[Federal Register Volume 79, Number 80 (Friday, April 25, 2014)]
[Notices]
[Pages 22973-22975]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-09434]


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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: Notice is hereby given that the Office of Research Integrity 
(ORI) has taken final action in the following case:
    Li Chen, Ph.D., Mount Sinai School of Medicine: Based on evidence 
and findings of an investigation report by Mount Sinai School of 
Medicine (MSSM) transmitted to the United States Department of Health 
and Human Services (HHS), Office of Research Integrity (ORI), in April 
2010 and additional analysis conducted by ORI in its oversight review, 
ORI found that Dr. Li Chen, former Postdoctoral Fellow, Department of 
Gene and Cell Medicine, MSSM, engaged in research misconduct in 
research that was supported by National Institute of Diabetes and 
Digestive and Kidney Diseases (NIDDK), National Institutes of Health 
(NIH), grant R01 DK062972 and National

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Institute of General Medical Sciences (NIGMS), NIH, grant P20 GM075019 
and was submitted in grant applications R01 DK074695 and R01 DK083286 
to NIDDK, NIH, P20 GM075019 to NIGMS, NIH, and R01 NS062054 to the 
National Institute of Neurological Disorders and Stroke (NINDS), NIH.
    ORI found that the Respondent intentionally, knowingly, and 
recklessly fabricated and falsified data reported in four (4) 
publications, one (1) submitted manuscript, and four (4) grant 
applications:
     Chen, L., & Woo, S.L.C. ``Complete and persistent 
phenotypic correction of phenylketonuria in mice by site-specific 
genome integration of murine phenylalanine hydroxylase cDNA.'' Proc. 
Natl. Acad. Sci. U.S.A. 102(43):15581-15586, October 2005 (hereafter 
referred to as ``PNAS 2005'').
     Chen, L., Thung, S.N., & Woo, S.L.C. ``Metabolic Basis of 
Sexual Dimorphism in PKU Mice After Genome-targeted PAH Gene Therapy.'' 
Mol. Ther. 15:1079-1085, June 2007; Retracted in December 2010 
(hereafter referred to as ``Mol. Ther. June 2007'').
     Chen, L., & Woo, S.L.C. ``Correction in Female PKU Mice by 
Repeated Administration of mPAH cDNA Using phiBT1 Integration System.'' 
Mol. Ther. 15:1789-1795, October 2007; Retracted in December 2010 
(hereafter referred to as ``Mol. Ther. Oct. 2007'').
     Chen, L., & Woo, S.L.C. ``Site-Specific Transgene 
Integration in the Human Genome Catalyzed by [Ouml]BT1 Phage 
Integrase.'' Hum. Gene Ther. 19:143-151, February 2008; Retracted in 
August 2010 (hereafter referred to as ``HGT 2008'').
     Chen, L., Roy, I., Prasad, P.N., & Woo, S.L.C. 
``Nanoparticle-Based Gene Therapy for Metabolic Disorders: Hepatic 
Delivery of Minicircle DNA for Complete Correction of 
Phenylketonuria.'' Submitted for publication in Proc. Natl. Acad. Sci. 
U.S.A. (hereafter referred to as the ``PNAS 2008 manuscript'').
     R01 DK074695, ``Genome-targeted PAH Gene Integration in 
PKU Mice and Sexual Dimorphism,'' Savio L.C. Wood, Ph.D., Principal 
Investigator (P.I.) (hereafter referred to as ``R01 DK074695'').
     P20 GM075019, ``Growth, Differentiation & Genetic 
Alteration of Human ES Cells,'' Gordon M. Keller, Ph.D., P.I. 
(hereafter referred to as ``P20 GM075019'').
     R01 NS062054, ``Nanoparticle-medicated Gene Therapy for 
PKU,'' Savio L. Woo, Ph.D., P.I. (hereafter referred to as ``R01 
NS062054'').
     R01 DK083285, ``Nanoparticle-Mediated Gene Therapy PKU,'' 
Savio L. Woo, Ph.D., P.I. (hereafter referred to as ``R01 DK083285'').
    The Respondent fabricated figures reporting the chromosomal 
locations of integration sites, fabricated data reporting the use of 
polymerase chain reaction (PCR) to determine integration frequencies, 
falsified data representing the detection of chromosomal translocations 
in human cells, and fabricated figures by falsely reporting the results 
of High-Performance Liquid Chromatography (HPLC) assays. The Respondent 
also falsified experimental data for LacZ stained liver sections and 
for hematoxylin and eosin (H&E) stained liver sections.
    Specifically, ORI finds by a preponderance of the evidence that the 
Respondent engaged in misconduct in science and research misconduct by 
intentionally, knowingly, and recklessly:
    1. fabricating and/or falsifying nineteen (19) figures by falsely 
reporting that phenylketonuria (PKU) gene therapy experiments were 
successfully completed, when the available evidence shows the 
experiments were not performed; specifically the Respondent:
    (a) fabricated figures where DNA sequencing was purportedly used to 
identify the chromosomal locations of integration sites for the PAH 
gene in mouse and human cells, reported in seven (7) figures:
     PNAS 2005, Figure 2A
     HGT 2008, Figures 3b and 3c
     R01 NS062054, Figures 3 and 20
     R01 DK074695, Figure 6
     R01 DK083286, Figure 17
     P20 GM075019, Figure 4
    (b) fabricated data purportedly representing the use of PCR to 
determine integration frequencies for the phenylalanine hydroxylase 
(PAH) gene and the secreted embryonic alkaline phosphatase (SEAP) 
reporter gene, in mouse and human cells, reported in eleven (11) 
figures:
     PNAS 2005, Figures 2C and 3B
     Mol. Ther. June 2007, Figures 2a and 5a
     Mol. Ther. Oct. 2007, Figures 2d and 5a
     HGT 2008, Figure 4
     R01 NS062054, Figures 4b and 10a
     R01 DK074695, Figure 7b
     R01 DK083286, Figure 2b
    (c) falsified figures representing the detection of chromosomal 
tranlocations in human cells, purportedly determined by PCR in two (2) 
figures:
     HGT 2008, Figure 5a
     R01 NS062054, Figure 21a
    2. fabricating the results of HPLC assays to show generally lowered 
blood levels of phenylalanine after PKU gene therapy and to show liver 
levels of BH4 when the Respondent did not have the HPLC data 
needed to support those claims; specifically the Respondent:
    (a) fabricated serum phenylalanine graphs in:
     PNAS 2005, Figure 4B; this false data also is presented in 
R01 DK074695, Figure 10b
     Mol. Ther. June 2007, Figure 1a; this false data also is 
presented in R01 DK074695, Figure 11
     R01 DK083286, Figure 3; this false data also is presented 
in Mol. Ther. June 2007, Figure 3, and R01 NS062054, Figure 7
     Mol. Ther. Oct. 2007, Figure 4a; this false data also is 
presented in R01 NS062054, Figure 9a
     PNAS 2008 manuscript, Figure 4
    (b) fabricated graphs for BH4 levels in:
     Mol. Ther. June 2007, Figure 5c; this false data also is 
presented in R01 NS062054, Figure 8c
    3. falsely reporting the results of LacZ stained liver sections by 
reusing and relabeling an image and claiming that it represents 
different experiments; specifically, the same image was used to 
represent mice treated with a nanoplex gene delivery system in R01 
NS062054, Figure 14b (right panel), and also to represent a wholly 
different experiment for mice treated with 10 injections of the phiBT1 
integrase system alone in R01 NS062054, Figure 4c (right panel), and 
Mol. Ther. Oct. 2007, Figure 2b (D panel)
    4. falsely reporting the results of H&E stained liver sections in 
R01 NS062054, Figure 6, by using the identical image to represent four 
(4) different experimental treatments of H&E stained liver sections; 
specifically the Respondent reused and relabeled one image to represent 
liver sections from mice that received either 1 or 10 injections, with 
or without the phiBT1 integrase plasmid.
    The Respondent failed to take responsibility for the fabrication 
and falsification described in ORI's findings.
    The following administrative actions have been implemented for a 
period of three (3) years, beginning on April 11, 2014:
    (1) Respondent is debarred from any contracting or subcontracting 
with any agency of the United States Government and from eligibility 
for, or involvement in, nonprocurement programs of the United States 
Government referred to as ``covered transactions'' pursuant to HHS' 
Implementation (2 CFR part 376 et seq.) of Office of Management and 
Budget (OMB) Guidelines to Agencies on Governmentwide Debarment and 
Suspension, 2 CFR part 180 (collectively the ``Debarment 
Regulations''); and
    (2) Respondent is prohibited from serving in any advisory capacity 
to PHS,

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including but not limited to service on any PHS advisory committee, 
board, and/or peer review committee, or as a consultant.

FOR FURTHER INFORMATION CONTACT: Acting Director, Office of Research 
Integrity, 1101 Wootton Parkway, Suite 750, Rockville, MD 20852, (240) 
453-8800.

Donald Wright,
Acting Director, Office of Research Integrity.
[FR Doc. 2014-09434 Filed 4-24-14; 8:45 am]
BILLING CODE 4150-31-P