[Federal Register Volume 88, Number 71 (Thursday, April 13, 2023)]
[Notices]
[Pages 22461-22463]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-07850]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Office of the Secretary


Findings of Research Misconduct

AGENCY: Office of the Secretary, HHS.

ACTION: Notice.

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SUMMARY: Findings of research misconduct have been made against Carlo 
Spirli, Ph.D. (Respondent), who was an Assistant Professor of Medicine, 
Department of Digestive Diseases, Yale University (YU). Respondent 
engaged in research misconduct in research supported by U.S. Public 
Health Service (PHS) funds, specifically National Institute of Diabetes 
and Digestive and Kidney Diseases (NIDDK), National Institutes of 
Health (NIH), grants R01 DK079005 and P30 DK034989. The administrative 
actions, including debarment for a period of four (4) years, were 
implemented beginning on March 28, 2023, and are detailed below.

FOR FURTHER INFORMATION CONTACT: Sheila Garrity, JD, MPH, MBA, 
Director, Office of Research Integrity, 1101 Wootton Parkway, Suite 
240, Rockville, MD 20852, (240) 453-8200.

SUPPLEMENTARY INFORMATION: Notice is hereby given that the Office of 
Research Integrity (ORI) has taken final action in the following case:
    Carlo Spirli, Ph.D., Yale University: Based on the report of an 
investigation conducted by YU and additional analysis conducted by ORI 
in its oversight review, ORI found that Carlo Spirli, Ph.D., former 
Assistant Professor of Medicine, Department of Digestive Diseases, YU, 
engaged in research misconduct in research supported by PHS funds, 
specifically NIDDK, NIH, grants R01 DK079005 and P30 DK034989.
    ORI found that Respondent engaged in research misconduct by 
knowingly, intentionally, or recklessly falsifying and/or fabricating 
data included in the following four (4) published papers, two (2) 
presentations, and three (3) grant applications submitted for PHS 
funds:
     Cyclic AMP/PKA-dependent Paradoxical Activation of Raf/
MEK/ERK Signaling in Polycystin-2 Defective Mice Treated with 
Sorafenib. Hepatology. 2012 Dec;56(6):2363-74. doi: 10.1002/hep.25872 
(hereafter referred to as ``Hepatology 2012a'').
     Altered Store Operated Calcium Entry Increases Cyclic 
3',5'-Adenosine Monophosphate Production and Extracellular Signal-
Regulated Kinases 1 and 2 Phosphorylation in Polycystin-2-Defective 
Cholangiocytes. Hepatology. 2012 Mar;55(3):856-68. doi: 10.1002/
hep.24723 (hereafter referred to as ``Hepatology 2012b'').
     Protein Kinase A-Dependent pSer(675)-[beta]-catenin, a 
Novel Signaling Defect in a Mouse Model of Congenital Hepatic Fibrosis. 
Hepatology. 2013 Nov;58(5):1713-23. doi:10.1002/hep.26554 (hereafter 
referred to as ``Hepatology 2013'').
     Posttranslational Regulation of Polycystin-2 Protein 
Expression as a Novel Mechanism of Cholangiocyte Reaction and Repair 
from Biliary Damage. Hepatology. 2015 Dec; 62(6):1828-39. doi: 10.1002/
hep.28138 (hereafter referred to as ``Hepatology 2015''). Retraction 
in: Hepatology. 2022 Dec;76(6):1904. doi: 10.1002/hep.32595.
     PKA-Dependent p-SER675-b-Catenin Phosphorylation Increases 
Cholangiocyte Motility in Pkhd1del4/del4 Mouse, a Model of 
Fibropolycystic Liver Diseases Caused by Defective Fibrocystin 
Function. Presented at the European Association for the Study of the 
Liver (EASL) (hereafter referred to as ``EASL Presentation 2011'').
     Cyclic-AMP-Dependent, Rac1-Mediated Nuclear Translocation 
Of P-Ser-675[beta]-Catenin, A Novel Signaling Defect in Congenital 
Hepatic Fibrosis (CHF) and Caroli's Disease (CD). Presented at the 
American Association for the Study of Liver Diseases (AASLD) Annual 
Meeting, Boston, MA, in November 2012 (hereafter referred to as ``AASLD 
Presentation 2011'').
     R01 DK079005-11A1, ``Epithelial Angiogenic Signaling in 
Biliary Pathophysiology and in Polycystic Disease,'' submitted to 
NIDDK, NIH, on December 13, 2018. Administratively withdrawn by the 
funding agency on March 1, 2021.
     R01 DK090021-01 ``Mechanisms of fibrosis in fibrocystin-
deficiency associated cholangiopathies'' submitted to NIDDK, NIH, on 
February 2, 2010. Administratively withdrawn by the funding agency on 
July 1, 2012.
     R01 DK090021-01A1 ``Mechanisms of fibrosis in fibrocystin-
deficiency associated cholangiopathies'' submitted to NIDDK, NIH, on 
November 11, 2010.

[[Page 22462]]

Administratively withdrawn by the funding agency on July 1, 2015.
    Respondent knowingly, intentionally, or recklessly falsified and/or 
fabricated Western blot image data for cholangiopathies in a murine 
model of Congenital Hepatic Fibrosis (CHF) by reusing blot images, with 
or without manipulating them to conceal their similarities, and falsely 
relabeling them as data representing different experiments or proteins 
and falsifying quantitative data in associated graphs purportedly 
derived from those images in twenty-one (21) figures included in four 
(4) papers, two (2) presentations, and three (3) grant applications. In 
the absence of reliable image and numerical data, the figures, 
statistical analyses, and related text also are false.
    Specifically, the respondent reused Western blot images from the 
same source and falsely relabeled them to represent different proteins 
and/or experimental results in:

     Hepatology 2012a:

--Figure 3, representing different concentrations of sorafenib 
treatment in:
    [rtarr8] pERK blot panel, lanes 1-2 and 3-4 are the same
    [rtarr8] pERK blot panel, lanes 2, 4, and 5 are the same
--Figure 4C and Figure 6C (left), representing different concentrations 
of sorafenib treatment in:
    [rtarr8] CC3 blot panel, lanes 1 and 2 are the same
--Figure 4C, representing different concentrations of sorafenib 
treatment in:
    [rtarr8] Actin blot panel, lanes 3-7 for wild type (WT) and lanes 
8-12 for Pkd2cKO cholangiocytes are the same
--Figure 5A (left), representing B-Raf kinase activity with different 
concentrations of sorafenib treatment in WT:
    [rtarr8] ERK1/2 blot panel, lanes 1-2 and lanes 3-4 are the same
--Figure 5A (right), representing and Raf-1 kinase activity with 
different concentrations of sorafenib treatment in WT:
    [rtarr8] ERK1/2 blot panel, lanes 1-2 and lanes 3-4 are the same
     Hepatology 2012b:

--Figure 6A, representing thapsigargin treatment in WT and Pkd2KO 
cholangiocytes:
    [rtarr8] ERK blot panel, lanes 1-3 WT and lanes 4-6 Pkd2KO are the 
same
     Hepatology 2013:

--Figure 1A in:
    [rtarr8] pSer\675\-[beta]-Cat blot panel, lanes 1-3 for WT are a 
mirror image of lanes 4-6 for PC-KO
    [rtarr8] pSer\675\-[beta]-Cat blot panel, lane 1 for WT control and 
lane 9 for Pkhd1del4/del4, PKA inhibitor are the same
--Figure 5A:
    [rtarr8] Actin blot panel, lanes 1-4 for WT and lanes 6-9 for 
Pkhd1del4/del4 are the same
     Hepatology 2015:

--Figure 2A:
    [rtarr8] PC2 blot panel, lane 4 for ``TNF[alpha]'' and lane 5 for 
``Mix'' are the same
    [rtarr8] PC2 blot panel, lane 6 for ``DETA'' and lane 7 for 
``Thapsi'' are the same
    [rtarr8] Actin blot panel, lane 6 for ``DETA'' and lane 7 for 
``Thapsi'' are the same
--Figure 4A:
    [rtarr8] PC2 blot panel, lane 1 for ``Ctrl'' and lane 8 for 
``Mix+MG+GHX'' are the same
    [rtarr8] PC2 blot panel, lane 3 for ``Mix,'' lane 4 for 
``Mix+CHX,'' and lane 5 for ``MG'' are the same
--Figure 4C:
    [rtarr8] NEK1 blot panel, lane 6 for ``Thapsi'' and lane 7 for 
``DETA'' are the same
--Figure 5 (left):
    [rtarr8] PC2, blot panel, lane 1 for ``Ctrl'' and lane 2 for ``MG'' 
are the same
    [rtarr8] PC2 blot panel, lanes 3-4 for ``TNF[alpha]'' and 
``TNF[alpha]+MG'' and lanes 7-8 for ``Mix,'' and ``Mix+MG'' are the 
same
    [rtarr8] Actin blot panel, lanes 1-4 for ``Ctrl,'' ``MG,'' 
``TNF[alpha],'' and ``TNF[alpha]+MG'' and lanes 5-8 for ``INF[gamma],'' 
``INF[gamma]+MG,'' ``Mix,'' and ``Mix+MG'' are the same
--Figure 5 (right):
    [rtarr8] Actin blot panel, lanes 5-6 for ``INF[gamma]'' and 
``INF[gamma]+MG'' and lanes 7-8 for ``Mix'' and ``Mix+MG'' are the same
--Figure 6D:
    [rtarr8] LC3-II blot panel, lane 2 for ``Thapsi'' and lane 8 for 
``Chloroq'' are the same
--Figure 7B:
    [rtarr8] PC2 blot panel, lanes 11-12, 13-14, and 15-16 are the same 
representing six repeat experiments of ``DDC'' mice
    [rtarr8] PC2 blot panel, lanes 5-6, 7-8, and 9-10 are the same 
representing six repeat experiments of ``DDC+Bort'' mice
    [rtarr8] Actin blot panel, lanes 1-4 for ``Ctrl,'' lanes 5-8 for 
``DDC,'' and lanes 11-14 for ``DDC+Bort'' are the same
    [rtarr8] Actin blot panel, lanes 9-10 for ``DDC'' and lanes 15-16 
for ``DDC+Bort'' are the same
--Figure 8B:
    [rtarr8] Actin blot panel, lanes 1-5 for ``WT'' and lanes 6-10 for 
Mdr2-/- are the same

 AASLD Presentation 2012:

--Slide 7:
    [rtarr8] pSer\675\ [beta]-Cat blot panel, lanes 1-3 WT are the same 
as pSer\675\ [beta]-Cat blot panel, lanes 4-6 PC-KO in Figure 1A of 
Hepatology 2013
    [rtarr8] pSer\675\ [beta]-Cat blot panel, lanes 4-6 WT are the same 
as pSer\675\ [beta]-Cat blot panel, lanes 7-9 Pkhd1del4/del4 
in Figure 1A of Hepatology 2013
    [rtarr8] [beta]-Cat blot panel, lanes 1-3 WT are the same as 
[beta]-Cat blot panel, lanes 4-6 Pkhd1del4/del4 in Figure 1A 
of Hepatology 2013
    [rtarr8] [beta]-Cat blot panel, lanes 4-6 WT are the same as 
[beta]-Cat blot panel, lanes 7-9 Pkhd1del4/del4 in Figure 1A 
of Hepatology 2013

 R01 DK090021-01 and R01 DK090021-01A1:

--Figure 8 (and Slide 9 of EASL Presentation 2011):
    [rtarr8] p\675\-[beta]-Cat blot panel, lanes 8 and 9 are spliced in 
over the bands from unrelated sources
    [rtarr8] H3 Hyst blot, lane 8 is spliced in over the bands from 
unrelated sources

 R01 DK079005-11A1:

--Figure 12A:
    [rtarr8] VEGFR2 blot panel, lanes 5 and 6-8 are spliced in from 
unrelated sources
--Figure 12B:
    [rtarr8] VEGFR2 blot panel, lanes 7 and 8 are spliced in from 
unrelated sources

    Dr. Spirli entered into a Voluntary Exclusion Agreement (Agreement) 
and voluntarily agreed to the following:
    (1) Respondent will exclude himself voluntarily for a period of 
four (4) years beginning on March 28, 2023 (the ``Exclusion Period'') 
from any contracting or subcontracting with any agency of the United 
States Government and from eligibility for or involvement in 
nonprocurement or procurement transactions referred to as ``covered 
transactions'' in 2 CFR parts 180 and 376 (collectively the ``Debarment 
Regulations'').
    (2) During the Exclusion Period, Respondent will exclude himself 
voluntarily from serving in any advisory or consultant capacity to PHS 
including, but not limited to, service on any PHS advisory committee, 
board, and/or peer review committee.
    (3) Respondent will request that the following papers be corrected 
or retracted:

 Hepatology 2012;56:2363-74. doi: 10.1002/hep.25872

[[Page 22463]]

 Hepatology 2012;55(3):856-68. doi:10.1002/hep.24723
 Hepatology 2013;58(5):1713-23. doi: 10.1002/hep.26554

    Respondent will copy ORI and the Research Integrity Officer at YU 
on the correspondence with the journal.

    Dated: April 10, 2023.
Sheila Garrity,
Director, Office of Research Integrity, Office of the Assistant 
Secretary for Health.
[FR Doc. 2023-07850 Filed 4-12-23; 8:45 am]
BILLING CODE 4150-31-P