Notice2023-07850
Findings of Research Misconduct
Primary source
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Published
April 13, 2023
Issuing agencies
Health and Human Services Department
Abstract
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.
Full Text
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<title>Federal Register, Volume 88 Issue 71 (Thursday, April 13, 2023)</title>
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[Federal Register Volume 88, Number 71 (Thursday, April 13, 2023)]
[Notices]
[Pages 22461-22463]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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:
<bullet> 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'').
<bullet> 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'').
<bullet> 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'').
<bullet> 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.
<bullet> 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'').
<bullet> 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'').
<bullet> 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.
<bullet> 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.
<bullet> 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:
<bullet> 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
<bullet> 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
<bullet> 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 Pkhd1<SUP>del4/del4</SUP>, PKA inhibitor are the same
--Figure 5A:
[rtarr8] Actin blot panel, lanes 1-4 for WT and lanes 6-9 for
Pkhd1<SUP>del4/del4</SUP> are the same
<bullet> 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
<bullet> 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 Pkhd1<SUP>del4/del4</SUP>
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 Pkhd1<SUP>del4/del4</SUP> 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 Pkhd1<SUP>del4/del4</SUP> in Figure 1A
of Hepatology 2013
<bullet> 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
<bullet> 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:
<bullet> Hepatology 2012;56:2363-74. doi: 10.1002/hep.25872
[[Page 22463]]
<bullet> Hepatology 2012;55(3):856-68. doi:10.1002/hep.24723
<bullet> 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
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