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4. Figure S6 from Pharmacologic Properties and Preclinical Activity of Sasanlimab, A High-affinity Engineered Anti-Human PD-1 Antibody

Author

Al-Khami, Amir A., primary, Youssef, Sawsan, primary, Abdiche, Yasmina, primary, Nguyen, HoangKim, primary, Chou, Joyce, primary, Kimberlin, Christopher R., primary, Chin, Sherman M., primary, Kamperschroer, Cris, primary, Jessen, Bart, primary, Kern, Brent, primary, Budimir, Natalija, primary, Dillon, Christopher P., primary, Xu, Allison, primary, Clark, Jerry D., primary, Chou, Jeffrey, primary, Kraynov, Eugenia, primary, Rajpal, Arvind, primary, Lin, John C., primary, and Salek-Ardakani, Shahram, primary

Published
2023
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5. Data from Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Antitumor Effector/Memory CD8 T Cells in a Poorly Immunogenic Tumor Model

Author

Chen, Shihao, primary, Lee, Li-Fen, primary, Fisher, Timothy S., primary, Jessen, Bart, primary, Elliott, Mark, primary, Evering, Winston, primary, Logronio, Kathryn, primary, Tu, Guang Huan, primary, Tsaparikos, Konstantinos, primary, Li, Xiaoai, primary, Wang, Hui, primary, Ying, Chi, primary, Xiong, Mengli, primary, VanArsdale, Todd, primary, and Lin, John C., primary

Published
2023
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12. Supplementary Figure Legends from Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Antitumor Effector/Memory CD8 T Cells in a Poorly Immunogenic Tumor Model

Author

Chen, Shihao, primary, Lee, Li-Fen, primary, Fisher, Timothy S., primary, Jessen, Bart, primary, Elliott, Mark, primary, Evering, Winston, primary, Logronio, Kathryn, primary, Tu, Guang Huan, primary, Tsaparikos, Konstantinos, primary, Li, Xiaoai, primary, Wang, Hui, primary, Ying, Chi, primary, Xiong, Mengli, primary, VanArsdale, Todd, primary, and Lin, John C., primary

Published
2023
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14. Supplementary Figures 1 - 5 from Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Antitumor Effector/Memory CD8 T Cells in a Poorly Immunogenic Tumor Model

Author

Chen, Shihao, primary, Lee, Li-Fen, primary, Fisher, Timothy S., primary, Jessen, Bart, primary, Elliott, Mark, primary, Evering, Winston, primary, Logronio, Kathryn, primary, Tu, Guang Huan, primary, Tsaparikos, Konstantinos, primary, Li, Xiaoai, primary, Wang, Hui, primary, Ying, Chi, primary, Xiong, Mengli, primary, VanArsdale, Todd, primary, and Lin, John C., primary

Published
2023
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20. A distal region of the human TGM1 promoter is required for expression in transgenic mice and cultured keratinocytes

Author

Phillips, Marjorie A, Jessen, Bart A, Lu, Ying, Qin, Qin, Stevens, Mary E, and Rice, Robert H

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biotechnology, Genetics, Animals, Cell Line, Gene Expression, Genes, Reporter, Humans, Keratinocytes, Mice, Mice, Transgenic, Mutation, Promoter Regions, Genetic, Transcription Factors, Transcription, Genetic, Transglutaminases, Public Health and Health Services, Dermatology & Venereal Diseases, Clinical sciences
Abstract

BackgroundTGM1(transglutaminase 1) is an enzyme that crosslinks the cornified envelope of mature keratinocytes. Appropriate expression of the TGM1 gene is crucial for proper keratinocyte function as inactivating mutations lead to the debilitating skin disease, lamellar ichthyosis. TGM1 is also expressed in squamous metaplasia, a consequence in some epithelia of vitamin A deficiency or toxic insult that can lead to neoplasia. An understanding of the regulation of this gene in normal and abnormal differentiation states may contribute to better disease diagnosis and treatment.MethodsIn vivo requirements for expression of the TGM1 gene were studied by fusing various lengths of promoter DNA to a reporter and injecting the DNA into mouse embryos to generate transgenic animals. Expression of the reporter was ascertained by Western blotting and immunohistochemistry. Further delineation of a transcriptionally important distal region was determined by transfections of progressively shortened or mutated promoter DNA into cultured keratinocytes.ResultsIn vivo analysis of a reporter transgene driven by the TGM1 promoter revealed that 1.6 kilobases, but not 1.1 kilobases, of DNA was sufficient to confer tissue-specific and cell layer-specific expression. This same region was responsible for reporter expression in tissues undergoing squamous metaplasia as a response to vitamin A deprivation. Mutation of a distal promoter AP1 site or proximal promoter CRE site, both identified as important transcriptional elements in transfection assays, did not prevent appropriate expression. Further searching for transcriptional elements using electrophoretic mobility shift (EMSA) and transfection assays in cultured keratinocytes identified two Sp1 elements in a transcriptionally active region between -1.6 and -1.4 kilobases. While mutation of either Sp1 site or the AP1 site singly had only a small effect, mutation of all three sites eliminated nearly all the transcriptional activity.ConclusionsA distal region of the TGM1 gene promoter, containing AP1 and Sp1 binding sites, is evolutionarily conserved and responsible for high level expression in transgenic mice and in transfected keratinocyte cultures.

Published
2004

30. Microphysiological systems in early stage drug development: Perspectives on current applications and future impact

Author

Kopec, Anna K., primary, Yokokawa, Ryuji, additional, Khan, Nasir, additional, Horii, Ikuo, additional, Finley, James E., additional, Bono, Christine P., additional, Donovan, Carol, additional, Roy, Jessica, additional, Harney, Julie, additional, Burdick, Andrew D., additional, Jessen, Bart, additional, Lu, Shuyan, additional, Collinge, Mark, additional, Sadeghian, Ramin Banan, additional, Derzi, Mazin, additional, Tomlinson, Lindsay, additional, and Burkhardt, John E., additional

Published
2021
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31. Pharmacologic Properties and Preclinical Activity of Sasanlimab, A High-affinity Engineered Anti-Human PD-1 Antibody

Author

Al-Khami, Amir A., primary, Youssef, Sawsan, additional, Abdiche, Yasmina, additional, Nguyen, HoangKim, additional, Chou, Joyce, additional, Kimberlin, Christopher R., additional, Chin, Sherman M., additional, Kamperschroer, Cris, additional, Jessen, Bart, additional, Kern, Brent, additional, Budimir, Natalija, additional, Dillon, Christopher P., additional, Xu, Allison, additional, Clark, Jerry D., additional, Chou, Jeffrey, additional, Kraynov, Eugenia, additional, Rajpal, Arvind, additional, Lin, John C., additional, and Salek-Ardakani, Shahram, additional

Published
2020
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44. Evaluation of the cytotoxic effects of ophthalmic solutions containing benzalkonium chloride on corneal epithelium using an organotypic 3-D model

Author

Jessen Bart A and Khoh-Reiter Su

Subjects
Ophthalmology, RE1-994
Abstract

Abstract Background Benzalkonium chloride (BAC) is a common preservative used in ophthalmic solutions. The aim of this study was to compare the cytotoxic effects of BAC-containing ophthalmic solutions with a BAC-free ophthalmic solution using an organotypic 3-dimensional (3-D) corneal epithelial model and to determine the effects of latanoprost ophthalmic solution and its BAC-containing vehicle on corneal thickness in a monkey model. Methods The cytotoxicity of commercially available BAC-containing ophthalmic formulations of latanoprost (0.02% BAC) and olopatadine (0.01% BAC) was compared to that of BAC-free travoprost and saline in a corneal organotypic 3-D model using incubation times of 10 and 25 minutes. To compare the extent of differentiation of 3-D corneal cultures to monolayer transformed human corneal epithelial (HCE-T) cell cultures, expression levels (mRNA and protein) of the corneal markers epidermal growth factor receptor, transglutaminase 1 and involucrin were quantified. Finally, latanoprost ophthalmic solution or its vehicle was administered at suprapharmacologic doses (two 30 μL drops twice daily in 1 eye for 1 year) in monkey eyes, and corneal pachymetry was performed at baseline and at weeks 4, 13, 26 and 52. Results In the 3-D corneal epithelial culture assays, there were no significant differences in cytotoxicity between the BAC-containing latanoprost and olopatadine ophthalmic solutions and BAC-free travoprost ophthalmic solution at either the 10- or 25-minute time points. The 3-D cultures expressed higher levels of corneal epithelial markers than the HCE-T monolayers, indicating a greater degree of differentiation. There were no significant differences between the corneal thickness of monkey eyes treated with latanoprost ophthalmic solution or its vehicle (both containing 0.02% BAC) and untreated eyes. Conclusion The lack of cytotoxicity demonstrated in 3-D corneal cultures and in monkey studies suggests that the levels of BAC contained in ophthalmic solutions are not likely to cause significant direct toxicity to epithelium of otherwise normal corneas.

Published
2009
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