Nicole Vincelette, PhD

My research investigates how somatic mutations and mosaic chromosomal alterations (mCAs) reprogram hematopoiesis, alter the microenvironment, and drive the initiation and progression of hematologic malignancies. By uncovering the mechanisms linking genetic alterations to disease evolution, my team seeks to develop predictive models and targeted interventions that advance precision medicine in hematology.

Associations

• Malignant Hematology
• Molecular Medicine Program

My research focuses on uncovering the molecular mechanisms that drive disease progression in myelofibrosis and the transformation of chronic lymphocytic leukemia (CLL) into Richter’s syndrome. These diseases serve as model systems to study how somatic genomic alterations arising in hematopoietic stem cells reprogram blood formation, amplify inflammatory signaling, and accelerate malignant evolution. Specifically, I investigate how MYC-driven alarmin pathways sustain chronic inflammation, disrupt normal hematopoiesis, and promote aberrant myeloid expansion in myelofibrosis, as well as how these same programs facilitate the aggressive transformation of CLL into Richter’s syndrome. The overarching goal is to define how genetic alterations shape clonal evolution and to translate these insights into precision medicine strategies for hematologic malignancies. In parallel, I am examining how somatic chromosomal alterations in hematopoietic stem cells that heighten inflammatory responses contribute to the pathogenesis of non-hematologic diseases, such as non-alcoholic steatohepatitis (NASH) and liver fibrosis.

• Venkatachalam A, Correia C, Peterson KL, Hou X, Schneider PA, Strathman AR, Flatten KS, Sine CC, Balczewski EA, McGehee CD, Larson MC, Duffield LN, Meng XW, Vincelette ND, Ding H, Oberg AL, Couch FJ, Swisher EM, Li H, Weroha SJ, Kaufmann SH. Proapoptotic activity of JNK-sensitive BH3-only proteins underpins ovarian cancer response to replication checkpoint inhibitors. Mol Cancer. 2024 Oct.23(1):224. Pubmedid: 39375715. Pmcid: PMC11457406.
• Vincelette ND, Yu X, Kuykendall AT, Moon J, Su S, Cheng CH, Sammut R, Razabdouski TN, Nguyen HV, Eksioglu EA, Chan O, Al Ali N, Patel PC, Lee DH, Nakanishi S, Ferreira RB, Hyjek E, Mo Q, Cory S, Lawrence HR, Zhang L, Murphy DJ, Komrokji RS, Lee D, Kaufmann SH, Cleveland JL, Yun S. Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC-Alarmin Axis. Blood Cancer Discov. 2024 Jul.5(4):276-297. Pubmedid: 38713018. Pmcid: PMC11215389.
• Mo Q, Yun S, Sallman DA, Vincelette ND, Peng G, Zhang L, Lancet JE, Padron E. Integrative molecular subtypes of acute myeloid leukemia. Blood Cancer J. 2023 May.13(1):71. Pubmedid: 37156780. Pmcid: PMC10167212.
• Ward GA, Dalton RP, Meyer BS, McLemore AF, Aldrich AL, Lam NB, Onimus AH, Vincelette ND, Trinh TL, Chen X, Calescibetta AR, Christiansen SM, Hou HA, Johnson JO, Wright KL, Padron E, Eksioglu EA, List AF. Oxidized Mitochondrial DNA Engages TLR9 to Activate the NLRP3 Inflammasome in Myelodysplastic Syndromes. Int J Mol Sci. 2023 Feb.24(4). Pubmedid: 36835307. Pmcid: PMC9966808.
• Burger KL, Fernandez MR, Meads MB, Sudalagunta PR, Oliveira PS, Renatino Canevarolo R, Alugubelli RR, Tungsevik A, De Avila G, Silva M, Graeter AI, Dai H, Vincelette ND, Prabhu A, Magaletti D, Yang C, Li W, Kulkarni A, Hampton OA, Koomen JM, Roush WR, Monastyrskyi A, Berglund AE, Silva AS, Cleveland JL, Shain KH. CK1δ and CK1ε Signaling Sustains Mitochondrial Metabolism and Cell Survival in Multiple Myeloma. Cancer Res. 2023 Dec.83(23):3901-3919. Pubmedid: 37702657. Pmcid: PMC10690099.
• McLemore AF, Hou HA, Meyer BS, Lam NB, Ward GA, Aldrich AL, Rodrigues MA, Vedder A, Zhang L, Padron E, Vincelette ND, Sallman DA, Abdel-Wahab O, List AF, McGraw KL. Somatic gene mutations expose cytoplasmic DNA to co-opt the cGAS/STING/NLRP3 axis in myelodysplastic syndromes. JCI Insight. 2022 Aug.7(15). Pubmedid: 35788117. Pmcid: PMC9462508.
• Ding H, Vincelette ND, McGehee CD, Kohorst MA, Koh BD, Venkatachalam A, Meng XW, Schneider PA, Flatten KS, Peterson KL, Correia C, Lee SH, Patnaik M, Webster JA, Ghiaur G, Smith BD, Karp JE, Pratz KW, Li H, Karnitz LM, Kaufmann SH. CDK2-Mediated Upregulation of TNFα as a Mechanism of Selective Cytotoxicity in Acute Leukemia. Cancer Res. 2021 May.81(10):2666-2678. Pubmedid: 33414171. Pmcid: PMC8137540.
• Yun S, Vincelette ND, Yu X, Watson GW, Fernandez MR, Yang C, Hitosugi T, Cheng CH, Freischel AR, Zhang L, Li W, Hou H, Schaub FX, Vedder AR, Cen L, McGraw KL, Moon J, Murphy DJ, Ballabio A, Kaufmann SH, Berglund AE, Cleveland JL. TFEB links MYC signaling to epigenetic control of myeloid differentiation and acute myeloid leukemia. Blood Cancer Discov. 2021 Mar.2(2):162-185. Pubmedid: 33860275. Pmcid: PMC8043621.
• Gajzer D, Logothetis CN, Sallman DA, Calon G, Babu A, Chan O, Vincelette ND, Volpe VO, Al Ali NH, Basra P, Talati C, Kuykendall AT, Mo Q, Padron E, Sweet K, Komrokji RS, Lancet JE, Yun S, Zhang L. MYC overexpression is associated with an early disease progression from MDS to AML. Leuk Res. 2021 Dec.111:106733. Pubmedid: 34749168. Pmcid: PMC8643343.
• Ward GA, McGraw KL, Abbas-Aghababazadeh F, Meyer BS, McLemore AF, Vincelette ND, Lam NB, Aldrich AL, Al Ali NH, Padron E, Pinilla-Ibarz J, Masala E, Santini V, Kosmider O, Fontenay M, Fenaux P, Johnson J, Fridley BL, List AF. Oxidized mitochondrial DNA released after inflammasome activation is a disease biomarker for myelodysplastic syndromes. Blood Adv. 2021 Apr.5(8):2216-2228. Pubmedid: 33890980. Pmcid: PMC8095151.
• Yun S, Chan O, Kerr D, Vincelette ND, Idrees A, Mo Q, Sweet K, Lancet JE, Kharfan-Dabaja MA, Zhang L, Sokol L. Survival outcomes in blastic plasmacytoid dendritic cell neoplasm by first-line treatment and stem cell transplant. Blood Adv. 2020 Jul.4(14):3435-3442. Pubmedid: 32722779. Pmcid: PMC7391135.
• Yun S, Sharma R, Chan O, Vincelette ND, Sallman DA, Sweet K, Padron E, Komrokji R, Lancet JE, Abraham I, Moscinski LC, Cleveland JL, List AF, Zhang L. Prognostic significance of MYC oncoprotein expression on survival outcome in patients with acute myeloid leukemia with myelodysplasia related changes (AML-MRC). Leuk Res. 2019 Sep.84:106194. Pubmedid: 31357093. Pmcid: PMC7375354.
• Basiorka AA, McGraw KL, Abbas-Aghababazadeh F, McLemore AF, Vincelette ND, Ward GA, Eksioglu EA, Sallman DA, Ali NA, Padron E, Pinilla-Ibarz J, Komrokji R, Masala E, Santini V, Kosmider O, Fontenay M, Fenaux P, Sokol L, Wei S, Fridley B, List AF. Assessment of ASC specks as a putative biomarker of pyroptosis in myelodysplastic syndromes: an observational cohort study. Lancet Haematol. 2018 Sep.5(9):e393-e402. Pubmedid: 30072146. Pmcid: PMC6505461.
• Yun S, Vincelette ND. Ivosidenib in IDH1-Mutated Acute Myeloid Leukemia. N Engl J Med. 2018 Sep.379(12):1186. Pubmedid: 30260155.
• Abraham I, Yami MA, Yun S, Kim HJ, Vincelette ND, McBride A, MacDonald K. Survival outcomes in iron chelated and non-chelated patients with lower-risk myelodysplastic syndromes: Review and pooled analysis of observational studies. Leuk Res. 2017 Jun.57:104-108. Pubmedid: 28343141.
• Yun S, Vincelette ND, Acharya U, Abraham I. Risk of Atrial Fibrillation and Bleeding Diathesis Associated With Ibrutinib Treatment: A Systematic Review and Pooled Analysis of Four Randomized Controlled Trials. Clin Lymphoma Myeloma Leuk. 2017 Jan.17(1):31-37.e13. Pubmedid: 27780690.
• Yun S, Vincelette ND, Segar JM, Dong Y, Shen Y, Kim DW, Abraham I. Comparative Effectiveness of Newer Tyrosine Kinase Inhibitors Versus Imatinib in the First-Line Treatment of Chronic-Phase Chronic Myeloid Leukemia Across Risk Groups: A Systematic Review and Meta-Analysis of Eight Randomized Trials. Clin Lymphoma Myeloma Leuk. 2016 Jun.16(6):e85-e94. Pubmedid: 27101984.
• Yun S, Vincelette ND, Abraham I. Multiple Causes of Cardiotoxic Effects in Patients With Chronic Myeloid Leukemia. JAMA Oncol. 2016 Jun.2(6):828-829. Pubmedid: 27281623.
• Yun S, Vincelette ND, Abraham I, Robertson KD, Fernandez-Zapico ME, Patnaik MM. Targeting epigenetic pathways in acute myeloid leukemia and myelodysplastic syndrome: a systematic review of hypomethylating agents trials. Clin Epigenetics. 2016 Jun.8:68. Pubmedid: 27307795. Pmcid: PMC4908810.
• Yun S, Vincelette ND, Knorr KL, Almada LL, Schneider PA, Peterson KL, Flatten KS, Dai H, Pratz KW, Hess AD, Smith BD, Karp JE, Hendrickson AE, Fernandez-Zapico ME, Kaufmann SH. 4EBP1/c-MYC/PUMA and NF-κB/EGR1/BIM pathways underlie cytotoxicity of mTOR dual inhibitors in malignant lymphoid cells. Blood. 2016 Jun.127(22):2711-2722. Pubmedid: 26917778. Pmcid: PMC4891953.
• Yun S, Vincelette ND, Green MR, Wahner Hendrickson AE, Abraham I. Targeting immune checkpoints in unresectable metastatic cutaneous melanoma: a systematic review and meta-analysis of anti-CTLA-4 and anti-PD-1 agents trials. Cancer Med. 2016 Jul.5(7):1481-1491. Pubmedid: 27167347. Pmcid: PMC4867662.
• Alcharakh M, Yun S, Dong Y, Vincelette ND, Daud M, Manzoor S, Riaz IB, Anwer F. Blinatumomab-induced donor T-cell activation for post-stem cell transplant-relapsed acute CD19-positive biphenotypic leukemia. Immunotherapy. 2016 Jul.8(8):847-852. Pubmedid: 27381683.
• Yun S, Vincelette ND. Skin Lesions and Recurrent Fever in Acute Myeloid Leukemia Patient Treated With Allogeneic Stem Cell Transplant. JAMA Oncol. 2016 Dec.2(12):1649-1650. Pubmedid: 27583691.
• Yun S, Vincelette ND, Abraham I, Puvvada S, Anwer F. Outcome Comparison of Allogeneic versus Autologous Stem Cell Transplantation in Transformed Low-Grade Lymphoid Malignancies: A Systematic Review and Pooled Analysis of Comparative Studies. Acta Haematol. 2016 Dec.136(4):244-255. Pubmedid: 27802434.
• Yun S, Vincelette ND, Abraham I. Cardioprotective role of β-blockers and angiotensin antagonists in early-onset anthracyclines-induced cardiotoxicity in adult patients: a systematic review and meta-analysis. Postgrad Med J. 2015 Nov.91(1081):627-633. Pubmedid: 26399268.
• Yun S, Vincelette ND. Update on iron metabolism and molecular perspective of common genetic and acquired disorder, hemochromatosis. Crit Rev Oncol Hematol. 2015 Jul.95(1):12-25. Pubmedid: 25737209.
• Yun S, Vincelette ND, Mansour I, Hariri D, Motamed S. Late onset ipilimumab-induced pericarditis and pericardial effusion: a rare but life threatening complication. Case Rep Oncol Med. 2015 Apr.2015:794842. Pubmedid: 25918658. Pmcid: PMC4396732.
• Yun S, Ko J, Vincelette ND, Anwer F. Lymphomatous orbital infiltration and vision loss in diffuse large B-cell lymphoma. BMJ Case Rep. 2014 May.2014. Pubmedid: 24872494. Pmcid: PMC4039974.
• Yun S, Walker CN, Vincelette ND, Anwer F. Acute renal failure and type B lactic acidosis as first manifestation of extranodal T-cell lymphoblastic lymphoma. BMJ Case Rep. 2014 Jun.2014. Pubmedid: 24913086. Pmcid: PMC4054106.
• Yun S, Vincelette ND, Phan T, Anwer F. Spontaneous tumour lysis syndrome associated with contrast dye iohexol use in mantle cell lymphoma. BMJ Case Rep. 2014 Jul.2014. Pubmedid: 25028407. Pmcid: PMC4112310.
• Yun S, Anwer F, Vincelette ND. Dasatinib-induced pulmonary hypertension in chronic myelogenous leukaemia. BMJ Case Rep. 2014 Apr.2014. Pubmedid: 24810451. Pmcid: PMC3992554.

• Title: MYC-Alarmin Axis as a Novel Therapeutic Vulnerability in Myelofibrosis
  Award Number: N/A
  Sponsor: American Society of Hematology (ASH)
  Vincelette, N. (PD/PI)
• Title: The oncogenic roles of alarmins and monocytes in triple negative myelofibrosis
  Award Number: 1K22CA292451-01
  Sponsor: National Cancer Institute (NCI)
  Vincelette, N. (PD/PI)