[Federal Register Volume 78, Number 68 (Tuesday, April 9, 2013)]
[Pages 21125-21126]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-08207]



Office of the Secretary

Findings of Research Misconduct

AGENCY:  Office of the Secretary, HHS.

ACTION: Notice.


SUMMARY:  Notice is hereby given that the Office of Research Integrity 
(ORI) has taken final action in the following case:
    Andrew Aprikyan, Ph.D., University of Washington: Based on the 
report of an investigation conducted by the University of Washington 
(UW), the UW School of Medicine Dean's Decision, the Decision of the 
Hearing Panel at UW, and additional analysis conducted by ORI, ORI 
found by a preponderance of the evidence that Dr. Andrew Aprikyan, 
former Research Assistant Professor, Division of Hematology, UW, 
engaged in research misconduct in research supported by National Cancer 
Institute (NCI), National Institutes of Health (NIH), grant CA89135 and 
National Institute of Diabetes and Digestive and Kidney Diseases 
(NIDDK), NIH, grant DK18951, and applies to the following publications 
and grant applications:
     Blood pre-published online on January 16, 2003 (``NEM'')
     Experimental Hematology 31:372-381, 2003 (``CMA'')
     Blood 97:147-153, 2001 (``ISB'')
     R01 CA89135-01A1
     R01 HL73063-01
     R01 HL79615-01
    Blood pre-published online on January 16, 2003, has been retracted 
and Experimental Hematology 31:372-381, 2003, has been corrected.
    Specifically, ORI finds that by a preponderance of the evidence, 
Respondent falsified and/or fabricated results relating to the above 
publications and grants. Specifically, Respondent:
    1. Falsely reported sequencing data in the NEM manuscript to 
strengthen the hypothesis that NE mutations contributed to the 
phenotype observed in severe congenital neutropenia (SCN) patients. 
    a. Respondent falsely reported in Figures 2A and 3 that patient 3 
had the R191Q neutrophil elastase (NE) mutation, when the majority of 
the sequencing experiments showed that the mutation was not present.
    b. Respondent fabricated text (p. 12) reporting that sequencing of 
RT-PCR products confirmed the expression of the NE mutants in the SCN 
patients and that no mutations were present in the granulocyte colony 
stimulating factor receptor (G-CSFR) gene and the Wiskott-Aldrich 
Syndrome (WAS) gene in SCN patients, when based on the lack of original 
records the experiments were not performed. The false claim for G-CSFR 
sequencing was also reported in CA89135-03.
    2. Falsely reported a two-fold increase in apoptosis of human 
promyelocytic (HL-60) cells transfected with NE mutants compared to 
wild type NE in Figure 4A, NEM, Figure 6A, CMA, Figure 8, HL73063-01, 
and Figure 7, HL79615-01. Respondent used arbitrary flow cytometry data 
files to generate histograms with the desired result. The false results 
supported the hypothesis that the NE mutations were sufficient for 
impaired survival of human myeloid cells.
    3. Falsified NE and [szlig]-actin Western blots in Figure 4B Blood, 
pre-published online January 16, 2003, Figure 5B of the manuscript 
initially submitted to Blood April 2002, and Figure 6B Experimental 
Hematology 31:372-381, 2003, by falsely labeling lanes to support the 
hypothesis that accelerated apoptosis in mutant NE transfect HL-60 
cells was due to the mutation and not the level of protein present. 
    a. Respondent used portions of a single NE Wester blot to 
represent: Figure 4B as HL-60 cells transfected with L92H, R191Q, and 
wtNE, when the cells were transfected with R191Q, P110L, and D145-152; 
Figure 5B as HL-60 transfected with wtNE, mutNE, and EGFP when they 
were cells transfected with NE mutants, P110L, D145-152, and 194
    b. Respondent used portions of a single [szlig]-actin Western blot 
to represent: Figure 4B as HL-60 cells transfected

[[Page 21126]]

with L92H, R191Q, and wtNE, when they were cells transfected with I31T, 
P110L, and G185R mutants; Figure 5B as HL-60 cells transfected with 
wtNE, mutNE, and EGFP, when they were cells transfected with P110L, 
I31T, and INE; Figure 6B as HL-60 cells transfected with G185R, mock, 
D145-152, and P110L NE mutants, when they were cells transfected with 
I31T, P110L, G185R, and 32. The false [szlig]-actin Western blot in 
Figure 6B was also included in HL73063-01, Figure 8 (where the I31Tlane 
was labeled correctly), and HL79615-01, Figure 7.
    4. Falsified the reported methodology for flow cytometry 
experiments in Figure 4A, NEM, Figures 1 and 2, and Tables 2 and 3, 
CMA, and Figures 4, 5, and 6, ISB, to validate the key hypothesis 
showing accelerated apoptosis in SCN and CN patients. The methodology 
claimed that flow cytometry experiments were gated for GFP+ 
populations, or that cell purity was greater than 96%, when based on 
the available original records, the experiments were not performed as 
    5. Falsified Figure 2, CMA, Figure 2, HL73063-01, Figure 3, 
HL79615-01, and Figure 5, CA89135-01A1, demonstrating that the 
overnight cultures of CD34+ and CD33+ bone marrow cells from SCN/AML 
patients showed normal cell survival, and only the CD15+ overnight 
cultures showed accelerated apoptosis, when the actual record available 
contradicted this result. Respondent used flow cytometry data files to 
generate histograms with the desired result to support the hypothesis 
that the progression from SCN to leukemia (AML) involves acquired G-
CSFR mutations that override the pro-apoptotic effect of the NE 
mutations in primitive progenitor cells.
    Dr. Aprikyan has entered into a Settlement Agreement in which he 
denied ORI's findings of research misconduct based on the UW Faculty 
Adjudication Hearing Panel decision. The settlement is not an admission 
of liability on the part of the Respondent. Respondent entered into the 
Agreement solely because contesting the findings would cause him undue 
financial hardship and stress, lead to lengthy and costly appellate 
proceedings, and he wished to seek finality. Respondent agreed not to 
appeal the ORI findings of research misconduct set forth above. He has 
agreed, beginning on March 12, 2013:
    (1) If within two (2) years from the effective date of the 
Agreement, Respondent receives or applies for U.S. Public Health 
Service (PHS) support, Respondent agreed to have his research 
supervised for a period of two (2) years; Respondent agreed that prior 
to the submission of an application for PHS support for a research 
project on which his participation is proposed and prior to his 
participation in any capacity on PHS-supported research, Respondent 
shall ensure that a plan for supervision of his duties is submitted to 
ORI for approval; the supervision plan must be designed to ensure the 
scientific integrity of his research contribution; Respondent agreed 
that he shall not participate in any PHS-supported research until such 
a supervision plan is submitted to and approved by ORI; Respondent 
agreed to maintain responsibility for compliance with the agreed upon 
supervision plan;
    (2) If within two (2) years from the effective date of the 
Agreement, Respondent receives PHS support, Respondent agreed that for 
two (2) years, any institution employing him shall submit, 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; and
    (3) Respondent agreed not to serve in any advisory capacity to PHS 
including, but not limited to, service on any PHS advisory committee, 
board, and/or peer review committee, or as a consultant for a period of 
two (2) years beginning with the effective date of the Agreement.

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

David E. Wright,
Director, Office of Research Integrity.
[FR Doc. 2013-08207 Filed 4-8-13; 8:45 am]