See a therapist and get serious help

Meet Dr David Danielpour, a US cancer researcher in his late sixties, and since 1998 professor at Case Western Reserve University in Cleveland, Ohio. He just taught Cheshire aka Actinopolyspora biskrensis as well as yours truly how reproducibility in science really works, plus some basic manners.

The lesson begins with this PubPeer thread:

David Danielpour, Sarah Corum , Scott M. Welford , Eswar Shankar Hypoxia represses early responses of prostate and renal cancer cells to YM155 independent of HIF-1α and HIF-2α Current Research in Pharmacology and Drug Discovery (2022) doi: 10.1016/j.crphar.2021.100076

Professor Danielpour explained on PubPeer:

“All the original full image film exposures for this manuscript were meticulously reviewed by me and the editor team of the journal ” Current Research in Pharmacology and Drug Discovery” , as part of this journal’s standard submission requirements. All the images in this manuscript are correct, confirmed and accurate.

The image bands in question have no similarity at all to each other, even with a wild imagination, except perhaps under influence of hallucinogens or psychosis. My recommendation to the person who posted this message is: See a therapist and get serious help.”

Author from @cwru chides me for asking to see original data, suggesting that I’m under the influence of hallucinations or psychosis. 😼 pic.twitter.com/bNQKKE3r2o

— Cheshire (@Thatsregrettab1) August 1, 2022

He also posted raw data, an image of a gel X-Ray film to prove that the gel bands are not identical. He then informed Elisabeth Bik who advised some politeness:

“Politeness goes two ways. One earns politeness by being respectful of others and not by unnecessarily pointing fingers and causing unnecessary trouble. We are on this earth for a relatively short time. The wisest thing is to apply time and energy to helping others rather than hurting them and diminishing the quality of their life and dignity.“

Still, even if this was possibly a false alarm, maybe Cheshire had a good reason to politely ask a question? After all, Prof Danielpour has more on PubPeer, like this:

Sanjeev Shukla , Haripaul Sharma , Ata Abbas , Gregory T. MacLennan , Pingfu Fu , David Danielpour, Sanjay Gupta Upregulation of SATB1 is associated with prostate cancer aggressiveness and disease progression PLoS ONE (2013) doi: 10.1371/journal.pone.0053527 

Or this:

Shinako Araki , Jacob A. Eitel , Christopher N. Batuello , Khadijeh Bijangi-Vishehsaraei , Xian-Jin Xie , David Danielpour , Karen E. Pollok , David A. Boothman, Lindsey D. Mayo TGF-beta1-induced expression of human Mdm2 correlates with late-stage metastatic breast cancer Journal of Clinical Investigation (2010) doi: 10.1172/jci39194

This was also a very mysterious case:

H Wang , K Song , T L Krebs , J Yang , D Danielpour Smad7 is inactivated through a direct physical interaction with the LIM protein Hic-5/ARA55 Oncogene (2008) doi: 10.1038/onc.2008.291 

Danielpour never commented on the apparent duplication of the purple-boxed bands. Otherwise, he explained to me:

“Figure 3c, right side bottom lane (beta-actin probing) I think is some odd electron distortion of the enhanced image made by the editorial office of the journal.“

He also shared the original Figure 1D which lacks the duplicated part:

“Below is what we submitted to the journal for the other article in question. It is the same figure in a former student’s Ph.D. dissertation (https://etd.ohiolink.edu/apexprod/rws_etd/send_file/send?accession=case1220931692&disposition=inline). As you can see, the figures and one online by the journal site’s in PubMed. “

The paper was published in 2012 with the problematic Figure 1d, and the PubMed version without the duplication was, according to NCBI record, uploaded by authors in 2012. But then again, Hui Wang PhD thesis file was created in September 2009 and it has the “normal” version of the figure.

Very mysterious. Maybe Dr Danielpour was again wrongly accused? Maybe Oncogene‘s naughty Editor-in-Chief Justin Stebbing played an evil trick on him?

Danielpour started to comment on PubPeer already in 2015:

The last author wrote on PubPeer in 2015:

“None of the figure issues displayed by Peer 1 are a problem or change the results of our studies or the significance of our published work.

The data and figures displayed were generated in 1995 by an undergraduate student in my laboratory. Although 20 years ago, the findings he made hold up to this day, as confirmed by multiple individuals in my laboratory…”

The journal did nothing because Danielpour recycled data in two papers of same publisher, hence no copyright infringement. JBC so far also hasn’t resolved other problems in Danielpour’s papers:

In 2015, Danielpour expressed on PubPeer his trust in Jerry Chipuk, who is now professor at Icahn School of Medicine at Mount Sinai:

“However, knowing the first author’s thoroughness and honestly, I do trust that all was done well and all will hold up…”

After graduating with Danielpour, Chipuk went on to publish fudged data in Doug Green‘s lab at St Jude Children’s Research Hospital.

And look at this picture:

Jerry Chipuk and Michael Karin presenting at the CDD Cambridge Conference pic.twitter.com/4CBkPiwVyh

— gerry melino (@melino_G) September 9, 2019

Eeek, Michael Karin….

In 2018, Danielpour and his PhD student Reema Wahdan-Alaswad, now research instructor at University of Colorado Denver, corrected a paper:

Reema S. Wahdan-Alaswad , Kara L. Bane , Kyung Song , Dorjee T.N. Shola , Jorge A. Garcia , David Danielpour Inhibition of mTORC1 kinase activates Smads 1 and 5 but not Smad8 in human prostate cancer cells, mediating cytostatic response to rapamycin Molecular Cancer Research (2012) doi: 10.1158/1541-7786.mcr-11-0615

The correction notice addressed Figures 1C and 2A:

“Specifically, the blot labeled “β-actin” in Figure 1C contained an erroneous Akt1 exposure rather than a GAPDH exposure, and the blot labeled “Cyclin D2” in Figure 2A contained an erroneous Cyclin D1 exposure rather than a Cyclin D2 exposure. The corrected blots depicting GAPDH and Cyclin D2 exposures are shown below.”

But according to Cheshire, they forgot the Figure 2E:

Danielpour protested:

“There is nothing wrong with the actual original image in Fig 2D in the journal. Over-enhancing contrast of any original figure can easily cause abnormal-looking distortions and give the appearance of splicing. It is not rocket science.“

I presume it is illegal to visualise for fingerprints at a crime scene if you can#t see those with naked eye? I saw not just a splice in the last lane, but also a box covering the first lane:

But then Danielpour explained why image data is actually not important:

“I am not concerned about this at all based on the type of experiment, agarose gel electrophoresis of DNA. The procedure is inherently prone to such issues. [followed by a lesson on agarose electrophoresis, -LS] It is basic physics.

This is not worth my trouble looking further into, as the amount of redundant supportive data to support the same result is overwhelmingly strong. Try to read the manuscript and see for yourself the strength of the overall study.

I ensure that investigators in my lab overly repeat data multiple ways. This ensures that data are real and reproducible. Experimental error is part of science. That is why statistics is so important. I ensure my people apply sufficient redundancy to make the full picture of the paper and storyline statically significant. My standards of sound science improved through years of experience.”

Not all of Danielpour’s work is perfectly reproducible. In 2020, he retracted a paper:

Reema S. Wahdan-Alaswad , Kyung Song , Tracy L. Krebs , Dorjee T.N. Shola , Jose A. Gomez , Shigemi Matsuyama , David Danielpour Insulin-like growth factor I suppresses bone morphogenetic protein signaling in prostate cancer cells by activating mTOR signaling Cancer Research (2010) doi: 10.1158/0008-5472.can-10-1119

The paper was retracted in 2020, also Fig 4 proved fake and raw data unavailable:

“This article (1) is being retracted at the request of the corresponding author. Errors were found in Figs. 1A, 3C, and 4D that diminish the reliability of this study.”

I asked Danielpour what caused the retraction. He explained:

“I retracted that paper because it did not meet up to my standards of rigor and reproducibility, even though there were multiple data sets supporting the same overall data and conclusion. I do not believe in publishing stories that are not solid and highly reproducible and so I err on the side of being overly cautious and slow in publishing stories.”

I for one fully agree that any research on mTOR by standard is bound to be solid and highly reproducible, by the best minds of science working in that tremendously trust-inspiring field.

Still, why the retraction and the manipulated data? Was there an investigation maybe? Danielpour was adamant:

“For the record, the HHS-ORI did not investigate me. My student Reema, who generated and assembled all the manuscript figures was investigated. HHS-ORI did not share the details of their final report with me, only that there was no evidence of any data manipulation or scientific misconduct. All the errors were innocent, sloppy and minor mistakes. She did not receive any penalty for those minor errors. HHS-ORI left the decision to me to retract or correct the errors. I decided to retract it for the sake of keeping with rigorous science.“

He later specified:

“someone from my university working with ORI informed me briefly about the conclusions of the ORI but did not share the detailed report. My lab members have never used photoshop for generating figures.”

But how come Danielpour was privy to the confidential results on an investigation he was not a party of, I asked him. Did someone breach confidentiality? He explained:

“I was involved in the initial part of the investigation. I do not think this is a violation of confidential information. As I clearly stated to you, I was not the person under investigation.“

Now this makes even less sense. If Danielpour was a witness, he wouldn’t be entitled to confidential information about the accused. If he was initially party to the investigation, then he must have been informed in writing that he was not part of it anymore, ie that he was are absolved. If he was the notifier who reported his student for suspected research misconduct, he get the report or at least a summary letter. But he says he has no documents.

Maybe the ORI investigation found something different from what Danielpour tells everyone it found?

Back in 2015, Danielpour wrote on PubPeer:

“With age I am also learning to be more tolerant of students disliking me for being considered as a mentor who is obsessed with repetition and reproducibility. One of my students said that I am notorious for over-killing reproducibility. However, I now learned to take it one level up: critical experiments need to be repeated by two or more members of the lab. That is my current definition of reproducibility.”

Ok, let me show how Danielpour and his collaborators ensure reproducibility of their research. here a recent paper, published with the predatory publisher e-Century (which doesn’t even issue doi). The journal was founded by western scientists like Guido Kroemer and Anil Sood, raise your hand if you are shocked. This Danielpour study was nevertheless whitelisted on NCBI PubMed because of a loophole: the NIH-funded US authors like Danielpour uploaded it there.

Murali K Mamidi, William E Samsa, David Danielpour, Ricky Chan, and Guang Zhou The transcription co-factor JAB1/COPS5, serves as a potential oncogenic hub of human chondrosarcoma cells in vitro Am J Cancer Res. (2021) PMCID: PMC8569363

The most innocent explanation is that the authors did the JAB1 knock-down experiment only once, ran just one gel, and used it in at least 3 figures. But then again, it wouldn’t have worked to analyse this one experiment on just one single gel (as the re-used tubulin loading control suggests): the Jab-1, Sox-9 and Cul-1 antibodies the authors used are all of rabbit origin, and the latter two proteins are similar in molecular weight. Basically, this is not a way to do science. Maybe three gels were run, and one library loading control of unclear origin was used. But this is the most innocuous explanation of how Danielpour’s famed reproducibility is achieved.

I wonder if this study suggesting to cure cancer with Vitamin E therapy is reproducible:

Samantha Morley , Varsha Thakur , David Danielpour, Robert Parker , Hiroyuki Arai , Jeffrey Atkinson , Jill Barnholtz-Sloan , Eric Klein , Danny Manor Tocopherol transfer protein sensitizes prostate cancer cells to vitamin E The Journal of biological chemistry (2010) doi: 10.1074/jbc.m110.169664

In a 2015 correction the authors admitted the strange splicing, invented some splicing where there was none (for symmetry!), but chose to pretend there was no gel lane duplication (in orange above):

And to me, Danielpour said this:

“As a scientist, I am rather familiar with lab members making mistakes, all of which I have seen are innocent and experimental errors. What I mean is human-, equipment-, and technology-type errors. That is why I apply high standards of reproducibility and rigor. I always ensure the data in a publication from my lab are highly reproducible through multiple experiments, which is why papers from my lab have so much data. I am highly admired by my colleagues for the high level of rigor and reproducibility I continue to apply to research. Of course, no one is perfect. We all make mistakes, including clearly yourself Mr. Schneider.“

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