A Johns Hopkins researcher who shared the 2019 Nobel Prize in Medicine or Physiology has retracted four papers from the Proceedings of the National Academy of Sciences (PNAS) for concerns about images in the articles, reports Retraction Watch. It’s not his first retraction either.
Gregg Semenza is “one of today’s pre-eminent researchers on the molecular mechanisms of oxygen regulation”, the work for which he shared the 2019 Nobel, according to Hopkins. But even before that, the pseudonymous Claire Francis began pointing out potential image duplications and other manipulations in Semenza’s work on PubPeer, as described in October 2020 by Leonid Schneider.
The four papers retracted are:
Hypoxia-inducible factors mediate co-ordinated RhoA-ROCK1 expression and signalling in breast cancer cells;
Mutual antagonism between hypoxia-inducible factors 1α and 2α regulates oxygen sensing and cardio-respiratory homeostasis;
Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumour-induced mobilisation of circulating angiogenic cells; and
Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells.
A representative notice:
“We are retracting this article due to concerns with Figure 5. In Figure 5A, there is a concern that the first and second lanes of the HIF-2α panel show the same data, and that the first and second lanes of the HIF-1α panel show the same data, despite all being labelled as unique data. In Figure 5D, there is a concern that the second and third lanes of the HIF-1β panel show the same data, despite being labelled as unique data.
“We believe that the overall conclusions of the paper remain valid, but we are retracting the work due to these underlying concerns about the figure. Confirmatory experimentation has now been performed and the results can be found in a preprint article posted on bioRxiv, ‘Homeostatic responses to hypoxia by the carotid body and adrenal medulla are based on mutual antagonism between HIF-1α and HIF-2α’ (https://doi.org/10.1101/2022.07.11.499380). We apologise for the inconvenience.“
Altogether, the papers have been cited more than 750 times, according to Clarivate’s Web of Science. From 1998 until 2013, Semenza was principal investigator on NIH grants totalling more than $9m.
“Francis” tells Retraction Watch:
“I saw problematic Gregg Semenza publications before his Nobel Prize. I recognised his name when he got his Nobel Prize and went back for a second look. Had I got him wrong? No, there were more problematic publications.”
One of Semenza’s co-authors on one of the papers is Denis Wirtz, the vice provost for research at Hopkins.
Semenza, who did not immediately respond to a request for comment, is hardly the only Nobel Prize winner to later retract papers. We described four such cases in 2019, and Frances Arnold did the same in 2020. Daniel Kahneman walked back some claims, although he did not retract a paper per se.
It is also not Semenza’s first retraction. In 2011, a paper he co-authored with Naoki Mori – a name familiar to Retraction Watch readers – was retracted.
bioRxiv Pre-print Study details
Homeostatic responses to hypoxia by the carotid body and adrenal medulla are based on mutual antagonism between HIF-1α and HIF-2α
Guoxiang Yuan, Ying-Jie Peng, Vaddi Damodar Reddy, Vladislav Makarenko, Jayasri Nanduri, Shakil Khan, Joseph Garcia, Ganesh Kumar, Gregg Semenza, Nanduri Prabhakar
Posted on bioRxiv on 11 July 2022
Abstract
Respiration and blood pressure (BP) are regulated to maintain optimal delivery of O2 to every cell in the body. Arterial hypoxemia is sensed by the carotid body (CB), which initiates sympathetic reflex arcs to the diaphragm to increase ventilation, and to the adrenal medulla (AM) to increase catecholamine secretion and thereby increase BP. However, the underlying molecular mechanisms have not been fully delineated. Here, we report that the relative activities of hypoxia-inducible factor-1 (HIF-1) and HIF-2 determine the set point for the CB and AM, with respect to their maintenance of BP and respiration. In Hif2a+/- mice, which are heterozygous for a knockout allele at the locus encoding HIF-2α, expression of HIF-1α and NADPH oxidase 2 was increased in the CB and AM, resulting in an oxidised intracellular redox state with augmented sensitivity to hypoxia, increased BP, and respiratory abnormalities, which were all normalised by treatment with a HIF-1α inhibitor or a superoxide anion scavenger. By contrast, in Hif1a+/- mice, which are heterozygous for a knockout allele at the locus encoding HIF-1α, the expression of HIF-2α and superoxide dismutase 2 was increased in the CB and AM, resulting in a reduced intracellular redox state with impaired CB and ventilatory responses to chronic hypoxia, which were normalised by treatment with a HIF-2α inhibitor. None of the abnormalities that were observed in Hif1a+/- or Hif2a+/- mice were observed in Hif1a+/-; Hif2a+/- double- heterozygous mice. Our results demonstrate that redox balance in the CB and AM, which is determined by mutual antagonism between HIF-α isoforms, establishes the set point for responses of the CB and AM to hypoxia, and is required for the maintenance of normal BP and respiration.
Retraction Watch article – Nobel Prize winner Gregg Semenza retracts four papers (Open access)
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