Adam J. Poe

Cedars-Sinai Medical Center

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Alexander V. Ljubimov

Cedars-Sinai Medical Center

Mehrnoosh Saghizadeh

University of California, Los Angeles

Anne A. Knowlton

University of California, Davis

Drirh Khare

Cedars-Sinai Medical Center

Ruchi Shah

Cedars-Sinai Medical Center

Mangesh Kulkarni

McGowan Institute for Regenerative Medicine

Andrei A. Kramerov

Cedars-Sinai Medical Center

Vasu Punj

University of Southern California

Aleksandra Leszczynska

University of California, San Diego

Jie Tang

Ministry of Agriculture and Rural Affairs

Cooperative Institutions

Cedars-Sinai Medical Center

University of California, Los Angeles

University of California, Davis

University of California System

University of California, Irvine

UCLA Health

VA Northern California Health Care System

University of Nevada, Reno

Institute of Immunology

University of California, San Diego

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miR-146a regulatory roles in limbal epithelial homeostasis

Investigative Ophthalmology & Visual Science (2019)

Adam J. Poe Mangesh Kulkarni Jason Wang Aleksandra Leszczynska Jie Tang

Homeostasis

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Integrated Transcriptome and Proteome Analyses Reveal the Regulatory Role of miR-146a in Human Limbal Epithelium via Notch Signaling

Cells (2020)

Adam J. Poe Mangesh Kulkarni Aleksandra Leszczynska Jie Tang Ruchi Shah

MiR-146a is upregulated in the stem cell-enriched limbal region vs. central human cornea and can mediate corneal epithelial wound healing. The aim of this study was to identify miR-146a targets in human primary limbal epithelial cells (LECs) using genomic and proteomic analyses. RNA-seq combined with quantitative proteomics based on multiplexed isobaric tandem mass tag labeling was performed in LECs transfected with miR-146a mimic vs. mimic control. Western blot and immunostaining were used to confirm the expression of some targeted genes/proteins. A total of 251 differentially expressed mRNAs and 163 proteins were identified. We found that miR-146a regulates the expression of multiple genes in different pathways, such as the Notch system. In LECs and organ-cultured corneas, miR-146a increased Notch-1 expression possibly by downregulating its inhibitor Numb, but decreased Notch-2. Integrated transcriptome and proteome analyses revealed the regulatory role of miR-146a in several other processes, including anchoring junctions, TNF-α, Hedgehog signaling, adherens junctions, TGF-β, mTORC2, and epidermal growth factor receptor (EGFR) signaling, which mediate wound healing, inflammation, and stem cell maintenance and differentiation. Our results provide insights into the regulatory network of miR-146a and its role in fine-tuning of Notch-1 and Notch-2 expressions in limbal epithelium, which could be a balancing factor in stem cell maintenance and differentiation.

Adherens junction

10.3390/cells9102175

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Citations (13)

The ZupT transporter plays an important role in zinc homeostasis and contributes to Salmonella enterica virulence

Metallomics (2013)

Mauro Cerasi Janet Z. Liu Serena Ammendola Adam J. Poe Patrizia Petrarca

Zinc is an essential metal for cellular homeostasis and function in both eukaryotes and prokaryotes. To acquire this essential nutrient, bacteria employ transporters characterized by different affinity for the metal. Several studies have investigated the role of the high affinity transporter ZnuABC in the bacterial response to zinc shortage, showing that this transporter has a key role in adapting bacteria to zinc starvation. In contrast, the role of the low affinity zinc importer ZupT has been the subject of limited investigations. Here we show that a Salmonella strain lacking ZupT is impaired in its ability to grow in metal devoid environments and that a znuABC zupT strain exhibits a severe growth defect in zinc devoid media, is hypersensitive to oxidative stress and contains reduced levels of intracellular free zinc. Moreover, we show that ZupT also plays a role in the ability of S. Typhimurium to colonize the host tissues. During systemic infections, the single zupT mutant strain was attenuated only in Nramp1(+/+) mice, but competition experiments between znuABC and znuABC zupT mutants revealed that ZupT contributes to metal uptake in vivo independently of the presence of a functional Nramp1 transporter. Altogether, the here reported results show that ZupT plays an important role in Salmonella zinc homeostasis, being involved in metal import both in vitro and in infected animals.

Salmonella enterica

Homeostasis

10.1039/c3mt00352c

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Citations (61)

Exosomes as agents of change in the cardiovascular system

Journal of Molecular and Cellular Cardiology (2017)

Adam J. Poe Anne A. Knowlton

Cell type

Exosome

Cell Signaling

10.1016/j.yjmcc.2017.08.002

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Citations (42)

Proteomics profiling to elucidate miR-146a targets in primary limbal epithelial cells

Mehrnoosh Saghizadeh Adam J. Poe Mangesh Kulkarni Andrei A. Kramerov Alexander V. Ljubimov

Profiling (computer programming)

Primary (astronomy)

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Transportation Energy Conservation in Colorado

Jack Kinstlinger Adam J. Poe

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Regulatory role of miR-146a in corneal epithelial wound healing via its inflammatory targets in human diabetic cornea

The Ocular Surface (2022)

Adam J. Poe Ruchi Shah Drirh Khare Mangesh Kulkarni Hong Phan

10.1016/j.jtos.2022.06.001

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Exosomes and cardiovascular cell–cell communication

Essays in Biochemistry (2018)

Adam J. Poe Anne A. Knowlton

Exosomes have become an important player in intercellular signaling. These lipid microvesicles can stably transfer miRNA, protein, and other molecules between cells and circulate throughout the body. Exosomes are released by almost all cell types and are present in most if not all biological fluids. The biologically active cargo carried by exosomes can alter the phenotype of recipient cells. Exosomes increasingly are recognized as having an important role in the progression and treatment of cardiac disease states. Injured cardiac cells can release exosomes with important pathological effects on surrounding tissue, in addition to effecting other organs. But of equal interest is the possible benefit(s) conferred by exosomes released from stem cells for use in treatment and possible repair of cardiac damage.

Cell Signaling

Cell type

10.1042/ebc20170081

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Citations (26)

Electrotaxis of cardiac progenitor cells, cardiac fibroblasts, and induced pluripotent stem cell-derived cardiac progenitor cells requires serum and is directed via PI3′K pathways

Heart Rhythm (2017)

Bert J. Frederich Valeriy Timofeyev Phung N. Thai M. Haddad Adam J. Poe

10.1016/j.hrthm.2017.06.038

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Identification of Wnt-5a Receptors Important in Diabetic and Non-Diabetic Corneal Epithelial Wound Healing

Investigative Ophthalmology & Visual Science (2025)

Ruchi Shah Cynthia Amador Adam J. Poe Tanya M. Spektor Priyanka Bhandary

Purpose: Persistent epithelial alterations such as delayed wound healing are a key feature of diabetic corneal disease. Previously, we reported that epigenetic changes in the diabetic cornea led to the suppression of Wnt-5a, and that addition of Wnt-5a accelerated wound healing. In this study, we set to determine which Wnt receptor(s) mediated Wnt-5a induced stimulation of diabetic corneal epithelial wound healing. Methods: Human limbal epithelial cells (LECs) were isolated from postmortem diabetic and non-diabetic donor eyes for single-cell RNA sequencing (scRNA-seq) and DNA methylation analysis. These analyses were validated by qRT-PCR, western blot, or immunostaining of corneal tissue sections. Cultured primary LECs were transfected with small interfering RNA (siRNA) to specific Wnt receptors to evaluate their role in scratch wound healing in the presence or absence of 200 ng/mL Wnt-5a. Results: Single-cell RNA sequencing analysis revealed differential gene expression of Wnt receptors, ROR2, MCAM, FZD5, FZD6, and FZD7. DNA methylation arrays showed hypomethylation of ROR2 gene promoter in diabetic versus non-diabetic LECs by 41.3% (**P < 0.01) resulting in increased ROR2 protein expression. Non-diabetic cells transfected with siRNA to knockdown ROR2 but not FZD5, FZD6, FZD7, MCAM, and RYK showed significantly decreased wound healing by approximately 50% (*P < 0.05) versus control siRNA. In diabetic LECs, knockdown of ROR2 significantly inhibited wound healing by 40% (*P < 0.05) and of FZD5 partially blocked wound healing that could not be restored by the addition of Wnt-5a. Conclusions: Wnt-5a seems to mediate wound healing in diabetic LECs mainly through receptor tyrosine kinase like orphan receptor 2 with Frizzled-5 serving as a possible co-receptor with a smaller effect.

Diabetic ulcers

10.1167/iovs.66.2.64

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