Julius Caesar & Daria – Brazilian Tango in Stanford

Our protagonists are:

Julio Cesar Batista Ferreira is Professor of Systems Biology at the University of Sao Paolo in Brazil, and his former mentor at Stanford University in USA, Daria Mochly-Rosen. She is associate director of Stanford’s Cardiovascular Institute and endowed Professor of Translational Medicine at the Department of Chemical Systems Biology, while Ferreira is Visiting Associate Professor there.

Mochly-Rosen is originally from Israel, she moved to Stanford in 1997 and rose through the ranks. She used to act as Senior Associate Dean for Research of the Stanford University School of Medicine (2006-2013), and she is also the Founding President of Stanford’s SPARK Global:

“SPARK is a unique partnership between university and industry founded by Professor Daria Mochly-Rosen in 2006 at Stanford University in USA. The purpose is to provide the education and mentorship necessary to advance research discoveries from the bench to the bedside. SPARK provides access to specialized knowledge and technical expertise regarding drug and diagnostic development and sources of funding to support translational efforts.”

Ferreira was Mochly-Rosen’s graduate student 2007-2009 and stayed on as postdoc until 2012, when he returned to his University of Sao Paolo to become associate professor, and later on member of Brazilian Academy of Sciences. Now you will see which groundbreaking research discoveries these two scientists tried to translate into clinician medicine. Ferreira has almost 20 papers on PubPeer, many with Mochly-Rosen. Like this, where they sought to help alcoholics suffering from heart disorders:

A duplicated dataset, maybe a mistake? Yet I recognise among the authors Marie-Hélène Disatnik, who, before joining Mochly-Rosen’s lab as postdoc, previously graduated with fake science in Thomas Rando‘s lab, also in Stanford. Read here:

More of the failed heart research, again with Disatnik, and what were they thinking publishing in a journal where authors must upload raw data:

Julio C. B. Ferreira , Juliane C. Campos , Nir Qvit , Xin Qi , Luiz H. M. Bozi , Luiz R. G. Bechara , Vanessa M. Lima , Bruno B. Queliconi , Marie-Helene Disatnik , Paulo M. M. Dourado , Alicia J. Kowaltowski , Daria Mochly-Rosen A selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats Nature Communications (2019) doi: 10.1038/s41467-018-08276-6 

This paper was celebrated with a press release by the Brazilian funding agency FAPESP where we were informed that Ferreira and Mochy-Rosen already patented this new drug for heart failure and seek industrial collaborators. Why, yes, in Nature Communications Mochly-Rosen and her colleagues dishonestly claimed: “The authors declare no competing interests.”

Mochly-Rosen is also the founder of the multi-million dollar heavy biotech startup Mitoconix (which was registered in Israel), and we also learn that she “was the founder and CSO of Kai Pharmaceuticals, a peptide therapeutic company that was acquired by Amgen in 2011 for $315 million.” The lead product of this company, Etelcalcetide (KAI-4169), later received approvals from FDA and EMA for treatment of kidney disease. The patent for KAI-4169 is however assigned to other people though, not Mochly-Rosen. She also co-founded another company, Aldea Pharmaceuticals, which strived to treat “acute and chronic aldehyde metabolism disorders“, which since 2011 raised many millions in investment ($24 million in 2014 alone), and advanced to “permanently closed” in the same year.

In August 2014, shortly before Aldea’s collapse, Stanford celebrated Mochly-Rosen’s paper Zambelli et al 2014 and her miracle painkiller Alda-1 (aldehyde dehydrogenase activator 1):

““Finding a new pain medication is important because we need a safer drug; there are 17,000 deaths from prescription opiate overdoses a year alone,” said Daria Mochly-Rosen, professor of chemical and systems biology. […] “We made what may appear as a crazy leap,” Mochly-Rosen said.”

As Bagne-Ueta et al 2018 mentions, Mochly-Rosen’s Alda-1 patent was sold to the Taiwanese company Foresee Pharmaceuticals.

Ferreira also found cures for many diseases. How about this from his lab, a creative therapy for muscle loss:

Juliane C. Campos , Leslie M. Baehr , Nikolas D. Ferreira , Luiz H. M. Bozi , Allen M. Andres , Márcio A. C. Ribeiro , Roberta A. Gottlieb , Sue C. Bodine, Julio C. B. Ferreira β ₂ ‐adrenoceptor activation improves skeletal muscle autophagy in neurogenic myopathy The FASEB Journal (2020) doi: 10.1096/fj.201902305r

As it happens, also the PhD thesis of Ferreira’s doctorate student Juliane Cruz Campos contains duplications. She is a visiting postdoc in Harvard now, sponsored by a fellowship from the Sao Paulo Research Foundation (FAPESP). I see a great future for her, she does have the artistic talent to follow into her mentor’s footsteps:

Juliane C. Campos , Leslie M. Baehr , Kátia M. S. Gomes , Luiz R. G. Bechara , Vanessa A. Voltarelli , Luiz H. M. Bozi , Márcio A. C. Ribeiro , Nikolas D. Ferreira , José B. N. Moreira , Patricia C. Brum , Sue C. Bodine , Julio C. B. Ferreira Exercise prevents impaired autophagy and proteostasis in a model of neurogenic myopathy Scientific Reports (2018) doi: 10.1038/s41598-018-30365-1 

Which brings us to another problematic collaboration, with Ferreira’s fellow professor at University of Sao Paolo, Patricia Brum. She has currently 14 very problematic papers on PubPeer. Often as last author, like here:

Here more collaborations between Brum, Ferreira and Mochly-Rosen, and of course young shooting star Dr Campos is on board:

Julio C.B. Ferreira , Jose B.N. Moreira , Juliane C. Campos , Marcelo G. Pereira , Katt C. Mattos , Marcele A. Coelho , Patricia C. Brum Angiotensin receptor blockade improves the net balance of cardiac Ca2+ handling-related proteins in sympathetic hyperactivity-induced heart failure Life Sciences (2011) doi: 10.1016/j.lfs.2011.01.009

I am not sure how heart and skeletal muscle deficiency can be cured with fake western blots, but then again, they are the experts, right? Also here:

Juliane C. Campos , Bruno B. Queliconi , Luiz H. M. Bozi , Luiz R. G. Bechara , Paulo M. M. Dourado , Allen M. Andres , Paulo R. Jannig , Kátia M. S. Gomes , Vanessa O. Zambelli, Cibele Rocha-Resende , Silvia Guatimosim , Patricia C. Brum , Daria Mochly-Rosen, Roberta A. Gottlieb, Alicia J. Kowaltowski , Julio C. B. Ferreira Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure Autophagy (2017) doi: 10.1080/15548627.2017.1325062

The Brum-Ferreira-Mochly collaboration goes back at least a decade:

Julio C. B. Ferreira , Berta Napchan Boer , Max Grinberg , Patricia Chakur Brum, Daria Mochly-Rosen Protein quality control disruption by PKCβII in heart failure; rescue by the selective PKCβII inhibitor, βIIV5-3 PLoS ONE (2012) doi: 10.1371/journal.pone.0033175 

Ferreira announced on PubPeer, for all of the above threads, to “submit a correction to the journal, if needed.” He also wrote to me a similar message in an email from 29 September 2023:

“Dear Leonid,
We are carefully going through pubpeer comments and examining the original data. We will submit a correction to the journal, if needed, and update it in pubpeer.
Julio“

Mochly-Rosen never replied to my emails. Well, here is how they correct their papers, again on the topic of alcoholism:

Che-Hong Chen , Julio C.B. Ferreira, Amit U. Joshi , Matthew C. Stevens , Sin-Jin Li , Jade H.-M. Hsu , Rory Maclean , Nikolas D. Ferreira , Pilar R. Cervantes , Diana D. Martinez , Fernando L. Barrientos , Gibran H.R. Quintanares , Daria Mochly-Rosen Novel and prevalent non-East Asian ALDH2 variants; Implications for global susceptibility to aldehydes’ toxicity EBioMedicine (2020)
doi: 10.1016/j.ebiom.2020.102753  

In October 2023, Ferreira announced:

“The histogram under the 3B blots has been replotted after reviewing the data and is in agreement with the original histogram. The corrected Fig. 3B and original blots are provided below. We already contacted the editor of the journal.”

This was his new, corrected figure:

In fact, it seems many people in Mochly-Rosen lab struggle with basic ethics and honesty. This one is a bit older:

Gouri Yogalingam , Sunhee Hwang , Julio C. B. Ferreira , Daria Mochly-Rosen Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) phosphorylation by protein kinase Cδ (PKCδ) inhibits mitochondria elimination by lysosomal-like structures following ischemia and reoxygenation-induced injury Journal of Biological Chemistry (2013) doi: 10.1074/jbc.m113.466870 

The first author Gouri Yogalingam, now Senior Scientist at the Californian biotech Bio Marin Pharmaceutical, explained on PubPeer:

“This paper was completed after I left the lab. I don’t recall stitching together different lanes of gels to make a figure like this if that’s what the claim is. It seems too difficult to do. Pub Peer is claiming that the lanes have been duplicated but while I see the similarities I also see differences. There is a gap between one band and another but I recall that the X-ray film would have grainy marks on them sometimes and sometimes if gels didn’t transfer well or were dirty you could get lines between the bands. I’m not sure what the claim is here and don’t recall details from a decade ago but I stand by the data shown here and the conclusions made.”

But of course, Gouri. It’s the amazing reproducibility of your stellar heart research, not gel band duplications. Let’s look at another paper.

First and co-corresponding author Nir Qvit, now Assistant Professor at Bar Ilan University in Israel, accused the PubPeer commentor of slander and forgery:

“He/She copied and pasted panel Fig. 6H from our JBC paper (see attached below as published originally) on top of our original panel Fig. 6J.”

True, the online version of the paper shows no duplication. But the one on Sci-Hub does, yet Qvit insisted that copy was somehow forged by third parties. Of course, there is an alternative explanation. Sci-Hub stores the “In Press” version of Qvit’s paper (i.e., authors’ original accepted manuscript), which must have received a stealth correction during the copy-editing stage. Journals feel they don’t have to issue Corrigenda when “mistakes” are fixed by the publisher during the typesetting, before the official publication. Also, Ferreira uploaded the same In Press copy on ResearchGate, but Qvit insisted:

“We can not recall that the authors have made any changes or contacted JBC in 2021.”

It gets better! In the same PubPeer thread, a gel band duplication was alleged between this and an earlier paper by same authors, which Qvit disproved by uploading extended gels. The originally highlighted bands were indeed not identical. But! Other duplications were found thanks to what Qvit supplied:

Qvit refused to discuss this. But sure, he never makes mistakes:

Nir Qvit , Amanda J. Lin , Aly Elezaby , Nicolai P. Ostberg , Juliane C. Campos , Julio C. B. Ferreira , Daria Mochly-Rosen A Selective Inhibitor of Cardiac Troponin I Phosphorylation by Delta Protein Kinase C (δPKC) as a Treatment for Ischemia-Reperfusion Injury Pharmaceuticals (2022) doi: 10.3390/ph15030271

Qvit explained that the image reuse was intentional and correct, extended from the research in 2016, and he never claimed “the controls in the three studies were the same” and anyway, “in Israel we do not use the Wistar rats, so I mistakenly wrote Spargue Dawley rats.”

Yet Qvit and Mochly-Rosen already had to correct their 2016 paper for a similar problem:

Nir Qvit, Opher S. Kornfeld , Daria Mochly-Rosen Engineered Substrate-Specific Delta PKC Antagonists to Enhance Cardiac Therapeutics Angewandte Chemie International Edition (2016) doi: 10.1002/anie.201605429

Actually, maybe it is Mochly-Rosen who trained Ferreira, Qvit and others in bad science, who then trained the next generation like Campos? Her own PubPeer record includes papers without Ferreira.

In 2019, Mochly-Rosen presented a cure for Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, dementia and Huntington’s disease, a drug named P110 which she says prevents mitochondrial fragmentation. The paper is announced to be corrected for a second time:

Amit U. Joshi , Paras S. Minhas , Shane A. Liddelow , Bereketeab Haileselassie , Katrin I. Andreasson , Gerald W. Dorn , Daria Mochly-Rosen Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration Nature Neuroscience (2019) doi: 10.1038/s41593-019-0486-0 

In December 2020, a Correction was issued by the authors:

“In the version of this article initially published, two graphs were inadvertently duplicated in Fig. 2: the left graph in Fig. 2f and the right graph in Fig. 2k. These graphs have been replotted after reviewing the data; results and conclusions were not affected.”

Then, in August 2023, Paul S Brookes found this:

The first author Amit Joshi, c-holder of the P110 patent and now Senior Director at the Californian biotech startup Autobahn Labs, still saw no reason to worry:

“A series of unintentional actions led to the submission of ‘mock’ placeholder images, which were meant to be replaced with the correct images. We have notified the Editor of the journal about these errors and provided them with all the relevant raw data. It is crucial to emphasize that these mistakes in figure preparation in the indicated image panels do not in any way reflect the actual outcomes of the study.”

Elsewhere we learn that study’s patented drug P110 has been “licensed to Mitoconix Bioscience, a company that DM-R founded, that develops new treatment for Huntington’s disease“. In 2017, Mochly-Rosen’s Mitoconix raised $20 million with her Huntington Disease drug, which is the same P110:

“Mitoconix Bio’s lead product MTC-1203, is a first-in-class selective inhibitor of excessive mitochondrial division for treating Huntington’s disease and other neurodegenerative disorders. MTC-1203 has demonstrated efficacy in mouse models of Huntington’s and Parkinson’s diseases.”

For some reason, Mitoconix went bust soon after in June 2019 (as Mochly-Rosen explained on PubPeer, before the paper was published). Kind of reminiscent of her other startup Aldea’s way – raise many millions from investors and close shop right after. Unlike Aldea’s, Mitoconix website has been deleted, but there are online archives and even a PowerPoint presentation for those nostalgic:

Maybe, just maybe, Mitoconix and Aldea with their miracle drugs failed, because, I am speculating, taking wild guesses and stabbing in the dark here, because Mochly-Rosen’s preclinical science was dodgy, held together only by photoshopped blots and recycled microscopy images?

Mochly-Rosen may have many talents, but reliable science is apparently not one of them. Look at this study of hers with a certain James Fagin, Professor at Memorial Sloan Kettering, whose own PubPeer record is very worrisome:

Jeffrey A. Knauf , Laura S. Ward , Yuri E. Nikiforov , Marina Nikiforova , Efisio Puxeddu , Mario Medvedovic , Tamar Liron , Daria Mochly-Rosen , James A. Fagin Isozyme-specific abnormalities of PKC in thyroid cancer: evidence for post-transcriptional changes in PKC epsilon The Journal of Clinical Endocrinology & Metabolism (2002) doi: 10.1210/jcem.87.5.8441 

Just so you know Fagin is capable of, again with his mentee Jeffrey Knauf:

Roberta Malaguarnera, Kuen-Yuan Chen , Tae-Yong Kim , Jose M. Dominguez , Francesca Voza , Bin Ouyang , Sushil K. Vundavalli , Jeffrey A. Knauf, James A. Fagin Switch in signaling control of mTORC1 activity after oncoprotein expression in thyroid cancer cell lines The Journal of Clinical Endocrinology & Metabolism (2014) doi: 10.1210/jc.2013-3976 

There are many more cloned gel bands in that paper, but Knauf declared on PubPeer in May 2019 the raw data to be unavailable, all conclusions unaffected, any anyway, “quantification of band intensity (see raw values below) done at the time shows that they are not identical“. Knauf’s name is on almost all of Fagin’s fake papers on PubPeer, and he still works in Fagin’s lab as “Associate Attending Biologist”.

Anyway, those papers are Fagin’s problem. But Mochly-Rosen and Ferreira have their own problematic papers to deal with. I suggest sending them the way Mitoconix went.

This was not an honest mistake by Ferreira and Campos:

Idula Ramesh , Juliane C. Campos , Pamela Lee , Yang Song , Genaro Hernandez , Jon Sin , Kyle C. Tucker , Hannaneh Saadaeijahromi , Michael Gurney, Julio C. B. Ferreira, Allen M. Andres Mitophagy protects against statin-mediated skeletal muscle toxicity The FASEB Journal (2019) doi: 10.1096/fj.201900807rr 

Not likely a mere oversight by Ferreira and Brum:

M. G. Pereira , J. C. B. Ferreira , C. R. Bueno , K. C. Mattos , K. T. Rosa , M. C. Irigoyen , E. M. Oliveira , J. E. Krieger, Patricia Chakur Brum Exercise training reduces cardiac angiotensin II levels and prevents cardiac dysfunction in a genetic model of sympathetic hyperactivity-induced heart failure in mice European Journal of Applied Physiology (2009) doi: 10.1007/s00421-008-0967-4 

The crazy thing is that the Brazilian researcher Ferreira learned such rotten approach to science in Stanford. But then again, not only the (recently resigned) Stanford President Marc Tessier Lavigne but even Nobel Prize laureates there struggle with research ethics. Look at Thomas Südhof.

Maybe Stanford is a bad place for science.

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