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[Federal Register Volume 89, Number 222 (Monday, November 18, 2024)]
[Notices]
[Pages 90833-90834]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-26756]

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DEPARTMENT OF VETERANS AFFAIRS

Findings of Research MisconductC

AGENCY: Department of Veterans Affairs.

ACTION: Notice.

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SUMMARY: The Department of Veterans Affairs (VA), gives notice, 
pursuant to Veterans Health Administration (VHA) Directive 1058.02 
``Research Misconduct'' section 8.l, that the Department has made 
findings of research misconduct against Alan Lichtenstein, M.D. 
(``Respondent''), a former staff physician at the VA Greater Los 
Angeles Healthcare System, Los Angeles, CA. The Respondent did not 
appeal the findings or corrective actions against him.

FOR FURTHER INFORMATION CONTACT: Shara Kabak, Research Misconduct 
Officer, Office of Research Oversight (10RO), 810 Vermont Avenue NW, 
Washington, DC 20420, (202) 632-7620 (this is not a toll-free number).

SUPPLEMENTARY INFORMATION: VA has made final findings of research 
misconduct against Alan Lichtenstein, M.D. (``Respondent''), a former 
staff physician at the VA Greater Los Angeles Healthcare System in Los 
Angeles, CA.
    Based on the recommended findings of a joint investigation 
conducted by VA Greater Los Angeles Healthcare System and University of 
California, Los Angeles School of Medicine, the Department found that 
the Respondent engaged in research misconduct by recklessly falsifying 
data included in at least ten of the following thirteen published 
papers:
     DEPTOR is linked to a TORC1-p21 survival proliferation 
pathway in multiple myeloma. Genes & Cancer. 2014 Nov;5(11-12):407-19. 
doi: 10.18632/genesandcancer.44 (hereafter, ``Genes Cancer 2014'').
     Cytotoxic properties of a DEPTOR-mTOR inhibitor in 
multiple myeloma cells. Cancer Research. 2016 Oct 1;76(19):5822-5831. 
doi: 10.1158/0008-5472. CAN-16-1019 (hereafter, ``Cancer Res. 2016'').
     Interleukin-6 activates phosphoinositol-3 kinase in 
multiple myeloma tumor cells by signaling through RAS-dependent and, 
separately, through p85-dependent pathways. Oncogene. 2004 Apr 
22;23(19):3368-75. doi: 10.1038/sj.onc.1207459 (hereafter, ``Oncogene 
2004'').
     MNK1-induced eIF-4E phosphorylation in myeloma cells: a 
pathway mediating IL-6-induced expansion and expression of genes 
involved in metabolic and proteotoxic responses. PLoS One. 2014 Apr 
8;9(4):e94011. doi: 10.1371/journal.pone.0094011 (hereafter, ``PLoS One 
2014''). Retraction in: PLoS One. 2023 Sep 8;18(9):e0291491. doi: 
10.1371/journal.pone.0291491.
     Mammalian target of rapamycin inhibitors activate the AKT 
kinase in multiple myeloma cells by up-regulating the insulin-like 
growth factor receptor/insulin receptor substrate-1/
phosphatidylinositol 3-kinase cascade. Molecular Cancer Therapeutics. 
2005 Oct;4(10):1533-40. doi: 10.1158/1535-7163.MCT-05-0068 (hereafter, 
``Mol Cancer Ther. 2005'').
     Inhibition of SAPK2/p38 enhances sensitivity to mTORC1 
inhibition by blocking IRES-mediated translation initiation in 
glioblastoma. Molecular Cancer Therapeutics. 2011 10:2244-2256 
Dec;10(12):2244-56. doi: 10.1158/1535-7163.MCT-11-0478 (hereafter, 
``Mol Cancer Ther. 2011'').
     Specific blockade of Rictor-mTOR association inhibits 
mTORC2 activity and is cytotoxic in glioblastoma. PLoS One. 2017; Apr 
28;12(4):e0176599. doi: 10.1371/journal.pone.0176599 (hereafter, ``PLoS 
One 2017''). Correction in: PLoS One. 2019 Feb 6;14(2):e0212160. doi: 
10.1371/journal.pone.0212160. Retraction in: PLoS One. 2023 Sep 
8;18(9):e0291490. doi: 10.1371/journal.pone.0291490.
     MNK kinases facilitate c-myc IRES activity in rapamycin-
treated multiple myeloma. Oncogene. 2013 Jan 10;32(2):190-7. doi: 
10.1038/onc.2012.43 (hereafter, ``Oncogene 2013''). Expression of 
Concern in: Oncogene. 2023 Oct;42(41):3088. doi: 10.1038/s41388-023-
02818-z.
     The PP242 mammalian target of rapamycin (mTOR) inhibitor 
activates extracellular signal-regulated kinase (ERK) in multiple 
myeloma cells via a target of rapamycin complex 1 (TORC1)/eukaryotic 
translation initiation factor 4E (eIF-4E)/RAF pathway and activation is 
a mechanism of resistance. Journal of Biological Chemistry. 2012 Jun 
22;287(26):21796-805. doi: 10.1074/jbc.M111.304626 (hereafter, ``J Biol 
Chem. 2012'').
     Therapeutic potential of targeting IRES-dependent c-myc 
translation in multiple myeloma cells during ER stress. Oncogene. 2016 
Feb 25;35(8):1015-24. doi: 10.1038/onc.2015.156 (hereafter, ``Oncogene 
2016''). Retraction in: Oncogene. 2023 Sep;42(40):3016. doi: 10.1038/
s41388-023-02820-5.
     SGK kinase activity in multiple myeloma cells protects 
against ER stress apoptosis via a SEK-dependent mechanism. Molecular 
Cancer Research. 2016 Apr;14(4):397-407. doi: 10.1158/1541-7786.MCR-15-
0422 (hereafter, ``Mol Cancer Res. 2016'').
     A novel therapeutic induces DEPTOR degradation in multiple 
myeloma cells with resulting tumor cytotoxicity. Molecular Cancer 
Therapeutics. 2019 Oct;18(10):1822-1831. doi: 10.1158/1535-7163.MCT-19-
0115 (hereafter, ``Mol Cancer Ther. 2019'').
     Downstream effectors of oncogenic ras in multiple myeloma 
cells. Blood. 2003 Apr 15;101(8):3126-35. doi: 10.1182/blood-2002-08-
2640 (hereafter, ``Blood 2003'').
    Specifically, the Department found that the Respondent recklessly 
committed research misconduct by reusing the same Western blot or 
kinase assay image to falsely represent the results related to the 
following pairs of experiments such that at least one of the sets of 
images in each of the pairs listed below is inaccurate:
     p-4E-BP1-T37/46, p-4E-BP1-S65 and Tubulin expression in 
Figure 3B of Genes Cancer 2014 and Figure 1F of Cancer Res. 2016.

[[Page 90834]]

     P-AKT-S473 expression in Figure 3C in Genes Cancer 2014 
and lanes 1-4 of DEPTOR expression in Figure 3C of Cancer Res. 2016 
with resizing.
     Lanes 7-9 of p70S6K1 expression in Figure 1A of Genes 
Cancer 2014 and DEPTOR expression in Figure 4C of Cancer Res. 2016.
     STAT3 associated kinase activity in Figure 4A and lanes 1-
4 of p110 mu associated kinase activity in Figure 5B of Oncogene 2004.
     Lanes 7-8 of ACTIN expression in Figure 1A and lanes 7-8 
of ACTIN expression in Figure 1C of PLoS One 2014.
     Lanes 3-4 of P-MNK and T-MNK expression in Figure 1C of 
PloS One 2014 and lanes 1-2 of FKHD-P and FKHD-T expression (top 
panels) in Figure 1B of Mol Cancer Ther. 2005.
     Lanes 4-8 of P-AKT (S473) and actin expression in Figure 
2A of Mol Cancer Ther. 2011 and AKT and S6K expression in Figure 1F of 
PloS One 2017 with a 180 degree rotation of the P-AKT/AKT panels.
     Lanes 1-2 of T-HSP27 expression and lanes 4-5 of GAPDH 
expression in Figure 2B of Oncogene 2013.
     Lanes 1-3 of p-erk and lanes 2-4 of t-erk expression in 
Figure 3B and lanes 1-3 of erk(T202/Y204) and erk expression in Figure 
4A of J Biol Chem. 2012.
     [alpha]-tubulin expression in Figure 4D and 4E of Genes 
Cancer 2014.
     C-myc expression in Figure 1B and lanes 1-4 of T-p70 
expression in Figure 1E of Oncogene 2016.
     T-4E-BP1 ([alpha], [beta] and [gamma] phosphorylated 
forms) expression (middle panel) and lanes 1-4 of T-4E-BP ([alpha], 
[beta] and [gamma] phosphorylated forms) expression (right panel) of 
Supplemental Figure 2A of Oncogene 2016.
     T-S6 expression and C-myc expression in Figure 1F of 
Oncogene 2016.
     Lanes 2-5 of MNK-P and MNK-T expression (left panel) in 
Figure 3A and ERK-T and Hsp-27-T expression in Figure 4A of Oncogene 
2016.
     MNK1, MNK2 and GAPDH expression in Figure 3E of Oncogene 
2016 and MNK1, MNK2 and GAPDH expression in Figure 3A of PloS One 2014.
     ire-1-total expression (right panel) in Figure 5B of Mol 
Cancer Res. 2016 and mTor expression in Figure 8A of Genes Cancer 2014 
with resizing.
     The right panel of ACTIN expression in Figure 2A and the 
right panel of ACTIN expression in Figure 2g of Mol Cancer Ther. 2019.
     Lanes 1-6 of DEPTOR and mTOR expression in Figure 1A of 
Genes Cancer 2014 and DEPTOR and mTor expression in Figure 6A of Mol 
Cancer Ther. 2019.
     IRS-1 expression in lanes 4-5 and lanes 8-9 in Figure 6B 
of Mol Cancer Ther. 2005.
     AKT expression (bottom panel) in Figure 1Aand lanes 7-9 of 
IRS-1 expression in Figure 6B of Mol Cancer Ther. 2005.
     Lanes 4-6 of IGF-R expression and lanes 4-6 of FLAG 
expression in Figure 5B of Mol Cancer Ther. 2005 with a 180-degree 
rotation.
     Lanes 2-3 of AKT-T expression (4th panel) in and lanes 1-2 
of AKT-T expression (6th panel) in Figure 1C of Mol Cancer Ther. 2005.
     Lanes 1-2 of AKT-P expression (top panel) and lanes 1-2 of 
AKT-P expression (5th panel) in Figure 1E of Mol Cancer Ther. 2005.
     Lanes 1-3 and lanes 5-7 of FKH-T expression in Figure 3C 
of Blood 2003.
     Lane 1 of p70 expression and Ser411 expression in Figure 
4B and lane 4 of Ser411 expression and lanes 1-2 of Ser411 expression 
in Figure 4c of Blood 2003.
     Lanes 1 and 3 of ERK-P expression and lanes 2 and 4 of 
ERK-T expression in Figure 2C of Blood 2003.
    Based on these findings of research misconduct, which the 
Respondent did not appeal, the Department has imposed the following 
corrective actions:
    (1) Prohibition from conducting VA research for at least 2 years;
    (2) Notification to the relevant journals of the research 
misconduct findings.

Signing Authority

    Denis McDonough, Secretary of Veterans Affairs, signed and approved 
this document on November 12, 2024, and authorized the undersigned to 
sign and submit the document to the Office of the Federal Register for 
publication electronically as an official document of the Department of 
Veterans Affairs.

Jeffrey M. Martin,
Assistant Director, Office of Regulation Policy & Management, Office of 
General Counsel, Department of Veterans Affairs.
[FR Doc. 2024-26756 Filed 11-15-24; 8:45 am]
BILLING CODE 8320-01-P
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