[Federal Register Volume 87, Number 69 (Monday, April 11, 2022)]
[Notices]
[Pages 21129-21130]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-07632]


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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 Toni M. 
Brand, Ph.D. (Respondent), who was a graduate student in the Department 
of Human Oncology, University of Wisconsin-Madison (UWM), and 
subsequently a research fellow in the Department of Otolaryngology--
Head and Neck Surgery, University of California San Francisco (UCSF). 
Respondent engaged in research misconduct in research supported by U.S. 
Public Health Service (PHS) funds, specifically National Cancer 
Institute (NCI), National Institutes of Health (NIH), grants P30 
CA014520, K99 CA160639, T32 CA108462, and U54 CA209891, National Center 
for Research Resources (NCRR), NIH, grant UL1 RR025011, National Center 
for Translational Sciences (NCATS), NIH, grants U54 TR000021 and UL1 
TR000427, National Institute of General Medical Sciences (NIGMS), NIH, 
grant T32 GM081061, and National Institute of Dental and Craniofacial 
Research (NIDCR), NIH, grant R01 DE023685. The administrative actions, 
including supervision for a period of four (4) years, were implemented 
beginning on March 23, 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:
    Toni M. Brand, Ph.D., University of Wisconsin-Madison and 
University of California San Francisco: Based on the reports of 
investigations conducted by UWM and UCSF and additional analysis 
conducted by ORI in its oversight review, ORI found that Dr. Toni M. 
Brand, who was a graduate student in the Department of Human Oncology, 
UWM, and subsequently a research fellow in the Department of 
Otolaryngology--Head and Neck Surgery, UCSF, engaged in research 
misconduct in research supported by PHS funds, specifically NCI, NIH, 
grants P30 CA014520, K99 CA160639, T32 CA108462, and U54 CA209891, 
NCRR, NIH, grant UL1 RR025011, NCATS, NIH, grants U54 TR000021 and UL1 
TR000427, NIGMS, NIH, grant T32 GM081061, and NIDCR, NIH, grant R01 
DE023685.
    ORI found that Respondent engaged in research misconduct by 
knowingly or recklessly falsifying or fabricating western blot data, by 
reusing and relabeling data to represent expression of proteins in 
control experiments measuring the purity of cytoplasmic and nuclear 
cell fractionation, measurements of proteins of interest, and 
measurements of the same protein under different experimental 
conditions or loading controls, included in twenty-four (24) figures in 
the following grant application submitted to NIDCR, NIH, her Ph.D. 
Thesis Dissertation, and seven (7) published papers:
    <bullet> K99 DE027699-01, ``Targeting HPV-driven immunosuppressive 
signaling pathways in head and neck cancer,'' submitted to NIDCR, NIH, 
on June 8, 2017.
    <bullet> Ph.D. Thesis Dissertation, ``Investigations of Nuclear HER 
family receptors in cancer and resistance to cetuximab therapy,'' 
Department of Human Oncology, UWM, March 21, 2014 (hereafter referred 
to as ``Thesis'').
    <bullet> Mapping C-terminal transactivation domains of the nuclear 
HER family receptor tyrosine kinase HER3. PLoS One 2013 Aug 
8;8(8):e71518; doi: 10.1371/journal.pone.0071518. eCollection 2013 
(hereafter referred to as ``PLoS One 2013'').
    <bullet> Nuclear EGFR as a molecular target in cancer. Radiother 
Oncol. 2013 Sep;108(3):370-7; doi: 10.1016/j.radonc.2013.06.010 
(hereafter referred to as ``Radiother Oncol. 2013''). Corrected in: 
Radiother Oncol. 2019 Jan;130:195; doi: 10.1016/j.radonc.2018.10.011.
    <bullet> Nuclear epidermal growth factor receptor is a functional 
molecular target in triple-negative breast cancer. Mol Cancer Ther. 
2014 May;13(5):1356-68; doi: 10.1158/1535-7163.MCT-13-1021 (hereafter 
referred to as ``Mol Cancer Ther. 2014''). Corrected in: Mol Cancer 
Ther. 2019 Apr;18(4):868; doi: 10.1158/1535-7163.MCT-18-1183.
    <bullet> AXL mediates resistance to cetuximab therapy. Cancer Res. 
2014 Sep 15;74(18):5152-64; doi: 10.1158/0008-5472.CAN-14-0294 
(hereafter referred to as ``Cancer Res. 2014'').
    <bullet> The receptor tyrosine kinase AXL mediates nuclear 
translocation of the epidermal growth factor receptor. Sci Signal. 2017 
Jan 3;10(460):eaag1064; doi: 10.1126/scisignal.aag1064 (hereafter 
referred to as ``Sci Signal. 2017''). Retracted in: Sci Signal. 2021 
Nov 9;14(708):eabn0168; doi: 10.1126/scisignal.abn0168.
    <bullet> Human Papillomavirus Regulates HER3 Expression in Head and 
Neck Cancer: Implications for Targeted HER3 Therapy in HPV + Patients. 
Clin Cancer Res. 2017 Jun 15;23(12):3072-3083; doi: 10.1158/1078-
0432.CCR-16-2203 (hereafter referred to as ``Clin Cancer Res. 2017''). 
Corrected in: Clin Cancer Res. 2021 Jul 15;27(14):4129; doi: 10.1158/
1078-0432.CCR-21-2141.
    <bullet> Cross-talk Signaling between HER3 and HPV16 E6 and E7 
Mediates Resistance to PI3K Inhibitors in Head and Neck Cancer. Cancer 
Res. 2018 May 1;78(9):2383-95; doi: 10.1158/0008-5472.CAN-17-1672 
(hereafter referred to as ``Cancer Res. 2018'').

[[Page 21130]]

    Specifically, ORI found that Respondent knowingly or recklessly 
falsified or fabricated data in:
    <bullet> Figure 6B of Thesis and Figure 6B of PLoS One 2013 by 
reusing a Tubulin western blot panel from cytoplasmic sample to 
represent Histone H3 panel in nuclear sample
    <bullet> Figure 6, panel C, of Thesis and Figure 6C of PLoS One 
2013 by using identical Her3 western blot data to represent samples 
from different cell lines and using a Tubulin western blot panel from 
an unrelated experiment.
    <bullet> Figure 6C, inset 1, of Thesis and Figure 6C, inset 1, of 
PLoS One 2013 by inappropriately cropping the histone H3 nuclear sample 
to represent equal loading of the samples when the actual data showed 
an unequal amount.
    <bullet> Figure 6C, inset 2, of Thesis and Figure 6C, inset 2, of 
PLoS One 2013 by using identical Her3 western panel to represent 
samples from different cell lines and falsifying loading control by 
using a Cyclin D western blot panel to represent Tubulin.
    <bullet> Figure 7A and inset 2 of Thesis and Figure 7A and inset 2 
of PLoS One 2013 by using identical Her3 western panel to represent 
samples from different cell lines.
    <bullet> Figure 2B, SKBr3 inset, of Radiother Oncol. 2013 by 
representing unrelated western panel as Tubulin loading control for the 
cytoplasmic samples.
    <bullet> Figure 2B, SUM229 inset, of Radiother Oncol. 2013 by 
representing unrelated western panel as Tubulin loading control in non-
nuclear samples.
    <bullet> Figure 4B of Mol Cancer Ther. 2014 by using identical 
pSFKY419 western blot panels to represent expression in different cell 
lines.
    <bullet> Figure 2D of prpS6 western blot panel from HP cell line in 
Cancer Res. 2014 by using a western blot panel from an unrelated 
experiment.
    <bullet> Figure 1A of Sci Signal. 2017 by using identical western 
blot panels to represent Histone H3 in non-nuclear samples and Tubulin 
in nuclear samples.
    <bullet> Figure 2A of Sci Signal. 2017 by using loading control 
panels from an unrelated experiment in the HC8 experiment.
    <bullet> Figure 2C of Sci Signal. 2017 by using a panel from an 
unrelated experiment to represent histoneH3 in the nuclear samples.
    <bullet> Figure 2C inset of Sci Signal. 2017 by using a panel from 
an unrelated experiment to represent tubulin.
    <bullet> Figure 4A of Sci Signal. 2017 by reusing identical panels 
to represent tubulin (negative) control experiments.
    <bullet> Figure 5E of Sci Signal. 2017 by selective cropping and 
use of loading control panels from unrelated experiments.
    <bullet> Tubulin western blot panels in Figure 3A of K99 DE027699-
01 by reusing the same data to represent two different cell lines or 
related data to represent a different cell line.
    <bullet> Figure 3A of Clin Cancer Res. 2017 by using the identical 
western blot data to represent expression of HER3 and HER3-Y1197 in the 
SCC47 cell line.
    <bullet> Supplemental Figure 3A of Cancer Res. 2018 by using 
identical western blot data to represent pAKT-S473 and pAKT-T308 
expression in the SCC90 sample.
    <bullet> Figure 1C of Clin Cancer Res. 2017 and Figure 1B of K99 
DE027699-01 by representing the same western blot panels to represent 
E6 and E7 expression in different experiments.
    Respondent neither admits nor denies ORI's findings of research 
misconduct. 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 her research supervised for a period of 
four (4) years beginning on March 23, 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 during the Supervision Period. 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 her 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 her participation was not proposed on a research project 
for which an application for PHS support was submitted and that she has 
not participated in any capacity in PHS-supported research.
    (5) During the Supervision Period, Respondent will exclude herself 
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 papers be corrected 
or retracted:

    <bullet> PLoS One 2013 Aug 8;8(8):e71518
    <bullet> Cancer Res. 2014 Sep 15;74(18):5152-64
    <bullet> Cancer Res. 2018 May 1;78(9):2383-95

    Respondent will copy ORI and the Research Integrity Officers at UWM 
and UCSF on the correspondence with the journals.

    Dated: April 5, 2022.
Wanda K. Jones,
Acting Director, Office of Research Integrity, Office of the Assistant 
Secretary for Health.
[FR Doc. 2022-07632 Filed 4-8-22; 8:45 am]
BILLING CODE 4150-31-P