The Italian sleuth Aneurus Inconstans is always at your service when Italian science superstars need to be celebrated, be it in Italy or in USA. Today’s hero is a US cancer researcher with Italian roots: Salvatore Pizzo, Distinguished Professor of Pathology at Duke University in North Carolina. He is also a Fellow of American Association for the Advancement of Science (AAAS) since 1999.

Pizzo is 80 years young and urgently need to retire both himself and his papers.

It is not just Pizzo’science which is questionable. There was this lawsuit Dodd vs Pizzo from 2002, where Leslie G. Dodd (now professor at University of North Carolina Chapel Hill) sued Pizzo and Duke University for discrimination, harassment and “intentional or negligent infliction of emotional distress against both Defendants and assault and battery against Defendant Pizzo only.”

Dodd was hired by Pizzo in 1993 and promoted in 1996, they began a sexual relationship which Dodd ended in 1997, but which Pizzo wanted to continue, allegedly offering Dodd “improved job conditions” in return. Dodd claimed Pizzo began retaliating against her, and she lost her position as as Division Chief of Cytology. She also gave to protocol that Pizzo had been “ordering an expensive item of equipment which she did not request over her forged signature, . . . generating expressions of ill will in the Department of Pathology against Plaintiff, causing other professors to refuse to work with her, and having her work subjected to uncalled for and unusual quality reviews.” The court decided with:

“Granted as to Plaintiff’s Title VII claims of hostile work environment, sex discrimination, and retaliation, but denied as to Plaintiff’s Title VII claim of quid pro quo sexual harassment”

And now, Aneurus will tell you about Sal Pizzo’s scientific activities. And not just his! There will also be Pizzo’s Canadian collaborator Rick Austin, with bonus other Duke researchers and their collaborators.

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Cancer at Duke? Better call Sal!

By Aneurus Inconstans

Academia is breaking bad. When neither controls nor controllers are in place, any human enterprise soon turns into a circus or worse, and academia is no exception. Over the years the public got educated on the importance of research for society and human health, without knowing that academic research is often ruled by overgrown kids who play scientists.

Below is a twenty-year-old study, flagged by our sleuth colleague Clare Francis, where the offending blots are describing at the same time p-eIF2α and Akt, or the trio GRP78, XBP-1 and GADD34, or p-eIF2α and p-Akt, or the quintet GRP78, p-ERK, p-eIF2α, p-FKHR and p-Akt, plus two actin controls reused for different conditions. The article is supposed to show that insulin-dependent mechanisms overcome the insulin-induced ER stress by up-regulating the unfolded protein response (UPR) and the anti-apoptotic pathway to promote cell survival. Look yourself if we can trust the outcome:

Uma Kant Misra, Salvatore Vincent Pizzo* Up-regulation of GRP78 and antiapoptotic signaling in murine peritoneal macrophages exposed to insulin Journal of Leukocyte Biology (2005) doi: 10.1189/jlb.1104685

“I have NEVER faked data. I tried to locate Uma but haven’t been able to reach him. Uma would be well over 100 and I believe he has passed on. The data shown in our papers was always from single gels unless otherwise stated.”

Sal Pizzo

Were these two old professors really pipetting day and night all alone? No students or postdocs to help? No-one to shift blame to?

We all hope Uma is still with us and maybe Sal will eventually find him somewhere. Meanwhile, although unable to reach Uma, Sal decided to defend his old friend (and himself) unconditionally, and threatened legal actions:

“We have never done this. If you wish to carry on what appears to be a vendetta please supply me the name of your lawyer and I will have my lawyer contact him.”

Sal Pizzo

This fairy-tale in the shape of a scientific paper claims that α₂-Macroglobulin and CS-GRP78 regulate acetyl-CoA synthesis and thus function as epigenetic modulators by enhancing histone acetylation in cancer cells. Look at this joke:

Udhayakumar Gopal, Salvatore V. Pizzo* Cell surface GRP78 promotes tumor cell histone acetylation through metabolic reprogramming: a mechanism which modulates the Warburg effect Oncotarget (2017) doi: 10.18632/oncotarget.22431 

Even more recent is the next work from 2019, published in the Journal of Biological Chemistry, a journal that used to be at the forefront against science fraud, whereas now is just one of the many Elsevier’s dustbins.

The first author is again Gopal, while in second position we find Yvonne Mowery (3 papers on PubPeer, all with Sal), who moved in 2023 from Duke to the UPMC Hillman Cancer Center in Pittsburg as associate professor in radiation oncology. In third position in the author list sits a certain Kenneth Young, who is a lab administrator at DUMC in the department of radiation oncology. The paper investigates how GRP78 contributes to radio-resistance in pancreatic ductal adenocarcinoma (PDAC) cells. Remarkably, the authors found out that targeting GRP78 with C38 monoclonal antibodies increased the efficacy of radiation therapy against PDAC. Pity that all is fake:

Udhayakumar Gopal, Yvonne Mowery, Kenneth Young, Salvatore Vincent Pizzo* Targeting cell surface GRP78 enhances pancreatic cancer radiosensitivity through YAP/TAZ protein signaling Journal of Biological Chemistry (2019) doi: 10.1074/jbc.ra119.009091

The same GAPDH control has been reused for different cell types and treatments:

Udhayakumar Gopal, Mario Gonzalez-Gronow, Salvatore Vincent Pizzo* Activated α2-Macroglobulin Regulates Transcriptional Activation of c-MYC Target Genes through Cell Surface GRP78 Protein Journal of Biological Chemistry (2016) doi: 10.1074/jbc.m115.708131

Another one for Big Mario:

Mario Gonzalez-Gronow, Steven J. Kaczowka, Sturgis Payne, Fang Wang, Govind Gawdi, Salvatore V. Pizzo* Plasminogen Structural Domains Exhibit Different Functions When Associated with Cell Surface GRP78 or the Voltage-dependent Anion Channel Journal of Biological Chemistry (2007) doi: 10.1074/jbc.m703342200

The legacy of Super Mario again:

Uma Kant Misra, Mario Gonzalez-Gronow, Govind Gawdi, Fang Wang, Salvatore Vincent Pizzo* A novel receptor function for the heat shock protein Grp78: silencing of Grp78 gene expression attenuates α2M*-induced signalling Cellular Signalling (2004) doi: 10.1016/j.cellsig.2004.01.003

Yet the absolute masterpiece by Sal and Uma is the next one. The article was published in 2012 when they were aged 70 and 90, respectively. No-one at Duke wondered how these two guys were capable of producing so much data all alone. Six blots are reused within the paper, another ten are shared across eight other works, namely Mol Cancer Ther 2009, JBC 2011, J Cell Biochem 2011, PLoS One 2013, PLoS One 2014, JBC 2006, JBC 2005, J Leuk Biol 2005), each time describing different things.

Credits go to Clare Francis for digging out this mess. The article allegedly demonstrates that the binding of α₂M* to prostate cancer cell surface GRP78 upregulates mTORC1 and mTORC2 activation and promotes protein synthesis in the prostate cancer cells. Unfortunately nothing in this paper can be taken seriously:

Uma K. Misra , Salvatore V. Pizzo* Receptor-Recognized α2-Macroglobulin Binds to Cell Surface-Associated GRP78 and Activates mTORC1 and mTORC2 Signaling in Prostate Cancer Cells PLoS ONE (2012) doi: 10.1371/journal.pone.0051735

Most of those issues illustrated above were identified using ImageTwin.

On PubPeer thirteen papers are co-signed by only Sal and Uma, while ten others have three authors with Uma first and Sal last, plus one middle author. Other recurrent names on Sal’s papers are Steven J. Kaczowka, Sturgis Payne, Govind Gawdi and Rohit Deedwania.

One thing is certain: anyone in Carolina with issues of prostate cancer better DON’T call Sal.

Look at this stuff:

The most funny one:

Eye rolling? Right. I’ll stop here showing Sal & Co’s scientific atrocities, I believe the message is pretty clear.

Leonid wrote to Sal and to several Duke University’s executives for explanations, including Duke’s research integrity officer Dr Donna Kessler.

Sal’s initial attitude of denial first and threatening later, together with the worrisome “no reply” strategy by Dr Kessler, was abandoned due to Leonid’s persistence and the piling-up of issues on PubPeer. In fact, suddenly the following email materialized. It is from Alan D. Proia, who holds a double professorship in pathology and ophthalmology (highlights mine):

“Dear Dr. Schneider,

Dr. Pizzo requested that I independently review the images in question since I did not participate in the research and have no vested interest in the publications.

I agree that the images you questioned appear to have been duplicated with different labels in the publications. I base this opinion on 44 years in pathology, which requires comparing images as part of my routine practice. I also have a Ph.D. in biochemistry so I am proficient in comparing gel images.

Dr. Pizzo is extremely concerned and upset that errors, of which he was unaware, may have occurred.  Dr. Pizzo has authorized me to request a complete review of this issue from Dr. Donna Kessler’s scientific misconduct review office of Duke University. 

Dr. Pizzo believes that all the notebooks with original data are still in storage, which will facilitate an investigation. He has also requested that Dr. Kristi Orstian assist Dr. Kessler if help is needed with the review.

Dr. Pizzo thanks you for bringing this matter to his attention. He is committed to an open and comprehensive investigation of this matter and hopes it can be conducted swiftly.

Please let me know if you have any other concerns that I may help address. 

Sincerely yours,

Alan D. Proia, M.D., Ph.D.”

In the string of attached emails indeed Sal asked to Dr Proia to take care of this can of worms:

“Alan, I need advice. Could you call sometime. Sal“

Yes Alan, you better call Sal. However, in all honesty, I wonder why it is Sal himself deciding who should review his own papers. Second, since it is Dr Kessler the head of the scientific misconduct review office of Duke, then what is she exactly paid for?

Perhaps I’m nitpicking. After all an internal investigation is ongoing now, no?

Here is the issue in that paper, one blot describes different proteins:

You can appreciate this is not a simple duplication as the TF and p-eIF2α blots are cropped differently. Dr Austin offered his thoughts via email on the matter (highlights mine):

“Dear Everyone,
the image in question was generated by the first author of the study, Dr. Ali Al-Hashimi. I believe that this was an error during the submission of the original images involved. I have asked Dr. Al-Hashimi to provide the original blot for the p-eIF2alpha and submit the correct figure. I want to emphasize that this error in the image has no bearing on the findings of the paper as we examined multiple markers of ER stress, both at the mRNA and protein level. I will respond once Dr. Al-Hashimi determined where the error occurred and to provide the correct image. “

Richard C. Austin

Asking the first author to provide the original blot for the p-eIF2α would mean Austin found out the erroneous blot was that one and not TF? But then why waiting for Dr. Al-Hashimi to determine where the error occurred?

The Fellow of Canadian Academy of Health Sciences (appointed in 2022) says that the error has no bearing on whatsoever. How does Dr Austin know when he is still investigating?

Unfortunately, this is not the only error in Dr Austin’s papers, 9 of his articles are flagged on PubPeer for pretty bad stuff. Here is one, posted in September 2022 by our sleuth colleague Cheshire, two sets of micrographs overlap and are supposed to describe different genotypes and treatments:

Byun JH, Lebeau PF, Platko K, Carlisle RE, Faiyaz M, Chen J, MacDonald ME, Makda Y, Yousof T, Lynn EG, Dickhout JG, Krepinsky JC, Weaver F, Igdoura SA, Seidah NG, Austin RC* Inhibitory Antibodies against PCSK9 Reduce Surface CD36 and Mitigate Diet-Induced Renal Lipotoxicity Kidney360 (2022) doi: 10.34067/kid.0007022021

On PubPeer Dr Austin was again keen to reassure there’s no bearing:

Somehow Austin and his people cannot place two micrographs together without doing a mess. How is that?

Below another example by Austin. Micrographs (blue and green boxes) have been reused across articles for different genotypes (Pcsk9^-/- and Pcsk9^+/+, respectively). On top of that, another four sets of images (dashed boxes) were reused without any disclosure in the two papers published shortly apart. Do they take one single image for each experiment, which in turn is never repeated a second time?

Lebeau PF, Byun JH, Platko K, MacDonald ME, Poon SV, Faiyaz M, Seidah NG, Austin RC* Diet-induced hepatic steatosis abrogates cell-surface LDLR by inducing PCSK9 expression in mice J Biol Chem. (2019) doi: 10.1074/jbc.ra119.008094

Lebeau PF, Byun JH, Platko K, Al-Hashimi AA, Lhoták Š, MacDonald ME, Mejia-Benitez A, Prat A, Igdoura SA, Trigatti B, Maclean KN, Seidah NG, Austin RC* Pcsk9 knockout exacerbates diet-induced non-alcoholic steatohepatitis, fibrosis and liver injury in mice JHEP Reports (2019) doi: 10.1016/j.jhepr.2019.10.009

But as seen before, it doesn’t go any better with Western blots for Austin. In the paper below the same control is used for different treatments. It’s a collaborative work with Austin’s department colleague Geoff H. Werstuck, who is incidentally also the first author of one of the papers highlighted above:

Anna J. Kim , Yuanyuan Shi , Richard C. Austin, Geoff H. Werstuck* Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3 Journal of Cell Science (2005) doi: 10.1242/jcs.01562

Do you now understand, dear readers, in what hands cancer research is?

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More luminaries at Duke and around the USA

We leave the wilderness of Ontario and return to Duke. According to the Times Higher Education (THE) university ranking, Duke is 26^th in the world, while it’s 57^th in the QS ranking.

It should then be truly an amazing institution where the eager young minds of tomorrow are nurtured, no?

I wandered through the faculty members of DUMC and, almost instantaneously, the third and the fourth and the fifth person I checked fell into the net of my scrutiny. Can you believe it?

Please meet James L. Abbruzzese (15 papers on PubPeer, 5 retractions), distinguished professor emeritus of medical oncology, specialized in clinical study and treatment of pancreatic cancer. To be fair, Dr Abbruzzese is always a middle author on those articles. In fact, most of Abbruzzese’s problematic papers have as leading authors these two guys:

1. Paul J. Chiao (25 papers on PubPeer, 1 retraction and 1 EoC), professor at MD Anderson Cancer Center in Houston, Texas (a place that For Better Science readers know like a second home)
2. Fazlul H. Sarkar, sacked professor of pathology at the Karmanos Cancer Center of the Wayne State University in Detroit, Michigan, who sports 79 articles on PubPeer with 41 retractions (FORTY-ONE)

Important to say, while Sarkar was sacked and Abbruzzese has retired, Chiao is still out there doing damage. But what else could one expect from MD Anderson other than protecting its fleet of crooks?

Below is one of Chiao’s & Abbruzzese’s co-productions. It’s pure beauty. Please pay attention to the background’s smoothness behind the copy-pasted bands:

Zhongkui Li, Guido M. Sclabas, Bailu Peng, Kenneth R. Hess, James L. Abbruzzese, Douglas B. Evans, Paul J. Chiao* Overexpression of synuclein-gamma in pancreatic adenocarcinoma Cancer (2004) doi: 10.1002/cncr.20321

Again the magic Chiao-Abbruzzese duo, everything is beautifully fake:

Fujioka S, Schmidt C, Sclabas GM, Li Z, Pelicano H, Peng B, Yao A, Niu J, Zhang W, Evans DB, Abbruzzese JL, Huang P, Chiao PJ* Stabilization of p53 is a novel mechanism for proapoptotic function of NF-kappaB J Biol Chem (2004) doi: 10.1074/jbc.m313435200

One of Abbruzzese’s retractions with Sarkar:

Zhiwei Wang, Dejuan Kong, Sanjeev Banerjee, Yiwei Li, N. Volkan Adsay, James Abbruzzese, Fazlul H. Sarkar* Down-regulation of platelet-derived growth factor-D inhibits cell growth and angiogenesis through inactivation of Notch-1 and nuclear factor-kappaB signaling Cancer Research (2007) doi: 10.1158/0008-5472.can-07-2803 [Retracted]

And then, icing on the cake. Below is a retracted paper bearing Abbruzzese, Chiao and Sarkar all together. The same actin control is duplicated, flipped and rotated three times, plus there are other duplications that were never illustrated on PubPeer:

Both Chiao and Sarkar would deserve their own FBS article, but we have no time and have to move one.

Poteet E, Choudhury GR, Winters A, Li W, Ryou MG, Liu R, Tang L, Ghorpade A, Wen Y, Yuan F, Keir ST, Yan H, Bigner DD, Simpkins JW, Yang SH* Reversing the Warburg Effect as a Treatment for Glioblastoma J Biol Chem. (2013) doi: 10.1074/jbc.M112.440354.

“The justification has been provided to the editor in the correction response in 2018. We have provided editor the original whole blot membranes images, invert images, and images with brightness adjustment. The p-mTOR and mTOR in 5B, although look very similar in the original figure, they are very different after brightness adjustment.”

S.-H. Yang

You tell me, dear readers, if p-mTOR and mTOR can be different:

Again Dr Yang wanted to dispel any doubts:

“The ACC in 6C and Cyclin E1 in 6D, although look very similar in the original figure, they had very different molecular weight. The ACC blots were at the top section of the membrane, while the Cyclin E1 were at the middle section of the membrane. To avoid future confusion, we have provided the editor additional immunoblots (look very different) for the correction.”

S.-H. Yang

They had very different molecular weight? Of course dear Dr Yang!

I’m afraid that Dr Yang torpedoed himself. Either he is visually impaired or he is cheating, and I’ll leave you to imagine which option I’m leaning towards, dear readers.

Feng H, Lopez GY, Kim CK, Alvarez A, Duncan CG, Nishikawa R, Nagane M, Su AJ, Auron PE, Hedberg ML, Wang L, Raizer JJ, Kessler JA, Parsa AT, Gao WQ, Kim SH, Minata M, Nakano I, Grandis JR, McLendon RE, Bigner DD, Lin HK, Furnari FB, Cavenee WK, Hu B, Yan H, Cheng SY* EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis J Clin Invest (2014) doi: 10.1172/jci73093

Below is another Cheng’s work that aims to defeat cancer, and once more Cheshire’s grin floated in. You’ll find again the whole package: duplicated and rotated micrographs and blots within and across papers describing different things:

Haizhong Feng , Bo Hu , Kun-Wei Liu , Yanxin Li , Xinghua Lu , Tao Cheng , Jia-Jean Yiin , Songjian Lu , Susan Keezer , Tim Fenton , Frank B. Furnari , Ronald L. Hamilton , Kristiina Vuori , Jann N. Sarkaria , Motoo Nagane , Ryo Nishikawa , Webster K. Cavenee , Shi-Yuan Cheng* Activation of Rac1 by Src-dependent phosphorylation of Dock180Y1811 mediates PDGFRα-stimulated glioma tumorigenesis in mice and humans J Clin Invest (2011) doi: 10.1172/jci58559

Those highlighted numbers in the caption above (listed by Cheshire) are the grants spent (or partly spent) to produce that fairy-tale. This is what your money is used for, dear taxpayers.

Perhaps you can spot some recurring co-authors in Cheng’s fake papers. Please meet Haizhong Feng (10 papers on PubPeer) currently professor at the Renji Hospital of the Shanghai Jiao Tong University, Frank B. Furnari (11 papers on PubPeer) professor of medicine at the Moores Cancer Center of UC San Diego, and Webster K. Cavenee (11 papers on PubPeer) distinguished professor at the Ludwig Institute for Cancer Research of UCSD.

Here below another lovely Cheng-Feng-Cavenee-Furnari production, this time in PNAS no the less, “Contributed by Webster K. Cavenee“, the National Academy of Sciences member:

Haizhong Feng, Bo Hu, Michael J Jarzynka, Yanxin Li, Susan Keezer, Terrance G Johns, Careen K Tang, Ronald L Hamilton, Kristiina Vuori, Ryo Nishikawa, Jann N Sarkaria, Tim Fenton, Tao Cheng, Frank B Furnari, Webster K Cavenee, Shi-Yuan Cheng* Phosphorylation of dedicator of cytokinesis 1 (Dock180) at tyrosine residue Y722 by Src family kinases mediates EGFRvIII-driven glioblastoma tumorigenesis PNAS (2012) doi: 10.1073/pnas.1121457109

Back to Duke.

Chen M, Zhang J, Sampieri K, Clohessy JG, Mendez L, Gonzalez-Billalabeitia E, Liu XS, Lee YR, Fung J, Katon JM, Menon AV, Webster KA, Ng C, Palumbieri MD, Diolombi MS, Breitkopf SB, Teruya-Feldstein J, Signoretti S, Bronson RT, Asara JM, Castillo-Martin M, Cordon-Cardo C, Pandolfi PP* An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer Nature Genetics (2018) doi: 10.1038/s41588-017-0027-2.

The constellation of authors in the paper described above deserves a presentation.

1. The corresponding author is Pier Paolo Pandolfi (43 papers on PubPeer), sacked Harvard professor, now scientific director at the William N. Pennington Cancer Institute in Reno, Nevada. Chen and Pandolfi used to work together at the Beth Israel Deaconess Cancer Center of Harvard Medical School before Pandolfi was kicked out for sexual harassment. All three Chen’s paper on PubPeer are with Pandolfi.
2. Second-last name is Carlos Cordon-Cardo (33 papers on PubPeer), chair of the Department of Pathology, Molecular and Cell-Based Medicine at the Icahn School of Medicine Mount Sinai, New York City.
3. Third-last name is Mireia Castillo-Martin (8 papers on PubPeer), previously also at Mount Sinai, now research group leader at the Champalimaud Foundation in Lisbon, Portugal.
4. Fourth-last is John M. Asara (16 papers on PubPeer), associate professor and director of the mass spectrometry core facility at Beth Israel Deaconess Cancer Center of Harvard Medical School.
5. Fifth-last is Roderick T. Bronson (14 papers on PubPeer) core unit director at the Department of Microbiology and Immunobiology, Harvard Medical School.
6. Sixth-last is Sabina Signoretti (25 papers on PubPeer), researcher at Dana-Farber Cancer Institute in Boston, Massachusetts, another place infested by an incredible number of questionable scientists.
7. Seventh-last is Julie Teruya-Feldstein (8 papers on PubPeer), director of hematopathology at the Icahn School of Medicine Mount Sinai, NYC.

There’s no time now to go through the questionable science by those names listed above. Just know that if you click on the links to their pubpeered articles you will open a whole new Pandora’s box and arrive at Lewis Cantley, Ronald DePinho, Douglas Green, John Blenis, Wenyi Wei, George Daley, Raghu Kalluri, Giulio Draetta, James Collins and hundreds more. Please check it out yourselves if you care to know how deep the rabbit hole goes.

Does anyone know if the tragic characters I discussed in this blog post also have a role as hospital doctors? That is, in addition to producing bogus data, do they also treat patients? While waiting to discover the mystery, I extend my heartfelt wishes of a speedy recovery to all cancer patients all over the globe, and today in particular to those of Carolina. Yes, I’m gone to Carolina in my mind.

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