J. Saadi Imam

The University of Texas Medical Branch at Galveston

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Scott A. Helgeson

Mayo Clinic in Florida

Manjeet K. Rao

The University of Texas Health Science Center at San Antonio

Miles Wilkinson

University of California, San Diego

Jennifer S. Lee-Chang

The University of Texas Health Science Center at San Antonio

Kalyan Buddavarapu

Asuragen (United States)

Charles D. Burger

Mayo Clinic in Florida

Yao-Fu Chang

The University of Texas Health Science Center at San Antonio

Yao-Fu Chang

The University of Texas Health Science Center at San Antonio

Jayanthi Gudikote

The University of Texas MD Anderson Cancer Center

M. Caroline Burton

Mayo Clinic

Cooperative Institutions

Mayo Clinic in Florida

WinnMed

Jacksonville College

The University of Texas Health Science Center at San Antonio

The University of Texas Health Science Center at Houston

Mayo Clinic

The University of Texas MD Anderson Cancer Center

Mayo Clinic in Arizona

Cancer Research Institute of the Slovak Academy of Sciences

National Institutes of Health

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Penicillin Skin Testing in the ICU is Associated With a Greater Change to Narrow-Spectrum Antibiotics

CHEST Journal (2017)

Keith Sacco Scott A. Helgeson J. Saadi Imam M. Caroline Burton

Drug allergy

Penicillin allergy

10.1016/j.chest.2017.08.043

Cite

Citations (0)

RNA splicing promotes translation and RNA surveillance

Nature Structural & Molecular Biology (2005)

Jayanthi Gudikote J. Saadi Imam Ramon F Garcia Miles Wilkinson

Nonsense-Mediated Decay

Nonsense mutation

10.1038/nsmb980

Cite

Citations (92)

Severe PAH Secondary to Dasatinib: PAH Treatment Required?

CHEST Journal (2016)

Scott A. Helgeson J. Saadi Imam Charles D. Burger

Discontinuation

Pulmonary wedge pressure

10.1016/j.chest.2016.08.1327

Cite

Citations (2)

Alternatively Spliced T-cell Receptor Transcripts Are Up-regulated in Response to Disruption of Either Splicing Elements or Reading Frame

Journal of Biological Chemistry (2007)

Yao-Fu Chang Wai-Kin Chan J. Saadi Imam Miles Wilkinson

Nonsense mutations create premature termination codons (PTCs), leading to the generation of truncated proteins, some of which have deleterious gain-of-function or dominant-negative activity. Protecting cells from such aberrant proteins is non-sense-mediated decay (NMD), an RNA surveillance pathway that degrades transcripts harboring PTCs. A second response to nonsense mutations is the up-regulation of alternatively spliced transcripts that skip the PTC. This nonsense-associated altered splicing (NAS) response has the potential to rescue protein function, but the mechanism by which it is triggered has been controversial. Some studies suggest that, like NMD, NAS is triggered as a result of nonsense mutations disrupting reading frame, whereas other studies suggest that NAS is triggered when nonsense mutations disrupt exonic splicing enhancers (ESEs). Using T-cell receptor-beta (TCRbeta), which naturally acquires PTCs at high frequency, we provide evidence that both mechanisms act on a single type of mRNA. Mutations that disrupt consensus ESE sites up-regulated an alternatively spliced TCRbeta transcript that skipped the mutations independently of reading frame disruption and the NMD factor UPF1. In contrast, reading frame-disrupting mutations that did not disrupt consensus ESE sites elicited UPF1-dependent up-regulation of the alternatively spliced TCRbeta transcript. Restoration of reading frame prevented this up-regulation. Our results suggest that the response of an mRNA to a nonsense mutation depends on its context.

10.1074/jbc.m704372200

Cite

Citations (31)

The Nonsense-Mediated Decay RNA Surveillance Pathway

Annual Review of Biochemistry (2007)

Yao-Fu Chang J. Saadi Imam Miles Wilkinson

Nonsense-mediated mRNA decay (NMD) is a quality-control mechanism that selectively degrades mRNAs harboring premature termination (nonsense) codons. If translated, these mRNAs can produce truncated proteins with dominant-negative or deleterious gain-of-function activities. In this review, we describe the molecular mechanism of NMD. We first cover conserved factors known to be involved in NMD in all eukaryotes. We then describe a unique protein complex that is deposited on mammalian mRNAs during splicing, which defines a stop codon as premature. Interaction between this exon-junction complex (EJC) and NMD factors assembled at the upstream stop codon triggers a series of steps that ultimately lead to mRNA decay. We discuss whether these proofreading events preferentially occur during a “pioneer” round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC.

Nonsense-Mediated Decay

Nonsense

10.1146/annurev.biochem.76.050106.093909

Cite

Citations (1,221)

Comparison of Brain Natriuretic Peptide Levels to Simultaneously Obtained Right Heart Hemodynamics in Stable Outpatients with Pulmonary Arterial Hypertension

Diseases (2018)

Scott A. Helgeson J. Saadi Imam John E. Moss David O. Hodge Charles D. Burger

Pulmonary arterial hypertension (PAH) is a progressive disease that requires validated biomarkers of disease severity. While PAH is defined hemodynamically by right heart catheterization (RHC), brain natriuretic peptide (BNP) is recommended by guidelines to assess disease status. Retrospectively collected data in 138 group 1 PAH patients were examined for the correlation of BNP levels to simultaneously obtained right heart catheterization (RHC). Patients were mostly Caucasian women, with functional class III symptoms, mean BNP of 406 ± 443 pg/mL, and an average right atrial pressure (RAP) of 9.9 ± 5.7 mm Hg and mean pulmonary artery pressure (mPAP) of 47.3 ± 14.7 mm Hg. Significant correlation was demonstrated between BNP and RAP (p = 0.021) and mPAP (p = 0.003). Additional correlation was seen with right heart size on echocardiography: right atrial (RAE; p = 0.04) and right ventricular enlargement (p = 0.03). An increased BNP level was an independent predictor of mortality (p < 0.0001), along with RAP (p = 0.039) and RAE (p = 0.018). Simultaneous collection of BNP at the time of RHC confirmed the correlation of BNP with right heart hemodynamics. The current results reinforce the use of BNP level as a continuous variable to assess disease severity in group 1 PAH.

Brain natriuretic peptide

10.3390/diseases6020033

Cite

Citations (22)

Successful Pulmonary Vasodilator Therapy in a Patient With Group 5 Pulmonary Hypertension in Association With Neurofibromatosis

CHEST Journal (2016)

J. Saadi Imam Scott A. Helgeson Mohamad Zetir Charles D. Burger

Pulmonary wedge pressure

10.1016/j.chest.2016.08.1336

Cite

Citations (0)

Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis

Genes & Development (2006)

Manjeet K. Rao John Pham J. Saadi Imam James A. MacLean Deepa Murali

Using a novel tissue-specific RNA interference (RNAi) approach that mimics the principle by which naturally occurring microRNAs (miRNA) are made, we demonstrate that the Wilms' tumor 1 (WT1) transcription factor has an essential role in spermatogenesis. Mice depleted of WT1 in Sertoli nurse cells suffered from increased germ cell apoptosis, loss of adherens junctions, disregulation of adherence junction-associated genes, and impaired fertility. These effects were recapitulated in transgenic mice expressing a dominant-negative form of WT1 in Sertoli cells, demonstrating the validity of our RNAi approach. Our results indicate that the tumor suppressor WT1 promotes Sertoli cell-germ cell signaling events driving spermatogenesis.

Adherens junction

10.1101/gad1367806

Cite

Citations (117)

Genomic Loss of Tumor Suppressor miRNA-204 Promotes Cancer Cell Migration and Invasion by Activating AKT/mTOR/Rac1 Signaling and Actin Reorganization

PLoS ONE (2012)

J. Saadi Imam Jason R. Plyler Hima Bansal Suresh I. Prajapati Sanjay Bansal

Increasing evidence suggests that chromosomal regions containing microRNAs are functionally important in cancers. Here, we show that genomic loci encoding miR-204 are frequently lost in multiple cancers, including ovarian cancers, pediatric renal tumors, and breast cancers. MiR-204 shows drastically reduced expression in several cancers and acts as a potent tumor suppressor, inhibiting tumor metastasis in vivo when systemically delivered. We demonstrated that miR-204 exerts its function by targeting genes involved in tumorigenesis including brain-derived neurotrophic factor (BDNF), a neurotrophin family member which is known to promote tumor angiogenesis and invasiveness. Analysis of primary tumors shows that increased expression of BDNF or its receptor tropomyosin-related kinase B (TrkB) parallel a markedly reduced expression of miR-204. Our results reveal that loss of miR-204 results in BDNF overexpression and subsequent activation of the small GTPase Rac1 and actin reorganization through the AKT/mTOR signaling pathway leading to cancer cell migration and invasion. These results suggest that microdeletion of genomic loci containing miR-204 is directly linked with the deregulation of key oncogenic pathways that provide crucial stimulus for tumor growth and metastasis. Our findings provide a strong rationale for manipulating miR-204 levels therapeutically to suppress tumor metastasis.

Tumor progression

10.1371/journal.pone.0052397

Cite

Citations (160)

Non-CF bronchiectasis: Orphan disease no longer

Respiratory Medicine (2020)

J. Saadi Imam Alexander G. Duarte

Chest physiotherapy

10.1016/j.rmed.2020.105940

Cite

Citations (51)