@article {704966,
	title = {Mapping cellular senescence networks in human diabetic foot ulcers},
	journal = {Geroscience},
	year = {2023},
	abstract = {Cellular senescence, a cell fate defined by irreversible cell cycle arrest, has been observed to contribute to chronic age-related conditions including non-healing wounds, such as diabetic foot ulcers. However, the role of cellular senescence in the pathogenesis of diabetic foot ulcers remains unclear. To examine the contribution of senescent phenotypes to these chronic wounds, differential gene and network analyses were performed on publicly available bulk RNA sequencing of whole skin biopsies of wound edge diabetic foot ulcers and uninvolved diabetic foot skin. Wald tests with Benjamini-Hochberg correction were used to evaluate differential gene expression. Results showed that cellular senescence markers, CDKN1A, CXCL8, IGFBP2, IL1A, MMP10, SERPINE1, and TGFA, were upregulated, while TP53 was downregulated in diabetic foot ulcers compared to uninvolved diabetic foot skin. NetDecoder was then used to identify and compare context-specific protein-protein interaction networks using known cellular senescence markers as pathway sources. The diabetic foot ulcer protein-protein interaction network demonstrated significant perturbations with decreased inhibitory interactions and increased senescence markers compared to uninvolved diabetic foot skin. Indeed, TP53 (p53) and CDKN1A (p21) appeared to be key regulators in diabetic foot ulcer formation. These findings suggest that cellular senescence is an important mediator of diabetic foot ulcer pathogenesis.},
	url = {https://link.springer.com/article/10.1007/s11357-023-00854-x},
	author = {Yu, GT and Monie, D D and Khosla, S and Tchkonia, T and Kirkland, JL and Wyles, SP}
}
@article {695933,
	title = {Hybrid tumors with perineurioma components: a systematic review of the literature and illustrative case},
	journal = {Acta Neurochir (Wein)},
	volume = {165},
	number = {4},
	year = {2023},
	pages = {935-945},
	abstract = {
	Purpose:\&nbsp;Hybrid peripheral nerve sheath tumors (HPNST) are a newly recognized class of peripheral nerve sheath tumor, composed of at least two areas characteristic of perineurioma, schwannoma, or neurofibroma. The literature consists only of case reports and small series; therefore, we present an illustrative case and an analysis of all reported cases of HPNST with a perineurioma component in the literature.



	Methods:\&nbsp;A systematic search of the literature was performed to identify all reported cases of hybrid perineurioma-schwannoma or perineurioma-neurofibroma in the world{\textquoteright}s literature. Individual cases were analyzed for demographics, clinical features, imaging, and outcomes.



	Results:\&nbsp;A total of 159 cases were identified across 41 studies. Hybrid tumors tended to present in mid-adulthood (median 38.5 years), predominantly affected females (57\%, 89/156), as a painless (63\%, 63/100) mass, or swelling. Ten patients (10/74, 14\%) had a history of neurofibromatosis 1, and 2 patients a history of neurofibromatosis 2 (2/74, 3\%). The majority (78\%, 122/157) of cases occurred superficially, most commonly in the lower extremity (25\%, 39/157). Perineurioma-schwannoma was the most reported (86\%, 137/159) pathologic diagnosis, with 3 cases presenting with malignant features. Two cases reocurred after resection.



	Conclusion:\&nbsp;HPNST tend to occur in mid-adulthood and present as slowly progressive, painless, superficial masses, with a heterogeneous appearance on imaging. These entities pose a unique diagnostic challenge and likely remain under-recognized in the literature and current clinical practice. They pose low risk of recurrence or malignant transformation, and future work regarding the association with neurofibromatosis and genetic profiles is needed.



	Keywords:\&nbsp;Hybrid tumor; Neurofibroma; Perineurioma; Peripheral nerve sheath; Schwannoma.

},
	url = {https://link.springer.com/article/10.1007/s00701-022-05413-5},
	author = {Lenartowicz, Karina A. and Monie, Dileep D. and Amrami, Kimberly K. and Klein, Christopher J. and Giannini, Caterina and Spinner, Robert J.}
}
@article {696176,
	title = {Strategies, considerations, and recent advancements in the development of liquid biopsy for glioblastoma: a step towards individualized medicine in glioblastoma},
	journal = {Neurosurg Focus},
	volume = {53},
	number = {6},
	year = {2022},
	pages = {E14},
	abstract = {
	\&nbsp;



	Objective:\&nbsp;Glioblastoma (GBM) is a devasting primary brain tumor with less than a 5\% 5-year survival. Treatment response assessment can be challenging because of inflammatory pseudoprogression that mimics true tumor progression clinically and on imaging. Developing additional noninvasive assays is critical. In this article, the authors review various biomarkers that could be used in developing liquid biopsies for GBM, along with strengths, limitations, and future applications. In addition, they present a potential liquid biopsy design based on the use of an extracellular vesicle-based liquid biopsy targeting nonneoplastic extracellular vesicles.



	Methods:\&nbsp;The authors conducted a current literature review of liquid biopsy in GBM by searching the PubMed, Scopus, and Google Scholar databases. Articles were assessed for type of biomarker, isolation methodology, analytical techniques, and clinical relevance.



	Results:\&nbsp;Recent work has shown that liquid biopsies of plasma, blood, and/or CSF hold promise as noninvasive clinical tools that can be used to diagnose recurrence, assess treatment response, and predict patient outcomes in GBM. Liquid biopsy in GBM has focused primarily on extracellular vesicles, cell-free tumor nucleic acids, and whole-cell isolates as focal biomarkers. GBM tumor signatures have been generated via analysis of tumor gene mutations, unique RNA expression, and metabolic and proteomic alterations. Liquid biopsies capture tumor heterogeneity, identifying alterations in GBM tumors that may be undetectable via surgical biopsy specimens. Finally, biomarker burden can be used to assess treatment response and recurrence in GBM.



	Conclusions:\&nbsp;Liquid biopsy offers a promising avenue for monitoring treatment response and recurrence in GBM without invasive procedures. Although additional steps must be taken to bring liquid biopsy into the clinic, proof-of-principle studies and isolation methodologies are promising. Ultimately, CSF and/or plasma-based liquid biopsy is likely to be a powerful tool in the neurosurgeon{\textquoteright}s arsenal in the near future for the treatment and management of GBM patients.



	\&nbsp;

},
	url = {https://thejns.org/focus/view/journals/neurosurg-focus/53/6/article-pE14.xml},
	author = {Megan MJ Bauman and Samantha M Bouchal and Monie, Dileep D and Abudumijiti Aibaidula and Rohin Singh and Parney, Ian F}
}
@article {Wen162,
	title = {NKG7 Is a T-cell{\textendash}Intrinsic Therapeutic Target for Improving Antitumor Cytotoxicity and Cancer Immunotherapy},
	journal = {Cancer Immunol Res},
	volume = {10},
	number = {2},
	year = {2022},
	pages = {162{\textendash}181},
	publisher = {American Association for Cancer Research},
	abstract = {Cytotoxic CD8+ T cells (CTL) are a crucial component of the immune system notable for their ability to eliminate rapidly proliferating malignant cells. However, the T-cell intrinsic factors required for human CTLs to accomplish highly efficient antitumor cytotoxicity are not well defined. By evaluating human CD8+ T cells from responders versus nonresponders to treatment with immune checkpoint inhibitors, we sought to identify key factors associated with effective CTL function. Single-cell RNA-sequencing analysis of peripheral CD8+ T cells from patients treated with anti{\textendash}PD-1 therapy showed that cells from nonresponders exhibited decreased expression of the cytolytic granule-associated molecule natural killer cell granule protein-7 (NKG7). Functional assays revealed that reduced NKG7 expression altered cytolytic granule number, trafficking, and calcium release, resulting in decreased CD8+ T-cell{\textendash}mediated killing of tumor cells. Transfection of T cells with NKG7 mRNA was sufficient to improve the tumor-cell killing ability of human T cells isolated from nonresponders and increase their response to anti{\textendash}PD-1 or anti{\textendash}PD-L1 therapy in vitro. NKG7 mRNA therapy also improved the antitumor activity of murine tumor antigen{\textendash}specific CD8+ T cells in an in vivo model of adoptive cell therapy. Finally, we showed that the transcription factor ETS1 played a role in regulating NKG7 expression. Together, our results identify NKG7 as a necessary component for the cytotoxic function of CD8+ T cells and establish NKG7 as a T-cell{\textendash}intrinsic therapeutic target for enhancing cancer immunotherapy.},
	issn = {2326-6066},
	doi = {10.1158/2326-6066.CIR-21-0539},
	url = {https://cancerimmunolres.aacrjournals.org/content/10/2/162},
	author = {Wen, Ti and Barham, Whitney and Li, Ying and Zhang, Henan and Gicobi, Joanina K. and Hirdler, Jacob B. and Liu, Xin and Ham, Hyoungjun and Peterson Martinez, Kodi E. and Lucien, Fabrice and Lavoie, Roxane R. and Li, Hu and Correia, Cristina and Monie, Dileep D. and An, Zesheng and Harrington, Susan M. and Wu, Xiaosheng and Guo, Ruifeng and Dronca, Roxana S. and Mansfield, Aaron S. and Yan, Yiyi and Markovic, Svetomir N. and Park, Sean S. and Sun, Jie and Qin, Hong and Liu, Minetta C. and Vasmatzis, George and Billadeau, Daniel D. and Dong, Haidong}
}
@article { Systemsneuroimmunologyareviewofmultiomicsmethodologiestocharacterizeneuroimmunologicalinteractionsinspinalandcranialdiseases,
	title = {Systems neuroimmunology: a review of multiomics methodologies to characterize neuroimmunological interactions in spinal and cranial diseases},
	journal = {Neurosurg Focus},
	volume = {52},
	number = {2},
	year = {2022},
	pages = {E9},
	publisher = {American Association of Neurological Surgeons},
	abstract = {Neuroimmunology plays a critical role in our understanding of the pathophysiological processes that underlie a variety of diseases treated by neurosurgeons, including degenerative disc disease (DDD), glioblastoma (GBM), aneurysmal subarachnoid hemorrhage (aSAH), and others. Compared with traditional methods in neuroimmunology, which study one pathway or gene at a time, emerging multiomics methodologies allow for holistic interrogation of multiple immune-signaling pathways to test hypotheses and the effects of therapeutics at a systems level. In this review, the authors summarize key concepts for gathering and analyzing multiomics data so that neurosurgeons can contribute to the emerging field of systems neuroimmunology. Additionally, they describe 3 use cases, based on original research published by their group and others, that utilize transcriptomic, metabolomic, and proteomic analyses to study immune-signaling pathways in DDD, aSAH, and GBM. Through these use cases, techniques for performing machine learning and network-based analyses to generate new clinical insights from multiomics data are shared. The authors hope that neurosurgeons might use this review as a summary of common tools and principles in systems immunology to better engage in creating the immunotherapies of tomorrow.},
	doi = {10.3171/2021.11.FOCUS21571},
	url = {https://thejns.org/focus/view/journals/neurosurg-focus/52/2/article-pE9.xml},
	author = {Cameron Zamanian and Archis R Bhandarkar and Monie, Dileep D and F M Moinuddin and Richard G Vile and Alfredo Qui{\~n}ones-Hinojosa and Bydon, Mohamad}
}
@article {Monie1679,
	title = {Innate immunity and cytokine signaling pathways drive resistance to HSV-1 oncolytic immunovirotherapy in glioblastoma},
	journal = {Cancer Res},
	volume = {81},
	number = {Suppl 13},
	year = {2021},
	pages = {1679},
	publisher = {American Association for Cancer Research},
	abstract = {Glioblastoma multiforme (GBM) is a particularly aggressive primary brain tumor that is relatively common in adults. The disease comes with a dismal prognosis, often with expected survival just over a year when treated with surgery, chemotherapy, and radiation. A promising addition to our GBM treatment arsenal are oncolytic viruses (OVs), a class of immunotherapy now in clinical trials. The most effective OVs home in on tumor cells, killing them and releasing tumor-associated antigens that elicit antitumor immunity. This effectiveness, however, varies depending on the cell state{\textemdash}a property that may be influenced by the composition of the extracellular matrix (ECM) of GBM. Cellular communication network factor 1 (CCN1) is found in the ECM of the majority of GBMs and is predictive of resistance to OVs, particularly those derived from herpes simplex virus type 1 (HSV-1). In this study, our aim is to understand how extracellular CCN1 alters the GBM intracellular state in a manner that confers resistance to OVs. We began by using our NetDecoder platform to build CCN1-specific prioritized protein-protein interaction (PPI) networks from published LN229 human GBM transcriptomic datasets. From this network, we identified 12 PPI edges that dominate the network flow in CCN1-high LN229 cells when compared to CCN1-low controls. The 21 unique nodes that comprise these binary PPI edges were extracted and subjected to downstream biological process overrepresentation analyses using Gene Ontology. We found that the cytokine-mediated signaling pathway (FDR = 4.2 x 10-11; enrichment ratio = 15.8) and the cellular response to cytokine stimulus (FDR = 3.1 x 10-9; enrichment ratio = 10.9) were highly enriched when mapped to these nodes. We conclude that CCN1, acting as a paracrine signal in the GBM tumor microenvironment, primes the cell to inhibit HSV-1 and other candidate OV replication prior to any virus interactions, thus contributing to immunovirotherapy resistance. While CCN1 and its cell surface integrin binding partners are ostensible drug targets for overcoming this resistance, pharmacologic interventions that target CCN1-specific high flow edges in our prioritized PPI network may be more effective.},
	issn = {0008-5472},
	doi = {10.1158/1538-7445.AM2021-1679},
	url = {https://cancerres.aacrjournals.org/content/81/13_Supplement/1679},
	author = {Monie, Dileep D. and Correia, Cristina and Cheng Zhang and Ung, Choong and Vile, Richard G. and Li, Hu}
}
@article {676303,
	title = {Modular network mechanism of CCN1-associated resistance to HSV-1-derived oncolytic immunovirotherapies for glioblastomas},
	journal = {Sci Rep},
	volume = {11},
	number = {11198},
	year = {2021},
	pages = {1-12},
	abstract = {Glioblastomas (GBMs) are the most common and lethal primary brain malignancy in adults. Oncolytic virus (OV) immunotherapies selectively kill GBM cells in a manner that elicits antitumor immunity. Cellular communication network factor 1 (CCN1), a protein found in most GBM microenvironments, expression predicts resistance to OVs, particularly herpes simplex virus type 1 (HSV-1). This study aims to understand how extracellular CCN1 alters the GBM intracellular state to confer OV resistance. Protein{\textendash}protein interaction network information flow analyses of LN229 human GBM transcriptomes identified 39 novel nodes and 12 binary edges dominating flow in CCN1high cells versus controls. Virus response programs, notably against HSV-1, and cytokine-mediated signaling pathways are highly enriched. Our results suggest that CCN1high states exploit IDH1 and TP53, and increase dependency on RPL6, HUWE1, and COPS5. To validate, we reproduce our findings in 65 other GBM cell line (CCLE) and 174 clinical GBM patient sample (TCGA) datasets. We conclude through our generalized network modeling and system level analysis that CCN1 signals via several innate immune pathways in GBM to inhibit HSV-1 OVs before transduction. Interventions disrupting this network may overcome immunovirotherapy resistance.},
	url = {https://www.nature.com/articles/s41598-021-90718-1},
	author = {Monie, D D and Correia, C and C Zhang and Ung, CY and Vile, RG and H. Li}
}
@article {671507,
	title = {Emerging workforce readiness in regenerative healthcare},
	journal = {Regen Med},
	volume = {16},
	number = {3},
	year = {2021},
	pages = {197-206},
	abstract = {The biology of regenerative medicine has steadily matured, providing the foundation for randomized clinical trials and translation into validated applications. Today, the growing regenerative armamentarium is poised to impact disease management, yet a gap in training next-generation healthcare providers, equipped to adopt and deliver regenerative options, has been exposed. This special report highlights a multiyear experience in developing and deploying a comprehensive regenerative curriculum for medical trainees. For academicians and institutions invested in establishing a formalized regenerative medicine syllabus, the Regenerative Medicine and Surgery course provides a patient-focused prototype for next-generation learners, offering a dedicated educational experience that encompasses discovery, development and delivery of regenerative solutions. Built with the vision of an evolving regenerative care model, this transdisciplinary endeavor could serve as an adoptable education portal to advance the readiness of the emergent regenerative healthcare workforce globally.},
	url = {https://www.futuremedicine.com/doi/10.2217/rme-2020-0137},
	author = {Wyles, Saranya P and Monie, Dileep D and Paradise, Christopher R and Meyer, Fredric B and Hayden, Richard E and Terzic, Andre}
}
@article {669880,
	title = {Synthetic and systems biology principles in the design of programmable oncolytic virus immunotherapies for glioblastoma},
	journal = {Neurosurg Focus},
	volume = {50},
	number = {2},
	year = {2021},
	pages = {E10},
	abstract = {Oncolytic viruses (OVs) are a class of immunotherapeutic agents with promising preclinical results for the treatment of glioblastoma (GBM) but have shown limited success in recent clinical trials. Advanced bioengineering principles from disciplines such as synthetic and systems biology are needed to overcome the current challenges faced in developing effective OV-based immunotherapies for GBMs, including off-target effects and poor clinical responses. Synthetic biology is an emerging field that focuses on the development of synthetic DNA constructs that encode networks of genes and proteins (synthetic genetic circuits) to perform novel functions, whereas systems biology is an analytical framework that enables the study of complex interactions between host pathways and these synthetic genetic circuits. In this review, the authors summarize synthetic and systems biology concepts for developing programmable, logic-based OVs to treat GBMs. Programmable OVs can increase selectivity for tumor cells and enhance the local immunological response using synthetic genetic circuits. The authors discuss key principles for developing programmable OV-based immunotherapies, including how to 1) select an appropriate chassis, a vector that carries a synthetic genetic circuit, and 2) design a synthetic genetic circuit that can be programmed to sense key signals in the GBM microenvironment and trigger release of a therapeutic payload. To illustrate these principles, some original laboratory data are included, highlighting the need for systems biology studies, as well as some preliminary network analyses in preparation for synthetic biology applications. Examples from the literature of state-of-the-art synthetic genetic circuits that can be packaged into leading candidate OV chassis are also surveyed and discussed.},
	url = {https://thejns.org/focus/view/journals/neurosurg-focus/50/2/article-pE10.xml},
	author = {Monie, Dileep D. and Bhandarkar, Archis R. and Parney, Ian F. and Correia, Cristina and Jann N. Sarkaria and Vile, Richard G. and Li, Hu}
}
@article {MONIE20201940,
	title = {Ependymal Petechial Hemorrhages in Bacterial Meningitis},
	journal = {Mayo Clin Proc},
	volume = {95},
	number = {9},
	year = {2020},
	pages = {1940-1941},
	issn = {0025-6196},
	doi = {https://doi.org/10.1016/j.mayocp.2020.07.005},
	url = {http://www.sciencedirect.com/science/article/pii/S0025619620307552},
	author = {Monie, Dileep D. and Fredric B. Meyer}
}
@article {655136,
	title = {Oncolytic Virus-Derived Type I Interferon Restricts CAR T Cell Therapy},
	journal = {Nat Commun},
	volume = {11},
	number = {1},
	year = {2020},
	pages = {3187},
	abstract = {The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test whether the inflammatory nature of oncolytic viruses and their ability to remodel the tumor microenvironment may help to recruit and potentiate the functionality of CAR T cells. Contrary to our hypothesis, VSVmIFNβ infection is associated with attrition of murine EGFRvIII CAR T cells in a B16EGFRvIII model, despite inducing a robust proinflammatory shift in the chemokine profile. Mechanistically, type I interferon (IFN) expressed following infection promotes apoptosis, activation, and inhibitory receptor expression, and interferon-insensitive CAR T cells enable combinatorial therapy with VSVmIFNβ. Our study uncovers an unexpected mechanism of therapeutic interference, and prompts further investigation into the interaction between CAR T cells and oncolytic viruses to optimize combination therapy.},
	url = {https://www.nature.com/articles/s41467-020-17011-z},
	author = {Laura Evgin and Amanda L. Huff and Phonphimon Wongthida and Jill Thompson and Tim Kottke and Jason Tonne and Matthew Schuelke and Katayoun Ayasoufi and Christopher B. Driscoll and Kevin G. Shim and Pierce Reynolds and Monie, Dileep D. and Aaron J. Johnson and Matt Coffey and Sarah L. Young and Gary Archer and John Sampson and Jose Pulido and Luis Sanchez Perez and Richard Vile}
}
@article {Monie169.17,
	title = {Network-guided bioengineering of oncolytic immunovirotherapies for glioblastoma},
	journal = {J Immunol},
	volume = {204},
	number = {Suppl 1},
	year = {2020},
	pages = {169.17{\textendash}169.17},
	publisher = {American Association of Immunologists},
	abstract = {Glioblastoma is the most common and lethal primary brain tumor in adults, with a median survival less than 15 months despite current standard of care. Oncolytic immunovirotherapies (OVs) have shown promise in early clinical trials. OVs are engineered to specifically target cancer cells, trigger autophagic programmed cell death, and release tumor antigens in the context of T-cell activating cytokines. Cellular communication network factor 1 (CCN1) is an extracellular matrix protein expressed in 70\% of glioblastomas that has been shown to drastically reduce OV efficacy, particularly herpes simplex virus type 1 (HSV-1). Our objectives were to decode protein-protein interaction (PPI) networks activated by CCN1, identify critical nodes in resistance networks, and use this analysis to design OVs that overcome CCN1-mediated resistance. We used NetDecoder to elucidate phenotype-specific PPI subnetworks in LN229 human glioblastoma cells with tetracycline-inducible CCN1 expression. Publicly available microarray data on CCN1-induced and control samples established differentially expressed genes, which served as sources in our PPI network to derive prioritized context-specific subnetworks. We found that 11 source genes collaborate via 39 deep nodes to confer OV resistance to CCN1-expressing glioblastomas. Of these, a router (IKBKE) and a sink (YBX1) have been previously implicated in glioblastoma pathogenesis. We conclude that autophagy regulator HSP90AA1, a critical node, may be targeted to improve OV efficacy in CCN1-expressing glioblastomas. Furthermore, WebGestalt overrepresentation analysis of subnetwork nodes suggests that oncolytic adenovirus may be more effective than HSV-1 as a synthetic biology chassis.},
	issn = {0022-1767},
	url = {https://www.jimmunol.org/content/204/1_Supplement/169.17},
	author = {Monie, Dileep D. and Cheng Zhang and Correia, Cristina and Ung, Choong and Vile, Richard G. and Li, Hu}
}
@article {645793,
	title = {Revealing the Tumor-immune Landscape Through Spatially-resolved Radiomics: Case Studies},
	journal = {Neuro Oncol},
	volume = {21},
	number = {Suppl 6},
	year = {2019},
	pages = {vi169-vi170},
	abstract = {
	BACKGROUND: Conventional magnetic resonance imaging (MR) guides patient care in GBM. However, there is mounting awareness that MR enhancement is non-specific reflecting either tumor progression or non-tumoral\&nbsp;inflammatory changes. Histological evaluation of GBM is held as the gold standard for disease assessment. However, the invasiveness of this methodology and the sample sparsity limit its usefulness. Methods to infer histological underpinnings of MRI are needed to improve clinical care.



	METHODS: A transfer learning mixed effects model based on T1Gd and FLAIR MR voxel based image features trained and cross-validated to predict FPKM values of CD68, CASP3, CD8A and IL13RA2. Training data included RNAseq from 38 image-localized biopsies from 15 newly-diagnosed GBM patients. These models were then applied to two independent patients, chosen based on therapy and the quality of image registration, at three different time points, just prior to receiving IL13RA2 targeted CAR-T therapy for rGBM, after 2 cycles and after 4 cycles, resulting in a voxel-based prediction of the relative expression levelsof these genes.



	RESULTS: Cross-validation of the proposed machine learning models demonstrated a Pearson Correlation coefficient between predicted and observed FPKM values of 0.89 (CD68), 0.92 (CASP3), 0.93 (CD8A), and 0.88 (IL13RA2). When the models were applied to the two CAR-T patients, CD68-modeled expression levels were seen to increase throughout therapy for one patient, while remaining stable for the other. Survival from first CAR-T infusion was, respectively, 412 and 83 days suggesting that the increased CD68 was indicative of therapeutic effectivity. Further, the spatial activity predictions were consistent with expected therapeutic action as the correlation coefficient between CASP3 and the product of IL13R2 and CD8A expression was 0.81, suggesting the T-cells targeting IL13RA2 were inducing cell death.



	CONCLUSIONS: Preliminary results with our model highlights the potential of spatially resolved radiomic maps to provide insight into regional therapeutic effectivity.

},
	url = {https://academic.oup.com/neuro-oncology/article/21/Supplement_6/vi169/5619818},
	author = {Andrea Hawkins-Daarud and Hyunsoo Yoon and Monie, Dileep and Kyle Singleton and Sara Ranjbar and Nhan Tran and Behnam Badie and Russell Rockne and Christine E. Brown and Leland Hu and Jeff Bruce and Peter D. Canoll and Jing Li and Kristin Swanson}
}
@article {629769,
	title = {Venous thromboembolic events in patients undergoing craniotomy for tumor resection: incidence, predictors, and review of literature},
	journal = {J Neurosurg},
	volume = {132},
	number = {1},
	year = {2019},
	month = {2019 Jan 04},
	pages = {10-21},
	abstract = {
	OBJECTIVE: The authors sought to investigate the incidence and predictors of venous thromboembolic events (VTEs) after craniotomy for tumor resection, which are not well established, and the efficacy of and risks associated with VTE chemoprophylaxis, which remains controversial.



	METHODS: The authors investigated the incidence of VTEs in a consecutive series of patients presenting to the authors{\textquoteright} institution for resection of an intracranial lesion between 2012 and 2017. Information on patient and tumor characteristics was collected and independent predictors of VTEs were determined using stepwise multivariate logistic regression analysis. Review of the literature was performed by searching MEDLINE using the keywords "venous thromboembolism," "deep venous thrombosis," "pulmonary embolism," "craniotomy," and "brain neoplasms."



	RESULTS: There were 1622 patients included for analysis. A small majority of patients were female (52.6\%) and the mean age of the cohort was 52.9 years (SD 15.8 years). A majority of intracranial lesions were intraaxial (59.3\%). The incidence of VTEs was 3.0\% and the rates of deep venous thromboses and pulmonary emboli were 2.3\% and 0.9\%, respectively. On multivariate analysis, increasing patient age (unit OR 1.02, 95\% CI 1.00-1.05; p = 0.018), history of VTE (OR 7.26, 95\% CI 3.24-16.27; p \&lt; 0.001), presence of motor deficit (OR 2.64, 95\% CI 1.43-4.88; p = 0.002), postoperative intracranial hemorrhage (OR 4.35, 95\% CI 1.51-12.55; p \&lt; 0.001), and prolonged intubation or reintubation (OR 3.27, 95\% CI 1.28-8.32; p \&lt; 0.001) were independently associated with increased odds of a VTE. There were 192 patients who received VTE chemoprophylaxis (11.8\%); the mean postoperative day of chemoprophylaxis initiation was 4.6 (SD 3.8). The incidence of VTEs was higher in patients receiving chemoprophylaxis than in patients not receiving chemoprophylaxis (8.3\% vs 2.2\%; p \&lt; 0.001). There were 30 instances of clinically significant postoperative hemorrhage (1.9\%), with only 1 hemorrhage occurring after initiation of VTE chemoprophylaxis (0.1\%).



	CONCLUSIONS: The study results show the incidence and predictors of VTEs after craniotomy for tumor resection in this patient population. The incidence of VTE within this cohort appears low and comparable to that observed in other institutional series, despite the lack of routine prophylactic anticoagulation in the postoperative setting.

},
	issn = {1933-0693},
	doi = {10.3171/2018.7.JNS181175},
	url = {https://thejns.org/view/journals/j-neurosurg/132/1/article-p10.xml},
	author = {Rinaldo, Lorenzo and Brown, Desmond A and Bhargav, Adip G and Rusheen, Aaron E and Naylor, Ryan M and Gilder, Hannah E and Monie, Dileep D and Youssef, Stephanie J and Parney, Ian F}
}
@article {574881,
	title = {Pathogenesis of thrombosis: cellular and pharmacogenetic contributions},
	journal = {Cardiovasc Diagn Ther},
	volume = {7},
	number = {Suppl 3},
	year = {2017},
	pages = {S291-S298},
	abstract = {Our understanding of thrombosis formation has evolved significantly ever since physician Rudolf Virchow proposed his {\textquotedblleft}triad{\textquotedblright} theory in 1856. Modern science has elucidated the mechanisms of stasis, hypercoagulability, and endothelial dysfunction. Today, we have a firm understanding of the key molecular factors involved in the coagulation cascade and fibrinolytic system, as well as the underlying genetic influences. This knowledge of cellular and genetic contributors has been translated into diverse pharmaceutical interventions. Here, we examine the molecular and cellular mechanisms of thrombosis and its associated pathologies. We also review the current state of pharmacologic interventions, including pro- and anti-thrombotics, direct oral anticoagulants, and anti-platelet therapies. The pharmacogenetic factors that guide clinical decision making and prognosis are described in detail. Finally, we explore new approaches to thrombosis drug discovery, repurposing, and diagnostics. We argue that network biology tools will enable a systems pharmacology revolution in the next generation of interventions, facilitating precision medicine applications and ultimately leading to improved patient outcomes.},
	url = {http://cdt.amegroups.com/article/view/17035},
	author = {Monie, Dileep D and DeLoughery, Emma P}
}
@inbook {247856,
	title = {Bioprinting of Dynamic Human Organs-on-Chips: Enabling Technologies for Rapid Drug Development and Personalized Medicine},
	booktitle = {Bioprinting in Regenerative Medicine},
	year = {2015},
	month = {2015},
	pages = {123-137},
	publisher = {Springer},
	organization = {Springer},
	edition = {1},
	address = {Cham, Switzerland},
	abstract = {
	Dynamic human organs-on-chips are microfluidic devices capable of reproducing the physiology of human organs, accurately simulating both normal and disease states. These microphysiological systems offer more predictive and ethical alternatives both to animal-based preclinical drug studies and to cell-based in vitro diagnostics. But multiple organs-on-chips must be connected together in order to emulate the full human body. Therefore, new and more complex organs-on-chips that are more representative and versatile need to be designed and developed. The most salient challenge lies in their fabrication. Current prototypes rely on traditional microfluidic and microelectromechanical system methods that are too time-consuming for rapid prototyping, troubleshooting, and customization. Newer three-dimensional bioprinting technologies can help facilitate fabrication and deployment of next generation organs-on-chips. This review of the literature provides background on the clinical utility of dynamic human organs-on-chips. It lays out their design and fabrication requirements in the context of state of the art bioprinting technologies. It also proposes development pathways for bioprinted organs-on-chips to engineer more predictive designs. Finally, regulatory considerations and the impact of future bioprinting approaches on organ-on-chips are discussed with emphasis on enabling an era of personalized medicine.

},
	url = {https://link.springer.com/chapter/10.1007/978-3-319-21386-6_6},
	author = {Monie, Dileep D and Sujata K. Bhatia},
	editor = {Kursad Turksen}
}
@article {219496,
	title = {PBS-1086, a Rel inhibitor of NF-κB, ameliorates collagen-induced arthritis in mice},
	journal = {Eur J Inflamm},
	volume = {10},
	number = {1},
	year = {2012},
	pages = {51-59},
	abstract = {
	The family of nuclear factor-kappaB (NF-κB) transcription factors is intimately involved in the regulation of expression of numerous genes in the setting of the inflammatory response. Inflammation, cartilage degradation, cell proliferation, angiogenesis and pannus formation are hallmarks of the pathogenesis of both collagen-induced arthritis (CIA) in rodents and rheumatoid arthritis (RA) in humans. The aim of this study is to investigate the effect of PBS-1086, a Rel inhibitor of NF-κB, on the modulation of the inflammatory response in mice subjected to CIA in comparison to the effect of etanercept. CIA was induced in mice by an intradermal injection of bovine type II collagen (CII) emulsion and complete Freund{\textquoteright}s adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice developed erosive hind paw arthritis when immunised with CII in CFA. Macroscopic clinical evidence of CIA first appeared as peri-articular erythema and oedema in the hind paws. The incidence of CIA was 100\% by day 28 in the CII challenged mice and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PBS-1086 starting at the onset of arthritis (day 21) ameliorated the clinical signs at days 21-35 and improved histological status in the joint and paw. In addition, it also reduced the neutrophil infiltration which is a key mediator of RA. In this study, we demonstrate that PBS-1086 exerts an anti-inflammatory effect during chronic inflammation and ameliorates the tissue damage associated with CIA. The anti-inflammatory activities of PBS-1086 are comparable to those of etanercept treatment.

},
	url = {https://journals.sagepub.com/doi/abs/10.1177/1721727X1201000106},
	author = {D. Impellizzeri and E. Mazzon and R. Di Paola and M. Galuppo and P. Bramanti and Zhang, J. and K. Bobb and D. Monie and J. Meshulam and D.R. Sliskovic and S. Cuzzocrea}
}
@article {219466,
	title = {Inhibition of immune activation by a novel nuclear factor-kappa B inhibitor in HTLV-I-associated neurologic disease},
	journal = {Blood},
	volume = {117},
	number = {12},
	year = {2011},
	month = {2011 Mar 24},
	pages = {3363-9},
	abstract = {The human T-lymphotropic virus type I (HTLV-I) causes a chronic inflammatory disorder of the central nervous system termed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-I encodes a protein known to activate several host-signaling pathways involved in inflammation, such as the nuclear factor-κB (NF-κB). The contribution of the NF-κB pathway to the pathogenesis of HAM/TSP, however, has not been fully defined. We show evidence of canonical NF-κB activation in short-term cultures of peripheral blood mononuclear cells (PBMCs) from subjects with HAM/TSP. NF-κB activation was closely linked to HTLV-I viral protein expression. The NF-κB activation in HAM/TSP PBMCs was reversed by a novel small-molecule inhibitor that demonstrates potent and selective NF-κB antagonist activity. Inhibition of NF-κB activation led to a reduction in the expression of lymphocyte activation markers and resulted in reduced cytokine signaling in HAM/TSP PBMCs. Furthermore, NF-κB inhibition led to a reduction in spontaneous lymphoproliferation, a key ex vivo correlate of the immune activation associated with HAM/TSP. These results indicate that NF-κB activation plays a critical upstream role in the immune activation of HAM/TSP, and identify the NF-κB pathway as a potential target for immunomodulation in HAM/TSP.},
	keywords = {Benzamides, Cell proliferation, Cells, Cultured, Cyclohexanones, Drug Evaluation, Preclinical, HeLa Cells, Human T-lymphotropic virus 1, Humans, Immunologic Factors, Immunotherapy, Leukocytes, Mononuclear, Lymphocyte Activation, NF-kappa B, Paraparesis, Tropical Spastic, Signal Transduction, Viral Load},
	issn = {1528-0020},
	doi = {10.1182/blood-2010-10-306571},
	url = {https://ashpublications.org/blood/article/117/12/3363/20405/Inhibition-of-immune-activation-by-a-novel-nuclear},
	author = {Oh, Unsong and McCormick, Matthew J and Datta, Dibyadeep and Turner, Richard V and Bobb, Kathryn and Monie, Dileep D and Sliskovic, D Robert and Tanaka, Yuetsu and Zhang, Jie and Meshulam, Jeffrey and Jacobson, Steven}
}
@article {219491,
	title = {NFkB activation promotes immune activation in HTLV-I-associated myelopathy / tropical spastic paraparesis},
	journal = {Retrovirology},
	volume = {8},
	number = {Suppl 1},
	year = {2011},
	pages = {A117},
	abstract = {Evidence suggests that HTLV-I-induced immune activation plays a key role in the pathogenesis of HAM/TSP. The HTLV-I-encoded transactivating protein Tax is known to activate nuclear factor kappa B (NFkB), a key host signaling pathway regulating immune response, but the contribution of the NFkB pathway to the immune activation associated with HAM/TSP has yet to be fully defined. We examined NFkB activation in peripheral blood mononuclear cells (PBMC) from subjects with HAM/TSP, and tested the effect of NFkB inhibition on key ex vivo correlates of immune activation in HAM/TSP.
We examined the role of NFkB activation during immune activation associated with HAM/TSP by using small molecule NFkB inhibitors, including a newly developed selective inhibitor of NFkB, PBS-1086.
NFkB activation was assessed in peripheral-blood mononuclear cells (PBMC) from subjects with HAM/TSP and in healthy donors (HD). Nuclear translocation of the NFkB RelA was significantly higher in PBMC from subjects with HAM/TSP compared to HD (p=0.032) following short-term (20 h) culture, indicating increased activation of the NFkB pathway in HAM/TSP. Treatment with the small molecule inhibitor PBS-1086 reduced NFkB activation (p\&lt;0.01). PBS-1086 reduced expression of CD25 and CD69 in HAM/TSP PBMC as well as phosphorylation of STAT5 in a dose-dependent manner (p\&lt;0.01 for all). PBS-1086 also inhibited spontaneous lymphoproliferation of HAM/TSP PBMC in a dose-dependent manner (p=0.0286). PBS-1086 treatment resulted in a mean proviral load reduction of 20\% compared to untreated PBMC in a 72 h culture.
These results indicate that NFkB activation plays a critical upstream role in the immune activation associated with HAM/TSP, and identify the NFkB pathway as a potential therapeutic target for immune modulation in HAM/TSP.},
	issn = {1742-4690},
	doi = {10.1186/1742-4690-8-S1-A117},
	url = {http://www.retrovirology.com/content/8/S1/A117},
	author = {McCormick, Matthew and Oh, Unsong and Datta, Dibyadeep and Turner, Richard and Bobb, Kathryn and Monie, Dileep and Sliskovic, Drago and Zhang, Jie and Meshulam, Jeffrey and Jacobson, Steven}
}
@article {oh2010nfkb,
	title = {NFkB activation promotes immune activation in HTLV-I-associated myelopathy/tropical spastic paraparesis},
	journal = {J Neurovirol},
	volume = {16},
	number = {Suppl 1},
	year = {2010},
	pages = {63{\textendash}64},
	publisher = {Taylor \& Francis},
	abstract = {
	Background: Human T lymphotropic virus type I (HTLV-I) is the etiologic agent of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic inflammatory disorder of the central nervous system. Evidence suggests that viral-induced immune activation plays a key role in the pathogenesis of HAM/TSP. The HTLV-I-encoded transactivating protein Tax is known to activate nuclear factor kappa B (NFkB), a key host signaling pathway regulating immune response, but the contribution of the NFkB pathway to the immune activation associated with HAM/TSP has yet to be fully defined. To further delineate the role of NFkB activation in HAM/TSP, we examined NFkB activation in peripheral-blood mononuclear cells (PBMC) from subjects with HAM/TSP, and tested the effect of NFkB inhibition on key ex vivo correlates of immune activation in HAM/TSP.



	Materials and Methods: We examined the role of NFkB activation during immune activation associated with HAM/TSP by using small molecule NFkB inhibitors, including a newly developed selective inhibitor of NFkB, PBS-1086. NFkB activation was measured by a DNA-binding ELISA on nuclear extracts from PBMC of subjects with HAM/TSP and healthy donors to detect nuclear translocation of NFkB subunits. Immune activation in HAM/TSP PBMC was measured by tritiated thymidine incorporation, a marker for spontaneous proliferation, and by FACS analysis of the lymphocyte activation markers CD25 and CD69 and the pro-inflammatory cytokine STAT5. Proviral loads in untreated and inhibitor-treated HAM/TSP samples were measured by real time PCR.



	Results: NFkB activation was assessed in peripheral-blood mononuclear cells (PBMC) from subjects with HAM/TSP and in healthy donors (HD). Nuclear translocation of the NFkB RelA was significantly higher in PBMC from subjects with HAM/TSP compared to HD (p = 0.032) following short-term (20 h) culture, indicating increased activation of the NFkB pathway in HAM/TSP. Treatment with the small molecule inhibitor PBS-1086 reduced NFkB activation (p \&lt; 0.01). PBS-1086 reduced expression of CD25 and CD69 in HAM/TSP PBMC as well as phosphorylation of STAT5 in a dose-dependent manner (p \&lt; 0.01 for all). PBS-1086 also inhibited spontaneous lymphoproliferation of HAM/TSP PBMC in a dose-dependent manner. PBS-1086treatment resulted in a mean proviral load reduction of 20\% compared to untreated PBMC in a 72 h culture.



	Discussion: These results indicate that NFkB activation plays a critical upstream role in the immune activation associated with HAM/TSP, and identify the NFkB pathway as a potential therapeutic target for immune modulation in HAM/TSP.

},
	url = {http://link.springer.com/content/pdf/10.3109\%2F13550284.2010.522868.pdf},
	author = {Oh, Unsong and McCormick, Matthew and Datta, Dibyadeep and Turner, Richard and Bobb, Kathryn and Monie, Dileep and Sliskovic, D Robert and Zhang, Jie and Meshulam, Jeffrey and Jacobson, Steven}
}
@article {Hunter15042010,
	title = {The radiosensitizing and cytotoxic effects of PBS-1086, a Rel inhibitor of NF-KB, in breast cancer cells},
	journal = {Cancer Res},
	volume = {70},
	year = {2010},
	pages = {3561},
	abstract = {Recent RNA interference screening has identified p53 and ras mutations to be synthetic lethal with the canonical and non-canonical pathways of NF-κB. We have synthesized inhibitors that antagonize bindings of RelA (p65), RelB and c-rel to the NF-κB sites and thus inhibit both the canonical and non-canonical paths. One such compound, PBS-1086, is evaluated here as a radiosensitizer in wild type and p65-/- mouse embryonic fibroblasts (MEFs), and as a radiosensitizing and chemotherapeutic agent in the p53 deficient and KRAS (G13D) mutant breast cancer cell line, MDA-MB-231.We found that p65-/- MEFs were >= 2-fold more sensitive than p65+/+ MEFs to irradiation (IR) in clonogenic survival assays, thus demonstrating that NF-κB activation conferred radio-resistance. Incubation with PBS-1086 at 1.4 {\textmu}M, a non-cytotoxic concentration, radiosensitized p65+/+ MEFs (LD50 value of 1.5 Gy for IR + PBS-1086 compared with 2.3 Gy for IR alone). PBS-1086 had no effect on radio-sensitization of p65-/- MEFs, which indicated the radiosensitizing effect of PBS-1086 was mediated through p65. Similar radiosensitizing effects were observed by using RNA interference technique to down-regulate the expression level of p65 by \&gt; 95\% in p65+/+ MEFs but not in p65-/- MEFs. We also confirmed the inhibition of the NF-κB by PBS-1086 or p65 siRNA in MEFs. NF-κB-dependent luciferase expression increased by 2.5 fold after 10 Gy IR in p65+/+ MEFs. Treatment with PBS-1086 or p65 siRNA reduced luciferase expression significantly. Similarly, IR increased p65+/+ MEFs nuclear extract NF-κB DNA binding activities by 2 fold, which was significantly decreased by either PBS-1086 incubation or p65 siRNA treatment in these cells.Next, we studied PBS-1086 in MDA-MB-231 breast cancer cells with constitutive NF-κB activation. First, we tested PBS-1086 as a single agent on the growth of the breast cancer cells. Significant cytotoxic effect to PBS-1086 was observed with an LD50 value of 0.4 μM to the MDA-MB-231 cells. Then we tested synergistic effect of PBS-1086 with irradiation in these cells. Incubation with 0.2 {\textmu}M PBS-1086 significantly enhanced radiation effect by 1.5 fold (LD50 value of 1.66 Gy IR for IR + PBS-1086 compare with 2.55 Gy for IR alone).In conclusion, we have demonstrated that a Rel inhibitor of NF-KB can potentiate radioactivity through blocking the canonical pathway. It can also selectively kill tumor cells with p53 and KRAS mutations, perhaps through blocking the canonical and non-canonical pathways.Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3561.},
	doi = {10.1158/1538-7445.AM10-3561},
	url = {http://cancerres.aacrjournals.org/content/70/8_Supplement/3561.abstract},
	author = {Hunter, Jill E. and Willmore, Elaine and Irving, Julie A E and Sliskovic, D Robert and Monie, Dileep and Bobb, Kathryn and Zhang, Jie and Durkacz, Barbara W.}
}
@article {219471,
	title = {Measuring the activity of BioBrick promoters using an in vivo reference standard},
	journal = {J Biol Eng},
	volume = {3},
	year = {2009},
	month = {2009},
	pages = {4},
	abstract = {BACKGROUND: The engineering of many-component, synthetic biological systems is being made easier by the development of collections of reusable, standard biological parts. However, the complexity of biology makes it difficult to predict the extent to which such efforts will succeed. As a first practical example, the Registry of Standard Biological Parts started at MIT now maintains and distributes thousands of BioBrick standard biological parts. However, BioBrick parts are only standardized in terms of how individual parts are physically assembled into multi-component systems, and most parts remain uncharacterized. Standardized tools, techniques, and units of measurement are needed to facilitate the characterization and reuse of parts by independent researchers across many laboratories. RESULTS: We found that the absolute activity of BioBrick promoters varies across experimental conditions and measurement instruments. We choose one promoter (BBa_J23101) to serve as an in vivo reference standard for promoter activity. We demonstrated that, by measuring the activity of promoters relative to BBa_J23101, we could reduce variation in reported promoter activity due to differences in test conditions and measurement instruments by approximately 50\%. We defined a Relative Promoter Unit (RPU) in order to report promoter characterization data in compatible units and developed a measurement kit so that researchers might more easily adopt RPU as a standard unit for reporting promoter activity. We distributed a set of test promoters to multiple labs and found good agreement in the reported relative activities of promoters so measured. We also characterized the relative activities of a reference collection of BioBrick promoters in order to further support adoption of RPU-based measurement standards. CONCLUSION: Relative activity measurements based on an in vivoreference standard enables improved measurement of promoter activity given variation in measurement conditions and instruments. These improvements are sufficient to begin to support the measurement of promoter activities across many laboratories. Additional in vivo reference standards for other types of biological functions would seem likely to have similar utility, and could thus improve research on the design, production, and reuse of standard biological parts.},
	issn = {1754-1611},
	doi = {10.1186/1754-1611-3-4},
	url = {https://jbioleng.biomedcentral.com/articles/10.1186/1754-1611-3-4},
	author = {Kelly, Jason R and Rubin, Adam J and Davis, Joseph H and Ajo-Franklin, Caroline M and Cumbers, John and Czar, Michael J and de Mora, Kim and Glieberman, Aaron L and Monie, Dileep D and Endy, Drew}
}
@booklet {ducker2008compositions,
	title = {Compositions and methods for treating viral infections},
	year = {2008},
	note = {WO Patent App. PCT/US2008/002,177},
	publisher = {Google Patents},
	url = {http://www.google.com/patents/WO2008103346A1?cl=en},
	author = {Ducker, C. and Fouts, T.R. and Monie, D D}
}
@article {S.L.Merbs05102007,
	title = {Expression of Photoreceptor-Specific Genes Correlates With DNA Hypomethylation},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {48},
	year = {2007},
	pages = {3778},
	abstract = {
	Purpose: One element of transcriptional regulation is the local epigenetic configuration of a gene. DNA methylation is an epigenetic phenomenon that controls various genomic functions without altering the DNA sequence. The promoter sequences of housekeeping genes are typically unmethylated, and aberrant methylation is known to shut down expression of tumor suppressor genes in cancer. To investigate whether DNA methylation might play a role in tissue-specific expression of photoreceptor genes, we investigated the methylation status of photoreceptor-specific genes and correlated the degree of methylation with the expression of those genes.



	Methods: Genomic DNA from WERI and Y79 human retinoblastoma cell lines and 293 cells were treated with bisulfite. Primers were designed to amplify only the bisulfite modified DNA in 300-500bp segments of the 1000bp upstream of the TSS through the first exon of selected photoreceptor-specific genes (RPB3, RHO, OPN1SW, OPN1MW, and OPN1LW). Direct sequencing of the PCR products was performed. The ratio of unmethylated/methylated (T/C) DNA was calculated for each CpG site. Expression of the same genes was measured by real time PCR. The cell line experiments were then reproduced in the mouse, comparing the methylation status of RBP3, RHO, OPN1SW and OPN1MW in retina, brain, kidney and testes with the expression level of those genes.



	Results: None of the photoreceptor-specific genes were detected in 293 cells, Y79 cells expressed RPB3 but only very low levels of the opsins, and WERI cells expressed RBP3, OPN1MW and OPN1LW. The CpG sites 1000bp upstream of the TSS through the end of the first exon in all photoreceptor-specific genes were primarily methylated in 293 cells, consistent with the non-expression. In Y79 cells, the photoreceptor-specific genes were primarily methylated, except for RPB3, which was primarily unmethylated. The RPB3, OPN1MW, and OPN1LW genes were primarily unmethylated in WERI cells, and the RHO and OPN1SW genes were methylated. The same correlation between expression and the lack of methylation was found in corresponding experiments in mice. Photoreceptor-specific genes were overall less methylated in the retina, than in the other non-expressing tissues.



	Conclusions: We have demonstrated that the relative lack of DNA methylation in some photoreceptor-specific genes correlates with the expression of those genes, both in human tissue culture cells and in several mouse tissues. Whether the methylation in part directs the tissue-specific non-expression, or is simply a consequence of the non-expression is yet to be determined.

},
	url = {https://iovs.arvojournals.org/article.aspx?articleid=2386470},
	author = {Merbs, S. L. and Hackler, L., Jr. and Khan, M. A. and Monie, D D and Zack, D. J.}
}
@inbook {219501,
	title = {Pulmonary Hypertension},
	booktitle = {In a Page Cardiology},
	year = {2007},
	pages = {148-149},
	publisher = {Lippincott Williams \& Wilkins},
	organization = {Lippincott Williams \& Wilkins},
	address = {Philadelphia},
	author = {Monie, Dileep},
	editor = {Prasad, Rajnish and Kahan, Scott}
}
@article {219476,
	title = {The crystal structure of exfoliative toxin B: a superantigen with enzymatic activity},
	journal = {Biochemistry},
	volume = {38},
	number = {32},
	year = {1999},
	month = {1999 Aug 10},
	pages = {10239-46},
	abstract = {The exfoliative toxins (ETs) cause staphylococcal scalded skin syndrome, a disease characterized by specific separation of layers of the skin. Evidence suggests that the toxins act as serine proteases, though the specific substrate and mode of action are not known for certain. The crystal structure of exfoliative toxin A (ETA) was reported earlier and shown to be similar to that of the chymotrypsin-like serine proteases. Here, we report the 2.4 A resolution crystal structure of the other exfoliative toxin, ETB, which is 40\% identical to ETA. The overall structures of ETA and ETB are similar including the positions of key residues within the active site. The structure of ETB supports the previous findings that the ETs are serine proteases that cleave substrates after glutamic acid residues. In this study we also discuss a number of structural differences including a large 14 residue loop insertion which may be a key feature involved in the differing biological properties of the ETs, particularly the pyrogenic and lethal activities of ETB not shared by ETA.},
	keywords = {Amino Acid Sequence, Anions, Binding Sites, Catalytic Domain, Crystallography, X-Ray, Exfoliatins, Glycine, Histocompatibility Antigens Class II, Models, Molecular, Molecular Sequence Data, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Antigen, T-Cell, Staphylococcus aureus, Superantigens},
	issn = {0006-2960},
	doi = {10.1021/bi990721e},
	url = {https://pubs.acs.org/doi/10.1021/bi990721e},
	author = {Vath, G M and Earhart, C A and Monie, D D and Iandolo, J J and Schlievert, P M and Ohlendorf, D H}
}
@article {219481,
	title = {Unique superantigen activity of staphylococcal exfoliative toxins},
	journal = {J Immunol},
	volume = {162},
	number = {8},
	year = {1999},
	month = {1999 Apr 15},
	pages = {4550-9},
	abstract = {Certain strains of Staphylococcus aureus express one or both of two related, but immunologically distinct, exfoliative toxins (ETA and ETB). These toxins induce the symptoms associated with staphylococcal scalded skin syndrome. Both ETs have been shown to stimulate T cell proliferation. Recently, it was reported that ETA is a superantigen that stimulates T cells bearing human Vbeta2 or several murine Vbetas. However, other investigators have proposed that the superantigenicity reported for ETA resulted from contaminants in commercial preparations. This present study addresses those conflicting reports by assessing the biological and immunologic activities of highly purified rETs. ETA and ETB required APCs to induce selective polyclonal expansion of several human Vbetas (huVbetas), although, neither toxin expanded huVbeta2. ETB induced expansion of murine T cells bearing Vbetas 7 and 8, those that have the highest homology to the huVbetas expanded by ETA and ETB. Although flow cytometry of ETB-stimulated T cells matched PCR results, stimulation by ETA reduced percentages of T cells positive for several huVbetas that had been shown to have increased levels of mRNA transcripts. ETA and ETB induced contrasting reactions in vivo. In rabbits, ETB was moderately pyrogenic and enhanced susceptibility to lethal shock, while ETA lacked both activities. Predictions based on comparisons with other superantigens suggest molecular regions potentially involved in receptor binding in the ETA crystal structure and a modeled ETB three-dimensional structure. These results show that ETs are superantigens with unique properties that could account for the discrepancies reported.},
	keywords = {Animals, Cells, Cultured, Clone Cells, Epitopes, T-Lymphocyte, Exfoliatins, Gene Expression Regulation, Genes, T-Cell Receptor beta, Humans, Immunophenotyping, Injections, Intravenous, Lymphocyte Activation, Lymphocyte Count, Mice, Mice, Inbred C3H, Models, Molecular, Rabbits, Superantigens, T-Lymphocytes},
	issn = {0022-1767},
	url = {https://www.jimmunol.org/content/162/8/4550.long},
	author = {Monday, S R and Vath, G M and Ferens, W A and Deobald, C and Rago, J V and Gahr, P J and Monie, D D and Iandolo, J J and Chapes, S K and Davis, W C and Ohlendorf, D H and Schlievert, P M and Bohach, G A}
}
