03-28197. Findings of Scientific Misconduct

AGENCY:

Office of the Secretary, HHS.

ACTION:

Notice.

SUMMARY:

Notice is hereby given that the Office of Research Integrity (ORI) and the Assistant Secretary for Health have taken final action in the following case:

Craig H. Gelband, Ph.D., University of Florida: Based on the reports of two investigations conducted by the University of Florida (UF) (UF Reports) and additional analysis conducted by ORI in its oversight review, the U.S. Public Health Service (PHS) found that Craig H. Gelband, Ph.D., Associate Professor, Department of Physiology, College of Medicine at UF, engaged in scientific misconduct in research. Publications and manuscripts containing the falsified data cited support from National Institutes of Health (NIH) grants, or falsified data was included in NIH grant applications, as follows:

• R29 HL52189-01A2, then R01 HL52189-05, “Regulation of renal vascular cells in hypertension”.
• R01 HL56921, “AT1 receptor control in chronic hypertension”.
• F32 HD08496, “Role of MNA V2.3 in uterine contraction”.
• R01/R37 HL49254, “Ionic & pharmacological regulation of vascular cells”.
• F32 HL08531, “Hormonal regulation of renal artery ionci currents”
• P01 DK41315, “Regulatory mechanism in colonic motility-program project”.
• R01 HL69034-01, “Mechanisms of cerebral resistance artery constriction.”

Specifically, PHS found that:

I. Dr. Craig H. Gelband falsified data based on contractile tension recording in antisense experiments on the angiotensin enzyme (ACE), purportedly using renal arteriolar smooth muscle tension preparation:

A. by falsely labeling the tension recordings in Figures 5, 6, and 7 in a publication by Wang, H., Reaves, P.Y., Gardon, M.L., Keene, K., Goldberg, D.S., Gelband, C.H., Katovich, M.J. & Raizada, M.K. “Angiotensin I—converting enzyme antisense gene therapy causes permanent antihypertensive effects in the SHR.” Hypertension 35[part 2]: 2002-208, 2000 (subsequently referred to as the “Hypertension 2000 paper #1”), when he had earlier reported the same contractile records as being from experiments on the angiotensin receptor (not the enzyme), in Figures 6, 7, and 8 of an earlier mini-review by Martens, J.R. & Gelband, C.H. “Ion channels in vascular smooth muscle: Alterations in essential hypertension.” PSEBM 218:192-200, 1998 (subsequently referred to as the PSEBM paper);

B. by falsifying three of the four sets of the mean data that were in fact the same for both the F0 and F1 mean data in Figures 5 and 6 of the Hypertension 2000 paper #1. Dr. Gelband also dishonestly provided the institution with the falsified/fabricated tables of the mean data and the associated false standard error values as evidence that he had conducted the experiments for Figures 5 and 6; and

C. by falsifying EC₅₀ values in Table 1 in NIH grant application HL52189-05; the EC₅₀ values had been interpolated from the falsified mean and SEM data shown in Figures 5 and 6 in the Hypertension 2000 paper #1.

II. Dr. Gelband falsified data in the reporting of research, misrepresenting current/voltage (I/V) data to be results from totally different experimental models or preparations in six publications (including one manuscript “In-Press”) and in NIH grant application HL52189-05, specifically:

A. as Figure 1A, in Gelband, C.H., Wang, H., Gardon, M.L., Keene, K., Goldberg, D.S., Reaves, P., Katovich, M.J., Raizada, M.K. “Angiotensin 1-converting enzyme antisense prevents altered renal vascular reactivity, but not high blood pressure, in spontaneously hypertensive rats.” Hypertension 35 [part 2]:209-213, 2000 (subsequently referred to as the “Hypertension 2000 paper #2”).

B. as Figure 2, in Martens, J.R., Fergus, D.J., Tamkun, M.M., England, S.K., Gelband, C.H. “Identification of voltage-gated K⁺ channel genes contributing to the decreased renal arteriolar K⁺ current in hypertension.” J. Biol. Chem (MS M01389200), online, in press (subsequently referred to as the “JBC paper”). J. Biol Chem Online (submitted and withdrawn).

C. as Figure 4A, in Gelband, C.H. “Protein kinase C regulation of renal vascular Kν and Ca⁺⁺ channels in hypertension.” Hypertension Online paper, withdrawn (subsequently referred to as the “Hypertension Online paper”).

D. as Figure 3, in Gelband, C.H., Reaves, P.Y., Evans, J., Wang, H., Katovich, M.J., & Raizade, M.K. “Angiotensin II Type 1 receptor antisense gene therapy prevents altered renal vascular calcium homeostasis in hypertension.” Hypertension 33[part II]:360-365, 1999 (subsequently referred to as the “Hypertension 1999 paper”).

E. as Figures 4A and 4B in Martens, J.R., Reaves, P.Y., Lu, D., Katovich, M.J., Berecek, K.H., Bishop, A.P., Raizade, M.K., & Gelband, C.H. “Preventions of renovascular and cardiac pathophysiological changes in hypertension by angiotensin II type 1 receptor antisense gene therapy.” Proc. Natl. Acad. Sci. 95:2664-2669, 1998 (subsequently referred to as the “PNAS paper”).

F. as Figure 5A, in Reaves, P.Y., Gelband, C.H., Wang, H., Yang, H., Lu, D., Berecek, K.H., Katovich, M.J., Raizada, M.K. “Permanent cardiovascular protection from hypertension by the AT1 receptor antisense gene therapy in hypertensive rat offspring.” Circ. Res. 85:344-350, 1999 (subsequently referred to as the “Circ. Res. 1999 paper”).

1. Dr. Gelband also falsified data in the proposing of research by submitting the above data as Figures 3, 14A, 14B, and 15 in NIH grant application HL52189-05.

III. Dr. Gelband falsified traces of potassium currents in Figure 4 of the J. Biol. Chem paper (see PHS Finding II) where they were claimed to have been recorded from smooth muscle cells from rats treated with antisense to potassium channels, and/or in Figure 3 of the Hypertension Online paper (see PHS Finding II) where they were claimed to have been records from rat renal cells treated with phorbol esters and PKC inhibitors. Furthermore, the potassium currents were recorded from neurons, not from smooth muscles as falsely reported in these publications.

Dr. Gelband falsified data in the proposing of research by submitting the falsified traces of potassium currents as Figure 9 in NIH grant application HL52189-05.

IV. Dr. Gelband falsified data by claiming in Figure 8 of NIH grant application HL52189-05 and in Figure 2 of the Hypertension Online paper (see PHS Finding II) to have generated in his laboratory Western blot data on protein kinase C isoenzymes in renal vascular smooth muscle cells, while in fact the data were actually from cultured neurons collected in another laboratory and published in Pan, S.J., Zhu, M., Raizada, M.K., Sumners, C., & Gelband, C.H. “Angiotensin II-mediated inhibition of neuronal delayed rectifier K⁺ current: Role of protein kinase C-a.” American Journal of Physiology 281:C17-C23, 2001 (subsequently referred to as the AJP paper).

V. Dr. Gelband falsified data by misrepresenting experimental traces he provided as the unnumbered topmost figure on Page 26 of NIH grant application HL69034-01, as being recordings showing effect of indolactam inhibition in posterior cerebral arteriolar smooth muscle cells, while the identical tracings had been published by Dr. Gelband as Figures 2C and 7D of the AJP paper (see PHS Issue 4), where they had been reported as being tracings from neuronal cells.

VI. Dr. Gelband falsified data in the unnumbered rightmost figure on Page 25 of NIH grant application HL69034-01, by misrepresenting the data as showing potential changes induced in cerebral arterial myocytes by IP3 and heparin, while the same data were published by Dr. Gelband as Figure 5C in a 1997 publication: Gelband, C.H. & Gelband, H. “CA²⁺ release from intracellular stores is an initial step in hypoxic pulmonary vasoconstriction of rat pulmonary artery resistance vessels.” Circulation 96:3647-3654, 1997 (subsequently referred to as the “Circulation paper”) as representing changes in intracellular calcium concentration of pulmonary artery cells induced by ryanodyne and hypoxia.

VII. Dr. Gelband falsified electro-physiological records by reusing the same current-voltage trace as the resonse of renal vascular cells exposed for 2 seconds to Angiotensin II (Figure 4C) and to Caffeine (Figure 4B) on p. 124 of the publication Gelband, C.H. & Hume J.R. “[Ca²⁺]_I Inhibition of K⁺ Channels in Canine Renal Artery. A Novel Mechanism for Agonist-Induced Membrane Depolarization.” Circulation Research 77(1):121-130, 1995 (subsequently referred to as the “Circ. Res. 1995 paper”).

Dr. Gelband also submitted the falsified data above in Figure 4 in NIH grant application R29 JL52189-01A2.

VIII. Dr. Gelband fabricated laboratory research records for four Western blot experiments during the investigation, withholding from the institution his associate's notebook from which he had removed four labeled autoradiographic films from separate and different experiments, and using the removed films to fabricate a laboratory notebook containing falsified Western blots, which he provided to UF as evidence that he had conducted the experiments under investigation.

The terms of this Agreement are as follows:

(1) Respondent agreed to exclude himself voluntarily from any contracting or subcontracting with any agency of the United States Government and from eligibility or involvement in nonprocurement programs of the United States Government referred to as “covered transactions” as defined in the debarment regulations at 45 CFR part 76, for a period of ten (10) years, beginning on October 3, 2003.

(2) Respondent agreed to exclude himself voluntarily from serving in any advisory capacity to PHS including but not limited to service on any PHS advisory committee, board, and/or peer review committee, or as a consultant, for a period of ten (10) years, beginning on October 3, 2003.

(3) Within 30 days of the effective date of this Agreement, Respondent agreed to submit letters of retraction to the following journals concerning the specified data in the listed articles:

A. Hypertension 2000 paper #1: Figures 5, 6, and 7 merited retraction. A retraction has been submitted relevant to this paper.

B. Hypertension 2000 paper #1: Figure 1A merited retraction. A retraction has been submitted relevant to this paper.

C. JBC paper: Figure 2 and Figure 4 merited retraction. It has already been withdrawn.

D. Hypertension Online paper: Figure 4A and Figure 3 merited retraction. It has already been withdrawn.

E. Hypertension 1999 paper: Figure 3 must be retracted.

F. PNAS paper: Figure 4A and 4B must be retracted.

G. Circ. Res. 1999 paper: Figure 5A must be retracted.

H. Circ. Res. 1995 paper: Figure 4C or 4B must be retracted.

FOR FURTHER INFORMATION CONTACT:

Director, Division of Investigative Oversight, Office of Research Integrity, 1101 Wootton Parkway, Suite 750, Rockville, MD 20852, [phone].

Chris B. Pascal,

Director, Office of Research Integrity.