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Center for Advance Preclinical Research: Selected Publications

Heterogeneity of Neuroendocrine Transcriptional States in Metastatic Small Cell Lung Cancer Tumors and Patient-Derived Models. Lissa D, Takahashi N, Desai P, Manukyan I, N, Schultz C, Rajapakse V, Velez M, Mulford D, Roper N, Nichols S, Vilimas R, Sciuto L, Chen Y, Guha U, Rajan A, Atkinson D, El Meskini R, Weaver Ohler Z, and Thomas A. Nature Communications (in press)

Immune mechanisms of resistance to cediranib in ovarian cancer. Gopinathan G, Berlato C, Lakhani A, Szabova L, Pegrum C, Pedrosa A-R, Laforets F, Maniati E, Balkwill FR. Molecular Cancer Therapeutics 21 Mar 2022,
DOI: 10.1158/1535-7163.mct-21-0689 PMID: 35313341 .

T Cell-Mediated Antitumor Immunity Cooperatively Induced By TGFβR1 Antagonism and Gemcitabine Counteracts Reformation of the Stromal Barrier in Pancreatic Cancer. Li D, Schaub N, Guerin TM, Bapiro TE, Richards FM, Chen V, Talsania K, Kumar P, Gilbert DJ, Schlomer JJ, Kim SJ, Sorber R, Teper Y, Bautista W, Palena C, Ock CY, Jodrell DI, Pate N, Mehta M, Zhao Y, Kozlov S, Rudloff U. Molecular Cancer Therapeutics. 2021 Oct;20(10):1926-1940. DOI: 10.1158/1535-7163.MCT-20-0620. Epub 2021 Aug 10. PMID: 34376576; PMCID: PMC8492543.

Novel humanized mesothelin expressing genetically engineered mouse models underscore challenges in delivery of complex therapeutics to pancreatic cancers. Hagerty B, O'Sullivan TN, Zhang X, Collins NK, Custer Lawrence W, Bassel LL, Pate N, Xu J, Guerin TM, Kozlov S and Alewine C.  Molecular Cancer Therapeutics July 26 2021 DOI: 10.1158/1535-7163.MCT-21-0017

Distinct Biomarker Profiles and TCR Sequence Diversity Characterize the Response to PD-L1 Blockade in a Mouse Melanoma Model. El Meskini R, Atkinson D, Kulaga A, Abdelmaksoud A, Gumprecht M, Pate N, Hayes S, Oberst M, Kaplan IM, Raber P, Van Dyke T, Sharan SK, Hollingsworth R, Day C-P, Merlino G, Weaver Ohler Z. Molecular Cancer Research; Published Online First April 22, 2021; DOI: 10.1158/1541-7786. MCR-20-0881

Verification of CRISPR editing and finding transgenic inserts by Xdrop indirect sequence capture followed by short- and long-read sequencing. Blondal T, Gamba C, Moller Jagd L, Su L, Demirov D, Guo S, Johnston CM, Riising EM, Wu X, Mikkelsen MJ, Szabova L, Mouritzen. P.  Methods. 2021 Jul; 191:68-77. DOI: 10.1016/j.ymeth.2021.02.003. Epub 2021 Feb 12. PMID: 33582298

Multi-model preclinical platform predicts clinical response of melanoma to immunotherapy. Eva Pérez-Guijarro, Howard H. Yang, Romina E. Araya, Rajaa El Meskini, Helen T. Michael, Suman Kumar Vodnala, Kerrie L. Marie, Cari Graff-Cherry, Sung Chin, Anthony J. Iacovelli, Alan Kulaga, Anyen Fon, Aleksandra M. Michalowski, Willy Hugo, Roger S. Lo, Nicholas P. Restifo, Terry Van Dyke, Shyam K. Sharan, Romina S. Goldszmid, Zoe Weaver Ohler, Maxwell P. Lee, Chi-Ping Day, Glenn Merlino (2020) Nature Medicine volume 26, pages781–791(2020); DOI https://doi.org/10.1038/s41591-020-0818-3

Clonal Evolution and Heterogeneity of Osimertinib Acquired Resistance Mechanisms in EGFR Mutant Lung Cancer. Nitin Roper, Anna-Leigh Brown, Jun S Wei, Svetlana Pack, Christopher Trindade, Chul Kim, Olivia Restifo 6, Shaojian Gao, Sivasish Sindiri, Farid Mehrabadi, Rajaa El Meskini, Zoe Weaver Ohler 9, Tapan K Maity, Abhilash Venugopalan, Constance M Cultraro, Elizabeth Akoth, Emerson Padiernos, Haobin Chen, Aparna Kesarwala, DeeDee K Smart, Naris Nilubol, Arun Rajan, Zofia Piotrowska, Liqiang Xi, Mark Raffeld, Anna R Panchenko, Cenk Sahinalp, Stephen Hewitt, Chuong D Hoang, Javed Khan, Udayan Guha. PMID: 32483558 PMCID: PMC7263628 DOI: 10.1016/j.xcrm.2020.100007 Cell Rep Med 2020 Apr 21;1(1):100007.

Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate anti-tumor immune responses. Jesse M. Jaynes1,2*, Rushikesh Sable, Michael Ronzetti4*, Wendy Bautista-Guzman5*, Zachary Knotts3, Abisola Abisoye-Ogunniyan2,6, Dandan Li3, Raul Calvo4, Myagmarjav Dashnyam4, Anju Singh4, Theresa Guerin5, Jason White2, Sarangan Ravichandran7, Parimal Kumar8, Keyur Talsania9, Vicky Chen9, Anghesom Ghebremedhin2,Balasubramanyam Karanam, Ahmad Bin Salam2, Ruksana Amin2, Taivan Odzorig3, Taylor Aiken6,10, Victoria Nguyen3, Yansong Bian3, Jelani C. Zarif11,12, Amber E. de Groot13,14, Monika Mehta8, Lixin Fan15, Xin Hu4, Anton Simeonov4, Nathan Pate5, Mones Abu-Asab16, Marc Ferrer4, Noel Southall4, Chan-Young Ock17, Yongmei Zhao9, Henry Lopez18, Serguei Kozlov5, Natalia de Val19,20, Clayton C. Yates, Bolormaa Baljinnyam, Juan Marugan, Udo Rudloff (2020) Science Translational Medicine  12 Feb 2020: Vol. 12, Issue 530, eaax6337 DOI: 10.1126/scitranslmed.aax6337

LC-MS/MS assay coupled with carboxylic acid magnetic bead affinitycapture to quantitatively measure cationic host defense peptides(HDPs) in complex matrices with application to preclinical pharmacokinetic studies. Maura J. O’Neill, King Chan, Jesse M. Jaynes, Zachary Knotts, Xia Xu, Abisola Abisoye-Ogunniyan, Theresa Guerin, Jerome Schlomer, Dandan Li, Jeffrey W. Cary, Kanniah Rajasekaran, Clayton Yates, Serguei Kozlov, Thorkell Andresson, Udo Rudloff
Journal of Pharmaceutical and Biomedical Analysis 181 (2020) 11309

Undermining glutaminolysis bolsters chemotherapy while NRF2 promotes chemoresistance in KRAS-driven pancreatic cancers. Mukhopadhyay S, Goswami D, Adiseshaiah PP, Burgan W, Yi M, Guerin TM, Kozlov SV, Nissley DV, McCormick F. Cancer Res. 2020 Jan 7. pii: canres.1363.2019. doi: 10.1158/0008-5472.CAN-19-1363. [Epub ahead of print] PMID:31911550

Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis. Frankowski KJ, Wang C, Patnaik S, Schoenen FJ, Southall N, Li D, Teper Y, Sun W, Kandela I, Hu D, Dextras C, Knotts Z, Bian Y, Norton J, Titus S, Lewandowska MA, Wen Y, Farley KI, Griner LM, Sultan J, Meng Z, Zhou M, Vilimas T, Powers AS, Kozlov S, Nagashima K, Quadri HS, Fang M, Long C, Khanolkar O, Chen W, Kang J, Huang H, Chow E, Goldberg E, Feldman C, Xi R, Kim HR, Sahagian G, Baserga SJ, Mazar A, Ferrer M, Zheng W, Shilatifard A, Aubé J, Rudloff U, Marugan JJ, Huang S. Sci Transl Med. 2018 May 16;10(441). pii: eaap8307. doi:10.1126/scitranslmed.aap8307. PubMed PMID: 29769289.

Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-KrasG12D/+;Tp53R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer. Tomas Vilimas1 · Amy Q. Wang2 · Samarjit Patnaik3 · Emma A. Hughes4 · Marc D. Singleton5 · Zachary Knotts6 · Dandan Li6 · Kevin Frankowski7 · Jerome J. Schlomer8 · Theresa M. Guerin8 · Stephanie Springer8 · Catherine Drennan8 · Christopher Dextras3 · Chen Wang9 · Debra Gilbert8 · Noel Southall3 · Marc Ferrer3 · Sui Huang9 · Serguei Kozlov8 · Juan Marugan3,10 · Xin Xu2 · Udo Rudloff6 Cancer Chemotherapy and Pharmacology; December 2018, Volume 82, Issue 6, pp 1067–1080 https://doi.org/10.1007/s00280-018-3699-0

Protein Synthesis Inhibition Activity of Mesothelin Targeting Immunotoxin LMB-100 Decreases Concentrations of Oncogenic Signaling Molecules and Secreted Growth Factors. Salma El-Behaedi 1,†, Rebekah Landsman 1,‡, Michael Rudloff 1,§, Emily Kolyvas 1,k, Rakan Albalawy 1,¶, Xianyu Zhang 1, Tapan Bera 1, Keith Collins 2, Serguei Kozlov 3 and Christine Alewine #2 Published: 31 October 2018 Toxins 2018, 10, 447; doi:10.3390/toxins10110447

A Transplantable Syngeneic Allograft Mouse Model for Nongestational Choriocarcinoma of the Ovary. Ludmila Szabova1 , Baktiar Karim2, Melanie Gordon1, Lucy Lu3, Nathan Pate1, and Zoe Weaver Ohler1 Veterinary Pathology 1-5; DOI: 10.1177/0300985818823669 January 13, 2019

The Indenoisoquinoline TOP1 Inhibitors Selectively Target Homologous Recombination-Deficient and Schlafen 11-Positive Cancer Cells and Synergize with Olaparib. Laetitia Marzi , Ludmila Szabova , Melanie Gordon , Zoe Weaver Ohler , Shyam K Sharan, Michael L Beshiri, Moudjib Etemadi, Junko Murai, Kathleen Kelly, Yves Pommier. Clin Cancer Res. 2019 Oct 15;25(20):6206-6216.

Id1 Ablation Protects Hematopoietic Stem Cells from Stress-Induced Exhaustion and Aging. Singh SK, Singh S, Gadomski S, Sun L, Pfannenstein A, Magidson V, Chen X, Kozlov S, Tessarollo L, Klarmann KD, Keller JR. Cell Stem Cell. 2018 Aug 2;23(2):252-265.e8. doi: 10.1016/j.stem.2018.06.001. Epub 2018 Jun28. PubMed PMID: 30082068.

Near infrared photoimmunotherapy in a transgenic mouse model of spontaneous epidermal growth factor receptor (EGFR)-expressing lung cancer. Nakamura Y, Weaver Ohler Z, Householder D, Nagaya T, Sato K, Okuyama S, Ogata F, Daar D, Hoa T, Choyke PL Kobayashi H. Mol Cancer Ther 16:408-414, 2017. DOI: 10.1158/1535-7163.MCT-16-0663. PMID: 28151706.

Synergistic targeted inhibition of MEK and dual PI3K/mTOR diminishes viability and inhibits tumor growth of canine melanoma underscoring its utility as a preclinical model for human mucosal melanoma. Wei BR, Michael HT, Halsey CH, Peer CJ, Adhikari A, Dwyer JE, Hoover SB, El Meskini RKozlov S, Weaver Ohler Z, Figg WD, Merlino G, Simpson RM. Pigment Cell Melanoma Res 29(6):643-655, 2016. DOI: 10.1111/pcmr.12512. Epub 2016 Sep 22. PMID: 27463366

Selective inhibition of the p38 alternative activation pathway in infiltrating T cells inhibits pancreatic cancer progression.  Alam MS, Gaida MM, Bergmann F, Lasitschka F, Giese T, Giese NA, Hackert T, Hinz U, Hussain SP, Kozlov SV, Ashwell JD. Nat Med. 2015 Nov;21(11):1337-43.

A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors.  El Meskini R, Iacovelli AJ, Kulaga A, Gumprecht M, Martin PL, Baran M, Householder DB, Van Dyke T, Weaver Ohler Z. Dis Model Mech. 2015 Jan;8(1):45-56.

"Glowing head" mice: a genetic tool enabling reliable preclinical image-based evaluation of cancers in immunocompetent allografts. Day CP, Carter J, Weaver Ohler Z, Bonomi C, El Meskini R, Martin P, Graff-Cherry C, Feigenbaum L, Tüting T, Van Dyke T, Hollingshead M, Merlino G. PLoS One. 2014 Nov 4;9(11):e109956.

Pathway-specific engineered mouse allograft models functionally recapitulate human serous epithelial ovarian cancer. Szabova L, Bupp S, Kamal M, Householder DB, Hernandez L, Schlomer JJ, Baran ML, Yi M, Stephens RM, Annunziata CM, Martin PL, Van Dyke TA, Weaver Ohler Z, and Difilippantonio S.  PLoS One 9(4): e95649, 2014.

Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Walter AO, Sjin RT, Haringsma HJ, Ohashi K, Sun J, Lee K, Dubrovskiy A, Labenski M, Zhu Z, Wang Z, Sheets M, St Martin T, Karp R, van Kalken D, Chaturvedi P, Niu D, Nacht M, Petter RC, Westlin W, Lin K, Jaw-Tsai S, Raponi M, Van Dyke T, Etter J, Weaver Z, Pao W, Singh J, Simmons AD, Harding TC, and Allen A.  Cancer Discov. 3(12): 1404-15, 2013.

Temporal molecular and biological assessment of an erlotinib-resistant lung adenocarcinoma model reveals markers of tumor progression and treatment response. Weaver Z, Difilippantonio S, Carretero J, Martin PL, El Meskini R, Iacovelli AJ, Gumprecht M, Kulaga A, Guerin T, Schlomer J, Baran M, Kozlov S, McCann T, Mena S, Al-Shahrour F, Alexander D, Wong KK, and Van Dyke T.  Cancer Res. 72: 5921-33, 2012.

Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer. Szabova L, Yin C, Bupp S, Guerin TM, Schlomer JJ, Householder DB, Baran ML, Yi M., Song Y, Sun W, McDunn JE, Martin PL, Van Dyke T, and Difilippantonio S.  Cancer Res. 72(16): 4141-53, 2012.