[Federal Register Volume 89, Number 70 (Wednesday, April 10, 2024)]
[Notices]
[Pages 25273-25275]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-07575]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Office of the Secretary


Findings of Research Misconduct

AGENCY: Office of the Secretary, HHS.

ACTION: Notice.

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SUMMARY: Findings of research misconduct have been made against Gian-
Stefano Brigidi, Ph.D. (Respondent), who was a Postdoctoral Fellow, 
Department of Neurobiology, University of California San Diego (UCSD), 
and was an Assistant Professor, Department of Neurobiology, University 
of Utah (UU). Respondent engaged in research misconduct in research 
supported by U.S. Public Health Service (PHS) funds, specifically 
National Institute of Mental Health (NIMH), National Institutes of 
Health (NIH), grant F32 MH110141, National Human Genome Research 
Institute (NHGRI), NIH, grant T32 HG000044, National Institute of 
Neurological Disorders and Stroke (NINDS), NIH, grant P30 NS047101, and 
National Library of Medicine (NLM), NIH, grant T15 LM011271. The 
research was included in grant applications submitted for PHS funds, 
specifically R01 NS131809-01, R01 NS133405-01, DP2 NS127276-01, and R01 
NS111162-01A1 submitted to NINDS, NIH, and R21 MH121860-01, R21 
MH121860-01A1, F32 MH110141-01, F32 MH110141-01A1, and F32 MH110141-
01AS1 submitted to NIMH, NIH. The administrative actions, including 
supervision for a period of five (5) years, were implemented beginning 
on March 24, 2024, and are detailed below.

FOR FURTHER INFORMATION CONTACT: 
Sheila Garrity, JD, MPH, MBA, 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:
    Gian-Stefano Brigidi, Ph.D., University of California San Diego 
(UCSD) and University of Utah (UU): Based on the report of an 
assessment conducted by UU, and inquiry conducted by UCSD, the 
Respondent's admission, and additional analysis conducted by ORI in its 
oversight review, ORI found that Dr. Gian-Stefano Brigidi, former 
Postdoctoral Fellow in the Department of Neurobiology, UCSD, and former 
Assistant Professor, Department of Neurobiology, UU, engaged in 
research misconduct in research supported by PHS funds, specifically 
NIMH, NIH, grant F32 MH110141, NHGRI, NIH, grant T32 HG000044, NINDS, 
NIH, grant P30 NS047101, and NLM, NIH, grant T15 LM011271. The research 
was included in grant applications submitted for PHS funds, 
specifically R01 NS131809-01, R01 NS133405-01, DP2 NS127276-01, and R01 
NS111162-01A1 submitted to NINDS, NIH, and R21 MH121860-01, R21 
MH121860-01A1, F32 MH110141-01, F32 MH110141-01A1, and F32 MH110141-
01AS1 submitted to NIMH, NIH.
    ORI found that Respondent engaged in research misconduct by 
knowingly or intentionally falsifying and/or fabricating data and 
results by manipulating primary data values to falsely increase the n-
value, manipulating fluorescence micrographs and their quantification 
graphs to augment the role of ITFs in murine hippocampal neurons, and/
or

[[Page 25274]]

manipulating confocal images that were obtained through different 
experimental conditions in twenty (20) figures of one (1) published 
paper and four (4) PHS grant applications, one (1) panel of one (1) 
poster, and seven (7) slides of one (1) presentation:
     Genomic Decoding of Neuronal Depolarization by Stimulus-
Specific NPAS4 Heterodimers. Cell. 2019 Oct 3;179(2):373-391.e27. doi: 
10.1016/j.cell.2019.09.004 (hereafter referred to as ``Cell 2019'').
     Genomic mechanisms linking neuronal activity history with 
present and future functions. Poster for ``The Brigidi Lab--a neuronal 
activity lab in the Department of Neurobiology at the University of 
Utah'' (hereafter referred to as the ``UU Department of Neurobiology 
poster'').
     Decoding neural circuit stimuli into spatially organized 
gene regulation. Presentation presented to the UU Department of 
Neurobiology & Anatomy on January 23, 2020 (hereafter referred to as 
``UU Department of Neurobiology presentation'').
     DP2 NS127276-01, ``Decoding neuronal activity history at 
the genome through the spatially segregated inducible transcription 
factors,'' submitted to NINDS, NIH, on August 20, 2020, Awarded Project 
Dates: September 15, 2021-August 1, 2023.
     F32 MH110141-01, ``Regulation of excitatory-inhibitory 
balance by the local translation of the immediate early gene Npas4,'' 
submitted to NIMH, NIH, on August 10, 2015.
     F32 MH110141-01A1, ``Regulation of Excitatory-Inhibitory 
Balance by Local Translation of the Immediate Early Gene Npas4,'' 
submitted to NIMH, NIH, on December 8, 2015, Awarded Project Dates: 
August 1, 2016-July 31, 2018.
     F32 MH110141-01A1S1, ``Regulation of Excitatory-Inhibitory 
Balance by Local Translation of the Immediate Early Gene Npas4,'' 
submitted to NIMH, NIH, on December 8, 2016, Awarded Project Dates: 
December 1, 2016-July 31, 2017.
    The falsified and/or fabricated data also were included in twenty-
three (23) figures in the following five (5) PHS grant applications:
     R01 NS131809-01, ``Regulation and function of dendritic 
mRNA that encodes the neuronal transcription factor Npas4,'' submitted 
to NINDS, NIH, on June 6, 2022.
     R01 NS133405-01, ``Assessing the impact of the inducible 
transcription factor NPAS4 on spatial tuning in the mouse 
hippocampus,'' submitted to NINDS, NIH, on October 5, 2022.
     R01 NS111162-01A1, ``Molecular and cellular mechanisms 
underlying activity dependent gene regulation in neurons,'' submitted 
to NINDS, NIH, on March 5, 2019, Awarded Project Dates: December 15, 
2019-November 30, 2024.
     R21 MH121860-01, ``Identification of dendritically-
localized transcription factor mRNAs as a mechanism for conveying 
multiple streams of information to the nucleus,'' submitted to NIMH, 
NIH, on February 19, 2019.
     R21 MH121860-01A1, ``Identification of dendritically-
localized transcription factor mRNAs,'' submitted to NIMH, NIH, on 
March 16, 2020.
    Specifically, ORI found that:
    1. Respondent knowingly or intentionally combined two to three real 
data sets and two to five fabricated data sets to falsely increase the 
n-values reported in:
     Figures 1B, 1D, 1E, 1G, 1I, 1J, 1M-1O, 1Q-1T, S2B-S2D, 
S2F-S2H, S3I, S3L, S3M, and S6H of Cell 2019 and Slides 6-10, 13, and 
28 of the UU Department of Neurobiology presentation representing the 
quantification of NPAS4 immunohistofluorescence.
     Figures 2H, 2I, 2K, 2P, 3C, 3E, 4D-4G, 4K-4N, 4P-4Q, S3G, 
S5B, and S5C of Cell 2019 representing the quantification of Npas4 mRNA 
or puro-PLA puncta.
     Figures S1E, S1G, and S1H of Cell 2019 representing the 
quantification of whole-cell clamp recordings of CA1 PN.
     Figures 2 (lower panel) and 3c of F32 MH110141-01, Figures 
1g, 2b, 2d, and 4 of F32 MH110141-01A1S1, and Figures 1g, 2b, 2d, and 4 
of F32 MH110141-01A1 representing time points of NPAS4 quantification 
after no stimulation or post-stimulation in the alveus or radiatum SR, 
SO, SP, SLM, with or without the addition of an inhibitor.
    2. Respondent knowingly or intentionally manipulated confocal 
images that were obtained through different experimental conditions in:
     Figures 1A, 1C, and 1F of Cell 2019 and Slides 6-9 of the 
UU Department of Neurobiology presentation representing confocal images 
of hippocampal slices immunostained for NPAS4 and Neu.
     Figures S2A and S2E of Cell 2019 by manipulating and 
misrepresenting the GFP signals as NPAS4 signals in wildtype mice.
     Figures 1H, 1L, 1P, S3K, S6F, and S6G of Cell 2019 and 
Slides 9 and 28 of the UU Department of Neurobiology presentation by 
manipulating the raw images of hippocampal slices immunostained with 
NPAS4 and Neu and/or ARNT1 or ARNT2 by generating a mask of NPAS4 
immunofluorescent signal through GFP signal from tissue obtained from 
Thy1-GFP mice to intentionally enhance the appearance of the dendritic 
NPAS4 signal.
     Figures S6F and S6G of Cell 2019 by manipulating the raw 
images of hippocampus slices by overlaying a GFP channel over ARNT1 
channel and using the multiply feature in Photoshop to restrict ARNT1 
signal through GFP to enhance the ARNT1 signal in three panels.
     Slides 7, 9, and 28 of the UU Department of Neurobiology 
presentation by manipulating six images representing post-stimulation 
with different time points by using a GFP mask overlaid on top of raw 
NPAS4 immunofluorescence.
     Figure 4 of DP2 NS127276-01 and panel 1 of the UU 
Department of Neurobiology poster representing twelve images in columns 
2-4 labeled EGR, FOS, ATF4 by mislabeling the microscope images as 
immunofluorescent stained with antibodies against EGR, FOS, and ATF4 
when they actually were stained with anti-NPAS4 and selected images to 
support the immunofluorescence data in the ITF induction graphs.
     Figure 5 of DP2 NS127276-01 representing two confocal 
images in the far-right column by intentionally and selectively 
enhancing the brightness of the anti-NPAS4 immunofluorescent channel 
within the dashed box and left brightness unchanged in surrounding 
areas of the images.
     Figure 6 of DP2 NS127276-01 in twelve images in columns 2-
5 labeled Egr2, Fos, and Atf4 by intentionally mislabeling the 
microscope images as RNA in situ hybridization with probes against 
Egr2, Fos, and Atf4 when they actually were stained with NPAS4 probes 
and intentionally selecting and quantifying images in the 
quantification graphs to support the conclusions of the grant 
application.
    3. Respondent knowingly or intentionally manipulated the 
fluorescence micrographs and their quantification graphs to augment the 
role of ITFs in murine hippocampal neurons in Figures 2B-2G, 2J, 2L-2O, 
3B, 3D, 3F-3H, 4C, 4J, 4O, S1A-S1D, S1F, S1I-S1J, S3A-S3F, S3H, S3J, 
S3N-S3T, S5D-S5G, and S6A-S6E of Cell 2019; the falsified/fabricated 
data also were included in Figures 2B-2H, 3, 4B-4E, and 5C-5G of R21 
MH121860-01, Figures 2, 3B-3E, 4B-4C, 4E-4I, and 5B-5E of R21 MH121860-
01A1, Figures 3, 5, 6B, 7, 8, 10B-10D, 11A-11C, and 11E-11F in R01 
NS131809-01, Figure 8 of R01 NS133405-01, and Figures 3B-3C, 3E-3I, 4B-
4I, 5, 9, 10B-10E, and 11-12 of R01 NS111162-01A1.

[[Page 25275]]

    Respondent entered into a Voluntary Settlement Agreement 
(Agreement) and voluntarily agreed to the following:
    (1) Respondent will have his research supervised for a period of 
five (5) years beginning on March 24, 2024 (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 for a period of five (5) years from the effective date of the 
Agreement. 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 
are 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 and not plagiarized 
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.
    (6) Respondent will request that the following paper be corrected 
or retracted:
     Cell. 2019 Oct 3;179(2):373-391.e27. doi: 10.1016/
j.cell.2019.09.004.
    Respondent will copy ORI and the Research Integrity Officer at UCSD 
on the correspondence with the journal.

    Dated: April 4, 2024.
Sheila Garrity,
Director, Office of Research Integrity, Office of the Assistant 
Secretary for Health.
[FR Doc. 2024-07575 Filed 4-9-24; 8:45 am]
BILLING CODE 4150-31-P