Full Text Journal Articles by
Author Karen S Anderson

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An allosteric site on MKP5 reveals a strategy for small-molecule inhibition.

Zachary T K Gannam, Kisuk Min, Shanelle R Shillingford, Lei Zhang, James Herrington, Laura Abriola, Peter C Gareiss, Georgios Pantouris, Argyrios Tzouvelekis, Naftali Kaminski, Xinbo Zhang, Jun Yu, Haya Jamali, Jonathan A Ellman, Elias Lolis, Karen S Anderson, Anton M Bennett,

The mitogen-activated protein kinase (MAPK) phosphatases (MKPs) have been considered "undruggable," but their position as regulators of the MAPKs makes them promising therapeutic targets. MKP5 has been suggested as a potential target for the treatment of dystrophic muscle disease. Here, we identified an inhibitor of MKP5 using a p38α MAPK-derived, ... Read more >>

Sci Signal (Science signaling)
[2020, 13(646):]

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Structural investigation of 2-naphthyl phenyl ether inhibitors bound to WT and Y181C reverse transcriptase highlights key features of the NNRTI binding site.

Vincent N Duong, Joseph A Ippolito, Albert H Chan, Won-Gil Lee, Krasimir A Spasov, William L Jorgensen, Karen S Anderson,

Human immunodeficiency virus (HIV)-1 remains as a global health issue that is primarily treated with highly active antiretroviral therapy, a combination of drugs that target the viral life cycle. One class of these drugs are non-nucleoside reverse transcriptase inhibitors (NNRTIs) that target the viral reverse transcriptase (RT). First generation NNRTIs ... Read more >>

Protein Sci. (Protein science : a publication of the Protein Society)
[2020, :]

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Unique genomic and neoepitope landscapes across tumors: a study across time, tissues, and space within a single lynch syndrome patient.

Tanya N Phung, Elizabeth Lenkiewicz, Smriti Malasi, Amit Sharma, Karen S Anderson, Melissa A Wilson, Barbara A Pockaj, Michael T Barrett,

Lynch syndrome (LS) arises in patients with pathogenic germline variants in DNA mismatch repair genes. LS is the most common inherited cancer predisposition condition and confers an elevated lifetime risk of multiple cancers notably colorectal and endometrial carcinomas. A distinguishing feature of LS associated tumors is accumulation of variants targeting ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):12190]

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Targeting the TS dimer interface in bifunctional Cryptosporidium hominis TS-DHFR from parasitic protozoa: Virtual screening identifies novel TS allosteric inhibitors.

Victor G Ruiz, Daniel J Czyzyk, Vidya P Kumar, William L Jorgensen, Karen S Anderson,

Effective therapies are lacking to treat gastrointestinal infections caused by the genus Cryptosporidium, which can be fatal in the immunocompromised. One target of interest is Cryptosporidium hominis (C. hominis) thymidylate synthase-dihydrofolate reductase (ChTS-DHFR), a bifunctional enzyme necessary for DNA biosynthesis. Targeting the TS-TS dimer interface is a novel strategy previously ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2020, 30(16):127292]

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Identifying the role of PrimPol in TDF-induced toxicity and implications of its loss of function mutation in an HIV+ patient.

Vincent N Duong, Lei Zhou, María I Martínez-Jiménez, Linh He, Moises Cosme, Luis Blanco, Elijah Paintsil, Karen S Anderson,

A key component of antiretroviral therapy (ART) for HIV patients is the nucleoside reverse transcriptase inhibitor (NRTI) is tenofovir. Recent reports of tenofovir toxicity in patients taking ART for HIV cannot be explained solely on the basis of off-target inhibition of mitochondrial DNA polymerase gamma (Polγ). PrimPol was discovered as ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):9343]

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Structure-Guided Identification of DNMT3B Inhibitors.

Ana S Newton, John C Faver, Goran Micevic, Viswanathan Muthusamy, Shalley N Kudalkar, Nicole Bertoletti, Karen S Anderson, Marcus W Bosenberg, William L Jorgensen,

Methyltransferase 3 beta (DNMT3B) inhibitors that interfere with cancer growth are emerging possibilities for treatment of melanoma. Herein we identify small molecule inhibitors of DNMT3B starting from a homology model based on a DNMT3A crystal structure. Virtual screening by docking led to purchase of 15 compounds, among which 5 were ... Read more >>

ACS Med Chem Lett (ACS medicinal chemistry letters)
[2020, 11(5):971-976]

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Change in 21-gene Recurrence Score result after exposure to neo-adjuvant endocrine therapy in patients with operable breast cancer.

Talal Hilal, Lanyu Mi, Natalie M Ertz-Archambault, Daniel R Almquist, Karen S Anderson, Richard J Gray, Barbara A Pockaj, Donald W Northfelt,

Breast J (The breast journal)
[2020, 26(7):1449-1451]

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Weakly immunogenic CRISPR therapies.

Eric A Wilson, Karen S Anderson,

Nat Biomed Eng (Nature biomedical engineering)
[2019, 3(10):761-762]

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Personalized circulating tumor DNA analysis to detect residual disease after neoadjuvant therapy in breast cancer.

Bradon R McDonald, Tania Contente-Cuomo, Stephen-John Sammut, Ahuva Odenheimer-Bergman, Brenda Ernst, Nieves Perdigones, Suet-Feung Chin, Maria Farooq, Rosa Mejia, Patricia A Cronin, Karen S Anderson, Heidi E Kosiorek, Donald W Northfelt, Ann E McCullough, Bhavika K Patel, Jeffrey N Weitzel, Thomas P Slavin, Carlos Caldas, Barbara A Pockaj, Muhammed Murtaza,

Longitudinal analysis of circulating tumor DNA (ctDNA) has shown promise for monitoring treatment response. However, most current methods lack adequate sensitivity for residual disease detection during or after completion of treatment in patients with nonmetastatic cancer. To address this gap and to improve sensitivity for minute quantities of residual tumor ... Read more >>

Sci Transl Med (Science translational medicine)
[2019, 11(504):]

Cited: 3 times

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Structural insights into the recognition of nucleoside reverse transcriptase inhibitors by HIV-1 reverse transcriptase: First crystal structures with reverse transcriptase and the active triphosphate forms of lamivudine and emtricitabine.

Nicole Bertoletti, Albert H Chan, Raymond F Schinazi, Y Whitney Yin, Karen S Anderson,

The retrovirus HIV-1 has been a major health issue since its discovery in the early 80s. In 2017, over 37 million people were infected with HIV-1, of which 1.8 million were new infections that year. Currently, the most successful treatment regimen is the highly active antiretroviral therapy (HAART), which consists ... Read more >>

Protein Sci. (Protein science : a publication of the Protein Society)
[2019, 28(9):1664-1675]

Cited: 1 time

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Depomedroxyprogesterone acetate therapy for hot flashes in survivors of breast cancer: no unfavorable impact on recurrence and survival.

Natalie M Ertz-Archambault, Lana B Rogoff, Heidi E Kosiorek, Brenda J Ernst, Karen S Anderson, Barbara A Pockaj, Richard J Gray, Donald W Northfelt,

PURPOSE:Survivors of estrogen receptor-expressing breast cancer generally do not receive estrogen-based therapy for menopausal symptoms due to concern for provoking recurrence of disease. Single-dose depomedroxyprogesterone acetate has been shown to be among the most effective non-estrogen strategies for treatment of menopausal hot flashes, but long-term evidence for safety in survivors ... Read more >>

Support Care Cancer (Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer)
[2020, 28(5):2139-2143]

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The burden of 14 hr-HPV genotypes in women attending routine cervical cancer screening in 20 states of Mexico: a cross-sectional study.

Abraham Campos-Romero, Karen S Anderson, Adhemar Longatto-Filho, Marco A Luna-Ruiz Esparza, David J Morán-Portela, Javier A Castro-Menéndez, José L Moreno-Camacho, Diana Y Calva-Espinosa, Manuel A Acosta-Alfaro, Freddy A Meynard-Mejía, Marlene Muñoz-Gaitán, Jonathan Alcántar-Fernández,

In Mexico, HPV vaccines available immunize against genotypes 16/18 and 16/18/6/11; however, there is limited surveillance about carcinogenic subtypes in different states of the country that allow evaluating the effectiveness of vaccination and cervical cancer screening programs. Here, we report the regional and age-specific prevalence of 14 hr-HPV genotypes as ... Read more >>

Sci Rep (Scientific reports)
[2019, 9(1):10094]

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Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase.

Tomoaki Sasaki, Zachary T K Gannam, Shalley N Kudalkar, Kathleen M Frey, Won-Gil Lee, Krasimir A Spasov, William L Jorgensen, Karen S Anderson,

The development of efficacious NNRTIs for HIV/AIDS therapy is commonly met with the emergence of drug resistant strains, including the Y181C variant. Using a computationally-guided approach, we synthesized the catechol diether series of NNRTIs, which display sub-nanomolar potency in cellular assays. Among the most potent were a series of 2-cyanoindolizine ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2019, 29(16):2182-2188]

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Understanding the structural basis of species selective, stereospecific inhibition for Cryptosporidium and human thymidylate synthase.

Daniel J Czyzyk, Margarita Valhondo, William L Jorgensen, Karen S Anderson,

Thymidylate synthase (TS), found in all organisms, is an essential enzyme responsible for the de novo synthesis of deoxythymidine monophosphate. The TS active sites of the protozoal parasite Cryptosporidium hominis and human are relatively conserved. Evaluation of antifolate compound 1 and its R-enantiomer 2 against both enzymes reveals divergent inhibitor selectivity and ... Read more >>

FEBS Lett. (FEBS letters)
[2019, 593(15):2069-2078]

Cited: 1 time

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Multifunctional CRISPR-Cas9 with engineered immunosilenced human T cell epitopes.

Shayesteh R Ferdosi, Radwa Ewaisha, Farzaneh Moghadam, Sri Krishna, Jin G Park, Mo R Ebrahimkhani, Samira Kiani, Karen S Anderson,

The CRISPR-Cas9 system has raised hopes for developing personalized gene therapies for complex diseases. Its application for genetic and epigenetic therapies in humans raises concerns over immunogenicity of the bacterially derived Cas9 protein. Here we detect antibodies to Streptococcus pyogenes Cas9 (SpCas9) in at least 5% of 143 healthy individuals. ... Read more >>

Nat Commun (Nature communications)
[2019, 10(1):1842]

Cited: 3 times

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Novel allosteric covalent inhibitors of bifunctional Cryptosporidium hominis TS-DHFR from parasitic protozoa identified by virtual screening.

Victor Ruiz, Daniel J Czyzyk, Margarita Valhondo, William L Jorgensen, Karen S Anderson,

Protozoans of the genus Cryptosporidium are the causative agent of the gastrointestinal disease, cryptosporidiosis, which can be fatal in immunocompromised individuals. Cryptosporidium hominis (C. hominis) bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) is an essential enzyme in the folate biosynthesis pathway and a molecular target for inhibitor design. Previous studies have demonstrated ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2019, 29(11):1413-1418]

Cited: 1 time

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HPV: Immunology lessons from an ancient oncotarget.

Sri Krishna, Karen S Anderson,

Oncotarget (Oncotarget)
[2019, 10(13):1269-1270]

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The neoepitope landscape of breast cancer: implications for immunotherapy.

Pooja Narang, Meixuan Chen, Amit A Sharma, Karen S Anderson, Melissa A Wilson,

BACKGROUND:Cancer immunotherapy with immune checkpoint blockade (CKB) is now standard of care for multiple cancers. The clinical response to CKB is associated with T cell immunity targeting cancer-induced mutations that generate novel HLA-binding epitopes (neoepitopes). METHODS:Here, we developed a rapid bioinformatics pipeline and filtering strategy, EpitopeHunter, to identify and prioritize ... Read more >>

BMC Cancer (BMC cancer)
[2019, 19(1):200]

Cited: 3 times

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APOBEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma.

Vincent L Cannataro, Stephen G Gaffney, Tomoaki Sasaki, Natalia Issaeva, Nicholas K S Grewal, Jennifer R Grandis, Wendell G Yarbrough, Barbara Burtness, Karen S Anderson, Jeffrey P Townsend,

Recent studies have revealed the mutational signatures underlying the somatic evolution of cancer, and the prevalences of associated somatic genetic variants. Here we estimate the intensity of positive selection that drives mutations to high frequency in tumors, yielding higher prevalences than expected on the basis of mutation and neutral drift ... Read more >>

Oncogene (Oncogene)
[2019, 38(18):3475-3487]

Cited: 3 times

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Lost in the crowd: identifying targetable MHC class I neoepitopes for cancer immunotherapy.

Eric A Wilson, Karen S Anderson,

INTRODUCTION:The recent development of checkpoint blockade immunotherapy for cancer has led to impressive clinical results across multiple tumor types. There is mounting evidence that immune recognition of tumor derived MHC class I (MHC-I) restricted epitopes bearing cancer specific mutations and alterations is a crucial mechanism in successfully triggering immune-mediated tumor ... Read more >>

Expert Rev Proteomics (Expert review of proteomics)
[2018, 15(12):1065-1077]

Cited: 2 times

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DRONE: Direct Tracking of DNA Cytidine Deamination and Other DNA Modifying Activities.

Tomoaki Sasaki, Shalley N Kudalkar, Nicole Bertoletti, Karen S Anderson,

Enzymes that catalyze DNA modifying activities including cytidine deamination and cytosine methylation play important biological roles and have been implicated pathologically in diseases such as cancer. Here, we report Direct Resolution of ONE dalton difference (DRONE), an ultra high performance liquid chromatography (UHPLC)-based analytical method to track a single dalton ... Read more >>

Anal. Chem. (Analytical chemistry)
[2018, 90(20):11735-11740]

Cited: 0 times

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A Noninvasive Blood-based Combinatorial Proteomic Biomarker Assay to Detect Breast Cancer in Women over age 50 with BI-RADS 3, 4, or 5 Assessment.

Meredith C Henderson, Michael Silver, Quynh Tran, Elias E Letsios, Rao Mulpuri, David E Reese, Ana P Lourenco, Joshua LaBaer, Karen S Anderson, Josie Alpers, Carrie Costantini, Nitin Rohatgi, Haythem Ali, Karen Baker, Donald W Northfelt, Karthik Ghosh, Stephen R Grobmyer, Winnie Polen, Judith K Wolf,

PURPOSE:With improvements in breast cancer imaging, there has been a corresponding increase in false-positives and avoidable biopsies. There is a need to better differentiate when a breast biopsy is warranted and determine appropriate follow-up. This study describes the design and clinical performance of a combinatorial proteomic biomarker assay (CPBA), Videssa ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2019, 25(1):142-149]

Cited: 1 time

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The FGFR1 V561M Gatekeeper Mutation Drives AZD4547 Resistance through STAT3 Activation and EMT.

Molly R Ryan, Christal D Sohl, BeiBei Luo, Karen S Anderson,

FGFR1 has been implicated in numerous cancer types including squamous cell lung cancer, a subset of non-small cell lung cancer with a dismal 5-year survival rate. Small-molecule inhibitors targeting FGFR1 are currently in clinical trials, with AZD4547 being one of the furthest along; however, the development of drug resistance is ... Read more >>

Mol. Cancer Res. (Molecular cancer research : MCR)
[2019, 17(2):532-543]

Cited: 6 times

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Reply to Pandey et al.: Understanding the efficacy of a potential antiretroviral drug candidate in humanized mouse model of HIV infection.

Shalley N Kudalkar, Jagadish Beloor, Elias Quijano, Krasimir A Spasov, Won-Gil Lee, José A Cisneros, W Mark Saltzman, Priti Kumar, William L Jorgensen, Karen S Anderson,

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2018, 115(35):E8114-E8115]

Cited: 0 times

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Human Papilloma Virus Specific Immunogenicity and Dysfunction of CD8+ T Cells in Head and Neck Cancer.

Sri Krishna, Peaches Ulrich, Eric Wilson, Falguni Parikh, Pooja Narang, Shanshan Yang, Amelia K Read, Seunghee Kim-Schulze, Jin G Park, Marshall Posner, Melissa A Wilson Sayres, Andrew Sikora, Karen S Anderson,

Human papillomavirus subtype 16 (HPV16) is the primary cause of an increasing number of head and neck squamous cell carcinomas (HNSCC), providing strong rationale for T-cell immune therapies against HPV+ HNSCC. Here we assess immunogenicity of HPV16-specific CD8+ T cells (CTL) and characterize HPV-specific mechanisms of T-cell dysfunction. We identified ... Read more >>

Cancer Res. (Cancer research)
[2018, 78(21):6159-6170]

Cited: 7 times

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