Singapore investigation leads to two retractions, two more on the way

Authors have retracted papers from Cell Metabolism and the Journal of Biological Chemistry after an investigation in Singapore found issues, including falsified data. The investigation is ongoing, and two additional retractions, along with two corrections, are on the horizon.

The investigation looked into papers by first authors Sudarsanareddy Lokireddy, now a postdoc at Harvard, and Sandhya Sriram, a postdoc at the Agency for Science, Technology and Research in Singapore. Led by the Nanyang Technological University in Singapore, where some of the work was done, the investigation concluded that there were issues with six papers on which either Sriram or Lokireddy was first author.

All authors but Lokireddy have agreed to retractions or corrections. Ravi Kambadur of NTU, and Mridula Sharma at the National University of Singapore, are the last two authors on all the papers.

According to a notice from the NTU, the “investigation found a number of instances of alterations to data” in three papers on which Lokireddy is first author. One of those was retracted December 1 by Cell Metabolism:“The Ubiquitin Ligase Mul1 Induces Mitophagy in Skeletal Muscle in Response to Muscle-Wasting Stimuli,” which has been cited 73 times. The paper found that overexpression of the protein Mul1 was linked with the loss of mitochondria (mitophagy), which can induce wasting of skeletal muscle.

The retraction note explains that other work has made the same link, and provides more information on which figures in the paper were affected:

In the article, we reported that the expression of a mitochondrial specific E3 ligase, Mul1, was induced in response to wasting conditions, and that increased Mul1 expression caused mitophagy and muscle wasting. Following an investigation by Nanyang Technological University, it was determined that the first author, Sudarsanareddy Lokireddy, falsified data in Figures 2D, 4B, 6D, 6E, and S5B. Although other work has linked Mul1 with mitophagy, in order to protect the integrity of science as well as of our laboratory and institutes, we are retracting the paper. We sincerely apologize to our colleagues and readers for any adverse consequences that this may have caused. The co-authors agree with this statement, with the exception of the first author, Sudarsanareddy Lokireddy.

We reached out to last author Kambadur. Tony Mayer, the Research Integrity Officer at NTU, explained that the main problems with the data were in the Western blots:

In accordance with its policy of research integrity, Nanyang Technological University (NTU) conducted an investigation following allegations of research malpractice. The investigation found that the first author, Sudarsanareddy Lokireddy, had falsified research data, especially Western blots. The retraction was agreed by all the co-authors except Dr Lokireddy, who declined to join the retraction.

He also told us, that “two independent publications have linked Mul1 to mitophagy.” Those are:

• Cilenti L et al., Inactivation of Omi/HtrA2 protease leads to the deregulation of mitochondrial Mulan E3 ubiquitin ligase and increased mitophagy, BBA. 2014; 1843:1295-1307.
• Ambivero CT et al., Mulan E3 ubiquitin ligase interacts with multiple E2 conjugating enzymes and participates in mitophagy by recruiting GABARAP, Cellular Signalling. 2014; 26:2921-2929;

Mayer told us that the investigation included two other papers by Lokireddy, and in both

…he admitted falsification. His co-authors have all agreed on the retractions and the  journals have been notified.

Those papers are:

• Myostatin is a novel tumoral factor that induces cancer cachexia, published in Biochemical Journal (34 citations, according to Thomson Scientific’s Web of Knowledge)
• Myostatin Induces Degradation of Sarcomeric Proteins through a Smad3 Signaling Mechanism During Skeletal Muscle Wasting, published in Molecular Endocrinology (52 citations)

We reached out to those journals about the status of those papers. Clare Curtis, the Executive Editor of the Biochemical Journal, told us that the paper published in that journal will be retracted soon.

According to the notice from NTU, three papers on which Sriram is the first author had issues with data:

The investigation also found other instances where data were presented without proper explanation of how they were derived. These however do not alter the scientific conclusions of the papers concerned.

Mayer clarified that there was no misconduct in these papers — rather, there was “a lack of transparency about the presentation of data,” he noted.

One of those papers was withdrawn last month from the Journal of Biological Chemistry: “Myostatin induces DNA damage in skeletal muscle of streptozotocin-induced type 1 diabetic mice.” The note is in JBC‘s old style — cryptic:

This article has been withdrawn by the authors.

The authors have requested corrections for two other papers flagged by the investigation:

• Myostatin augments muscle-specific ring finger protein-1 expression through an NF-kB independent mechanism in SMAD3 null muscle published in Molecular Endocrinology (cited 5 times)
• Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF-kB published in Aging Cell, has been (cited 33 times)

According to the notice, the university is still investigating:

Disciplinary procedures and further investigation are currently ongoing. We will not be making comments while this is ongoing but only after conclusions have been made at a later date.

We have contacted Lokireddy and Sriram for comment. We’ll update this post with anything else we learn.

Update, 12/15 1:25 PM: A spokesperson for the Endocrine Society, which publishes Molecular Endocrinology, told us that the process to retract “Myostatin Induces Degradation of Sarcomeric Proteins through a Smad3 Signaling Mechanism During Skeletal Muscle Wasting” has been initiated, and the request to correct “Myostatin augments muscle-specific ring finger protein-1 expression through an NF-kB independent mechanism in SMAD3 null muscle” is being processed.

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