My Big Fat Greek Ophthalmology

You all will certainly recall Sholto David‘s blockbuster about Dana Farber Cancer Institute (DFCI) in Harvard. you may also recall a certain Greek haematologist there, named Constantine Mitsiades, or Mitsi, as I like to affectionately call this charming man.

Now, Mitsi used to wear glasses on his older photos, but now he doesn’t. And this is possibly because he has fellow Greeks in ophthalmology. This article is about Mitsi’s friends, and their friends, and everyone here is either Greek or at least honorary Greek.

In Greece, it is all about family. Mitsi has a brother who regularly features as coauthor – Nicholas Mitsiades, who is also a cancer researcher, but on prostate instead of blood. He was previously at Baylor College in Texas, since 2022 even further away, at the University of California Davis. I shall call him The Other Mitsi. He didn’t wear glasses in older pictures, but now does.

Both Mitsi and The Other Mitsi trained at DFCI as postdocs under Kenneth Anderson whom you sure know well from Sholto’s legendary DFCI bestseller. Because of the international news coverage, Anderson and his two Mitsis recently retracted several papers, while another one had to be corrected for duplicated mice:

There is so much dodgy cancer research by Anderson and the two Mitsis that it didn’t fit in the Sholto’s article. So here is some older PubPeer material posted by Clare Francis:

Dharminder Chauhan , Guilan Li , Daniel Auclair , Teru Hideshima , Paul Richardson , Klaus Podar, Nicholas Mitsiades , Constantine Mitsiades , Cheng Li , Ryung Suk Kim , Nikhil Munshi , Lan Bo Chen , Wing Wong , Kenneth C. Anderson Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays Blood (2003) doi: 10.1182/blood-2002-10-3146 

Here is Mitsi again, without his brother, but with Anderson’s entire DFCI gang:

Yu-Tzu Tai , Laurence P. Catley , Constantine S. Mitsiades , Renate Burger , Klaus Podar, Reshma Shringpaure , Teru Hideshima , Dharminder Chauhan , Makoto Hamasaki , Kenji Ishitsuka , Paul Richardson , Steven P. Treon , Nikhil C. Munshi , Kenneth C. Anderson Mechanisms by which SGN-40, a humanized anti-CD40 antibody, induces cytotoxicity in human multiple myeloma cells: clinical implications Cancer Research (2004) doi: 10.1158/0008-5472.can-03-3630

You probably can’t wait to finally see some Greek ophthalmologists I promised, right?

Now pay attention to a certain Greek co-author of Mitsi and the Anderson gang here, Vassiliki Poulaki – this lovely Greek lady used to be a lecturer for ophthalmology in Harvard, but in 2022 she “left the department in January for a private practice opportunity in Maryland“:

Constantine S Mitsiades, Nicholas Mitsiades, Vassiliki Poulaki , Robert Schlossman , Masaharu Akiyama, Dharminder Chauhan, Teru Hideshima, Steven P Treon, Nikhil C Munshi , Paul G Richardson , Kenneth C Anderson Activation of NF-kappaB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications Oncogene (2002) doi: 10.1038/sj.onc.1205664

The two Mitsis and Vassiliki have many common papers, also on PubPeer. Not by accident: they are personally related (according to White Pages and US Phone Book). As I learned, Vassiliki and The Other Mitsi used to be married.

And now, Mitsi, The Other Mitsi, Vassiliki, and a German whom the most dedicated readers of For Better Science might remember unfondly: Poulaki’s former associate and possibly a friend from the common time in Harvard – Antonia Joussen, now professor and head of the ophthalmology clinic at the Charité Berlin. Another co-author is Joussen’s former mentor from University of Cologne, Bernd Kirchhof:

Vassiliki Poulaki , Constantine S. Mitsiades , Antonia M. Joussen , Alexandra Lappas , Bernd Kirchhof , Nicholas Mitsiades Constitutive nuclear factor-kappaB activity is crucial for human retinoblastoma cell viability American Journal Of Pathology (2002) doi: 10.1016/s0002-9440(10)64499-9 

In June 2015, an editorial Note of Concern was published:

“This matter was simultaneously brought to the attention of the Editors by corresponding author Dr. Poulaki and by a concerned reader. Dr. Poulaki states, “We believe that the most likely explanation for this error is an inadvertent misidentification of the original files at the stage of image capture with Openlab software (PerkinElmer, Waltham, MA; circa 2001), which subsequently escaped our attention due to the quantitative similarity of panels B–F. We sincerely regret this inadvertent error.””

That reader was yours truly. My first article about Joussen was published on 2 June 2015, after several months of investigation. Joussen immediately deployed a Berlin lawyer to get my reporting about her deleted, luckily even German courts don’t forbid quoting from PubPeer.

Nothing was done on that and other papers by Joussen. That is because Charité Berlin, the universities of Cologne and Düsseldorf where Joussen used to work, issued orders never to investigate her papers. The German Research Council DFG was also scared of Joussen and terminated their own investigation, declaring her a victim of other people’s data manipulation:

Years ago, I spoke to several of her former colleagues and subordinates, after that I understood that Joussen’s PubPeer record was indeed harmless poppycock. She may look nice, but you wouldn’t want her as your boss. And: Charité knows everything, and they did take sides. Joussen is one of the most powerful ophthalmologists in Germany, not despite but because of everything. I wrote to Joussen and Charité again, this time only silence came back. Not even a lawyer’s cease-and-desist letter with demands for piles of money. Meh.

But let’s return to Joussen’s happy Greek adventures in Harvard, with Vassiliki, Mitsi, The Other Mitsi, and the former postdoctoral mentor of both Joussen and Vassiliki: Anthony Adamis. Tony is indeed another Greek ophthalmologist, he is member of the National Academy of Sciences and lecturer in Harvard but his main job now is at Genentech/Roche as Global Head of Ophthalmology, Immunology and Infectious Diseases. Adamis’ real interests were always in business, he founded biotech companies of his own and sits on boards of others.

Another eye-opening paper:

A M Joussen , S Huang , V Poulaki , K Camphausen , W D Beecken , B Kirchhof , A P Adamis In vivo retinal gene expression in early diabetes Investigative Ophthalmology & Visual Science (2001) Nov;42(12):3047-57.

Here are Joussen, Vassiliki and their mentor Tony again, plus another Greek – George Yancopoulos, co-founder, president and chief scientific officer of Regeneron Pharmaceuticals, a US biotech with a market value of over $100 BILLION:

Vassiliki Poulaki , Wenying Qin , Antonia M. Joussen, Peter Hurlbut , Stanley J. Wiegand , John Rudge , George D. Yancopoulos , Anthony P. Adamis Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF Journal of Clinical Investigation (2002) doi: 10.1172/jci13776 

Tony Adamis published dodgy stuff with other co-authors also, which should reassure everyone that Roche’s ophthalmology R&D is in safe and trustworthy hands:

Nobuo Jo , Carolina Mailhos , Meihua Ju , Eunice Cheung , John Bradley , Kazuaki Nishijima , Gregory S. Robinson , Anthony P. Adamis, David T. Shima Inhibition of platelet-derived growth factor B signaling enhances the efficacy of anti-vascular endothelial growth factor therapy in multiple models of ocular neovascularization American Journal Of Pathology (2006) doi: 10.2353/ajpath.2006.050588 

In 2015, a Note of Concern was published:

“Dr. Shima states that “this was a genuine error, and we are confident in the actual quantitative data presented in the figure. Not only have other investigators reproduced combination data,¹ we also presented in the article another experiment….”

As it happens, David Shima used to be VP for Ophthalmology at Roche 2013-2015, had 4 jobs in industry and academia since, and is presently #OpenToWork on LinkedIn. Coincidence or not, he has more papers on PubPeer. Another genuine error by Shima and Adamis:

Norihiro Nagai , Pete Lundh Von Leithner , Kanako Izumi-Nagai , Brett Hosking , Bo Chang , Ron Hurd , Peter Adamson , Anthony P. Adamis , Richard H. Foxton , Yin Shan Ng , David T. Shima Spontaneous CNV in a novel mutant mouse is associated with early VEGF-A-driven angiogenesis and late-stage focal edema, neural cell loss, and dysfunction Investigative Opthalmology & Visual Science (2014) doi: 10.1167/iovs.14-13989 

Now, more by Joussen and Mitsi’s Vassiliki, this time with Joussen’s personnel in Germany:

Kan Koizumi , Vassiliki Poulaki, Sven Doehmen , Gerhard Welsandt , Sven Radetzky , Alexandra Lappas , Norbert Kociok , Bernd Kirchhof , Antonia M. Joussen Contribution of TNF-alpha to leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis in vivo Investigative Ophthalmology & Visual Science (2003) doi: 10.1167/iovs.02-0589 

An Erratum was published in June 2016:

“It was brought to the attention of the authors that bands demonstrating caspase-3 enzymatic activity in rat retinas in Figure 8A could have been assembled from different blots. The authors have now repeated the Western blot analysis.”

This was never corrected because it’s FASEB Journal:

Irina Semkova , Sascha Fauser , Alexandra Lappas , Neil Smyth , Norbert Kociok , Bernd Kirchhof , Mats Paulsson , Vassiliki Poulaki, Antonia M. Joussen Overexpression of FasL in retinal pigment epithelial cells reduces choroidal neovascularization The FASEB Journal (2006) doi: 10.1096/fj.05-5653fje 

There is more on PubPeer, for Joussen and for Poulaki (often overlapping). But enough of Joussen – you certainly don’t want her to live in your head.

But back to America and its Greeks!

In the next case we have Mitsi, The Other Mitsi, Vassiliki, some other Greeks and a major Harvard professor of ophthalmology – Joan W Miller.

This evidence is rotting on PubPeer already since 2015:

Vassiliki Poulaki , Eirini Iliaki , Nicholas Mitsiades , Constantine S. Mitsiades , Yiannis N. Paulus , Deisy V. Bula , Evangelos S. Gragoudas , Joan W. Miller Inhibition of Hsp90 attenuates inflammation in endotoxin-induced uveitis The FASEB Journal (2007) doi: 10.1096/fj.06-7637com 

The penultimate author of that shameful fabrication is another Greek ophthalmologist and Distinguished Professor in Harvard: Evangelos Gragoudas. You will soon meet him again in another awful paper by fellow Greeks.

But before that – this peculiar study by Miller is on PubPeer since April 2021:

Miin Roh , Joan W. Miller, Karen W. Jeng-Miller , Jay C. Wang , Inês Laíns , Rebecca F. Silverman , John I. Loewenstein , Deeba Husain , Demetrios G. Vavvas, John B. Miller Subthreshold Exudative Choroidal Neovascularization Associated With Age-Related Macular Degeneration Identified by Optical Coherence Tomography Angiography Journal of VitreoRetinal Diseases (2020) doi: 10.1177/2474126420916607 

The last and corresponding author John B Miller is Harvard’s Assistant Professor of Ophthalmology. According to Wikipedia, Joan Miller is married to another John B. Miller, who is “a construction attorney and 2014 Republican candidate for Massachusetts Attorney General.” In fact, the paper’s last author is indeed their son. Another coauthor and Harvard ophthalmologist, Karen Jeng-Miller, is likely John B Miller Junior’s wife. Harvard bigwig Joan Miller may not be Greek, but she behaves like all Mediterranean nepotists. Family over everything!

The Miller family paper above brings us to yet another Greek ophthalmologist in Harvard: Professor Demetrios Vavvas. From his replies on Pubpeer, his profile picture doesn’t lie. Demetrios is apparently not very smart, which is why this professor has to compensate with a moustache, a bow tie and bullshit.

An easy case which Vavvas fixed by providing a replacement figure, without any explanation as to how the actin blot got duplicated after signal adjustment:

A much more complex case, with Joan Miller, Gragoudas, Demetrios, some other Greeks, and many duplicated blots:

Eleni K Konstantinou, Shoji Notomi , Cassandra Kosmidou , Katarzyna Brodowska , Ahmad Al-Moujahed , Fotini Nicolaou , Pavlina Tsoka , Evangelos Gragoudas, Joan W Miller, Lucy H Young, Demetrios G Vavvas Verteporfin-induced formation of protein cross-linked oligomers and high molecular weight complexes is mediated by light and leads to cell toxicity Scientific Reports (2017) doi: 10.1038/srep46581 

Now, the last author’s reply on PubPeer:

“Thank you for the questions about b actin loading control . Thankfully the questions trying to be answered does not depend on equal loading as only shift in molecular weight is the output. Furthermore, each non-acting protein can act as loading control in cases where the b-actin is questionable.
Thank you again“

It was not only about a reused actin blot, but never mind, have another look at Dementios’ profile picture and understand it is pointless to discuss science with him. Thanks to papers like this, the first author, yet another Greek ophthalmologist named Eleni Konstantinou, made it to Assistant Professor at Weill Cornell Medical College.

Another one by Dementios and Miller:

Bernard Dib, Haijiang Lin, Daniel E Maidana , Bo Tian, John B Miller, Peggy Bouzika, Joan W Miller , Demetrios G Vavvas Mitochondrial DNA has a pro-inflammatory role in AMD Biochimica et Biophysica Acta (2015) doi: 10.1016/j.bbamcr.2015.08.012

Dementios opined on PubPeer about the duplicated gel bands in Figure 2:

“Though they are look similar the color code also shows differences, like the lower band of the IL6 is thicker/more intense in Panel E. When I look at the high mag in my files they are not the same.”

Well, he is the eye doctor, he sees things better than you, no?

As you imagine, Dementios is Joan Miler’s protege. He is actually “the J.W. Miller Scholar in Retina Research, Associate Professor of Ophthalmology at Harvard Medical School”, so you think how difficult it would be for Harvard Medical School to investigate him or Joan Miller, or Joan’s other Greek friends, since her super-rich construction lawyer husband sponsors this whole travesty.

These doctors are an eye sore.

Update 20.03.2024 – in an earlier version of this article, I incorrectly suspected Vassiliki used to be married to Mitsi. In reality, she used to be married to The Other Mitsi.

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