Vivekanand Yadav, PhD
Title | Doctoral Research Faculty |
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Institution | Children's Mercy Kansas City |
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Department | Hematology/Oncology/BMT |
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Address | 2401 Gillham Rd Kansas City MO 64108
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vCard | Download vCard |
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Title | Assistant Professor |
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Institution | University of Missouri-Kansas City |
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Department | Pediatrics |
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Title | Assistant Professor |
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Institution | University of Kansas Medical Center |
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Department | Cancer Biology |
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Biography University of Pune, India | Ph.D | 01/2012 | Biotechnology | Karmanos Cancer Institute, Wayne State University, Detroit, USA | PostDoctoral | 06/2013 | Cancer Biology | University of Michigan, Ann Arbor, USA | PostDoctoral | 06/2018 | Neuro-Oncology | University of Michigan, Ann Arbor, USA | Research Investigator | 05/2022 | Pediatric Neuro-Oncology |
Assistant Professor, Dept. of Pediatrics, Children’s Mercy Research Institute (CMRI), Kansas City, MO, USAAssistant Professor, Department of Pediatrics, University of Missouri, Kansas City School of Medicine, Kansas, MO, USAAssistant Professor, Department of Cancer Biology, University of Kansas Cancer Center. Kansas City, KS, USA. 2025 - 2027 | Novel Therapeutic Strategies for Diffuse Midline Glioma Using High-Throughput Combination Drug Scree, Masonic Cancer Alliance | 2024 - 2026 | Determining the Therapeutic Efficacy of Novel Bi-specific CAR T Cells (anti-B7H3-GD2) in H3G34R/V-mu, Noahs’s Bandage Award | 2023 - 2024 | Excellence in Research, Joiner Faculty Travel Award 1st prize , Kansas University Comprehensive Cancer Center Research Symposium | 2021 - 2023 | New Investigator Award , Chad Tough Defeat DIPG Foundation | 2020 | Faculty award for basic science research, Department of Pediatrics, University of Michigan |
Overview - DIPG, DMG, Pediatric Brain Tumors, Genomic and Epigenetic Mechanism of Brain tumors
- B7-H3, CAR T cells , Immunotherapy, H3G34-mutant, DHG.
- High-throughput drug screening (HTS), CRISPR isogenic models, IUE mouse model, ONC201, CBD, ID1
- Combination therapy, pediatric high-grade glioma (pHGG), Tumor Microenvironment, Targeted Therapy
Research Diffuse midline gliomas (DMGs) are the most aggressive pediatric high-grade gliomas and are the leading cause of cancer-related deaths in children. At present, there are no effective therapies for DMGs tumors, and over 90% of patients die within 1.5 years of diagnosis. In his lab, Dr. Yadav is leading efforts to understand genetic and epigenetic dependencies and signaling pathways that arise as a consequence of the H3K27M mutation in DMG. His lab performs pre-clinical studies using a novel in utero electroporation (IUE)-derived genetically engineered mouse model to identify promising candidates that can be targeted as therapy for the treatment of DMG.
1-Identifying genomic and epigenetic drivers of pediatric brain tumors with specific genetic alterations (H3K27M or H3G34R/V) using next-generation sequencing and a novel in utero electroporation (IUE) genetically engineered mouse model.
Our Lab mission is to develop more effective treatment options for children with brain tumors.
Current Research Projects:
Project 1: CAR T Cell Immunotherapy for pHGGs: Advancinganti-B7-H3 CAR T cell therapy for (pHGGs), exploring the tumor microenvironment’s influence on CAR T efficacy.
Project Overview: • CAR T cell therapy offers new potential for treating pediatric high-grade gliomas (pHGGs), including DIPG/DMG and H3G34R/V-mutant diffuse hemispheric glioma (DHG), which currently lack effective treatments. We identified B7-H3 as a consistently overexpressed target in DHG and developed anti-B7-H3 CAR T cells that demonstrated potent, antigen-specific activity in vitro and in orthotopic DHG xenograft models, leading to significant tumor regression and improved survival. • To further advance this strategy, we established a novel immunocompetent IUE-based mouse model of H3G34R-mutant DHG. Ongoing studies are evaluating monospecific B7-H3 and bispecific B7-H3-GD2 CAR T cells in this model and investigating the influence of the tumor microenvironment and epigenetic regulation on CAR T efficacy using RNA-seq, CUT&RUN-seq, and functional immune assays. • Our work highlights B7-H3 CAR T therapy as a promising immunotherapeutic approach for DHG and supports its future clinical translation.
Project 2: Targeting ID1-Mediated ONC201 Resistance in H3K27M Diffuse Midline Gliomas Using Cannabidiol Combination Therapy.
Project Overview: • Our recent studies showed that inhibiting ID1 attenuates DMG cell invasion and migration while improving survival in H3K27M-DMG mouse models. ID1 is a direct downstream target of the ACVR1 pathway and has been identified as a biomarker of ONC201 response, with high ID1 expression correlating with ONC201 resistance. ONC201, a DRD2 antagonist with clinical promise in phase II trials for DMG, induces mitochondrial stress, disrupts OXPHOS, elevates ROS, and promotes apoptosis. However, resistance to ONC201 remains a significant clinical challenge, and the underlying mechanisms remain poorly understood. • This project aims to establish a clinically translatable therapeutic strategy combining CBD with ONC201 to overcome resistance in H3K27M-DMG. By elucidating resistance mechanisms and testing this combination, our findings will inform future clinical trials and address a critical unmet need in pediatric neuro-oncology.
Project 3: High-Throughput Drug Screening Identifies Novel Combination Therapies Targeting H3K27M-Mutant Diffuse Midline Gliomas.
Project Overview: • To identify new treatment strategies, we conducted a high-throughput screen of 1,520 FDA-approved drugs in isogenic H3K27M-mutant DMG models, identifying 86 promising candidates. Combination screens revealed that select drugs synergize with ONC201 and enhance radiosensitivity. Using an intrauterine electroporation (IUE)-based H3K27M DMG mouse model, we are validating these combinations in vivo. This work aims to advance novel combination therapies to improve outcomes for children with DMG.
Project 4: Targeting USP1 to Overcome Therapy Resistance and Enhance Radiosensitivity in H3K27M-Mutant Diffuse Midline Gliomas
• Project Overview: Diffuse midline gliomas (DMGs), driven by H3K27M mutations, are uniformly lethal pediatric brain tumors with limited treatment options and poor outcomes. Our studies identified ubiquitin-specific protease 1 (USP1) as a novel vulnerability in DMG. USP1 is upregulated in H3K27M-mutant tumors, and pharmacologic inhibition of USP1 reduces DMG cell proliferation, induces apoptosis, and downregulates key regulators of stemness and DNA repair. Ongoing work demonstrates that USP1 inhibition sensitizes DMG cells to ionizing radiation. Using our H3K27M DMG mouse model, we are evaluating USP1 inhibitors as radiosensitizers, aiming to develop new combination therapies for this devastating disease.
AWD018127 (Vivekanand Yadav)Aug 1, 2021 - Feb 29, 2024 The ChadTough Defeat DIPG Foundation for the 'New Investigator Award Epigenetically activated ID1 is a key transcriptional regulator of DIPG Invasion and is targetable with cannabidiol |
| (Vivekanand Yadav)Oct 1, 2022 - Sep 30, 2023 Tom Keaveny Award Upregulation of prenatal pontine ID1 signaling in DIPG, |
| (Vivekanand Yadav)Jan 1, 2024 - Dec 31, 2026 Noahs’s Bandage Award (PI: Vivekanand Yadav) Determining the Therapeutic Efficacy of Novel Bi-specific CAR T Cells (anti-B7H3-GD2) in H3G34R/V-mutated Pediatric High-Grade Gliomas (pHGGs). |
| (Vivekanand Yadav)Jun 1, 2025 - Dec 31, 2027 Masonic Cancer Alliance, Funding (PI: Vivekanand Yadav) Novel Therapeutic Strategies for Diffuse Midline Glioma Using High-Throughput Combination Drug Screening |
Bibliography
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Mbah NE, Myers AL, Sajjakulnukit P, Chung C, Thompson JK, Hong HS, Giza H, Dang D, Nwosu ZC, Shan M, Sweha SR, Maydan DD, Chen B, Zhang L, Magnuson B, Zhu Z, Radyk M, Lavoie B, Yadav VN, Koo I, Patterson AD, Wahl DR, Franchi L, Agnihotri S, Koschmann CJ, Venneti S, Lyssiotis CA. Therapeutic targeting of differentiation-state dependent metabolic vulnerabilities in diffuse midline glioma. Nat Commun. 2024 Oct 17; 15(1):8983. PMID: 39419964.
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Koschmann C, Al-Holou WN, Alonso MM, Anastas J, Bandopadhayay P, Barron T, Becher O, Cartaxo R, Castro MG, Chung C, Clausen M, Dang D, Doherty R, Duchatel R, Dun M, Filbin M, Franson A, Galban S, Garcia Moure M, Garton H, Gowda P, Marques JG, Hawkins C, Heath A, Hulleman E, Ji S, Jones C, Kilburn L, Kline C, Koldobskiy MA, Lim D, Lowenstein PR, Lu QR, Lum J, Mack S, Magge S, Marini B, Martin D, Marupudi N, Messinger D, Mody R, Morgan M, Mota M, Muraszko K, Mueller S, Natarajan SK, Nazarian J, Niculcea M, Nuechterlein N, Okada H, Opipari V, Pai MP, Pal S, Peterson E, Phoenix T, Prensner JR, Pun M, Raju GP, Reitman ZJ, Resnick A, Rogawski D, Saratsis A, Sbergio SG, Souweidane M, Stafford JM, Tzaridis T, Venkataraman S, Vittorio O, Wadden J, Wahl D, Wechsler-Reya RJ, Yadav VN, Zhang X, Zhang Q, Venneti S. A road map for the treatment of pediatric diffuse midline glioma. Cancer Cell. 2024 01 08; 42(1):1-5. PMID: 38039965.
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Ausejo-Mauleon I, Labiano S, de la Nava D, Laspidea V, Zalacain M, Marrod?n L, Garc?a-Moure M, Gonz?lez-Huarriz M, Herv?s-Corpi?n I, Dhandapani L, Vicent S, Collantes M, Pe?uelas I, Becher OJ, Filbin MG, Jiang L, Labelle J, de Biagi-Junior CAO, Nazarian J, Laternser S, Phoenix TN, van der Lugt J, Kranendonk M, Hoogendijk R, Mueller S, De Andrea C, Anderson AC, Guruceaga E, Koschmann C, Yadav VN, G?llego P?rez-Larraya J, Pati?o-Garc?a A, Pastor F, Alonso MM. TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory. Cancer Cell. 2023 11 13; 41(11):1911-1926.e8. PMID: 37802053.
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Messinger D, Harris MK, Cummings JR, Thomas C, Yang T, Sweha SR, Woo R, Siddaway R, Burkert M, Stallard S, Qin T, Mullan B, Siada R, Ravindran R, Niculcea M, Dowling AR, Bradin J, Ginn KF, Gener MAH, Dorris K, Vitanza NA, Schmidt SV, Spitzer J, Li J, Filbin MG, Cao X, Castro MG, Lowenstein PR, Mody R, Chinnaiyan A, Desprez PY, McAllister S, Dun MD, Hawkins C, Waszak SM, Venneti S, Koschmann C, Yadav VN. Therapeutic targeting of prenatal pontine ID1 signaling in diffuse midline glioma. Neuro Oncol. 2023 01 05; 25(1):54-67. PMID: 35605606.
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Schwark K, Messinger D, Cummings JR, Bradin J, Kawakibi A, Babila CM, Lyons S, Ji S, Cartaxo RT, Kong S, Cantor E, Koschmann C, Yadav VN. Receptor tyrosine kinase (RTK) targeting in pediatric high-grade glioma and diffuse midline glioma: Pre-clinical models and precision medicine. Front Oncol. 2022; 12:922928. PMID: 35978801.
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Cantor E, Wierzbicki K, Tarapore RS, Ravi K, Thomas C, Cartaxo R, Nand Yadav V, Ravindran R, Bruzek AK, Wadden J, John V, May Babila C, Cummings JR, Rahman Kawakibi A, Ji S, Ramos J, Paul A, Walling D, Leonard M, Robertson P, Franson A, Mody R, Garton HJL, Venneti S, Odia Y, Kline C, Vitanza NA, Khatua S, Mueller S, Allen JE, Gardner SL, Koschmann C. Serial H3K27M cell-free tumor DNA (cf-tDNA) tracking predicts ONC201 treatment response and progression in diffuse midline glioma. Neuro Oncol. 2022 08 01; 24(8):1366-1374. PMID: 35137228.
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Qin T, Mullan B, Ravindran R, Messinger D, Siada R, Cummings JR, Harris M, Muruganand A, Pyaram K, Miklja Z, Reiber M, Garcia T, Tran D, Danussi C, Brosnan-Cashman J, Pratt D, Zhao X, Rehemtulla A, Sartor MA, Venneti S, Meeker AK, Huse JT, Morgan MA, Lowenstein PR, Castro MG, Yadav VN, Koschmann C. ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization. Cell Rep. 2022 01 11; 38(2):110216. PMID: 35021084.
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Sweha SR, Chung C, Natarajan SK, Panwalkar P, Pun M, Ghali A, Bayliss J, Pratt D, Shankar A, Ravikumar V, Rao A, Cieslik M, Wilder-Romans K, Scott AJ, Wahl DR, Jessa S, Kleinman CL, Jabado N, Mackay A, Jones C, Martinez D, Santi M, Judkins AR, Yadav VN, Qin T, Phoenix TN, Koschmann CJ, Baker SJ, Chinnaiyan AM, Venneti S. Epigenetically defined therapeutic targeting in H3.3G34R/V high-grade gliomas. Sci Transl Med. 2021 Oct 13; 13(615):eabf7860. PMID: 34644147.
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Miklja Z, Yadav VN, Cartaxo RT, Siada R, Thomas CC, Cummings JR, Mullan B, Stallard S, Paul A, Bruzek AK, Wierzbicki K, Yang T, Garcia T, Wolfe I, Leonard M, Robertson PL, Garton HJ, Wahl DR, Parmar H, Sarkaria JN, Kline C, Mueller S, Nicolaides T, Glasser C, Leary SE, Venneti S, Kumar-Sinha C, Chinnaiyan AM, Mody R, Pai MP, Phoenix TN, Marini BL, Koschmann C. Everolimus improves the efficacy of dasatinib in PDGFRa-driven glioma. J Clin Invest. 2020 10 01; 130(10):5313-5325. PMID: 32603316.
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Chung C, Sweha SR, Pratt D, Tamrazi B, Panwalkar P, Banda A, Bayliss J, Hawes D, Yang F, Lee HJ, Shan M, Cieslik M, Qin T, Werner CK, Wahl DR, Lyssiotis CA, Bian Z, Shotwell JB, Yadav VN, Koschmann C, Chinnaiyan AM, Bl?ml S, Judkins AR, Venneti S. Integrated Metabolic and Epigenomic Reprograming by H3K27M Mutations in Diffuse Intrinsic Pontine Gliomas. Cancer Cell. 2020 09 14; 38(3):334-349.e9. PMID: 32795401.
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Wierzbicki K, Ravi K, Franson A, Bruzek A, Cantor E, Harris M, Homan MJ, Marini BL, Kawakibi AR, Ravindran R, Teodoro R, Yadav VN, Koschmann C. Correction to: Targeting and Therapeutic Monitoring of H3K27M-Mutant Glioma. Curr Oncol Rep. 2020 Apr 16; 22(5):47. PMID: 32297022.
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Wierzbicki K, Ravi K, Franson A, Bruzek A, Cantor E, Harris M, Homan MJ, Marini BL, Kawakibi AR, Ravindran R, Teodoro R, Yadav VN, Koschmann C. Targeting and Therapeutic Monitoring of H3K27M-Mutant Glioma. Curr Oncol Rep. 2020 02 06; 22(2):19. PMID: 32030483.
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Yadav VN, Altshuler D, Kadiyala P, Zamler D, Comba A, Appelman H, Dunn P, Koschmann C, Castro MG, L?wenstein PR. Molecular ablation of tumor blood vessels inhibits therapeutic effects of radiation and bevacizumab. Neuro Oncol. 2018 09 03; 20(10):1356-1367. PMID: 29660022.
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Pyaram K, Yadav VN. Advances in NKT cell Immunotherapy for Glioblastoma. J Cancer Sci Ther. 2018; 10(6). PMID: 30147849.
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Kumar J, Yadav VN, Phulera S, Kamble A, Gautam AK, Panwar HS, Sahu A. Species Specificity of Vaccinia Virus Complement Control Protein for the Bovine Classical Pathway Is Governed Primarily by Direct Interaction of Its Acidic Residues with Factor I. J Virol. 2017 10 01; 91(19). PMID: 28724763.
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Chandran M, Candolfi M, Shah D, Mineharu Y, Yadav VN, Koschmann C, Asad AS, Lowenstein PR, Castro MG. Single vs. combination immunotherapeutic strategies for glioma. Expert Opin Biol Ther. 2017 05; 17(5):543-554. PMID: 28286975.
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Yadav VN, Zamler D, Baker GJ, Kadiyala P, Erdreich-Epstein A, DeCarvalho AC, Mikkelsen T, Castro MG, Lowenstein PR. CXCR4 increases in-vivo glioma perivascular invasion, and reduces radiation induced apoptosis: A genetic knockdown study. Oncotarget. 2016 12 13; 7(50):83701-83719. PMID: 27863376.
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Calinescu AA, Yadav VN, Carballo E, Kadiyala P, Tran D, Zamler DB, Doherty R, Srikanth M, Lowenstein PR, Castro MG. Survival and Proliferation of Neural Progenitor-Derived Glioblastomas Under Hypoxic Stress is Controlled by a CXCL12/CXCR4 Autocrine-Positive Feedback Mechanism. Clin Cancer Res. 2017 Mar 01; 23(5):1250-1262. PMID: 27542769.
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Yadav VN, Castro MG, Lowenstein PR. Neurotropic Viral Infections, Carol Shoshkes Reiss. Viral Gene Therapy for Central Nervous System Diseases. 2016; 519-544.
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Kathania M, Zeng M, Yadav VN, Moghaddam SJ, Yang B, Venuprasad K. Ndfip1 regulates itch ligase activity and airway inflammation via UbcH7. J Immunol. 2015 Mar 01; 194(5):2160-7. PMID: 25632008.
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Baker GJ, Chockley P, Yadav VN, Doherty R, Ritt M, Sivaramakrishnan S, Castro MG, Lowenstein PR. Natural killer cells eradicate galectin-1-deficient glioma in the absence of adaptive immunity. Cancer Res. 2014 Sep 15; 74(18):5079-90. PMID: 25038230.
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Baker GJ, Yadav VN, Motsch S, Koschmann C, Calinescu AA, Mineharu Y, Camelo-Piragua SI, Orringer D, Bannykh S, Nichols WS, deCarvalho AC, Mikkelsen T, Castro MG, Lowenstein PR. Mechanisms of glioma formation: iterative perivascular glioma growth and invasion leads to tumor progression, VEGF-independent vascularization, and resistance to antiangiogenic therapy. Neoplasia. 2014 Jul; 16(7):543-61. PMID: 25117977.
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Lowenstein PR, Yadav VN, Chockley P, Castro M. There must be a way out of here: identifying a safe and efficient combination of promoter, transgene, and vector backbone for gene therapy of neurological disease. Mol Ther. 2014 Feb; 22(2):246-247. PMID: 24487564.
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Yadav VN, Pyaram K, Ahmad M, Sahu A. Species selectivity in poxviral complement regulators is dictated by the charge reversal in the central complement control protein modules. J Immunol. 2012 Aug 01; 189(3):1431-9. PMID: 22732591.
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Yadav VN, Hansen T, G?rbitz CH. 1,1'-(4,4'-Bipiperidine-1,1'-di-yl)bis-(2,2,2-trifluoro-ethanone). Acta Crystallogr Sect E Struct Rep Online. 2011 Jul 01; 67(Pt 7):o1691. PMID: 21837088.
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Pyaram K, Kieslich CA, Yadav VN, Morikis D, Sahu A. Influence of electrostatics on the complement regulatory functions of Kaposica, the complement inhibitor of Kaposi's sarcoma-associated herpesvirus. J Immunol. 2010 Feb 15; 184(4):1956-67. PMID: 20089702.
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Sreejith RK, Yadav VN, Varshney NK, Berwal SK, Suresh CG, Gaikwad SM, Pal JK. Conformational characterization of human eukaryotic initiation factor 2alpha: a single tryptophan protein. Biochem Biophys Res Commun. 2009 Dec 11; 390(2):273-9. PMID: 19800319.
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Singh AK, Yadav VN, Pyaram K, Mullick J, Sahu A. Mapping of functional domains in herpesvirus saimiri complement control protein homolog: complement control protein domain 2 is the smallest structural unit displaying cofactor and decay-accelerating activities. J Virol. 2009 Oct; 83(19):10299-304. PMID: 19640995.
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Yadav VN, Pyaram K, Mullick J, Sahu A. Identification of hot spots in the variola virus complement inhibitor (SPICE) for human complement regulation. J Virol. 2008 Apr; 82(7):3283-94. PMID: 18216095.
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Mullick J, Singh AK, Panse Y, Yadav V, Bernet J, Sahu A. Identification of functional domains in kaposica, the complement control protein homolog of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8). J Virol. 2005 May; 79(9):5850-6. PMID: 15827200.
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Year | Publications |
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2005 | 1 | 2008 | 1 | 2009 | 2 | 2010 | 1 | 2011 | 1 | 2012 | 1 | 2014 | 3 | 2015 | 1 | 2016 | 3 | 2017 | 2 | 2018 | 2 | 2020 | 4 | 2021 | 1 | 2022 | 3 | 2023 | 3 | 2024 | 1 |
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