Findings of Research Misconduct

Hat trick from ORI … (the first serving as a reminder why ORI is outside of the NIH)

Notice is hereby given that ORI has taken final action in the following case:

Based on the report of an investigation conducted by the NIH and additional analysis by ORI in its oversight review, ORI found that Bijan Ahvazi, PhD, former Director of the Laboratory of X-ray Crystallography, NIAMS, engaged in research misconduct in research supported by the Intramural Program.

ORI found that Respondent engaged in research misconduct by falsifying data related to or in the following published papers:

  1. Ahvazi, B., Boeshans, K.M., Idler, W., Baxa, U., & Steinert, P.M. “Structural basis for the coordinated regulation of transglutaminase 3 by guanine nucleotides and calcium/magnesium.” J. Biol. Chem. 279(8):7180-92, 2004 Feb 20 (withdrawn) (hereinafter “JBC 2004a”)
  2. Ahvazi, B., Boeshans, K.M., & Steinert, P.M. “Crystal structure of transglutaminase 3 in complex with BMP: Structural basis for nucleotide specificity.” J. Biol. Chem. 279:26716-25, 2004 (withdrawn) (hereinafter “JBC 2004b”)
  3. Ahvazi, B., Boeshans, K.M., Idler, W.,& Cooper, A.J.L. “Crystal structure of transglutaminase 3-cystamine complex: Binding of two cystamines to the nucleotide-binding pocket.” M6:06060, Submitted to J. Biol. Chem., 2006 (rejected) (hereinafter “JBC 2006”).

Specifically, ORI finds that Respondent:

1. falsely labeled Figure 3A in JBC 2004b representing an isothermal calorimetric titration experiment using guanine monophosphate (GMP) and transglutaminase 3 (TGase 3) when the figure was actually a relabeled version of an unrelated experiment that Respondent previously published as Figure 1A in JBC 2004a.

2. falsified Figure 4B, Figure 4C, and Figure 6D in JBC 2004b and Figure 5E in JBC 2006, by altering the original data in the following ways to represent the desired experiment:

a. falsified Figure 4B in JBC 2004b, by adding multiple data points to titration curves for four different concentrations of TGase 3 bound by different concentrations of tagged GTP[gamma]S and deleting 2 outlying data points from one of the curves

b. falsified Figure 4C in JBC 2004 b, representing a competition assay for the release of tagged GTPγS bound to TGase 3, by (1) falsely claiming that the release of the tagged nucleotide occurred with the addition of untagged GMP, when the result was from an assay using untagged GDP, (2) adding additional data points onto the titration curves, and (3) altering the scale of the abscissa

c. falsified Figure 6D in JBC 2004b, by using the false Figure 4B to also represent an additional competition experiment using unmodified nucleotide analog compounds and ATP; specifically, Respondent (1) falsified the units and labels of the axes, (2) falsified the labels of the curves, and (3) vertically inverted the curves

d. falsified Figure 5E in the JBC 2006 manuscript, representing a competition experiment for the release of tagged GTPγS bound to TGase 3 with the addition of cystamine, when the actual experiment was a competition experiment with the addition of untagged nucleotides.

Dr. Ahvazi has entered into a Voluntary Settlement Agreement and has voluntarily agreed for a period of 2 years, beginning on October 7, 2014:

(1) To have his U.S. PHS research supervised and to notify any employer(s)/institution(s) at which he may participate in PHS funded projects of the terms of his supervision; Respondent agrees that prior to the submission of an application for PHS support for a research project on which the Respondent’s participation is proposed and prior to Respondent’s participation in any capacity on PHS-supported research, Respondent shall ensure that a plan for supervision of Respondent’s duties is submitted to ORI for approval; the supervision plan must be designed to ensure the scientific integrity of Respondent’s research; Respondent agrees that he shall not participate in any PHS-supported research until such a supervision plan is submitted to and approved by ORI; Respondent agrees to maintain responsibility for compliance with the agreed upon supervision plan;

(2) that any institution employing him to work on PHS-supported projects 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) to exclude himself voluntarily from serving 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.


Notice is hereby given that ORI has taken final action in the following case:

Based on the report of an investigation conducted by UT Southwestern and analysis conducted by ORI in its oversight review, ORI found that  Takao Takahashi, MD, PhD, currently a faculty member in the Department of Surgical Oncology, Gifu University, Graduate School of Medicine, Gifu, Japan, and formerly a Visiting Scientist in the Hamon Center for Therapeutic Oncology Research, UT Southwestern, engaged in research misconduct in research supported by grant U01 CA084971.

ORI found that Respondent knowingly, intentionally, and recklessly falsified data reported in 4 publications:

  1. Takahashi, T., Shivapurkar, N., Reddy, J., Shigematsu, H., Miyajima, K., Suzuki, M., Toyooka, S., Zöchbauer-Müeller, S., Drach, J., Parikh, G., Zheng, Y., Feng, Z., Kroft, S.H., Timmons, C., McKenna, R.W., & Gazdar, A.F. “DNA methylation profiles of lymphoid and hematopoietic malignancies.” Clin Cancer Res. 10(9):2928-35, 2004 May 1 (hereafter referred to as “CCR 2004”); Retraction in: Clin Cancer Res. 19(1):307, 2013 Jan 1
  2. Takahashi, T., Suzuki, M., Shigematsu, H., Shivapurkar, N., Echebiri, C., Nomura, M., Stastny, V., Augustus, M., Wu, C.W., Wistuba, I.I., Meltzer, S.J., & Gazdar, A.F. “Aberrant methylation of Reprimo n human malignancies.” Int J Cancer 115(4):503-10, 2005 Jul 1 (hereafter referred to as “IJC 2005”); Retraction in: Int J. Cancer 132(2):498, 2013, Jan 15
  3. Takahashi, T., Shigematsu, H., Shivapurkar, N., Reddy, J., Zheng, Y., Feng, Z., Suzuki, M., Noomura, M., Augustus, M., Yin, J., Meltzer, S.J., & Gazdar, A.F. “Aberrant promoter methylation of multiple genes during multistep pathogenesis of colorectal cancers.” Int J Cancer 118(4):924-31, 2006 Feb 15 (hereafter referred to as “IJC 2006”); Retraction in: Int J Cancer 132(2):499, 2013 Jan 15
  4. Tokuyama, Y., Takahashi, T., Okumura, N., Nonaka, K., Kawaguchi, Y., Yamaguchi, K., Osada, S., Gazdar, A., & Yoshida, K. “Aberrant methylation of heparan sulfate glucosamine 3-O-sulfotransferase 2 genes as a biomarker in colorectal cancer.” Anticancer Res. 30(12):4811-8, 2010 Dec (hereafter referred to as “AR 2010”); Retraction in: Anticancer Res. 32(11):5138, 2012 Nov.

Respondent falsified data representing glyceraldehyde 3-phosphate dehydrogenase (GAPDH) loading controls and methylated/unmethylated PCR in RT-PCR gel panels.

Specifically, ORI found by a preponderance of the evidence that Respondent engaged in research misconduct by knowingly, intentionally, and recklessly falsely reporting the results of RT-PCR experiments by:

1. Reusing and relabeling an image and claiming it represents different experiments of human tumor cell lines subjected to different treatments; specifically, an identical image was used to represent the:

(a) GAPDH RT-PCR panels of several lymphoma, leukemia, multiple myeloma, and colorectal cancer cell lines in CCR 2004, Figures 1A and 1B, IJC 2005, Figure 1A, IJC 2006, Figures 1A and 2A, and AR 2010, Figure 1A

(b) GAPDH RT-PCR panels of the lymphoma cell lines BC-1 and Raji in CCR 2004, Figure 1B, lanes 1-3, and the colorectal cancer cell lines HCT116 and COLO201 in AR 2010, Figure 1C, lanes 4-6

(c) unmethylated form of p16 (p16UM) controls in the methylation-specific PCR (MSP) panels for the leukemia and multiple myeloma samples in CCR 2004, Figure 2

(d) p16UM MSP panels for the lymphoma and leukemia samples in CCR 2004, Figure 2, and the unmethylated bands MSP panel for the colorectal cancer (CRC) cell line in IJC 2005, Figure 5.

2. Manipulating an image and claiming it represents a gel with contiguous lanes; specifically, the RT-PCR products in the lanes of gels were cropped, spliced, and pasted together to form a single image for the MSP panels in IJC 2006, Figure 3.

Dr. Takahashi has entered into a Voluntary Settlement Agreement and has voluntarily agreed for a period of 3 years, beginning on August 26, 2014:

(1) To have his research supervised; Respondent agrees that prior to the submission of an application for U.S. PHS support for a research project on which the Respondent’s participation is proposed and prior to Respondent’s participation in any capacity on PHS-supported research, Respondent shall ensure that a plan for supervision of Respondent’s duties is submitted to ORI for approval; the supervision plan must be designed to ensure the scientific integrity of Respondent’s research; Respondent agrees that he shall not participate in any PHS-supported research until such a supervision plan is submitted to and approved by ORI; Respondent agrees to maintain responsibility for compliance with the agreed upon supervision plan;

(2) that 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) to exclude himself voluntarily from serving 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.


Notice is hereby given that ORI has taken final action in the following case:

Based on the report of an investigation conducted by UT Southwestern and analysis conducted by ORI in its oversight review, ORI found that Makoto Suzuki, MD, currently a Professor in the Department of Thoracic Surgery, Kumamoto University Hospital, Kumamoto, Japan, and formerly a Visiting Scientist in the Hamon Center for Therapeutic Oncology Research, UT Southwestern, engaged in research misconduct in research supported by grants P50 CA070907 and U01 CA084971.

ORI found that Respondent knowingly, intentionally, and recklessly falsified data reported in 6 publications:

  1. Suzuki, M., Hao, C., Takahashi, T., Shigematsu, H., Shivapurkar, N., Sathyanarayana, U.G., Iizasa, T., Fujisawa, T., Hiroshima, K., & Gazdar, A.F. “Aberrant methylation of SPARC in human lung cancers.” Br J Cancer 92(5):942-8, 2005 Mar 14 (hereafter referred to as “BJC 2005-1”); Retraction in: Br J Cancer 108(3):744, 2013 Feb 19
  2. Suzuki, M., Shigematsu, H., Shames, D.S., Sunaga, N., Takahashi, T., Shivapurkar, N., Iizasa, T., Frankel, E.P., Minna, J.D., Fujisawa, T., & Gazdar, A.F. “DNA methylation associated inactivation of TGFbeta-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers.” Br J Cancer 93(9):1029-37, 2005 Oct 31 (hereafter referred to as “BJC 2005-2”); Retraction in: Br J Cancer 109(12)3132, 2013 Dec 10
  3. Suzuki, M., Shigematsu, H., Takahashi, T., Shivapurkar, N., Sathyanarayana, U.G., Iizasa, T., Fujisawa, T., & Gazdar, A.F. “Aberrant methylation of Reprimo in lung cancer.” Lung Cancer 47(3):309-14; 2005 Mar (hereafter referred to as “LC 2005”); Retraction in: Lung Cancer 85(2):337, 2014 August
  4. Suzuki, M., Toyooka, S., Shivapurkar, N., Shigematsu, H., Miyajima, K., Takahashi, T., Stastny, V., Zern, A.L., Fujisawa, T., Pass, H.I., Carbone, M., & Gazdar, A.F. “Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection.” Oncogene 24(7):1302-8, 2005 Feb 10 (hereafter referred to as “ONC 2005”); Retraction in: Oncogene 33(21):2814, 2014 May 22
  5. Suzuki, M., Shigematsu, H., Shivapurkar, N., Reddy, J., Miyajima, K., Takahashi, T., Gazdar, A.F., & Frenkel, E.P. “Methylation of apoptosis related genes in the pathogenesis and prognosis of prostate cancer.” Cancer Lett. 242(2):222-30, 2006 Oct 28 (hereafter referred to as “CL 2006”)
  6. Suzuki, M., Shigematsu, H., Shames, D.S., Sunaga, N., Takahashi, T., Shivapurkar, N., Iizasa, T., Minna, J.D., Fujisawa, T., & Gazdar, A.F. “Methylation and gene silencing of the Ras-related GTPase gene in lung and breast cancers.” Ann Surg Oncol. 14(4):1397-404, 2007 Apr (hereafter referred to as “ASO 2007”).

Respondent falsified data representing GAPDH loading controls and methylated/unmethylated PCR in RT-PCR gel panels.

Specifically, ORI found by a preponderance of the evidence that Respondent engaged in research misconduct by knowingly, intentionally, and recklessly falsely reporting the results of RT-PCR experiments by:

1. Reusing and relabeling an image and claiming it represents different experiments of human tumor cell lines subjected to different treatments; specifically, an identical image was used to represent the:

(a) GAPDH RT-PCR panels in BJC 2005-01, Figure 1A, lanes 4-12, and Figure 1C, lanes 4-12

(b) GAPDH RT-PCR panels in BJC 2005-2, Figures 1A and 1B, and ASO 2007, Figures 1A and 1B

(c) unmethylated form of p16 (p16U) RT-PCR panel in CL 2006, Figure 1, lanes 3-10, positive and negative controls, and the p16 U RT-PCR panel in ONC 2005, Figure 2A.

2. Manipulating an image and claiming it represents a gel with contiguous lanes; specifically, the RT-PCR products in the lanes of gels were cropped, spliced, and pasted together to form a single image for the:

(a) GAPDH RT-PCR panels in LC 2005, Figures 1A and 1B

(b) methylated form of Decoy receptor 2 MSP panel in CL 2006, Figure 1

(c) methylated form of small Ras-related GTPase MSP panel in ASO 2007, Figure 3B.

Dr. Suzuki has entered into a Voluntary Settlement Agreement and has voluntarily agreed for a period of 3 years, beginning on August 26, 2014:

(1) To have his research supervised; Respondent agrees that prior to the submission of an application for U.S. PHS support for a research project on which the Respondent’s participation is proposed and prior to Respondent’s participation in any capacity on PHS-supported research, Respondent shall ensure that a plan for supervision of Respondent’s duties is submitted to ORI for approval; the supervision plan must be designed to ensure the scientific integrity of Respondent’s research; Respondent agrees that he shall not participate in any PHS-supported research until such a supervision plan is submitted to and approved by ORI; Respondent agrees to maintain responsibility for compliance with the agreed upon supervision plan;

(2) that 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) to exclude himself voluntarily from serving 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.

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