Genetics of Aging-Related Neurodegeneration: The Sylvan M. Cohen Annual Retreat & Poster Session 2017

077On Tuesday, May 23, 2017, the Institute on Aging (IOA) hosted their annual Sylvan M. Cohen Retreat and Poster Session in collaboration with co-sponsors, the Penn Neurodegeneration Genomics Center (PNGC).

The 2017 retreat focused on the ‘Genetics of Aging-related Neurodegeneration’ and for the second year in a row, it began with opening remarks from the Dean of the Perelman School of Medicine, J. Larry Jameson, MD, PhD. “I’m mainly here to thank you for your scientific collaboration,” said Dean Jameson. He used this time to express the importance and impact of these contributions in the field of genetics and aging, especially in trying to solve the puzzle of very complex conditions such as neurodegeneration.

Lectures were presented by Penn’s Gerard (Jerry) D. Schellenberg, PhD, Director of the PNGC, Adam Naj, PhD, Assistant professor of Epidemiology in Biostatistics and Epidemiology, and Nancy Zhang, PhD, Assistant professor of Statistics, as well as this year’s keynote speaker, Philip De Jager, MD, PhD, Associate Neurologist at Brigham and Women’s Hospital and Associate Professor of Neurology at Harvard Medical School.

Lectures:

  • “Alzheimer’s Disease Genetics; Progress in Gene Therapy” – Jerry Schellenberg, PhD
  • “Genetic Risk Factors Associated with Coincident Alzheimer’s and Parkinson Disease in Neuropathologically Confirmed Cases” – Adam Naj, PhD
  • “Structural Variant Profiling in Alzheimer’s Disease Genetics” – Nancy Zhang, PhD
  • “The molecular network map of the aging cortex: v1.0: an integrative approach targets the epigenomic and inflammatory components of Tau pathology” – Philip De Jager, MD, PhD

As usual, the event concluded with the annual poster session on aging. Prizes were awarded to the top posters in each of the following categories: Basic Science and Clinical Research/Education & Community.

Poster Winners:

BASIC SCIENCE:

1st Place:

172Title: “Integrative analysis identifies immune-related enhancers and IncRNAs perturbed by genetic variants associated with Alzheimer’s disease”
Presenter: Alexandre Amlie-Wolf
Authors: Alexandre Amlie-Wolf, Mitchell Tang, Jessica King, Beth Dombroski, Elizabeth Mlynarski,Yi-Fan Chou, Gerard D. Schellenberg, Li-San Wang
Affiliation(s): University of Pennsylvania, Genomics and Computational Biology Graduate Group

2nd Place:

173Title: “Differential Vulnerability to a-synuclein Pathology Among Neuronal Subpopulations”
Presenter: Luna Esteban
Authors: Luna Esteban, Dawn M. Riddle, Virginia M.Y. Lee, Kelvin C. Luk
Affiliation(s): Center for Neurodegenerative Disease Research

 


Clinical Research/Education & Community

1st Place:

175Title: “Correlates of Sleep Indices Among Community Dwelling Older Adults Enrolled in a Collaborative Care Management Program”
Presenter: Ashik Ansar
Authors: Ashik Ansar, MD, PhD, Shahrzad Mavandadi, PhD, Kristin Foust, Suzanne DiFilippo, RN, Joel E.. Streim, MD, David W. Oslin, MD
Affiliation(s): Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania

2nd Place:

176Title: “The Impact of Cognitive Reserve and Brain Atrophy on Survival in Neurodegenerative Diseases”
Presenter: Carrie Caswell
Authors: Carrie Caswell, MS (1), Sharon X. Xie, PhD (1), Murray Grossman, MD, EdD (1), Corey T. McMillan, PhD (1), Lauren M. Massimo, PhD, CRNP (1,2)
Affiliation(s): (1) University of Pennsylvania, (2) Penn State University

To view the full lectures from the 2017 Sylvan M. Cohen Annual Retreat, click here.

To view more photos from the 2017 Sylvan M. Cohen Annual Retreat, click here.

 

Penn’s CNDR celebrates 25 years of groundbreaking research with the supporters and friends who make it all possible

screen-shot-2016-11-08-at-3-01-13-pmThis year, the Center for Neurodegenerative Disease Research is celebrating its 25th anniversary in a big way. Penn Medicine organized an intimate anniversary event generously hosted by longtime supporters and friends of CNDR, Bob Lane, an Institute on Aging External Advisory Board (IOA EAB) member, and his wife Randi Zemsky, at their home in the Rittenhouse Square section of Philadelphia. 

 

The event celebrated the groundbreaking work of CNDR over the past 25 years and highlighted research breakthroughs still on the horizon. It was also an opportunity to bring together and thank many of the center’s supporters. The event was attended by David B. Roth, MD, PhD, Chair of the Department of Pathology and Laboratory Medicine, CNDR researchers, IOA EAB members, supporters of the Center and close friends of the hosts.

Stay tuned for our special edition CNDR 25th Anniversary Newsletter coming early next year.

“To sleep, per chance to age… and avoid Alzheimer’s disease”: A recap of the 2016 Sylvan M. Cohen Annual Retreat

On Wednesday, June 8, 2016, the Institute on Aging hosted its annual Sylvan M. Cohen Retreat and Poster Session. This year’s retreat, titled “To sleep, per chance to age… and avoid Alzheimer’s disease,” was co-sponsored by Penn’s Center for Sleep and Circadian Neurobiology and explored the effects of sleep loss and it’s possible link to Alzheimer’s and other neurodegenerative conditions.

corrected_DJquoteAs usual, the event began with lunch and a series of lectures, but this year we had the pleasure of having J. Larry Jameson, MD, PhD, dean of the Perelman School of Medicine (PSOM), join us for opening remarks.

He expressed his excitement to see such collaboration amongst the two sponsoring centers and encouraged more of this, not only in the PSOM, but also across the University as a whole. “One of the secrets at Penn Medicine is that we have these catalytic centers and institutes and it’s even more impressive that there is often cross fertilization between them,” explained Dean Jameson.

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Keynote speaker, David M. Holtzman, MD, professor and chairman, Department of Neurology at Washington University School of Medicine, kicked off the lectures by discussing his research in “Understanding the Relationships between Sleep, Protein Aggregation, and Alzheimer’s disease.”

Other topics, covered by our Penn Presenters, included (click for video interviews):

Immediately following the lectures, researchers from the University of Pennsylvania and beyond presented their current aging-related work at our annual Poster Session. Categories included basic science, clinical research, & education and community and awards were given to the top posters.

Poster Winners

BASIC SCIENCE

1st Place
BasicSciecne1Enhancing a WNT-telomere feedback loop restores intestinal stem cell function in a human organotypic model of dyskeratosis congenita
Presenter: Dong-Hun Woo
Authors: Dong-Hun Woo, Qijun Chen, Ting-Lin B. Yang, M. Rebecca Glineburg, Carla Hoge, Nicolae A. Leu, F. Brad Johnson, and Christopher J. Lengner

 

2nd Place
BasicSciecne2AB Plaques Mediate Neuritic Plaque-like Tau Pathology that is Distinct from Perikaryal Tau Inclusions
Presenters: Zhuohao He
Authors: Zhuohao He, Jing L. Guo, Jennifer D. McBride, Lakshmi Changolkar, Bin Zhang, Ronald J. Gathagan, Hyesung Kim, Sneha Narasimhan, Kurt R. Brunden, John Q. Trojanowski, Virginia M.-Y. Lee


CLINICAL RESEARCH and EDUCATION & COMMUNITY *

1st Place
ClinRes1Tau Pathology Influences Dementia Onset and Survival in Lewy Body Spectrum Disorders
Presenter: David Irwin
Authors: David J. Irwin, MD MSTR, Murray Grossman MD, Daniel Weintraub MD, Howard I. Hurtig MD, John E. Duda MD, Sharon X. Xie PhD, Edward B. Lee MD PhD, Vivianna M. Van Deerlin MD, PhD,Oscar L. Lopez MD, Julia K. Kofler MD, Peter T. Nelson, MD PhD, Randy Woltjer MD PhD, Joseph F. Quinn MD, Jeffery Kaye MD, James B Leverenz MD, Debby Tsuang MD, MSc, Katelan Longfellow MD, Dora Yearout BS, Walter Kukull PhD, C. Dirk Keene MD, PhD, Thomas J. Montine MD, PhD, Cyrus P. Zabetian MD MS, John Q. Trojanowski MD PhD

2nd Place
ClinRes2Clinical Profile of Older Adults with Mild or No Cognitive Impairment Who Receive Prescriptions for Cholinesterase Inhibitors and/or Memantine: A descriptive study from the PACE/PACENET BHL Caregiver Resources, Education and Support (CREST) Program
Presenter: Romika Dhar, MD
Authors: Romika Dhar, MD; Amy Benson, MSEd; Joel E. Streim, MD; David W. Oslin, MD

* Due to the number of posters submitted, the categories for Clinical Research and Education & Community were combined.

Screen Shot 2016-06-22 at 10.40.42 AM

To view some of the full lectures from our retreat, click here.
* Please note: Some of the lectures are not available to view due to unpublished data being presented *

View more photos from our 2016 Sylvan M. Cohen Retreat Facebook album here.

Penn Medicine’s Town Hall Meeting on ADRD Funding Opportunities

On Wednesday, June 1, 2016, the University of Pennsylvania Perelman School of Medicine’s Institute on Aging (IOA), Center for Neurodegenerative Disease Research (CNDR), and Penn Translational Neuroscience Center (PTNC) co-hosted their first Town Hall Meeting, open to all interested University of Pennsylvania researchers.

The idea behind this joint effort is to increase the awareness and knowledge of the variety of available National Institutes of Health (NIH) funding opportunities relating to Alzheimer’s disease and related disorders (ADRD) and the neurosciences, with many already underway here at Penn.

Screen Shot 2016-06-14 at 2.42.49 PM“In the last five years, NIH funding [for ADRD research] increased from $450 million to
nearly $1 billion,” explained John Q. Trojanowski, MD, PhD, IOA Director and CNDR Co-Director. “People who are not working in ADRD can get involved in this field. Penn is a hotbed of aging research, but there is always room to do more.”

Back in February of this year, NIA Director, Dr. Richard Hodes, MD paid a visit to the University of Pennsylvania to hear from Penn researchers and clinicians working in the fields of aging and neuroscience as well as immunology. During this visit, Dr. Hodes addressed many questions regarding the $2 billion NIH budget increase — with more than $350 million specifically earmarked for Alzheimer’s research — which was announced just a month prior. In response, Dr. Hodes broadly recommended and stressed the importance of making any and all connections to ADRD explicitly emphasized in upcoming proposals, without being misleading.

With that in mind, the main goal of this Town Hall Meeting was to encourage and welcome more collaboration across the Perelman School of Medicine within these areas of research — particularly with those whose past research has not yet explored such topics.

John Q. Trojanowski, MD, PhD discusses the goals and benefits of the Town Hall Meeting on ADRD Funding Opportunities:

 

Frances E. Jensen, MD, FACP discusses Neurosciences at Penn – Opportunities Overview:

 

Jerry Schellenberg, PhD discusses the new Penn Neurodegeneration Genomics Center and related resources at Penn:

 

For more information on the Town Hall Meeting, including a list of speakers, presentations, funding opportunities, current ADRD Grants at Penn, and more, click here.

Joseph A. Pignolo Award in Aging Research 2015: “REST and Stress Resistance in Aging and Alzheimer’s Research”

On Tuesday, March 1, 2016, the Institute on Aging presented their annual Joseph A. Pignolo Award in Aging Research. This year’s awardee was Bruce A. Yankner, MD, PhD, professor of Genetics and Neurology and Co-director of the Glenn Center for the Biology of Aging at Harvard Medical School, for his 2014 publication in Nature on “REST and Stress Resistance in Aging and Alzheimer’s Research.

IMG_0014

John Q. Trojanowski, MD, PhD (IOA Director), Bruce A. Yankner, MD, PhD (2016 Pignolo Awardee), and Robert J. Pignolo, MD, PhD (founder of the Pignolo Award in Aging Research).

This paper analyzes the gene expression changes that occur in the aging brain and shows the coherent pattern of changes in genes that turn on or off in the neurons of the brain as it ages. The greatest impact was seen in the REST (RE1 neuron-silencing transcription factor) gene. It was previously thought that this gene only functioned in fetal brain development—keeping neural genes at bay until the brain had a chance to build its underlying architecture—however, Dr. Yankner and his team found that it is also expressed in the adult human brain and is dramatically up-regulated in neurons as the brain ages. The significance of this in neurodegenerative research is that they discovered that in the brains of individuals with Alzheimer’s disease, the protein is actually much less up-regulated, or completely absent.

Using both mouse models and culture dishes in a laboratory, they found that regular stressors encountered by an aging brain such as oxidative stress—a disturbance in the balance between the production of reactive oxygen species and antioxidant defenses—and amyloid stress associated with AD had a significant impact on sustaining the REST gene.

“This was a galvanizing observation for us,” explained Dr. Yankner. “It suggested that some people can resist the onslaught of Alzheimer’s because they’re able to up-regulate this intrinsic defense mechanism [REST]. So, a very important question is why some people can do it and some people can’t…”

Dr. Yankner assumes there is a potential genetic underpinning, but also believes that environmental factors contribute as well.

In terms of future research, and based on their current findings, Dr. Yankner and his lab are interested in understanding exactly how REST accomplishes its different functions and manages to maintain neurons in a functional state for so many years. To do this, they are characterizing all of the genes and protein partners that interact with REST and are looking at them as potential therapeutic targets that may be used to delay the onset of Alzheimer’s disease.

View more photos from the 2016 Joseph A. Pignolo Award in Aging Research.

*This study was funded by the National Institute on Aging, the National Institutes of Health Common Fund (NCF), and the Paul F. Glenn Foundation for Medical Research.

 The main focuses of Dr. Yankner’s lab are to understand 1) the molecular biology of the aging brain and how that intersects with pathological aging in diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Frontotemporal degeneration (FTD) and 2) using humans as a model system by understanding how they age in the brain, from changes in genes, DNA, and proteins, and modeling this in cells in culture and genetically engineered model systems including C. elegans (Caenorhabditis elegans) nematode worms.

The Joseph A. Pignolo, Sr. Award in Aging Research is given out as part of the Institute on Aging (IOA) Visiting Scholars series to annually recognize an outstanding contribution to the field of biogerontology. It was created by geriatrician and gerontologist Robert J. Pignolo, M.D., Ph.D. in honor of his father.

NIA Director, Dr. Richard Hodes pays visit to Penn

Last month, President Obama announced an overall increase of two billion dollars to the National Institutes of Health (NIH) budget, with more than $350 million of this specifically earmarked for Alzheimer’s research, the largest-ever annual increase in federal Alzheimer’s research funding. On the heels of this announcement, National Institute on Aging (NIA) Director, Dr. Richard J. Hodes, MD, paid a rare visit to the University of Pennsylvania to hear from Penn researchers and clinicians working in the fields of aging, neuroscience, and immunology.

Hodes spent day 1 with aging and neuroscience experts from the IOA and Penn’s Center for Neurodegenerative Disease Research (CNDR). He participated in a series of round-table discussions wherein he offered advice, welcomed feedback on NIH/NIA funding processes and experiences, and learned about many of the different projects underway here at Penn.

The day began with a series of conversations with basic science researchers spanning a broad range of topics, including the genetics and basic biology of aging, featuring the work of Jerry Schellenberg, PhD, and Li-San Wang, PhD, in using the human genome to identify Alzheimer’s disease and related dementias and Brad Johnson, MD, PhD, and colleagues in understanding the biological forces that influence the development of AD. Johnson’s lab in primarily interested in telomeres, the structures that cap the ends of chromosomes, and how human aging is influenced by their maintenance and dysfunction.

Additional topics included the IOA and CNDR’s focus on training the next generation of researchers at all levels. This discussion, led by Virginia M.-Y. Lee, PhD, MBA, highlighted the work of several graduate and MD, PhD, students, some of whom started their connection with the IOA and CNDR as early as high school or during their undergraduate years. A conversation about drug discovery rounded out the morning sessions.

The afternoon commenced with a discussion with researchers from Penn’s Center for Health Incentives and Behavioral Economics and its work to improve public health economics and understand who in the population advanced directives should most be targeting, and more. Researchers from the Population Aging Research Center (PARC) and Penn’s NIA-funded P30 Center on the Demography and Economics of Aging also reviewed with Hodes their work in domestic and international factors in the demography and economics of aging including financial literacy and decision-making as well as ongoing studies involving their cohort of low-income communities in Africa to understand how aging is different in these populations.

The day concluded with presentations from Penn Nursing’s NewCourtland Center for Transitions and Health. Center representatives participating in the discussion shared their work focusing on cost and care of rehospitalization, ethical challenges in better understanding informed consent incentives, and more.

Two common themes that weaved their way through many of these discussions were the high importance the Penn placed on training the next generation of scientists and healthcare providers, and the benefit and impact of Pilot programs, a series of grants to provide seed funding for innovative research to junior faculty and young scientists, in launching research careers.

Of course, it is no surprise that the recent increase in the Alzheimer’s research budget was another popular subject. Many researchers outside of the Alzheimer’s realm questioned how, if at all, this may influence funding in their particular areas of research. In response, Dr. Hodes broadly recommended and stressed the importance of making any and all connections to Alzheimer’s and related dementias explicitly emphasized in upcoming proposals, without being misleading. With this in mind, he applauded the abundance of collaborations across centers here at Penn and strongly encouraged continuing down that path for future studies.

“I believe we presented Dr. Hodes with a close-up, in-depth look at a very broad and representative swath of all the aging and neuroscience research currently underway here at Penn that has the potential to influence our biological understanding of Alzheimer’s and related dementias now and into the future, and the clinical research and disease modifying therapies to help better treat, protect, and understand patients with AD and related dementias,” explained IOA Director, John Q. Trojanowski, MD, PhD. “We also reviewed Penn programs that focus on other key aspects of healthy aging and aging related demographic changes with the long term goal of improving the overall health of elders in our rapidly aging society.”

 

CNDR Retreat 2015: “Focusing on Parkinson’s Disease Alpha-Synuclein at the University of Pennsylvania”

Last Wednesday, October 7, 2015, Penn’s Center for Neurodegenerative Disease Research (CNDR) hosted their 15th Annual Marian S. Ware Research Retreat. This year, the theme was “Focusing on Parkinson’s Disease (PD) Alpha-synuclein at the University of Pennsylvania,” which included lectures from thirteen different University of Pennsylvania researchers (listed below) from the Perelman School of Medicine, School of Arts and Sciences, the School of Veterinary Medicine, and the Children’s Hospital of Philadelphia (CHOP) who are working on this protein and its role in PD.

Screen Shot 2015-10-12 at 2.14.15 PM

With over 150 guests and 26 posters, the day-long event was yet another success. The posters covered topics not only related to alpha-synuclein and PD, but a variety of other ongoing clinical and basic research studies on PD and other neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis (ALS). As usual, prizes were awarded to the top three posters.

1st Place Poster Winner

cndrretreat15_1stplaceTitle: Dopamine induces toxic oligomers of a-synuclein leading to neurodegeneration and motor impairment in vivo

Authors: Danielle Mor1,2 (pictured center, with CNDR Director, Virginia M.-Y. Lee, PhD [left] and Director of CNDR Drug Discovery, Kurt Brunden, PhD[right]); Elpida Tsika3; Joseph R. Mazzulli4; Jennifer Grossman5; John H. Wolfe2,6,7; Harry Ischiropoulos1,2,7

Affiliations: 1 Department of Neuroscience, School of Medicine, University of Pennsylvania; 2 Children’s Hospital of Philadelphia Research Institute; 3 Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Switzerland; 4 Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL; 5 Stern College for Women, Yeshiva University, New York, NY; 6 Department of Pathobiology, School of Veterinary Medicine; 7 Department of Pediatrics, School of Medicine, University of Pennsylvania

2nd Place Poster Winner

cndrretreat15_2ndplaceTitle: The Super Elongation Complex (SEC) modulates TDP-43 and G4C2 hexanucleotide repeat toxicity in amyotrophic lateral sclerosis disease models

Authors: Chia-Yu Chung (pictured), Nancy Bonini

Affiliation: Department of Biology, University of Pennsylvania

 

 


3rd Place Poster Winner

cndrretreat15_3rdplaceTitle: Can drug-induced Parkinsonism reveal pre-motor Parkinson disease?

Authors: James F. Morley (pictured), Gang Cheng, Jacob G. Dubroff, Jayne R. Wilkinson, John E. Duda

Affiliations: PADRECC and Nuclear Medicine, PVAMC.  Departments of Neurology and Radiology PSOM

 

 

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For more information on Penn’s Center for Neurodegenerative Disease Research, visit: www.med.upenn.edu/cndr