[Federal Register Volume 87, Number 57 (Thursday, March 24, 2022)]
[Notices]
[Pages 16750-16753]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-06247]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Office of the Secretary


Findings of Research Misconduct

AGENCY: Office of the Secretary, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: Findings of research misconduct have been made against Hui 
(Herb) Bin Sun, Ph.D. (Respondent), formerly Professor of Orthopedic 
Surgery and Radiation Oncology, Albert Einstein College of Medicine 
(AECM). Respondent engaged in research misconduct in research supported 
by U.S. Public Health Service (PHS) funds, specifically National 
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 
National Institutes of Health (NIH), grant R01 AR050968 and National 
Heart, Lung, and Blood Institute (NHLBI), NIH, grant P01 HL110900. The 
administrative actions, including supervision for a period of twelve 
(12) years, were implemented beginning on March 1, 2022, and are 
detailed below.

FOR FURTHER INFORMATION CONTACT: Wanda K. Jones, Dr.P.H., Acting 
Director, Office of Research Integrity, 1101 Wootton Parkway, Suite 
240, Rockville, MD 20852, (240) 453-8200.

SUPPLEMENTARY INFORMATION: Notice is hereby given that the Office of 
Research Integrity (ORI) has taken final action in the following case:
    Hui (Herb) Bin Sun, Ph.D., Albert Einstein College of Medicine: 
Based on the report of an investigation conducted by AECM and analysis 
conducted by ORI in its oversight review, ORI found that Dr. Sun, 
formerly Professor of Orthopedic Surgery and Radiation Oncology, AECM, 
engaged in research misconduct in research supported by PHS funds, 
specifically NIAMS, NIH, grant R01 AR050968 and NHLBI, NIH, grant P01 
HL110900.
    ORI found that Respondent engaged in research misconduct by 
intentionally, knowingly, or recklessly falsifying and/or fabricating 
data included in sixteen (16) grant applications submitted for PHS 
funds:
    <bullet> R01 AR065563-01, ``CITED2 and Chondroprotection,'' 
submitted to NIAMS, NIH, on 02/05/2013.

[[Page 16751]]

    <bullet> R01 AR066009-01, ``Remote Loading for Osteoarthritis,'' 
submitted to NIAMS, NIH, on 06/04/2013.
    <bullet> R01 AR065563-01A1, ``CITED2 and Chondroprotection,'' 
submitted to NIAMS, NIH, on 11/05/2014.
    <bullet> R41 AR070695-01, ``A novel product for tendinopathy 
treatment,'' submitted to NIAMS, NIH, on 01/05/2015.
    <bullet> R01 AG069693-01, ``Chondrocyte fate regulation and 
cartilage protection,'' submitted to National Institute on Aging (NIA), 
NIH, on 06/05/2015.
    <bullet> R01 AG039561-06, ``Human tendon stem progenitor cell aging 
and regeneration,'' submitted to NIA, NIH, on 03/15/2016 (original 
grant funding from 08/15/2012-04/30/2018).
    <bullet> R43 AT009414-01, ``A novel nutraceutical drug for 
tendinopathy treatment,'' submitted to National Center for 
Complementary and Alternative Medicine (NCCAM), NIH, on 04/05/2016.
    <bullet> R01 AR070431-01A1, ``The role of Panx1 in the pathogenesis 
and pain of osteoarthritis,'' submitted to NIAMS, NIH, on 07/19/2016.
    <bullet> R41 AG056246-01A1, ``A novel product for tendinopathy 
treatment,'' submitted to NIA, NIH, on 09/06/2016, funded from 09/15/
2017-08/31/2019.
    <bullet> R01 AG056623-01, ``Chondrocyte fate regulation and 
osteoarthritis,'' submitted to NIA, NIH, on 10/05/2016.
    <bullet> R01 AR072038-01, ``MSC-derived exosomes and tendon 
disorders,'' submitted to NIAMS, NIH, on 10/05/2016.
    <bullet> R43 AT009414-01A1, ``A novel nutraceutical drug for 
tendinopathy treatment,'' submitted to NCCAM, NIH, on 04/05/2017, 
funded from 08/01/2018-07/31/2020.
    <bullet> R01 AR073194-01, ``Chondrocyte fate regulation and 
cartilage protection,'' submitted to NIAMS, NIH, on 06/05/2017.
    <bullet> R01 AR074802-01, ``The role of Panx1 in the pathogenesis 
and pain of osteoarthritis,'' submitted to NIAMS, NIH, on 04/02/2018.
    <bullet> R01 AR074802-01A1, ``The role of Panx1 in the pathogenesis 
and pain of osteoarthritis,'' submitted to NIAMS, NIH, on 08/01/2018.
    <bullet> R44 AG065089-01, ``Botanical drug for spontaneous 
osteoarthritis,'' submitted to NIA, NIH, on 01/07/2019.
    ORI found that Respondent intentionally, knowingly, or recklessly 
reported falsified and/or fabricated Western blot and histological 
image data for chronic deep tissue conditions including osteoarthritis 
(OA) and tendinopathy in murine models. Respondent included image data 
that were falsely reused and relabeled as data representing different 
experiments in fifty (50) figures included in sixteen (16) PHS grant 
applications. In the absence of reliable image data, the figures, 
quantitative data in associated graphs purportedly derived from those 
images, statistical analyses, and related text also are false.
    Specifically, ORI found that:
    1. Respondent reported falsified Western blot images from the same 
source that were reused and relabeled to represent different proteins 
and/or experimental results in:
    <bullet> Figure 4B in R01 AR065563-01 and R01 AR065563-01A1 and 
Figure 11 in R01 AR069693-01, specifically:

-- ``[beta]-actin'' panel for ``Cartilage'' and ``[beta]-actin'' panel 
for ``Liver'' are the same
-- ``[beta]-actin'' panel for ``Bone'' and ``[beta]-actin'' panel for 
``Spleen'' are the same
-- ``Cited2'' blot band for Cartilage in ``WT'' and ``Sham'' are the 
same
-- ``Cited2'' blot band for Bone in ``WT'' and ``Sham'' are the same
-- ``Cited2'' blot band for Liver in ``WT'' and ``Sham'' are the same
-- ``Cited2'' blot band for Spleen in ``WT'' and ``Sham'' are the same

    <bullet> Figure 2A in R01 AG056623-01 and R44 AG065089-01 and 
Figure 1A in R01 AR073194-01, specifically:

--``[beta]-actin'' panel for ``Cartilage'' and ``[beta]-actin'' panel 
for ``Liver'' are the same
--Cited2 blot bands in ``WT'' and ``Sham'' within each of the three 
panels represent Cartilage, Bone, and Liver

    2. Respondent reported falsified Western blot data by copying blot 
panels representing rAAV-vector and rAAV-GFP in human cartilage 
explants from Figure 11C in R01 AR065563-01 and Figure 16 in R01 
AR066009-01 and manipulating and relabeling the same panels to 
represent ``Sham'' and ``KO'' samples in conditional knock out of 
Cited2 gene in cartilage of adult mice in:

<bullet> Figure 4B in R01 AR065563-01
<bullet> Figure 4B in R01 AR065563-01A1
<bullet> Figure 11 in R01 AR069693-01
<bullet> Figure 2A in R01 AG056623-01
<bullet> Figure 1A in R01 AR073194-01
<bullet> Figure 2A in R44 AG065089-01

    3. Respondent reported falsified photomicrographs of supraspinatus 
tendon tissue from tendinopathy rats exposed to different experimental 
conditions that were reused and relabeled in:

<bullet> Figure 2A in R01 AR072038-01 to falsely represent overuse 
tendinopathy in rats treated with ex-ADSC-2D (control exosomes)
<bullet> Figure 2A in R01 AG039561-06 to falsely represent overuse 
tendinopathy nude rats with placebo treatment
<bullet> Figure 4A in R41 AR070695-01 to falsely represent overuse 
tendinopathy nude rats with placebo treatment
<bullet> Figure 3A in R43 AT009414-01 and R43 AT009414-01A1 to falsely 
represent collagenase induced Achilles tendinopathy in rats with 
placebo treatment

    4. Respondent reported falsified photomicrographs that were reused 
and relabeled in:

<bullet> Figure 2A in R01 AR072038-01 to falsely represent overuse 
tendinopathy in rats injected with ex-ADSC-3D
<bullet> Figure 1A in R01 AG039561-06 to falsely represent collagenase-
induced tendinopathy in rats injected with Cited2 reprogrammed tendon 
stem/progenitor cells (TSPCs)

    5. Respondent reported falsified photomicrographs that were reused 
and relabeled from Figure 2C in R01 AR072038-01 representing cleaved 
collagen-1 stained supraspinatus tendon of overuse tendinopathy rats 
injected with placebo + ex-ADSC-2D (control exosomes) to falsely 
represent:

<bullet> Supraspinatus tendon tissue of overuse tendinopathy in rats 
after placebo injection in:
    --Figure 2C in R01 AR072038-01
    --Figure 5D in R41 AG056246-01A1
    --Figure 2B in R01 AG039561-06
<bullet> Achilles tendon tissue of collagenase-induced tendinopathy 
rats after placebo injection in Figure 3D in R43 AT009414-01

    6. Respondent falsified photomicrographs of human cartilage 
explants presented in R01 AG069693-01 that were reused and relabeled, 
specifically:

<bullet> Figure 12A representing NITEGE in non-arthritic (non-OA) 
sample in:
    --Figure 11A in R01 AR065563-01, Figure 8A in R01 AG069693-01, and 
Figure 1A in R01 AG056623 to falsely represent NITEGE stained non-OA 
sample
    --Figure 3 in R01 AR070431-01A1 to falsely represent IL-1[beta] 
stained OA sample
<bullet> Figure 8A representing ADAMTS5 in non-OA and OA samples in:
    --Figure 1A in R01 AG056623-01 to falsely represent p16 stained 
samples
<bullet> Figure 8A, two images representing matrix metalloproteinase 13 
(MMP-13) and ADAMTS5 of OA samples in:
    --Figure 3 in R01 AR070431-01A1 to

[[Page 16752]]

falsely represent NLRP3 or cleaved caspase 1
    --Figure 1A in R01 AG056623-01 to falsely represent p21 and p16
<bullet> Figure 8B, two images in sham or destabilization of the medial 
meniscus (DMM) operated mouse representing:
    --MMP-13 reused and relabeled in Figure 1B in R01 AG056623-01 to 
falsely represent p21
    --ADAMTS5 reused and relabeled in Figure 1B in R01 AG056623-01 to 
falsely represent p16

    7. Respondent reported falsified photomicrographs of non-OA or OA 
human cartilage explants presented in Figure 3 in R01 AR070431-01A1 
that were reused and relabeled representing:

<bullet> Cleaved caspase 3 to falsely represent [beta]-gal staining in 
Figure 1A in R01 AG056623-01
<bullet> NLRP3 or cleaved caspase-1 staining of non-OA human cartilage 
to falsely represent p21 and p16 in Figure 1A in R01 AG056623-01

    8. Respondent reported falsified photomicrographs from the 
following published papers that were reused and relabeled to falsely 
represent unrelated experimental results in NIH grant applications:
    <bullet> Green tea polyphenol treatment is chondroprotective, anti-
inflammatory and palliative in a mouse post-traumatic osteoarthritis 
model. Arthritis Res Ther. 2014 Dec 17;16(6):508; doi: 10.1186/sl3075-
014-0508-y (hereafter referred to as ``Arthritis Res Ther. 2014''). 
Erratum in: Arthritis Res Ther. 2019, Jan 3;21(1):1; doi: 10.1186/
s13075-018-1791-9.
    <bullet> Curcumin slows osteoarthritis progression and relieves 
osteoarthritis-associated pain symptoms in a post-traumatic 
osteoarthritis mouse model. Arthritis Res Ther. 2016 Jun 3; 18(1):128; 
doi: 10.1186/s13075-016-1025-y (hereafter referred to as ``Arthritis 
Res Ther. 2016'').
    <bullet> Procyanidins Mitigate Osteoarthritis Pathogenesis by, at 
Least in Part, Suppressing Vascular Endothelial Growth Factor 
Signaling. Int. J. Mol. Sci. 2016, 17:2065; doi:10.3390/ijms17122065 
(hereafter referred to as ``Int. J. Mol. Sci. 2016'').
    Specifically, in:

<bullet> R01 AR070431-01A1, Respondent reported a falsified image panel 
that was reused and relabeled from:
--Arthritis Res Ther. 2016:
[ssquf] Figure 6A representing type II collagen cleavage epitope (Col2-
3/4 M) vehicle control to falsely represent aggrecan cleavage in DMM WT 
in Figure 2E in R01 AR070431-01A1
[ssquf] Figure 6D representing ADAMTS5 staining of a vehicle control 
twice in Figure 2F in R01 AR070431-01A1 to falsely represent IL-1[beta] 
and cleaved caspase staining
--Arthritis Res Ther. 2014:
[ssquf] Figure 2C representing Col2-3/4 M in vehicle treated sham 
operated mice twice in Figures 2E and 2F in R01 AR070431-01A1 to 
falsely represent cleaved caspase and IL-1[beta] respectively in sham 
operated WT mice
[ssquf] Figure 2C representing Col2-3/4 M in epigallocatechin3-gallate 
(EGCG) treated DMM mice in Figure 2E in R01 AR070431-01A1 to falsely 
represent Col2-3/4 M in Panx1 KO DMM mice
[ssquf] Figure 3A representing cleaved aggrecan in sham operated EGCG 
treated mice in Figure 2E in R01 AR070431-01A1 to falsely represent 
cleaved aggrecan in sham operated untreated WT mice
[ssquf] Figure 3C representing cleaved aggrecan in DMM WT mice treated 
with EGCG in Figure 2E in R01 AR070431-01A1 to falsely represent 
cleaved aggrecan in DMM Panx1 KO mice
[ssquf] Figure 4A representing MMP-13 in sham operated EGCG treated 
mice in Figure 4E in R01 AR070431-01A1 to falsely represent antibody-
staining control
[ssquf] Figure 4C representing MMP-13 in sham operated, vehicle treated 
mice in:
    [rtarr8]Figure 2E in R01 AR074802-01 and R01 AR074802-01A1 to 
falsely represent ADAMTS5 staining in Pax1 KO DMM mice
    [rtarr8]Figure 2F in R01 AR074802-01 and R01 AR070431-01A1 to 
falsely represent NLRP3 staining of Pax1 KO DMM
[ssquf] Figure 4C representing MMP-13 in DMM vehicle treated mice in:
    [rtarr8]Figure 2E in R01 AR074802-01 and R01 AR074802-01A1 to 
falsely represent MMP-13 in DMM WT mice
    [rtarr8]Figure 2F in R01 AR074802-01 and R01 AR070431-01A1 to 
falsely represent NLRP3 in DMM WT mice
[ssquf] Figure 5C representing ADAMTS5 in sham operated EGCG treated 
mouse twice in Figures 2E in R01 AR074802-01 and R01 AR074802-01A1 to 
falsely represent ADAMTS5 in sham operated WT mice
[ssquf] Figure 5C representing ADAMTS5 in vehicle treated DMM operated 
mouse sample twice in Figures 2E in R01 AR074802-01 and R01 AR074802-
01A1 to falsely represent ADAMTS5 in DMM WT mouse sample
[ssquf] R01 AG056623-01, Respondent reported a falsified image panel 
that was reused and relabeled from:
--Int. J. Mol. Sci. 2016:
[ssquf] Figure 1A representing cartilage from ``sham'' wildtype C57BL/6 
mice treated with oral PBS in Figure 2B in R01 AG056623-01 to represent 
knee cartilage from ``sham'' Col2a1CreERTxCited2fl/fl mice injected 
with corn oil without tamoxifen
--Arthritis Res Ther. 2014:
[ssquf] Figure 4A representing MMP-13 in vehicle-treated mice 4-weeks 
post DMM surgery in:
    [rtarr8] Figure 8 in R01 AG056623-01 to falsely represent p21 in 
control mice following DMM surgery
    [rtarr8] Figure 3 in R01 AG056623-01 to falsely represent [beta]-
gal in Cited2 KO mice
[ssquf] Figure 4A representing MMP-13 in EGCG -treated mice 4-weeks 
post DMM surgery Figure 8 in R01 AG056623-01 to falsely represent p21 
following DMM surgery in mice overexpressing Cited2
[ssquf] Figure 4C representing MMP-13 in vehicle-treated mice 8-weeks 
post sham surgery in Figure 2C in R01 AG056623-01 to falsely represent 
p21 staining in Cited2 KO mice following DMM surgery
[ssquf] Figure 4C representing MMP-13 in in EGCG-treated mice 8-weeks 
post DMM surgery in Figure 2C in R01 AG056623-01 to falsely represent 
p21 in oil-injected control mice for Cited2 was conditionally deleted 
in cartilage by injection of corn oil without Tamoxifen
[ssquf] Figure 5A representing ADAMTS5 in vehicle-treated DMM-induced 
OA mice in:
    [rtarr8] Figure 8 in R01 AG056623-01 to falsely represent p16 in 
control mice following DMM surgery
    [rtarr8] Figure 2C in R01 AG056623-01 to falsely represent [beta]-
gal in Cited2 KO mice
    [rtarr8] Figure 3 in R01 AG056623-01 to falsely represent [beta]-
gal in WT control mice with conditional deletion of Cited2 in cartilage
[ssquf] Figure 5C representing ADAMTS5 in vehicle-treated DMM-induced 
OA mice in:
    [rtarr8] Figure 8 in R01 AG056623-01 to falsely represent Cited2 in 
Cited-overexpressing mice as well as [beta]-gal in control mice 
following DMM surgery
    [rtarr8] Figure 2C in R01 AG056623-01 to falsely represent p16 
staining in Cited2 KO mice
    [rtarr8] Figure 8 in R01 AG056623-01 to falsely represent p16 in 
control mice following DMM surgery

    Respondent neither admits nor denies ORI's findings of research 
misconduct.

[[Page 16753]]

The parties entered into a Voluntary Settlement Agreement (Agreement) 
to conclude this matter without further expenditure of time, finances, 
or other resources. The settlement is not an admission of liability on 
the part of the Respondent.
    Respondent voluntarily agreed to the following:
    (1) Respondent will have his research supervised for a period of 
twelve (12) years beginning on March 1, 2022 (the ``Supervision 
Period''). Prior to the submission of an application for PHS support 
for a research project on which Respondent's participation is proposed 
and prior to Respondent's participation in any capacity in PHS-
supported research, Respondent will submit a plan for supervision of 
Respondent's duties to ORI for approval. The supervision plan must be 
designed to ensure the integrity of Respondent's research. Respondent 
will not participate in any PHS-supported research until such a 
supervision plan is approved by ORI. Respondent will comply with the 
agreed-upon supervision plan.
    (2) The requirements for Respondent's supervision plan are as 
follows:
    i. A committee of 2-3 senior faculty members at the institution who 
are familiar with Respondent's field of research, but not including 
Respondent's supervisor or collaborators, will provide oversight and 
guidance. The committee will review primary data from Respondent's 
laboratory on a quarterly basis and submit a report to ORI at six (6) 
month intervals setting forth the committee meeting dates and 
Respondent's compliance with appropriate research standards and 
confirming the integrity of Respondent's research.
    ii. The committee will conduct an advance review of each 
application for PHS funds, or report, manuscript, or abstract involving 
PHS-supported research in which Respondent is involved. The review will 
include a discussion with Respondent of the primary data represented in 
those documents and will include a certification to ORI that the data 
presented in the proposed application, report, manuscript, or abstract 
is supported by the research record.
    (3) During the Supervision Period, Respondent will ensure that any 
institution employing him submits, in conjunction with each application 
for PHS funds, or report, manuscript, or abstract involving PHS-
supported research in which Respondent is involved, a certification to 
ORI that the data provided by Respondent are based on actual 
experiments or are otherwise legitimately derived and that the data, 
procedures, and methodology are accurately reported in the application, 
report, manuscript, or abstract.
    (4) If no supervision plan is provided to ORI, Respondent will 
provide certification to ORI at the conclusion of the Supervision 
Period that his participation was not proposed on a research project 
for which an application for PHS support was submitted and that he has 
not participated in any capacity in PHS-supported research.
    (5) During the Supervision Period, Respondent will exclude himself 
voluntarily from serving in any advisory or consultant capacity to PHS 
including, but not limited to, service on any PHS advisory committee, 
board, and/or peer review committee.

    Dated: March 21, 2022.
Wanda K. Jones,
Acting Director, Office of Research Integrity, Office of the Assistant 
Secretary for Health.
[FR Doc. 2022-06247 Filed 3-23-22; 8:45 am]
BILLING CODE 4150-31-P