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2. Neutrophilic dermatosis in a patient with an IKZF1 variant and a review of monogenic autoinflammatory disorders presenting with neutrophilic dermatoses

Author

Guirguis, Justina, primary, Iosim, Sonia, additional, Jones, Derek, additional, Likhite, Maryel, additional, Chen, Fei, additional, Kesserwan, Chimene, additional, Gindin, Tatyana, additional, Kahn, Philip J., additional, Beck, David, additional, Oza, Vikash S., additional, and Hillier, Kirsty, additional

Published
2024
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5. Analytical performance of lateral flow immunoassay for SARS-CoV-2 exposure screening on venous and capillary blood samples

Author

Black, Margaret A., primary, Shen, Guomiao, additional, Feng, Xiaojun, additional, Garcia Beltran, Wilfredo F., additional, Feng, Yang, additional, Vasudevaraja, Varshini, additional, Allison, Douglas, additional, Lin, Lawrence H., additional, Gindin, Tatyana, additional, Astudillo, Michael, additional, Yang, Diane, additional, Murali, Mandakolathur, additional, Iafrate, A. John, additional, Jour, George, additional, Cotzia, Paolo, additional, and Snuderl, Matija, additional

Published
2021
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6. Sequencing identifies multiple early introductions of SARS-CoV-2 to the New York City region

Author

Maurano, Matthew T., primary, Ramaswami, Sitharam, additional, Zappile, Paul, additional, Dimartino, Dacia, additional, Boytard, Ludovic, additional, Ribeiro-dos-Santos, André M., additional, Vulpescu, Nicholas A., additional, Westby, Gael, additional, Shen, Guomiao, additional, Feng, Xiaojun, additional, Hogan, Megan S., additional, Ragonnet-Cronin, Manon, additional, Geidelberg, Lily, additional, Marier, Christian, additional, Meyn, Peter, additional, Zhang, Yutong, additional, Cadley, John, additional, Ordoñez, Raquel, additional, Luther, Raven, additional, Huang, Emily, additional, Guzman, Emily, additional, Arguelles-Grande, Carolina, additional, Argyropoulos, Kimon V., additional, Black, Margaret, additional, Serrano, Antonio, additional, Call, Melissa E., additional, Kim, Min Jae, additional, Belovarac, Brendan, additional, Gindin, Tatyana, additional, Lytle, Andrew, additional, Pinnell, Jared, additional, Vougiouklakis, Theodore, additional, Chen, John, additional, Lin, Lawrence H., additional, Rapkiewicz, Amy, additional, Raabe, Vanessa, additional, Samanovic, Marie I., additional, Jour, George, additional, Osman, Iman, additional, Aguero-Rosenfeld, Maria, additional, Mulligan, Mark J., additional, Volz, Erik M., additional, Cotzia, Paolo, additional, Snuderl, Matija, additional, and Heguy, Adriana, additional

Published
2020
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8. Analytical performance of lateral flow immunoassay for SARS-CoV-2 exposure screening on venous and capillary blood samples

Author

Black, Margaret A., primary, Shen, Guomiao, additional, Feng, Xiaojun, additional, Garcia Beltran, Wilfredo F., additional, Feng, Yang, additional, Vasudevaraja, Varshini, additional, Allison, Douglas, additional, Lin, Lawrence H., additional, Gindin, Tatyana, additional, Astudillo, Michael, additional, Yang, Diane, additional, Murali, Mandakolathur, additional, Iafrate, A. John, additional, Jour, George, additional, Cotzia, Paolo, additional, and Snuderl, Matija, additional

Published
2020
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9. Free Energy Perturbation Calculation of Relative Binding Free Energy between Broadly Neutralizing Antibodies and the gp120 Glycoprotein of HIV-1

Author

Clark, Anthony J., Gindin, Tatyana, Zhang, Baoshan, Wang, Lingle, Abel, Robert, Murret, Colleen S., Xu, Fang, Bao, Amy, Lu, Nina J., Zhou, Tongqing, Kwong, Peter D., Shapiro, Lawrence, Honig, Barry, and Friesner, Richard A.

Subjects
GPU, graphics processing unit, REST, replica exchange solute tempering, RMSE, RMS error, CDR H2, second heavy chain complementarity-determining region, PB, Poisson–Boltzmann, Computational Biology, binding affinity optimization, HIV Antibodies, HIV Envelope Protein gp120, Surface Plasmon Resonance, physics-based models, MD, molecular dynamics, computational chemistry, Antibodies, Neutralizing, Article, RSC3, resurfaced stabilized core 3, FEP, free energy perturbation, protein structure prediction, alchemical FEP, Thermodynamics, bNAbs, broadly neutralizing antibodies, PDB, protein data bank, Molecular Biology, Protein Binding
Abstract

Direct calculation of relative binding affinities between antibodies and antigens is a long-sought goal. However, despite substantial efforts, no generally applicable computational method has been described. Here, we describe a systematic free energy perturbation (FEP) protocol and calculate the binding affinities between the gp120 envelope glycoprotein of HIV-1 and three broadly neutralizing antibodies (bNAbs) of the VRC01 class. The protocol has been adapted from successful studies of small molecules to address the challenges associated with modeling protein–protein interactions. Specifically, we built homology models of the three antibody–gp120 complexes, extended the sampling times for large bulky residues, incorporated the modeling of glycans on the surface of gp120, and utilized continuum solvent-based loop prediction protocols to improve sampling. We present three experimental surface plasmon resonance data sets, in which antibody residues in the antibody/gp120 interface were systematically mutated to alanine. The RMS error in the large set (55 total cases) of FEP tests as compared to these experiments, 0.68 kcal/mol, is near experimental accuracy, and it compares favorably with the results obtained from a simpler, empirical methodology. The correlation coefficient for the combined data set including residues with glycan contacts, R2 = 0.49, should be sufficient to guide the choice of residues for antibody optimization projects, assuming that this level of accuracy can be realized in prospective prediction. More generally, these results are encouraging with regard to the possibility of using an FEP approach to calculate the magnitude of protein–protein binding affinities., Graphical Abstract Image 1, Highlights • Natural bNAbs against HIV-1 are a promising starting point for therapies. • FEP provides a promising technique to computationally predict antibody structure optimizations. • We show that FEP applied to bNAb mutations predicts binding affinity changes. • FEP can provide an efficient method to identify potency-enhancing mutations to bNAbs.

Published
2017

13. Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody

Author

Kwon, Young D., primary, Chuang, Gwo-Yu, additional, Zhang, Baoshan, additional, Bailer, Robert T., additional, Doria-Rose, Nicole A., additional, Gindin, Tatyana S., additional, Lin, Bob, additional, Louder, Mark K., additional, McKee, Krisha, additional, O’Dell, Sijy, additional, Pegu, Amarendra, additional, Schmidt, Stephen D., additional, Asokan, Mangaiarkarasi, additional, Chen, Xuejun, additional, Choe, Misook, additional, Georgiev, Ivelin S., additional, Jin, Vivian, additional, Pancera, Marie, additional, Rawi, Reda, additional, Wang, Keyun, additional, Chaudhuri, Rajoshi, additional, Kueltzo, Lisa A., additional, Manceva, Slobodanka D., additional, Todd, John-Paul, additional, Scorpio, Diana G., additional, Kim, Mikyung, additional, Reinherz, Ellis L., additional, Wagh, Kshitij, additional, Korber, Bette M., additional, Connors, Mark, additional, Shapiro, Lawrence, additional, Mascola, John R., additional, and Kwong, Peter D., additional

Published
2018
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14. Peptidomimetic blockade of MYB in acute myeloid leukemia

Author

Ramaswamy, Kavitha, primary, Forbes, Lauren, additional, Minuesa, Gerard, additional, Gindin, Tatyana, additional, Brown, Fiona, additional, Kharas, Michael G., additional, Krivtsov, Andrei V., additional, Armstrong, Scott A., additional, Still, Eric, additional, de Stanchina, Elisa, additional, Knoechel, Birgit, additional, Koche, Richard, additional, and Kentsis, Alex, additional

Published
2018
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15. Peptidomimetic blockade of MYB in acute myeloid leukemia

Author

Ramaswamy, Kavitha, primary, Forbes, Lauren, additional, Minuesa, Gerard, additional, Gindin, Tatyana, additional, Brown, Fiona, additional, Kharas, Michael, additional, Krivtsov, Andrei, additional, Armstrong, Scott, additional, Still, Eric, additional, de Stanchina, Elisa, additional, Knoechel, Birgit, additional, Koche, Richard, additional, and Kentsis, Alex, additional

Published
2017
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17. Peptidomimetic Blockade of MYB in Acute Myeloid Leukemia

Author

Ramaswamy, Kavitha, primary, Forbes, Lauren, additional, Brown, Fiona C, additional, Koche, Richard, additional, Gindin, Tatyana, additional, Minuesa, Gerard, additional, Kharas, Michael G., additional, Krivtsov, Andrei, additional, Armstrong, Scott A., additional, Still, Eric, additional, de Stanchina, Elisa, additional, Isenhart, Randi, additional, Guo, Guangwu, additional, Knoechel, Birgit, additional, and Kentsis, Alex, additional

Published
2016
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18. MLL/KMT2A translocations in diffuse large B-cell lymphomas

Author

Gindin, Tatyana, Vundavalli, Murty V., and Alobeid, Bachir

Subjects
Translocation (Genetics), B cells, Cytogenetics, immune system diseases, hemic and lymphatic diseases, Lymphomas
Abstract

Translocations of the histone-lysine N-methyltransferase 2A (KMT2A) gene, formerly known as myeloid lymphoid leukemia/mixed-lineage leukemia gene, are commonly associated with high-risk de novo or therapy-associated B-cell and T-cell lymphoblastic leukemias and myeloid neoplasms. Rare B-cell non-Hodgkin lymphomas harboring KMT2A translocations have been reported, but information regarding the clinical behavior of such cases is limited. Here, we describe two extranodal diffuse large B-cell lymphomas (DLBCLs): a primary thyroid DLBCL and a large cell transformation of a splenic marginal zone lymphoma, which displayed complex karyotypes and translocations involving chromosome 11q23 targeting the KMT2A gene. The pathological and clinical characteristics of these cases are discussed in the context of previously reported lymphomas associated with different types of KMT2A genetic aberrations. In contrast to the poor clinical outcomes of patients with acute leukemias and myeloid neoplasms associated with KMT2A translocations, patients with B-cell non-Hodgkin lymphomas, exhibiting similar translocations, appear to respond well to immunochemotherapy. Our findings add to the growing list of histone methyltransferase genes deregulated in DLBCL and highlight the diversity of mechanisms, altering the function of epigenetic modifier genes in lymphomas.

Published
2015
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19. Microsatellite instability detection using a large next-generation sequencing cancer panel across diverse tumour types

Author

Pang, Jiuhong, Gindin, Tatyana, Mansukhani, Mahesh, Fernandes, Helen, and Hsiao, Susan

Abstract

AimMicrosatellite instability (MSI), a hallmark of DNA mismatch repair deficiency, is a key molecular biomarker with multiple clinical implications including the selection of patients for immunotherapy, identifying patients who may have Lynch syndrome and predicting prognosis in patients with colorectal tumours. Next-generation sequencing (NGS) provides the opportunity to interrogate large numbers of microsatellite loci concurrently with genomic variants. We sought to develop a method to detect MSI that would not require paired normal tissue and would leverage the sequence data obtained from a broad range of tumours tested using our 467-gene NGS Columbia Combined Cancer Panel (CCCP).MethodsAltered mononucleotide and dinucleotide microsatellite loci across the CCCP region of interest were evaluated in clinical samples encompassing a diverse range of tumour types. The number of altered loci was used to develop a decision tree classifier model trained on the retrospectively collected cohort of 107 clinical cases sequenced by the CCCP assay.ResultsThe classifier was able to correctly classify all cases and was then used to analyse a test set of clinical cases (n=112) and was able to correctly predict their MSI status with 100% sensitivity and specificity. Analysis of recurrently altered loci identified alterations in genes involved in DNA repair, signalling and transcriptional regulation pathways, many of which have been implicated in MSI tumours.ConclusionThis study highlights the utility of this approach, which should be applicable to laboratories performing similar testing.

Published
2020
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21. Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody.

Author

Young D. Kwon, Gwo-Yu Chuang, Baoshan Zhang, Bailer, Robert T., Doria-Rose, Nicole A., Gindin, Tatyana S., Lin, Bob, Louder, Mark K., McKee, Krisha, O'Dell, Sijy, Pegu, Amarendra, Schmidt, Stephen D., Asokan, Mangaiarkarasi, Xuejun Chen, Misook Choe, Georgiev, Ivelin S., Jin, Vivian, Pancera, Marie, Rawi, Reda, and Keyun Wang

Abstract

Highly effective HIV-1-neutralizing antibodies could have utility in the prevention or treatment of HIV-1 infection. To improve the potency of 10E8, an antibody capable of near pan-HIV-1 neutralization, we engineered 10E8-surface mutants and screened for improved neutralization. Variants with the largest functional enhancements involved the addition of hydrophobic or positively charged residues, which were positioned to interact with viral membrane lipids orviral glycan-sialic acids, respectively. In both cases, the site of improvement was spatially separated from the region of antibody mediating molecular contact with the protein component of the antigen, thereby improving peripheral semi-specific interactions while maintaining unmodified dominant contacts responsible for broad recognition. The optimized 10E8 antibody, with mutations to phenylalanine and arginine, retained the extraordinary breadth of 10E8 but with ~10-fold increased potency. We propose surface-matrix screening as a general method to improve antibodies, with improved semi-specific interactions between antibody and antigen enabling increased potency without compromising breadth. [ABSTRACT FROM AUTHOR]

Published
2018
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22. Peptidomimetic blockade of MYB in acute myeloid leukemia.

Author

Minuesa, Gerard, Brown, Fiona, Kharas, Michael G., Still, Eric, Ramaswamy, Kavitha, Kentsis, Alex, Forbes, Lauren, Armstrong, Scott A., Gindin, Tatyana, Koche, Richard, Krivtsov, Andrei V., Knoechel, Birgit, and de Stanchina, Elisa

Subjects
PEPTIDOMIMETICS, ACUTE myeloid leukemia, GENE expression, TRANSCRIPTION factors, ADULT-child relationships
Abstract

Aberrant gene expression is a hallmark of acute leukemias. MYB-driven transcriptional coactivation with CREB-binding protein (CBP)/P300 is required for acute lymphoblastic and myeloid leukemias, including refractory MLL-rearranged leukemias. Using structure-guided molecular design, we developed a peptidomimetic inhibitor MYBMIM that interferes with the assembly of the molecular MYB:CBP/P300 complex and rapidly accumulates in the nuclei of AML cells. Treatment of AML cells with MYBMIM led to the dissociation of the MYB:CBP/ P300 complex in cells, its displacement from oncogenic enhancers enriched for MYB binding sites, and downregulation of MYB-dependent gene expression, including of MYC and BCL2 oncogenes. AML cells underwent mitochondrial apoptosis in response to MYBMIM, which was partially rescued by ectopic expression of BCL2. MYBMIM impeded leukemia growth and extended survival of immunodeficient mice engrafted with primary patient-derived MLL-rearranged leukemia cells. These findings elucidate the dependence of human AML on aberrant transcriptional coactivation, and establish a pharmacologic approach for its therapeutic blockade. [ABSTRACT FROM AUTHOR]

Published
2018
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23. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors

Author

Zhou, Tongqing, primary, Lynch, Rebecca M., additional, Chen, Lei, additional, Acharya, Priyamvada, additional, Wu, Xueling, additional, Doria-Rose, Nicole A., additional, Joyce, M. Gordon, additional, Lingwood, Daniel, additional, Soto, Cinque, additional, Bailer, Robert T., additional, Ernandes, Michael J., additional, Kong, Rui, additional, Longo, Nancy S., additional, Louder, Mark K., additional, McKee, Krisha, additional, O’Dell, Sijy, additional, Schmidt, Stephen D., additional, Tran, Lillian, additional, Yang, Zhongjia, additional, Druz, Aliaksandr, additional, Luongo, Timothy S., additional, Moquin, Stephanie, additional, Srivatsan, Sanjay, additional, Yang, Yongping, additional, Zhang, Baoshan, additional, Zheng, Anqi, additional, Pancera, Marie, additional, Kirys, Tatsiana, additional, Georgiev, Ivelin S., additional, Gindin, Tatyana, additional, Peng, Hung-Pin, additional, Yang, An-Suei, additional, Mullikin, James C., additional, Gray, Matthew D., additional, Stamatatos, Leonidas, additional, Burton, Dennis R., additional, Koff, Wayne C., additional, Cohen, Myron S., additional, Haynes, Barton F., additional, Casazza, Joseph P., additional, Connors, Mark, additional, Corti, Davide, additional, Lanzavecchia, Antonio, additional, Sattentau, Quentin J., additional, Weiss, Robin A., additional, West, Anthony P., additional, Bjorkman, Pamela J., additional, Scheid, Johannes F., additional, Nussenzweig, Michel C., additional, Shapiro, Lawrence, additional, Mascola, John R., additional, and Kwong, Peter D., additional

Published
2015
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32. T-cell acute lymphoblastic leukaemia after liver transplantation: post-transplant lymphoproliferative disorder or coincidental de novo leukaemia?

Author

Fang, Yanan, Pinkney, Kerice A, Lee, John C, Gindin, Tatyana, Weiner, Michael A, Alobeid, Bachir, and Bhagat, Govind

Abstract

Post-transplant lymphoproliferative disorders of T-cell origin are quite uncommon, and the vast majority represent neoplasms of mature, post-thymic T- or natural killer cells. Here, we report a rare case of T-cell acute lymphoblastic leukaemia (T-ALL), which occurred in an 18-year-old man who had undergone three liver transplants, initially for biliary atresia and subsequently for graft failure due to chronic rejection. He had received immunosuppression with cyclosporine and tacrolimus, as well as short-term treatment with OKT3. The T-ALL occurred 16 years after the first liver transplant. This case highlights the challenge for classifying rare neoplasms occurring in recipients of solid organ transplants that are currently not recognized to lie within the spectrum of post-transplant lymphoproliferative disorders. Given the long interval between the liver transplants and the development of T-ALL, a coincidental occurrence of the leukaemia cannot be ruled out. However, the potential roles of immunosuppressive therapy and other co-morbid conditions of the individual as possible risk factors for the pathogenesis of T-ALL are discussed. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2013
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33. Sequencing identifies multiple early introductions of SARS-CoV-2 to the New York City Region.

Author

Maurano MT, Ramaswami S, Zappile P, Dimartino D, Boytard L, Ribeiro-Dos-Santos AM, Vulpescu NA, Westby G, Shen G, Feng X, Hogan MS, Ragonnet-Cronin M, Geidelberg L, Marier C, Meyn P, Zhang Y, Cadley J, Ordoñez R, Luther R, Huang E, Guzman E, Arguelles-Grande C, Argyropoulos KV, Black M, Serrano A, Call ME, Kim MJ, Belovarac B, Gindin T, Lytle A, Pinnell J, Vougiouklakis T, Chen J, Lin LH, Rapkiewicz A, Raabe V, Samanovic MI, Jour G, Osman I, Aguero-Rosenfeld M, Mulligan MJ, Volz EM, Cotzia P, Snuderl M, and Heguy A

Abstract

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in Spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators., Competing Interests: Competing interest statement The authors declare no competing interests.

Published
2020
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34. MLL/KMT2A translocations in diffuse large B-cell lymphomas.

Author

Gindin T, Murty V, Alobeid B, and Bhagat G

Subjects
Aged, Female, Humans, Lymphoma, Large B-Cell, Diffuse pathology, Male, Translocation, Genetic, Histone-Lysine N-Methyltransferase genetics, Histone-Lysine N-Methyltransferase metabolism, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse metabolism, Myeloid-Lymphoid Leukemia Protein genetics, Myeloid-Lymphoid Leukemia Protein metabolism
Abstract

Translocations of the histone-lysine N-methyltransferase 2A (KMT2A) gene, formerly known as myeloid lymphoid leukemia/mixed-lineage leukemia gene, are commonly associated with high-risk de novo or therapy-associated B-cell and T-cell lymphoblastic leukemias and myeloid neoplasms. Rare B-cell non-Hodgkin lymphomas harboring KMT2A translocations have been reported, but information regarding the clinical behavior of such cases is limited. Here, we describe two extranodal diffuse large B-cell lymphomas (DLBCLs): a primary thyroid DLBCL and a large cell transformation of a splenic marginal zone lymphoma, which displayed complex karyotypes and translocations involving chromosome 11q23 targeting the KMT2A gene. The pathological and clinical characteristics of these cases are discussed in the context of previously reported lymphomas associated with different types of KMT2A genetic aberrations. In contrast to the poor clinical outcomes of patients with acute leukemias and myeloid neoplasms associated with KMT2A translocations, patients with B-cell non-Hodgkin lymphomas, exhibiting similar translocations, appear to respond well to immunochemotherapy. Our findings add to the growing list of histone methyltransferase genes deregulated in DLBCL and highlight the diversity of mechanisms, altering the function of epigenetic modifier genes in lymphomas., (Copyright © 2014 John Wiley & Sons, Ltd.)

Published
2015
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