex image courtesy of Robert Cudmore

Mouse CortexJellyfish

Roger Y. TsienMartin ChalfieOsamu Shimomura

Page 7: THE MULTIDIMENSIONAL MIND PART 1: Creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 - Creative Brains... · THE MULTIDIMENSIONAL MIND PART 1: Creative ... His goal is

10/31/2012

4

Axon

40µm

5µm

Mitochondrial Transport Mitochondrial Transport in Living Brain

Dimitrios Davalos and Katerina Akassoglou, Gladstone Institutes

Overview

Part II: Mouse Models, Jellyfish and Stem Cells: Mechanisms for Disease

• Animal models of Alzheimer’s disease

• Jellyfish proteins illuminate inner workings of cells

• Human-derived stem cells

What are stem cells?

• Definition: any cell with the capacity to differentiate into a more mature cell type

• Therapeutic applications

• Neurodegenerative disease

• Epilepsy

• Stroke

• Spinal cord injury

• etc

44

A B C

1

2

3

Page 8: THE MULTIDIMENSIONAL MIND PART 1: Creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 - Creative Brains... · THE MULTIDIMENSIONAL MIND PART 1: Creative ... His goal is

10/31/2012

5

Induced Pluripotent Stem Cells (iPS Cells)

Shinya Yamanaka 2012 Nobel Prize

iPS-derived Neurons with FTD Mutation

Corrected MutationIncreased

FTD Mutations

Yadong Huang, MD, PhD, Gladstone/UCSF

Research Scientists

Physician ScientistsClinical Trials

Personalized Medicine

Regenerative Applications of Stem Cells

Page 9: THE MULTIDIMENSIONAL MIND PART 1: Creative …minimedicalschool.ucsf.edu/syllabus/fall2012/11-1 - Creative Brains... · THE MULTIDIMENSIONAL MIND PART 1: Creative ... His goal is

10/31/2012

6

GladstoneLennart MuckePascal SanchezJorge PalopLaure VerretJens BrodbeckSteve FinkbeinerAaron DaubPunita SharmaEva LaDowAlisha HollowayYadong HuangDimitrios DavalosKaterina AkassoglouJordan XuTim Sweeney

UABErik Roberson

StanfordBianxiao CuiKai Zhang

UCSFBruce MillerHeidi KirschPaul GarciaSrikantan NagarajanSusanne HonmaAnne F. DowlingJohn HoudeManu HegdeMary MantleGil RabinoviciWilliam JagustAlex BeagleKamalini RanisingheMAC Database, Imaging and Research StaffResearch Patients and their Families

FundingNIH/NIA/ADRC, JD French Alzheimer’s Foundation, Stephen Bechtel, Jr Foundation

Acknowledgements http://memory.ucsf.edu