Cleveland Clinic heart researchers earn two expressions of concern

Cleveland Clinic, via Wikimedia

A team of heart researchers at Cleveland Clinic in Ohio has received expressions of concern for two papers in the Journal of Biological Chemistry, which says the images in the articles appear suspect. 

The papers, both of which appeared in 2004, come from the lab of Subha Sen, a highly-funded scientist who has received millions in NIH grants over the past decade. Sen’s work also has drawn scrutiny on PubPeer, with comments cropping up on the site roughly three years ago for many of her papers

In 2016, Sen’s group retracted a 2009 article in JBC titled “A unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks.” According to the notice: 

This article has been withdrawn by the authors. Evaluation by the journal with image analysis software determined that in Fig. 5A, lanes 1–3 of the RB1 immunoblot were duplicated in lanes 4–6, lane 4 of the ERBB2 immunoblot was duplicated in lane 6, lane 5 of the STAT3 immunoblot was duplicated in lane 8, and lanes 1–3 of the actin immunoblot were flipped horizontally and reused in lanes 6–8. The authors state that RB1, ERRB2, STAT3, and actin in Fig. 5A were created from phosphor-chemiluminescent digital imaging. The authors also state that they have replicate data supporting the conclusions of Fig. 5, A and B. In Fig. 6B, evaluation by the journal of the original data determined that single cell background fluorescence was duplicated. The authors maintain that the concern is about a single background cell not a positive cell to show transfection efficiency and is inconsequential to proving transfection.

Among the co-authors on that work was Carlo Croce, the embattled cancer researcher at The Ohio State University, whose most recent appearance in the news was his failed libel suit against the New York Times

The publishing collaboration with Croce appears to have been a one-off for Sen; their names don’t appear together on any other articles we could find. However, they do share a patent for a method of assessing heart disease, according to this document. The technique relies on the use of microRNA signatures — which is the subject of the retracted 2016 article in JBC

One of the new expressions of concern involves a paper titled “Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice.” The statement reads

The publisher of the Journal of Biological Chemistry is issuing an Expression of Concern to inform readers that credible concerns have been raised regarding some of the data and conclusions in the article listed above. The Journal of Biological Chemistry will provide additional information as it becomes available.

The second expression of concern, for “Myocardial Cell Death and Regeneration during Progression of Cardiac Hypertrophy to Heart Failure,” reads similarly. 

Sen has not responded to requests for comment from Retraction Watch.

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5 thoughts on “Cleveland Clinic heart researchers earn two expressions of concern”

  1. 27th March 2020 retraction for:

    J Mol Med (Berl). 2005 Dec;83(12):993-1004. Epub 2005 Aug 17.
    Role of the NF-kappaB signaling cascade and NF-kappaB-targeted genes in failing human hearts.
    Gupta S1, Sen S.
    Author information
    1
    Department of Molecular Cardiology, NB 50, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

    2020 retraction notice.
    https://link.springer.com/article/10.1007/s00109-005-0691-z#change-history
    27 March 2020 The Editor-in-Chief has retracted this article [1] because a number of lanes in Figs. 3, 4 and 6 of this article are duplicated.

  2. Two 6th Nov 2002 retractions Subha Sen.

    Retraction for:
    J Biol Chem
    . 2004 May 7;279(19):20422-34. doi: 10.1074/jbc.M308488200. Epub 2004 Feb 16.
    Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice
    Sagartirtha Sarkar 1, Douglas W Leaman, Sudhiranjan Gupta, Parames Sil, David Young, Annitta Morehead, Debabrata Mukherjee, Norman Ratliff, Yaping Sun, Mary Rayborn, Joe Hollyfield, Subha Sen
    Affiliations expand
    PMID: 14970239

    This article has an expression of concern and there are 6 comments on PubPeer (by: Adesmia Candida, Buteo Magnirostris, Hylaeus Kona)
    DOI: 10.1074/jbc.M308488200

    6th Nov 2020 retraction notice.
    https://www.jbc.org/content/295/45/15424
    VOLUME 279 (2004) PAGES 20422–20434

    This article has been withdrawn by Sagartirtha Sarkar, Douglas W. Leaman, Parames Sil, Annitta Morehead, Debabrata Mukherjee, Joe Hollyfield, and Subha Sen. Sudhiranjan Gupta, David Young, Norman Ratliff, Yaping Sun, and Mary Rayborn could not be reached. The images from 1-year-old mice shown in Fig. 1A were reused in the subsequent JBC article Sarkar, S., et al. (2004) J. Biol. Chem. 279, 52630–52642 as 9-month-old mice. The images shown in Fig. 1C (II) as 18-week-old mice were also reused in the same publication (Sarkar, S., et al. (2004) J. Biol. Chem. 279, 52630–52642) as 9-month-old mice. The GAPDH immunoblot shown in Fig. 2B (1) was reused in Sarkar, S., et al. (2004) J. Biol. Chem. 279, 52630–52642. The withdrawing authors do not agree to the Journal’s decision as the concerned images of Fig. 1 were reused in the second JBC article (Sarkar, S., et al. (2004) J. Biol. Chem. 279, 52630–52642) only to introduce the model in that article as per the reviewer’s suggestion, and no new data were put forward using these image panels. The withdrawing authors also disagree with the Journal’s statement of the reuse of the GAPDH immunoblot. The withdrawing authors requested the journal to not withdraw this publication because no data in this particular article are in question and the subsequent JBC article (Sarkar, S., et al. (2004) J. Biol. Chem. 279, 52630–52642) is to be withdrawn by the authors for the same figure panel duplication. The request was however declined by the Journal. The withdrawing authors have pointed out that the above-referenced article was 17 years ago, and their original documents were not saved after 15 years. In the absence of original data and figures, the withdrawing authors were unable to meet the criteria for the Journal. The withdrawing authors stand by the results and conclusions of this article and state that no data in this particular article were compromised in any way.

    Retraction for:
    J Biol Chem
    . 2004 Dec 10;279(50):52630-42. doi: 10.1074/jbc.M402037200. Epub 2004 Sep 21.
    Myocardial cell death and regeneration during progression of cardiac hypertrophy to heart failure
    Sagartirtha Sarkar 1, Mamta Chawla-Sarkar, David Young, Kazutoshi Nishiyama, Mary E Rayborn, Joe G Hollyfield, Subha Sen
    Affiliations expand
    PMID: 15385543

    This article has an expression of concern and there are 9 comments on PubPeer (by: Rhyacodrilus Falciformis, Hoya Camphorifolia, Adesmia Candida, Pseudobryomima Distans, Meredithia Nutleorum, Buteo Magnirostris, Hylaeus Kona)
    DOI: 10.1074/jbc.M402037200

    6 Nov 2020 retraction notice.
    https://www.jbc.org/content/295/45/15425

    VOLUME 279 (2004) PAGES 52630–52642

    This article has been withdrawn by Sagartirtha Sarkar, Mamta Chawla-Sarkar, Kazutoshi Nishiyama, Joe G. Hollyfield, and Subha Sen. David Young and Mary E. Rayborn could not be reached. The images from 9-month-old mice in Fig. 1A were reused from Sarkar, S., et al. (2004) J. Biol. Chem. 279, 20422–20434 as 1-year-old and 18-week-old mice. The withdrawing authors state that they showed the images of the heart at the recommendation of a reviewer to introduce the model. The first four lanes of the GAPDH immunoblot in Fig. 3B were reused in the last four lanes as well as in Figs. 3D, 6 (B and C), and 8B and Sarkar, S., et al. (2004) J. Biol. Chem. 279, 20422–20434. Additionally, the GAPDH immunoblots in Figs. 3D and 6 (B and C) are the same. In Fig. 3B, the first two lanes of the Fas immunoblot are the same. In Fig. 6B, the first two lanes of the cyclin D3 immunoblot are the same. In Fig. 6C, the first two lanes of the Cdk1 immunoblot are the same.

    The withdrawing authors do not agree that the first four lanes of the GAPDH immunoblot in Fig 3B were reused in the last four lanes as well as in Figs. 3D, 6 (B and C), and 8B and in Sarkar, S., et al. (2004) J. Biol. Chem. 279, 20422–20434. The withdrawing authors state that they provided evidence that these images are different based on different densitometric scan values for each lane under question, as well as few background differences among the GAPDH lanes. Similar evidence was also presented for the GAPDH immunoblots in Figs. 3D and 6 (B and C). However, the Journal did not agree with the withdrawing authors’ evidence. The withdrawing authors strongly disagree on any duplication between the first two lanes of the Fas immunoblot in Fig. 3B, the first two lanes of the cyclin D3 immunoblot in Fig. 6B, and the first two lanes of the Cdk1 immunoblot in Fig. 6C. The withdrawing authors could not produce any original autoradiograms or scans to support their claims for the publication, which is 17 years old due to closure of the laboratory for more than a decade. Therefore, due to the unavailability of the original data after so many years, the withdrawing authors decided to withdraw the manuscript. The withdrawing authors state that none of the results presented in this article were compromised and the conclusions of each experiment remain unaltered.

  3. Three 2021 retractions Subha Sen, Cleveland Clinic, Am J Physiol Heart Circ Physiol. Institutional investigation.

    1. https://journals.physiology.org/doi/full/10.1152/ajpheart.00082.2005_RET
    Gupta S,Young D,Sen S. Inhibition of NF-κB induces regression of cardiac hypertrophy, independent of blood pressure control, in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 289: H20–H29, 2005. First published March 4, 2005; doi: 10.1152/ajpheart.00082.2005 This article has been retracted and there are 3 comments on PubPeer (by: Cavendishia Grandifolia). The American Physiological Society is retracting this article because of concerns of inappropriate image manipulation in Figs. 4 and 8. An investigation of research misconduct was conducted by the Cleveland Clinic. Cleveland Clinic’s Board of Governors/Medical Executive Committee concurred with the investigation’s finding that it is more likely than not that one or more of the images in this publication have been falsified. The authors disagree with the findings of the Cleveland Clinic’s Board of Governors/Medical Executive Committee and the decision of the journal to retract the article. The authors stand by the results and conclusions of this article and state that no data in their article were compromised by any means.

    2. https://journals.physiology.org/doi/full/10.1152/ajpheart.00294.2009_RET
    Gupta S,Maitra R,Young D,Gupta A,Sen S. Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy. Am J Physiol Heart Circ Physiol 297: H627–H636, 2009; doi: 10.1152/ajpheart.00294.2009 3 comments on PubPeer (by: Adesmia Candida). The American Physiological Society is retracting this article because of concerns of inappropriate image manipulation in Figs. 1, 5, and 6. An investigation of research misconduct was conducted by the Cleveland Clinic. Cleveland Clinic’s Board of Governors/Medical Executive Committee concurred with the investigation’s finding that it is more likely than not that one or more of the images in this publication have been falsified. The authors disagree with the findings of the Cleveland Clinic’s Board of Governors/Medical Executive Committee and the decision of the journal to retract the article. The authors stand by the results and conclusions of this article and state that no data in their article were compromised by any means.

    3. https://journals.physiology.org/doi/full/10.1152/ajpheart.00763.2003_RETSarkar S,Vellaichamy E,Young D,Sen S. Influence of cytokines and growth factors in ANG II-mediated collagen upregulation by fibroblasts in rats: role of myocytes. Am J Physiol Heart Circ Physiol 287: H107–H117, 2004. First published April 1, 2004; doi: 10.1152/ajpheart.00763.2003 4 comments on PubPeer (by: Drosophila Stalkeri). The American Physiological Society is retracting this article because of concerns of inappropriate image manipulation in Figs. 2, 3, 4, and 7. An investigation of research misconduct was conducted by the Cleveland Clinic. Cleveland Clinic’s Board of Governors/Medical Executive Committee concurred with the investigation’s finding that it is more likely than not that one or more of the images in this publication have been falsified. The authors disagree with the findings of the Cleveland Clinic’s Board of Governors/Medical Executive Committee and the decision of the journal to retract the article. The authors stand by the results and conclusions of this article and state that no data in their article were compromised by any means.

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