Quality in Life, Wellness and Community

Dear Readers,

This month it is 3 years

since we officially opened the Knoebel

Institute and moved into our gorgeous new

building. Betty and Fritz Knoebel’s dream of an interdisciplinary aging institute at DU is coming into

fruition!

In these 3 years, we have secured $4.7

million in external research grants, and we have brought in more than $1 million

in donations. KIHA has recruited 10 research groups, which are focused on dementia and movement disorders,

healthy aging, financial security and aging, intergenerational programs and

much more. KIHA is truly an interdisciplinary place, with

collaborations with 9 other colleges at DU, and with researchers in 10 different countries and 12 US states. This hard

work and expansive growth could not have been done without the many

supporters and collaborators both within DU and in the community.

A heartfelt thank you goes out to Dr.

Lynn Taussig, who implemented KIHA, and to all of you who have helped us

build a first class research and outreach

program focused on Healthy Aging!! We are still growing and need your help to

expand successful programs at KIHA.

We hope that you have had a chance to

attend some of our many events and research seminars. New to this year is

the KIHA Mindfulness class that, both in the spring and fall. The instructor, Kara Traikoff, is a Professor in the Language

Department at DU and this fall is her second time teaching this class at KIHA.

Also join our weekly Tai Chi classes, led by Jean Gan, who teaches in

communities throughout Metro Denver. Our Tai Chi group has now been carrying on for 2.5 years and is a popular activity

in our community as well as among DU faculty and students. If you are

interested in either of these activities, please contact us (aging@DU.edu).

We also organize monthly “chalk talks” which are scientific faculty seminars, as well as monthly Grand Rounds where we

invite prominent scientists from around the world.

Hope to see you all soon!

Lotta

Dr. Lotta Granholm-Bentley, PhD/DDS

Executive Director

November 2019 Newsletter

From the Director

KIHA short report in numbers

Knoebel Institute for Healthy Aging | November 2019 Newsletter | page 2

KIHA researchers have implemented research in these areas:

• Memory loss and aging • Movement Disorders • Intergenerational Programs • Financial Security and aging • Gerotechnology

KIHA faculty have collaborated with 28 other DU faculty, located in 13 different departments and 9 different colleg-es. These interdisciplinary collaborations have resulted in close to 50 publications by KIHA faculty, affiliated fac-ulty and collaborators since the inception in 2016.

We have active collaborations with 9 colleges at DU.

KIHA Transformative Directions

Outside Collaborations

KIHA faculty are collaborating with many other Universities. During the last 3 years, KIHA faculty have collaborated with 53 other researchers from out-side DU, and KIHA-affiliated faculty add another 13 active collaborations to that list. KIHA faculty currently have col-laborations in 13 different US states and in 10 different coun-tries (see Map).

Knoebel Institute for Healthy Aging | November 2019 Newsletter | page 3

Focus on Research: Putting DU on the map

A new network of researchers is working to

expand knowledge and treatment for those with Down syn-drome and Alzheimer’s disease. People with Down syndrome

live longer lives than ever before and develop Alzheimer’s disease in their 40s or 50s. More than 300,000 people live

with Down syndrome in the USA alone, and yet few treat-ments exist for their age-related dementia. The Biobank

consortium is lead by Dr. Granholm and includes 11 sites, 3 in Europe and the rest in 7 states in the US (see below)

This consortium has received a 5-year infrastructure grant from the Bright Focus foundation and 3 different grants from

the National Institutes of Health to conduct mechanistic re-search on samples from those with Down syndrome.

Hunt Potter CU Anschutz

Eric Hamlett MUSC

Steve Carroll MUSC

Juan Fortea Barcelona

Aurelie Ledreux DU

Martin Margittai DU

Liz Head UC Irvine

Elliott Mufson Barrow NI

Agneta Nordberg Karolinska Inst.

Knoebel Institute for Healthy Aging | November 2019 Newsletter | page 4

Prominent Visitors

YALE FAMILY FOUNDATION

SCHOLAR May 2019

Dr. Ira Lott | Professor & Chair | Pediatrics

School of Medicine | UC Irvine

Dr. Lott is a child neurologist at the Uni-

versity of California, Irvine and Children’s

Hospital. He served as a Clinical Re-

search Associate at the National Institute

of Child Health and Human Development.

He was on the faculty at Harvard Medical

School as Clinical Director of the Eunice

Kennedy Schriver Center for Mental Retardation from 1974-1983. Dr. Lott is one of

the foremost experts in the world on Down Syndrome and shared a life-time of re-

search with KIHA scientists and community members. He is a long-time collaborator

and friend of Dr. Granholm’s.

Dr. Lott visits the KIHA labs together with Ms. Michelle Whit-

ten, President & CEO, Co-Founder of the Global Down Syn-

drome Foundation in Denver.

Dr. Stan Prusiner Visit

Dr. Stanley Prusiner with Drs. Granholm, Mar-

gittai, Ledreux and Condello.

Dr. Stanley Prusiner, MD, is the director of the Institute for Neurodegenerative Dis-eases at University of California, San Francisco (UCSF). He discovered prions, a class of infectious self-reproducing path-ogens that can spread independently.

Dr. Prusiner received the Nobel Prize in Physiology or Medicine in 1997. He continues to work with Prion diseases and has recently proposed that Alzheimer’s disease is a double prion disorder. Dr. Prusiner and his close collaborator Dr. Carlo Condello spent a day at the Knoebel Institute in October this year to establish a collabo-ration with KIHA investigators.

Knoebel Institute for Healthy Aging | November 2019 Newsletter | page 5

New scientist joins KIHA and NSM

In the summer of 2019, Dr. Sunil Kumar joined University of Denver as a tenure-track Assistant Professor in the Department of Chemistry and Biochemistry, and a faculty member of the Knoebel Institute for Healthy Aging. Dr. Kumar came to us from New York University (NYU) where he was a senior postdoctoral fellow in Prof. Andrew Hamilton’s laboratory, who is the 16

th president of

NYU campuses worldwide and his work is focused on molecular control of structure and reactivity of new compounds to be used to treat cancer, Alzheimer’s disease and other pathologies. Sunil re-ceived his PhD from Clemson University in South Carolina in 2011 and then proceeded to a postdoctoral position at Yale University, followed by NYU. His work is focused on the design of artificial protein mimetics to investigate the oligomerization and aggregation of proteins in-volved in amyloid relevant pathologies including neurodegenerative disorders and or-gan localized diseases. His laboratory and office space are located in KIHA. We are happy that Sunil has joined us, leading to natural collaborations with most research groups at KIHA and in the Chemistry Department.

Recent publications: Maity D, Kumar S, Curreli F, Debnath AK, Hamilton AD. α-Helix-Mimetic Foldamers for Targeting HIV-1 TAR RNA. Chemistry. 2019 May 28;25(30):7265-7269. doi: 10.1002/chem.201900139. Epub 2019 Apr 10. PMID: 30825250.

Lee CH, Yu JR, Kumar S, Jin Y, LeRoy G, Bhanu N, Kaneko S, Garcia BA, Hamilton AD, Reinberg D. Allosteric Activation Dictates PRC2 Activity Independent of Its Recruitment to Chromatin. Mol Cell. 2018 May 3;70(3):422-434.e6. doi: 10.1016/j.molcel.2018.03.020. Epub 2018 Apr 19. PMID: 29681499.

DU Academia Industry Alliance

Connecting Graduate Students with Industry

Who We Are The University of Denver’s Academia Industry Alliance is an or-ganization of primarily graduate students and postdoctoral researchers who aim to hold networking events, including quarterly happy hours, in an effort facilitate rela-tionships between these academic individuals and industry members - including en-trepreneurs, companies, and other staff within fields pertaining to science, technol-ogy, engineering, and mathematics (STEM) Our Goal We hope to offer a work force and academic perspective for individuals in industry-related STEM fields, educate academic members about career opportunities, and ultimately bridge the gap between academia and industry Find Out More Our first event will be a Holiday Party Charity Toy Drive on December 5th at Live @ Jack’s. This is hosted in collaboration with University of Colorado’s Academia In-dustry Alliance. Please email dunetworkingnerds@gmail.com for more info and to inquire about being added to the guest list.

KIHA in the Community

Knoebel Institute for Healthy Aging | November 2019 Newsletter | page 6

Jayla Sanchez-Warren, Director of the Area Agency on Aging

at Denver Regional Council of Governments, Lt Gov. Dianne

Primavera, and Dr. Lotta Granholm-Bentley

The Seniors’ Resource Center

(SRC) is the Denver area’s largest non-

profit dedicated to services for older

adults and those with developmental dis-

abilities. On September 12, the SCR

held its annual fundraising luncheon.

Among the speakers were the SRC

board chairman, Robert Hayes, the SRC

President Chris Lynn, as well as the Lt.

Governor, Dianne Primavera.

Parkinson’s 2.0

Translating science into treatment

The Movement Disorders Foundation and KIHA co-

hosted a community education event on October 5

about the latest work in research for this difficult neu-

rological condition. Dr. Rajeev Kumar (MD, Rocky

Mountain Movement Disorders’ Center), Dr. Daniel

Paredes (KIHA) and Dr. Brian Berman (MD, CU An-

schutz Movement Disorder Center) shared their views

on current as well as future treatment options. More

than 160 attendees attended the event.

If you are interested in these or other education events

please contact us at aging@du.edu

Walk to End Alzheimer’s

Team KIHA Pioneers KIHA faculty are dedicated to finding a cure

for Alzheimer’s disease through our translational research. Staff and students

support this dedication in a myriad of ways. All were happy to participate in the annual

walk for the Alzheimer’s Association to raise awareness and funds for Alzheimer's disease. On Saturday, September 14, the KIHA

Pioneers Team gathered at 7:30 am in Denver’s City Park to participate along with

12,000 other participants.

KIHA extends a hearty THANK YOU to all who

supported us by joining our team, walking with us, or donating and thank you to our Team captain, Sarah Thomas. Thanks to you

we raised more than $3,400, exceeding our team goal and close to 40 people signed up

to be on the KIHA PIONEER team!

KIHA in the Community

Knoebel Institute for Healthy Aging | November 2019 Newsletter | page 7

Walk to Defeat ALS | Team ALS Pioneers

Amyotrophic Lateral Sclerosis (ALS), or better known as Lou Gehrig’s disease, is a rapidly progressive and fatal neurodegenerative disease which causes one to lose

the ability to walk, speak, and breathe. On average, 15 cases of ALS arise with each day and those living with ALS have an average life expectancy of only 2-5 years.

There are no known causes for ALS and treatments are limited. Through our research at KIHA, we are devoted to increasing our understanding about ALS and to

finding cures and treatments. The ALS Pioneers team raised $1,355 and helped to contribute to the $325,000 total raised. These funds help to spread awareness about

ALS, support people with ALS, and to find cures. On Sunday, October 13th, the ALS Pioneers Team gathered at 9 am in Denver’s Sloan’s Lake Park to participate along

with 2,000 other participants.

KIHA extends a hearty THANK YOU to all who supported us by joining our team, walking with us, or donating.

Please join us for next year’s ALS or Alzheimer walks!

Knoebel Institute for Healthy Aging | November 2019 Newsletter | page 8

Kara Traikoff has been a part of the DU community for 10

years. Kara is a mindfulness instructor and coach trained through the Center for Mindfulness at UMASS Medical

School. Participants practice mindfulness in a variety of forms. The class involves experiential learning and open

dialogue around individual experiences. MBSR was originally developed by Dr. Jon Kabat-Zinn at UMASS.

A new class will begin in January of 2020.

KIHA in the Community

2019 marks the third year that KIHA offers Tai Chi! In 2019, Tai Chi will be

held on Fridays from noon until 1 pm in the ECS fifth floor event space.

Join KIHA’s instructor Jean Gan, who is a physical therapist and has taught Tai Chi

for more than seven years. Jean teaches Yang and Sun styles. She is convinced that Tai Chi is a huge benefit to healthy

aging! Everyone is welcome, regardless of age

or previous knowledge in Tai Chi. Drop by to learn or deepen your practice with

others.

If you have questions, email

aging@du.edu.

KIHA Mindfulness Based Stress Reduction Class MBSR

KIHA Offers Tai Chi to All

Tai Chi instructor Jean Gan

How can you help?

KIHA scientists are very successful in

grant funding but every Institute needs support from its community. Here are im-portant areas for support:

• Graduate student scholarships

• Faculty recruitment

• Equipment

For more information, please contact

Valerie Appelbaum valerie.appelbaum@du.edu or

303-871-4056

Knoebel Institute for Healthy Aging | November 2019 Newsletter | page 9

Recent Publications 1. Goetzl EJ, Elahi FM, Mustapic M, Kapogiannis D,

Pryhoda M, Gilmore A, Gorgens KA, Davidson B, Granholm A-C, and Ledreux A. (2018) Altered levels of plasma neuron-derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury. FASEB J. 2019 Jan 3:fj201802319R. doi: 10.1096/fj.201802319R. [Epub ahead of print] PMID: 30605353.

2. Chess E. and Greenfield J. Bridging the Gap Between Cognitive Health and Financial Capacity in Older Adults: A Scoping Review - 2019 GSA Annual Scientific Meeting (to be submitted as peer-reviewed article as well).

3. Ledreux A, Håkansson K, Carlsson R, Kidane M, Columbo L, Terjestam Y, Ryan E, Tusch E, Winblad B, Daffner K, Granholm AC, Mohammed AKH.Differential Effects of Physical Exercise, Cognitive Training, and Mindfulness Practice on Serum BDNF Levels in Healthy Older Adults. J Alzheimers Dis. 2019;71(4):1245-1261. doi: 10.3233/JAD-190756.

4. Hamlett ED, LaRosa A, Mufson EJ, Fortea J, Ledreux A, Granholm AC. Exosome release and cargo in Down syndrome. Dev Neurobiol. 2019 Jul;79(7):639-655. doi: 10.1002/dneu.22712. Epub 2019 Aug 6. Review.

5. Goetzl EJ, Ledreux A, Granholm AC, Elahi FM, Goetzl L, Hiramoto J, Kapogiannis D. Neuron-Derived Exosome Proteins May Contribute to Progression From Repetitive Mild Traumatic Brain Injuries to Chronic Traumatic Encephalopathy. Front Neurosci. 2019 May 8;13:452. doi: 10.3389/fnins.2019.00452. eCollection 2019.

6. Ren M, Hu Z, Chen Q, Jaffe A, Li Y, Sadashivaiah V, Zhu S, Rajpurohit N, Heon Shin J, Xia W, Jia Y, Wu J, Lang Qin S, Li X, Zhu J, Tian Q, Paredes D, Zhang F, Hong Wang K, Mattay VS, Callicott JH, Berman KF, Weinberger DR, Yang F.KCNH2-3.1 mediates aberrant complement activation and impaired hippocampal-medial prefrontal circuitry associated with working memory deficits. Mol Psychiatry. 2019 Sep 30. doi: 10.1038/s41380-019-0530-1. [Epub ahead of print].

Recently Awarded Grants 1. R01AG061566 - Granholm/Margittai/Mufson

(Multi PIs) - 02/01/2019-11/30/2023 NIH/NIA

Tau pathology in Down syndrome-related

Alzheimer’s disease.

2. R21AG056974 - Granholm (PI) - 07/15/2017-

03/31/2020 NIH/NIA “Biological Correlates of

Alzheimer in Down Syndrome” Our project is

focused on a novel biomarker method which can

accurately diagnose AD in DS, as well as the Tau

seeding capacity in samples from those with DS,

based on previous experiments in idiopathic AD.

Role: PI

3. R56AG055596 - Head (PI) Granholm

subcontract - 09/30/2018-08/31/2019 NIH/NIA

(subcontract) mTOR Activation and the

Pathogenesis of Alzheimer Disease in Down

Syndrome. Role: Subaward PI

4. CA2018010 - Granholm (PI) 10/01/2017-

09/30/2022 Bright Focus Foundation

International Brain Bank for Down syndrome-

related Alzheimer's disease

5. Aurelie Ledreux PI: Brain-derived exosomes as

biomarkers for Alzheimer's disease2018

Alzheimer’s Association Research Grants

(AARG)-$149,997 over 3yearsCan measuring tau

and beta-amyloid content in blood predict the

development of Alzheimer's?

6. Ledreux and Linseman PIs: “Alumia Pilot Data

Grant” 10/01/2019 – 09/30/2020. $57,000 total

costs.

7. Linseman PI: “Collaborative studies on TBI

between KIHA and Resilience Code” 10/01/2019

– 09/30/2021 $41,500 total costs.

New Publications and Awarded Grants