Civic Intelligence

Palo Alto Veterans Institute For

EIN 77-0207331 • 501(c)3 • Palo Alto, CA

View Organization Page

Profile

See Schedule OPAVIR's mission is advancing Veterans and public health through innovative research. PAVIR works with more than 100 Principal Investigators and 200 research staff to support basic science, clinical and health services research to realize its mission. PAVIR's diverse studies span the entire spectrum of health research from the investigation of diseases in the laboratory through testing new drug treatments and developing improved models of health care delivery to looking at outcomes both individually and on a large scale. PAVIR's research addresses health challenges that have been faced especially by Veterans, including post-traumatic stress disorder, traumatic brain injury, geriatric medicine, rehabilitation, sleep and other Veterans and public health issues. PAVIR's investigators have appointments at the VA Palo Alto Health Care System and most also hold appointments at the Stanford University School of Medicine.

3801 Miranda AvenuePalo Alto, CA 94304

www.pavir.org

Siviq Scores

Precomputed percentiles relative to similar nonprofits. These scores are descriptive rather than judgmental.

Liabilities / Assets

83rd percentile

0.70x

Higher debt load relative to assets than 83% of similar nonprofits.

501(c)3 • $25M-$50M nonprofits • Source year 2024

Liabilities / Revenue

59th percentile

0.38x

Higher debt load relative to revenue than 59% of similar nonprofits.

501(c)3 • $25M-$50M nonprofits • Source year 2024

Net Margin

18th percentile

-8.6%

Higher net margin than 18% of similar nonprofits.

501(c)3 • $25M-$50M nonprofits • Source year 2024

Top Officer Pay

65th percentile

$332,883

Higher top officer pay than 65% of similar nonprofits.

Top officer pay equals 1.1% of source-year revenue.

501(c)3 • $25M-$50M nonprofits • Source year 2024

Asset Growth

5th percentile

-17%

Faster asset growth than 5% of similar nonprofits.

501(c)3 • $25M-$50M nonprofits • Annualized from 2023 to 2024

Revenue Growth

40th percentile

3.7%

Faster revenue growth than 40% of similar nonprofits.

501(c)3 • $25M-$50M nonprofits • Annualized from 2023 to 2024

Balance Sheet
Liabilities / Assets83rd percentile

Assets

Up

$20,719,365

Up $5,076,357 (+32%) from 2022

Liabilities

Up

$12,724,388

Up $5,254,400 (+70%) from 2022

Net Assets

Down

$7,994,977

Down $178,043 (-2.2%) from 2022

Operations
Liabilities / Revenue59th percentileNet Margin18th percentile

Revenue

Up

$30,503,398

Up $580,626 (+1.9%) from 2022

Expenses

Up

$30,736,665

Up $972,534 (+3.3%) from 2022

Net Income

Down

-$233,267

Down $391,908 (-247%) from 2022

Trend Graphs

Balance Sheet Trend

Asset Growth5th percentile

Grouped bars show assets, liabilities, and net assets across loaded filings.

$30M$20M$10M$0Assets 2010: $7,639,401Liabilities 2010: $2,600,923Net Assets 2010: $5,038,4782010Assets 2011: $7,396,378Liabilities 2011: $2,711,546Net Assets 2011: $4,684,8322011Assets 2012: $8,704,349Liabilities 2012: $3,331,263Net Assets 2012: $5,373,0862012Assets 2013: $8,188,268Liabilities 2013: $2,468,396Net Assets 2013: $5,719,8722013Assets 2014: $8,621,232Liabilities 2014: $2,959,987Net Assets 2014: $5,661,2452014Assets 2015: $9,968,460Liabilities 2015: $3,531,805Net Assets 2015: $6,436,6552015Assets 2016: $10,945,542Liabilities 2016: $3,175,921Net Assets 2016: $7,769,6212016Assets 2017: $13,757,503Liabilities 2017: $5,466,398Net Assets 2017: $8,291,1052017Assets 2018: $12,338,139Liabilities 2018: $4,355,844Net Assets 2018: $7,982,2952018Assets 2019: $12,525,941Liabilities 2019: $4,192,343Net Assets 2019: $8,333,5982019Assets 2020: $12,982,406Liabilities 2020: $6,265,277Net Assets 2020: $6,717,1292020Assets 2021: $15,189,973Liabilities 2021: $7,191,146Net Assets 2021: $7,998,8272021Assets 2022: $15,643,008Liabilities 2022: $7,469,988Net Assets 2022: $8,173,0202022Assets 2023: $20,719,365Liabilities 2023: $12,724,388Net Assets 2023: $7,994,9772023

Highlighted filing

2023

Assets$20,719,365
Liabilities$12,724,388
Net Assets$7,994,977
Open 2023 Filing

Operations Trend

Revenue Growth40th percentile

Revenue, expenses, and net income by year, with the latest filing highlighted.

$40M$30M$20M$10M$0-$10MExpenses 2010: $21,826,8492010Expenses 2011: $24,566,3262011Expenses 2012: $24,563,5892012Revenue 2013: $22,945,241Expenses 2013: $22,596,907Net Income 2013: $348,3342013Revenue 2014: $24,249,138Expenses 2014: $24,309,655Net Income 2014: -$60,5172014Revenue 2015: $27,288,665Expenses 2015: $26,508,261Net Income 2015: $780,4042015Revenue 2016: $28,219,973Expenses 2016: $26,886,139Net Income 2016: $1,333,8342016Revenue 2017: $28,240,385Expenses 2017: $27,685,878Net Income 2017: $554,5072017Revenue 2018: $28,157,044Expenses 2018: $28,466,853Net Income 2018: -$309,8092018Revenue 2019: $31,059,629Expenses 2019: $30,708,326Net Income 2019: $351,3032019Revenue 2020: $29,572,642Expenses 2020: $31,188,918Net Income 2020: -$1,616,2762020Revenue 2021: $29,400,012Expenses 2021: $28,118,941Net Income 2021: $1,281,0712021Revenue 2022: $29,922,772Expenses 2022: $29,764,131Net Income 2022: $158,6412022Revenue 2023: $30,503,398Expenses 2023: $30,736,665Net Income 2023: -$233,2672023

Highlighted filing

2023

Revenue$30,503,398
Expenses$30,736,665
Net Income-$233,267
Open 2023 Filing

Filings

Most recent year

2023 • Form 990Summary only. Only limited summary data is available for this year.

Open filing
Assets
$20,719,365
Liabilities
$12,724,388
Net assets
$7,994,977
Revenue
$30,503,398
Expenses
$30,736,665
Net income
-$233,267
Balance SheetOperations
YearAssetsLiabilitiesNet AssetsRevenueExpensesNet Income
2023Summary only. Only limited summary data is available for this year.$20.7$12.7$7.99$30.5$30.7$0.23
2022Facts available. Structured filing facts are available, but richer extracted sections are limited.$15.6$7.47$8.17$29.9$29.8$0.16
2021XML pending. An XML filing is linked for this year, but detailed extraction is still pending.$15.2$7.19$8.00$29.4$28.1$1.28
2020Summary only. Only limited summary data is available for this year.$13.0$6.27$6.72$29.6$31.2$1.62
2019Facts available. Structured filing facts are available, but richer extracted sections are limited.$12.5$4.19$8.33$31.1$30.7$0.35
2018XML pending. An XML filing is linked for this year, but detailed extraction is still pending.$12.3$4.36$7.98$28.2$28.5$0.31
2017Facts available. Structured filing facts are available, but richer extracted sections are limited.$13.8$5.47$8.29$28.2$27.7$0.55
2016Detailed filing. Detailed filing data is available for this year.$10.9$3.18$7.77$28.2$26.9$1.33
2015Detailed filing. Detailed filing data is available for this year.$9.97$3.53$6.44$27.3$26.5$0.78
2014Detailed filing. Detailed filing data is available for this year.$8.62$2.96$5.66$24.2$24.3$0.06
2013Summary only. Only limited summary data is available for this year.$8.19$2.47$5.72$22.9$22.6$0.35
2012Facts available. Structured filing facts are available, but richer extracted sections are limited.$8.70$3.33$5.37$24.6
2011Facts available. Structured filing facts are available, but richer extracted sections are limited.$7.40$2.71$4.68$24.6
2010Facts available. Structured filing facts are available, but richer extracted sections are limited.$7.64$2.60$5.04$21.8
Latest Detailed Filing

The latest 2023 filing currently has summary financial data only. Showing the latest detailed filing from 2022 below.

Jump To
Filing Snapshot
Filing Period
Oct 1, 2021 to Sep 30, 2022
Signed
May 24, 2023
Return Version
2021v4.2
Gross Receipts
$29,922,772
Mission and Program Overview

Mission

See schedule opavir's mission is advancing veterans and public health through innovative research. Pavir works with more than 100 researchers and 215 staff to support basic science and clinical research to realize its mission. Pavir's research spans the investigation of diseases in the laboratory to testing new drug treatments and developing improved models of health care delivery. In addition to a focus on basic science and clinical research, pavir's research addresses health challenges that have been faced especially by veterans, including post-traumatic stress disorder and traumatic brain injury, geriatric medicine, rehabilitation, sleep and other veterans and public health diseases. Pavir's researchers have appointments at the va palo alto health care system, and most hold dual appointments at the stanford university school of medicine.

Advancing veteran and public health through innovative research.

Balance Sheet Detail
LineBeginningEndChange
Assets
Savings and Temporary Cash Investments$9,417,233$8,968,218▼ $449,015
Accounts Receivable$3,294,258$3,474,986▲ $180,728
Cash and Non-Interest-Bearing Accounts$1,418,346$2,249,260▲ $830,914
Land, Buildings, and Equipment, Net$792,121$655,299▼ $136,822
Prepaid Expenses and Deferred Charges$268,015$295,245▲ $27,230
Total Assets$15,189,973$15,643,008▲ $453,035
Liabilities
Deferred Revenue$3,389,862$3,932,574▲ $542,712
Accounts Payable and Accrued Expenses$3,789,802$3,537,414▼ $252,388
Unsecured Notes Loans Payable$11,482$0▼ $11,482
Total Liabilities$7,191,146$7,469,988▲ $278,842
Net Assets / Fund Balance
Net Assets Without Donor Restrictions$5,040,085$5,680,883▲ $640,798
Net Assets With Donor Restrictions$2,958,742$2,492,137▼ $466,605
Total Net Assets Fund Balance$7,998,827$8,173,020▲ $174,193
Total Liabilities and Net Assets / Fund Balance$15,189,973$15,643,008▲ $453,035

Asset Categories

AssetBook ValueDepreciationBasis
Equipment$655,299$2,979,695$3,634,994
Compensation and Service Providers
Top Officer Pay65th percentile

Employees

NameTitleFull / Part TimeBaseOtherTotal
Michael Anthony HinderyCEO thru 9/1/21-$219,081$29,844$248,925
Elaine StaatsCEO from 12/1/21FT$170,065$38,883$208,948
Lisa ClarkHR DirectorFT$173,401$16,596$189,997
Lily IbragimovDirector of Finance & AccountingFT$161,936$25,101$187,037
Xinguo JiangPrincipal InvestigatorFT$141,846$31,039$172,885
Mary L ThorntonDirector of OperationsFT$145,661$24,132$169,793
Wen Amy TianResearch ScientistFT$151,200$11,520$162,720
Maheen AdamsonPrincipal InvestigatorFT$148,770$13,074$161,844
Jennifer J CrockettAssoc Director of Research AdministrationFT$139,692$13,880$153,572
Ferid MuradDirector-$42,012$3,781$45,793

Board Members and Trustees

NameTitle
Odette HarrisDirector, Board Chair from 9/1/22
Andrew R HoffmanDirector
Lawrence LeungDirector
Mark NicollsDirector
Philip TsaoDirector
David J ClarkDirector until 8/31/22
Paul HeidenreichDirector, Secretary/Treasurer
Meghan KemnecStatutory Non-VA Director
Robert SlossStatutory Non-VA Director
Jennifer LeeStatutory VA Director
Lisa HowardStatutory VA Director
Mike KozalStatutory VA Director
Payam MassabandStatutory VA Director from 7/15/22
John PollardStatutory VA Director until 7/14/22
Revenue and Support

Revenue Composition

Contributions and Grants
$19,234,972
Program Service Revenue
$10,623,749
Investment Income
$33,233
Other Revenue
$30,818
All Other Contributions
$2,385,248
Change in Net Assets
$158,641

Audited Revenue Reconciliation

Revenue per Audited Statements
$29,922,772
Revenue Not Reported on Financial Statements
$0
Revenue Not Reported on Form 990
$15,552
Total Revenue per Audited Statements
$29,938,324
Total Revenue per Form 990
$29,922,772
Expenses and Functional Allocation

Major Expense Lines

Line ItemAmount
Salaries, Compensation, and Employee Benefits$15,439,467
Other Expenses$14,324,664
Grants and Similar Amounts Paid$0
Professional Fundraising Fees$0
Total Fundraising Expense$0

Functional Expense Allocation

Line ItemProgramManagementFundraisingTotal
Other Salaries and Wages$9,763,324$2,154,709-$11,918,033
Other Employee Benefits$895,275$265,560-$1,160,835
Fees for Services Other$983,537$23,089-$1,006,626
Payroll Taxes$732,241$223,343-$955,584
Pension Plan Contributions$568,423$177,230-$745,653
Current Officers, Directors, Trustees, and Key Employees$3,982$655,380-$659,362
Information Technology$336,068$289,589-$625,657
Depreciation Depletion$246,910$13,092-$260,002
Conferences and Meetings$138,431$36,181-$174,612
All Other Expenses$136,690$828-$137,518
Payment Travel Entrtnmnt Publicly Ofcl$103,916--$103,916
Other Expenses$95,708$1,577-$97,285
Fees for Services Accounting-$85,520-$85,520
Insurance-$69,139-$69,139
Travel$54,491$9,368-$63,859
Office Expenses$42,185$8,200-$50,385
Fees for Services Legal$9,905$23,659-$33,564
Total Functional Expenses$25,639,027$4,125,104$0$29,764,131

Audited Expense Reconciliation

Line ItemAmount
Expenses per Audited Statements$29,764,131
Total Expenses per Audited Statements$29,764,131
Total Expenses per Form 990$29,764,131
Expenses Not Reported on Financial Statements$0
Expenses Not Reported on Form 990$0
Fundraising, Events, and Gaming
Fundraising activities
No
Gaming activities
No
Professional fundraiser used
No

Fundraising and Gaming Totals

Line ItemAmount
Professional Fundraising Fees$0
Political and Lobbying Activity
Political campaign activity
No
Lobbying activity
No
Subject to proxy tax
No
Governance and Compliance

Governance Checklist

Compiled or reviewed by an accountant
No
Annual disclosure for covered persons
Yes
Audit committee
Yes
Backup withholding compliance
Yes
Business relationship with 35% controlled entity
No
Business relationship with family members
No
Business relationship with organization members
No
Material changes to governing documents
No
Compensation from other sources disclosed
No
CEO compensation reviewed
Yes
Other officer compensation reviewed
Yes
Conflict-of-interest policy
Yes
Audited financial statements prepared
No
Key decisions subject to board approval
Yes
Management duties delegated
No

Governance Explanations

Form 990, Part VI, Section A, line 7A

“PAVIR is a nonprofit corporation authorized by Title 38 US Code Sections 7361 through 7366 to be established at and affiliated with the Department of Veterans Affairs Palo Alto Health Care System (VAPAHCS). The referenced statute dictates that four Directors shall be those persons holding the VAPAHCS positions of Director, Chief of Staff, Associate Chief of Staff for Research and Associate Chief of Staff for Education.”

Form 990, Part VI, Section A, line 7B

“As stated in response to Form 990, Part VI, Line 7a above, VA has authority to impose requirements and restrictions on the organization through the referenced statute and regulations prescribed by the Secretary of Veterans Affairs.”

Form 990, Part VI, Section B, line 11B

“The Form 990 has been provided to all Board members for their review prior to the filing of related tax forms.”

Form 990, Part VI, Section B, line 12C

“Directors, officers and key employees complete training in and attest to compliance with PAVIR's conflict of interest policy, as well as disclosing interests which could give rise to conflicts, upon joining PAVIR and annually thereafter. Management tracks the dates, sends reminders and documents receipt of training, attestations, and disclosures, assuring compliance in each calendar year.”

Form 990, Part VI, Section B, line 15

“Annually, PAVIR collects and analyzes market, salary survey and compensation study data based on comparable industry and revenue. The Board's Compensation Committee reviews the data, taking into account performance and accomplishments when establishing the CEO's compensation. The Compensation Committee keeps minutes of its meetings and reports its actions to the full Board. Key employees' salaries are set by the CEO utilizing information from PAVIR's annual salary schedules.”

Form 990, Part VI, Section C, line 19

“The audited financial statements, organizing/governing documents, and conflict of interest policy are available upon written request.”

Form 990, Part VII and Schedule J, Part II:

“We wrote to each of the 14 Board members who were compensated by the VA Palo Health Care System requesting permission to obtain his/her compensation information for the calendar year ended December 31, 2021. All members declined in writing to provide their compensation information. None of the Board members received compensation in relation to their duties as Board members of PAVIR.”

Filing and Contact Details

Filer

Filer Name
Palo Alto Veterans Institute for
EIN
77-0207331
Phone
6502392800
Address
3801 Miranda Avenue, Palo Alto, CA 94304
Doing Business As
Pavir

Signing Officer

Name
Elaine Staats
Title
CEO
Phone
6502392802
Signed
2023-05-24
Discuss with paid preparer
Yes

Organization Details

Principal Officer
Elaine Staats
Formed
1988
Legal Domicile
CA
Voting Board Members
13
Independent Board Members
2
Employees
248
Volunteers
0

Preparer

Firm
Bpm Llp
Address
4200 Bohannon Drive Suite 250, Menlo Park, CA 94025-1021
Preparer
Carolyn R Amster
Phone
6508556800
Supplemental Narrative

Additional Explanations

Form 990, Part XI, line 9:

“returned contributions -1,792.”

Financial Statement Notes

Part X, Line 2:

“The Organization is a nonprofit corporation exempt from federal income tax under Internal Revenue Code Section 501(c)(3) and state income tax under California Revenue and Taxation Code Section 23701d. However, income from certain activities not directly related to the Organization's tax-exempt purpose may be subject to taxation as unrelated business income. The Organization qualifies for the charitable contribution deduction under IRC Section 170(b)(1)(A)(iii) and has been classified as an Organization that is not a private foundation under Section 509(a)(1). As of September 30, 2022 and 2021, the Organization had no unrecognized tax benefits or uncertain tax positions requiring accrual. Therefore, no provision for income taxes has been provided in the financial statements.”

Part XI, Line 2D - Other Adjustments:

“Returned Contributions”

Raw XML AppendixShowing 400 of 758 raw XML fields

This appendix keeps the raw XML leaves available for debugging and edge-case review. The human report above is the primary experience.

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IRS990/Desc0Targeted Strategies to Accelerate Evidence-Based Psychotherapy (EBP) Implementation in Military. Principal Investigators: Craig S. Rosen, Ph.D. and Carmen P. McLean, Ph.D. This four-year study, funded by the Department of Defense, is aimed at increasing use of evidence-based psychotherapies (therapies proven effective in research) in clinics on military bases. Despite efforts to train military providers in effective psychotherapies for posttraumatic stress disorder (PTSD), only a minority of service members receive these treatments. This trial tests whether a tailored process improvement approach (using a toolkit for matching specific change strategies to local barriers) is more effective than provider training alone in expanding the proportion of patients who receive an EBP. The project, led by investigators at the National Center for PTSD and Palo Alto Veterans Institute for Research (PAVIR), includes collaborators from five universities and eight military treatment facilities. Objectives: To test in a stepped-wedge randomized trial whether the Targeted Assessment and Context-Tailored Implementation of Change Strategies (TACTICS) increases use of evidence-based psychotherapy more than does provider training alone. Secondary outcomes include effects of TACTICS on average improvement in PTSD symptoms, and satisfaction with the TACTICS process. Accomplishments: All staff have been hired, eight military clinics representing all service branches were recruited and all regulatory approvals obtained. Provider training and clinic-tailored process improvement intervention to increase PE use has been implemented at all eight study sites. Provider survey data collection is completed. Barriers to implementing PE in the military health system and recommended policy level changes to address these barriers have been identified. Centralized extraction of study data and analysis in collaboration with the Defense Health Agency is ongoing. Potential Impact: If effective, TACTICS may represent a scalable approach to accelerating the use of behavioral health best practices in military settings.
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IRS990/Form990PartVIISectionAGrp/PersonNm0David J Clark
IRS990/Form990PartVIISectionAGrp/PersonNm1Odette Harris
IRS990/Form990PartVIISectionAGrp/PersonNm2Paul Heidenreich
IRS990/Form990PartVIISectionAGrp/PersonNm3Andrew R Hoffman
IRS990/Form990PartVIISectionAGrp/PersonNm4Lisa Howard
IRS990/Form990PartVIISectionAGrp/PersonNm5Meghan Kemnec
IRS990/Form990PartVIISectionAGrp/PersonNm6Mike Kozal
IRS990/Form990PartVIISectionAGrp/PersonNm7Jennifer Lee
IRS990/Form990PartVIISectionAGrp/PersonNm8Lawrence Leung
IRS990/Form990PartVIISectionAGrp/PersonNm9Payam Massaband
IRS990/Form990PartVIISectionAGrp/PersonNm10Ferid Murad
IRS990/Form990PartVIISectionAGrp/PersonNm11Mark Nicolls
IRS990/Form990PartVIISectionAGrp/PersonNm12John Pollard
IRS990/Form990PartVIISectionAGrp/PersonNm13Robert Sloss
IRS990/Form990PartVIISectionAGrp/PersonNm14Philip Tsao
IRS990/Form990PartVIISectionAGrp/PersonNm15Elaine Staats
IRS990/Form990PartVIISectionAGrp/PersonNm16Lisa Clark
IRS990/Form990PartVIISectionAGrp/PersonNm17Lily Ibragimov
IRS990/Form990PartVIISectionAGrp/PersonNm18Maheen Adamson
IRS990/Form990PartVIISectionAGrp/PersonNm19Jennifer J Crockett
IRS990/Form990PartVIISectionAGrp/PersonNm20Xinguo Jiang
IRS990/Form990PartVIISectionAGrp/PersonNm21Wen Amy Tian
IRS990/Form990PartVIISectionAGrp/PersonNm22Mary L Thornton
IRS990/Form990PartVIISectionAGrp/PersonNm23Michael Anthony Hindery
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IRS990/Form990PartVIISectionAGrp/TitleTxt0Director until 8/31/22
IRS990/Form990PartVIISectionAGrp/TitleTxt1Director, Board Chair from 9/1/22
IRS990/Form990PartVIISectionAGrp/TitleTxt2Director, Secretary/Treasurer
IRS990/Form990PartVIISectionAGrp/TitleTxt3Director
IRS990/Form990PartVIISectionAGrp/TitleTxt4Statutory VA Director
IRS990/Form990PartVIISectionAGrp/TitleTxt5Statutory Non-VA Director
IRS990/Form990PartVIISectionAGrp/TitleTxt6Statutory VA Director
IRS990/Form990PartVIISectionAGrp/TitleTxt7Statutory VA Director
IRS990/Form990PartVIISectionAGrp/TitleTxt8Director
IRS990/Form990PartVIISectionAGrp/TitleTxt9Statutory VA Director from 7/15/22
IRS990/Form990PartVIISectionAGrp/TitleTxt10Director
IRS990/Form990PartVIISectionAGrp/TitleTxt11Director
IRS990/Form990PartVIISectionAGrp/TitleTxt12Statutory VA Director until 7/14/22
IRS990/Form990PartVIISectionAGrp/TitleTxt13Statutory Non-VA Director
IRS990/Form990PartVIISectionAGrp/TitleTxt14Director
IRS990/Form990PartVIISectionAGrp/TitleTxt15CEO from 12/1/21
IRS990/Form990PartVIISectionAGrp/TitleTxt16HR Director
IRS990/Form990PartVIISectionAGrp/TitleTxt17Director of Finance & Accounting
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IRS990/MissionDesc0See Schedule OPAVIR's mission is advancing Veterans and public health through innovative research. PAVIR works with more than 100 Principal Investigators and 200 research staff to support basic science, clinical and health services research to realize its mission. PAVIR's diverse studies span the entire spectrum of health research from the investigation of diseases in the laboratory through testing new drug treatments and developing improved models of health care delivery to looking at outcomes both individually and on a large scale. PAVIR's research addresses health challenges that have been faced especially by Veterans, including post-traumatic stress disorder, traumatic brain injury, geriatric medicine, rehabilitation, sleep and other Veterans and public health issues. PAVIR's investigators have appointments at the VA Palo Alto Health Care System and most also hold appointments at the Stanford University School of Medicine.
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IRS990/ProgSrvcAccomActy2Grp/Desc0All of Us Research Program. Principal investigators: Philip Tsao, Ph.D. and Jennifer Lee, M.D., Ph.D.The All of Us Research Program (All of Us) is a large collaborative initiative sponsored by the National Institutes of Health (NIH). All of Us includes a consortium of awardees from multiple institutions, including the Department of Veterans Affairs. All of Us is working to improve healthcare through research by building a diverse database of participant self-report information, biospecimens, and Electronic Health Records that can inform future research on a variety of health conditions. VA participation in All of Us is overseen by three Co-PIs, located at the VA Palo Alto Healthcare System and the VA Boston Healthcare System. These two institutions serve as the Coordinating Centers for all participating VA sites, providing leadership and oversight. There are currently 15 VA sites, with plans to add additional sites in the upcoming years. All centralized recruitment, engagement campaigns, and compliance with program requirements is managed by the VA PIs and their respective Coordinating Center teams.
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IRS990/ProgSrvcAccomActy3Grp/Desc0Targeting Cerebrovascular TGF Signaling in Alzheimer's Disease. Principal Investigator: Jian Luo Ph.D.Alzheimer's disease (AD) is the most common type of dementia, afflicting millions of victims worldwide, but has thus far proven incurable. With an aging population, this devastating disease will become more widespread in the near future, making the search for effective treatments a principal objective. While the etiology of AD is poorly understood, recent studies indicate that neurovascular dysfunction is an integral part of AD. The transforming growth factor beta (TGF-beta) is a key molecular factor involved in cerebrovascular dysfunction and in various pathological aspects of AD. The objectives of this project are: 1) to characterize changes of TGF-beta signaling in brain endothelial cells during aging and in mouse models of AD. 2) determine the functional effects of modulating TGF-beta signaling in these models, using a novel small molecule TGF-beta pathway activator and other unique tools developed by our labs. Major accomplishments:1) Developed genetic mouse models and viral approaches to study TGF-beta signaling specifically in brain endothelial cells.2) Demonstrated that loss of TGF-beta signaling specifically in brain endothelial cells impairs endothelial and neurovascular function, while activation of TGF-beta signaling in brain endothelial cells improves neurovascular function and attenuates brain pathology in aging and in mouse models of AD.3) Further developed Compound 381 (C381), a novel small molecule TGF-beta pathway activator.4) Performed an "overdose" CRISPRi Screen and identified factors associated with lysosomal acidification and autophagy as the potential molecular target of C381.5) Demonstrated that C381 increases lysosomal proteolysis and protects lysosomes from LLOME damage.6) Demonstrated that C381 improves cognition and reduces pathology in APP751LonSwe-transgenic mice, a mouse model of AD.7) Developed a vessel isolation and nuclei extraction for sequencing (VINE-seq) to profile the major vascular and perivascular cell types of the mouse and human brain. 8) Identified brain-region- and species-enriched genes and pathways in human AD brains and in mouse models of AD. This work not only shows that TGF-beta signaling is reduced in brain endothelial cells in human AD brains and in Alzheimer model mice, but also uncovers the molecular basis of the human and mouse brain vasculature, which will inform our understanding of AD and therapy.Potential impacts:The main findings from this project demonstrate that the loss of TGF-beta signaling during aging and Alzheimer's disease impairs endothelial and neurovascular function, contributing to disease pathology, and importantly, reversing this loss in signaling has therapeutic potential. They will open new avenues in therapeutic development, as well as improve our mechanistic knowledge of this complex and poorly understood disease.Excitingly, our work has produced a promising drug candidate for the treatment of neurodegenerative diseases. We developed C381, a first-in-class compound capable of activating TGF-beta signaling and restoring lysosomal function. C381 has the potential both as a therapeutic and as a research compound to better understand TGF-beta signaling and lysosomal function. Of note, all IND-enabling (Investigational New Drug Application) toxicology studies for C381 have been completed, showing no major concerns. It is our hope to push C381 into clinical trials in the near future, where it can serve as a first-in-class drug for neurodegenerative conditions with lysosomal pathology and help pave the way for other molecules of its kind.
IRS990/ProgSrvcAccomActy3Grp/ExpenseAmt0836486
IRS990/ProgSrvcAccomActyOtherGrp/Desc0PAVIR is privileged to work with a large community of uniquely talented medical researchers across a broad spectrum of research areas as we fulfill our mission of advancing Veterans and public health through innovative research. The range of research activities is broad and includes special emphasis on major disease categories, all of which are prevalent in the VA's patient population. These include cardiovascular medicine, mental health, chronic inflammatory disease, stem cell/regenerative medicine, pain, sleep disorders, and many others. In addition to disease specific research, PAVIR is engaged in supporting research aimed at enhancing health care. PAVIR's research portfolio includes comparative studies in which research teams are learning which treatments are superior to others, how to augment or improve standard of care, as well as how to enhance the operation of health care. Furthermore, PAVIR is supporting educational activities, especially in areas of advancing clinical care for Veterans and fostering the professional development of our expert staff.
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