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Hematopathology


About Us

Italian Version

Our research program entails mostly two major arms. The first focus is on deciphering the properties of leukemic and hematopoietic progenitors responsible for the generation and propagation of human T-cell acute lymphoblastic leukemia (T-ALL). We are investigating the functional role of molecular and epigenetic pathways, frequently dysregulated in T-ALL at the initial stages of T-cell transformation and clonal establishment, as well as in the context of the maintenance and development of leukemia stem cells. To address these questions and offer the rationale for targeting disease-specific phenotype, we employ a combinatorial experimental approach including synthetic human models of T-cell leukemia, patient-derived xenograft (PDX) models, multiparameter flow cytometry, ChIP-seq, single-cell RNA sequencing (scRNA-Seq), AbSeq and gain/loss-of-function assays through lentiviral gene transduction and CRISPR/Cas9 gene editing.

 

As a more recent topic, we intend to identify new cellular targets of cell subsets, enriched with leukemia stem cells in patients with T-cell leukemias, in order to generate T/NK cells, expressing chimeric antigen receptor (CAR) against antigens selectively present in tumor populations resistant to conventional therapeutic treatments. This experimental activity is mainly focused on 1) the characterization of the cell heterogeneity of phenotypically defined subclones in response to conventional therapies by flow cytometry and scRNA-Seq; 2) the identification of the molecular players and immunological landscapes, responsible for aggressive clinical behaviors; and 3) the development of CAR-expressing cells targeting T-ALL populations resistant to standard treatments. This work is also of direct clinical relevance in providing detailed phenotypic characterizations required to define biomarkers for T-ALL prognosis and monitor patient-specific responses to therapy.

Studied Pathologies: T-cell acute lymphoblastic leukemia (T-ALL), T-cell leukemia, acute myeloid leukemia.

Head of the lab

Name: Dr. Vincenzo Giambra, PhD

University and Training:

Ph.D. in Molecular and Cell Biology, “Tor Vergata” University, Rome, Italy, 2003-2007
M.Sc. in Biotechnologies, “Tor Vergata” University, Rome, Italy, 2001-2003
B.Sc. in Biology, University of Palermo, Italy, 1995-2000

Work Experience:

Postdoctoral Fellow, 2007-2016
Dr. A. Weng lab, TFL, Vancouver, Canada.
Research Focus: Identification and characterization of leukemia stem cells in T-cell acute lymphoblastic leukemia (T-ALL).

Visiting Scientist, 2005-2007

Dr. B. Birshtein lab, Albert Einstein College of Medicine, New York, USA.
Research Focus: Role of DNA methylation in the 3’ Regulatory Region of IgH locus during the B cell development.

Ph.D. Research Student, 2003-2005

Dr. D. Frezza lab, Department of Biology, Tor Vergata University, Rome, Italy.
Thesis: Polymorphisms and DNA methylation: two ways to execute functional differences in the 3’ Regulatory Region of IgH locus.

Master’s Research Student, 2001-2003

Dr. D. Frezza lab, Department of Biology, Tor Vergata University, Rome, Italy.
Thesis: Techniques of structural analysis of HS1.2 enhancers of human immunoglobulins.

Scientific Area of Interest: Hematology, Hematopathology, Leukemia, Immunology, Notch Signaling, Flow Cytometry, Single Cell RNA-Sequencing

Collaborations: BC Cancer Agency, University of British Columbia, University of Rome “Tor Vergata”, Agostino Gemelli IRCCS University Hospital Foundation

Publications

Total list of Publications from 2011: n. 31

  1. Sansico F, Miroballo M, Bianco DS, Tamiro F, Colucci M, Santis E, Rossi G, Rosati J, Di Mauro L, Miscio G, Mazza T, Vescovi AL, Mazzoccoli G, Giambra V*, On Behalf Of Css-Covid Group.
    COVID-19 Specific Immune Markers Revealed by Single Cell Phenotypic Profiling.
    Biomedicines. 2021 Nov 29;9(12):1794. PMID: 34944610
  2. Colucci M, De Santis E, Totti B, Miroballo M, Tamiro F, Rossi G, Piepoli A, De Vincentis G, Greco A, Mangia A, Cianci R, Di Mauro L, Miscio G, Giambra V* Associations between Allelic Variants of the Human IgH 3' Regulatory Region 1 and the Immune
    Response to BNT162b2 mRNA Vaccine.
    Vaccines (Basel). 2021 Oct 19;9(10):1207. PMID: 34696315
  3. K Bhanumathy K, Balagopal A, Vizeacoumar FS, Vizeacoumar FJ, Freywald A, Giambra V*
    Protein Tyrosine Kinases: Their Roles and Their Targeting in Leukemia
    Cancers (Basel). 7;13(2):184. (2021) - PMID: 33430292 Review
  4. Tamiro F, Weng AP, Giambra V*
    Targeting Leukemia-Initiating Cells in Acute Lymphoblastic Leukemia
    Cancer Res. 2021 Jan 7. (2021) - PMID: 33414170 Review
  5. Giambra V*, Gusscott S, Gracias D, Song R, Lam SH, Panelli P, Tyshchenko K,Jenkins CR, Hood C, Lorzadeh A, Carles A, Hirst M, Eaves CJ, Weng AP*
    Epigenetic restoration of fetal-like IGF1 signaling inhibits leukemia stem cell activity
    Cell Stem Cell, 2018 Nov 1. PMID: 30269902
  6. Belmonte M, Hoofd C, Weng AP and Giambra V*,
    Targeting leukemia stem cells: which pathways drive self-renewal activity in T-cell acute lymphoblastic leukemia?,
    Current Oncology, Vol 23, No 1 (2016) (Review)
  7. Hoofd C, Wang X, Lam SH, Jenkins C, Wood B, Giambra V* and Weng AP**,
    CD44 promotes chemoresistance in T-ALL by increased drug efflux,
    Experimental Hematology, 2015 Dec 1. PMID:26708679
  8. Giambra V*, Jenkins C, Lam SH, Hoofd C, Belmonte M, Wang X, Gusscott S, Gracias D, and Weng AP*,
    Leukemia stem cells in T-ALL require active Hif1α and Wnt signaling,
    Blood, 2015 May 1. PMID: 25934477
  9. Montesano C**, Giambra V**, Frezza D, Palma P, Castelli-Gattinara G, Mattei M, Mancino G, Colizzi V, and Amicosante M,
    HS1,2 Ig enhancer alleles association to AIDS progression in a paediatric cohort infected with a monophyletic HIV-strain,
    BMRI Infectious Diseases, 2014;2014:637523 (2014) - PMID 25009819; PMCID: PMC4055013.
  10. Giambra V, Jenkins CR, Wang H, Lam SH, Shevchuk OO, Nemirovsky O, Wai C, Gusscott S, Chiang MY, Aster JC, Humphries KR, Eaves C, and Weng AP,
    Notch1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-Θ and reactive oxygen species,
    Nature Medicine, 18, 1693-1698 (2012) - PMID:23086478; PMCID: PMC3738873.
  11. Mangia A, Piazzolla V, Cocomazzi G, Ciciriello V, Giambra V, Antinucci S, Maiorana A, Giuliani F, Montomoli E, Cantaloni P, Manenti A, Serra N
    Cellular and humoral immune responses and breakthrough infections after two doses of BNT162b vaccine in healthcare workers (HW) 180 days after the second vaccine shot
    Frontiers in Public Health - in press
  12. Cocomazzi G, Piazzolla V, Squillante M,Antinucci S, Giambra V, Giuliani F, Maiorana A, Serra N, Mangia A
    Early Serological Response to BNT162b2 mRNA Vaccine in Healthcare Workers.
    Vaccines (Basel). 2021 Aug 16;9(8):913. PMID: 34452038
  13. Carbone A, De Santis E, Cela O, Giambra V, Miele L, Marrone G, Grieco A, Buschbeck M, Capitanio N, Mazza T, Mazzoccoli G
    The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro
    Model of Hepatocellular Carcinoma.
    Biomedicines. 2021 Aug 20;9(8):1057. PMID: 34440260
  14. Rossi G, Giambra V, de Waure C, Giacchetta I, Minervini MM, Abbenante MC, Spadano R, La Torre A, Scalzulli PR, Cascavilla N
    Log reduction of leukemic cells and minimal residual disease by flow cytometry represent effective predictors of clinical outcome in elderly patients with acute myeloid leukemia.
    Cytometry B Clin Cytom. 2022 Jan;102(1):26-33. PMID: 33983682
  15. Grandone E, Tiscia G, Pesavento R, De Laurenzo A, Ceccato D, Sartori MT, Mirabella L, Cinnella G, Mastroianno M, Dalfino L, Colaizzo D, Vettor R, Intrieri M, Ostuni A, Margaglione M; CSS- COVID Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation.
    J Thromb Thrombolysis. 2021 Oct;52(3):772-778. PMID: 33844150
  16. Micale L, Morlino S, Biagini T, Carbone A, Fusco C, Ritelli M, Giambra V, Zoppi N, Nardella G, Notarangelo A, Schirizzi A, Mazzoccoli G, Grammatico P, Wade EM, Mazza T, Colombi M, Castori M
    Insights into the molecular pathogenesis of cardiospondylocarpofacial syndrome: MAP3K7 c.737-7A > G variant alters the TGFβ-mediated α-SMA cytoskeleton assembly and autophagy
    Biochim Biophys Acta Mol Basis Dis. 1;1866(6):165742. (2020) - PMID: 32105826
  17. Frezza D, Martinez-Labarga C, Giambra V, Serone E, Scano G, Rickards O, D'Addabbo P, Novelletto A
    Concerted variation of the 3' regulatory region of Ig heavy chain and Gm haplotypes across human continental populations
    Am J Phys Anthropol. 171(4):671-682. (2020) – PMID: 31957883
  18. Venuto S, Monteonofrio L, Cozzolino F, Monti M, Appolloni I, Mazza T, Canetti D, Giambra V, Panelli P, Fusco C, Squeo GM, Croce AI, Pucci P, Malatesta P, Soddu S, Merla G, Micale L
    TRIM8 interacts with KIF11 and KIFC1 and controls bipolar spindle formation and chromosomal stability
    Cancer Lett. 31;473:98-106. (2020) – PMID: 31904480
  19. Grasselli C, Carbone A, Panelli P, Giambra V, Bossi M, Mazzoccoli G, De Filippis L
    Neural Stem Cells from Shank3-ko Mouse Model Autism Spectrum Disorders
    Mol Neurobiol. 57(3):1502-1515. (2020) – PMID: 31773410
  20. Rossi G, Giambra V, Minervini MM, De Waure C, Mancinelli S, Ciavarella M, Sinisi NP, Scalzulli PR, Carella AM, Cascavilla N
    Leukemia-associated immunophenotypes subdivided in "categories of specificity" improve the sensitivity of minimal residual disease in predicting relapse in acute myeloid leukemia
    Cytometry B Clin Cytom. 98(3):216-225. (2020) – PMID: 31697027
  21. Gusscott S, Tamiro F, Giambra V, Weng AP
    Insulin-like growth factor (IGF) signaling in T-cell acute lymphoblastic leukemia
    Adv Biol Regul. 74:100652. (2019) - PMID: 31543360 Review
  22. Morlino S, Carbone A, Ritelli M, Fusco C, Giambra V, Nardella G, Notarangelo A, Panelli P, Mazzoccoli G, Zoppi N, Grammatico P, Wade EM, Colombi M, Castori M, Micale L
    TAB2 c.1398dup variant leads to haploinsufficiency and impairs extracellular matrix homeostasis
    Hum Mutat. 40(10):1886-1898. (2019) - PMID: 31250519
  23. Rossi G, Falcone AP, Minervini MM, De Cillis GP, De Waure C, Sisti LG, Giambra V, Valente D, Chiello V, Scalzulli PR, Carella AM and Cascavilla N
    Minimal residual disease and log-reduction of plasma cells are associated with superior response after double autologous stem cell transplant in younger patients with multiple myeloma
    Cytometry B Clin Cytom. 2019 May;96(3) – PMID: 30549231
  24. Jenkins CE, Gusscott S, Wong RJ, Shevchuk OO, Rana G, Giambra V, Tyshchenko K, Islam R, Hirst M, Weng AP
    RUNX1 promotes cell growth in human T-cell acute lymphoblastic leukemia by transcriptional regulation of key target genes
    Exp Hematol. Aug;64:84-96, (2018) - PMID: 29733873
  25. Gusscott S, Jenkins CE, Lam SH, Giambra V, Pollak M, and Weng AP,
    Molecular determinants of IGF dependence in human T-cell acute lymphoblastic leukemia,
    Plos ONE, 2016 Aug 17;11(8):e0161158 - PMID: 27532210
  26. Sette M, D'Addabbo P, Kelly G, Cicconi A, Micheli E, Cacchione S, Poma A, Gargioli C, Giambra V, Frezza D.
    Evidence for a quadruplex structure in the polymorphic hs1.2 enhancer of the immunoglobulin heavy chain 3' regulatory regions and its conservation in mammals.
    Biopolymers, 2016 Nov;105(11):768-78. PMID: 27287611
  27. Serone E, Daleno C, Principi N, Poretti L, Iacoacci V, Gargioli C, Magrini A, Massoud R, D’Addabbo P, Cattalini M, Giambra V, Plebani A, Esposito S, and Frezza D,
    The change in Ig regulation from child to adults disconnects the correlation with the 3'RR hs1.2 polymorphism,
    BMC Immunol, 2014 Nov 13;15:45 (2014) – PMID:25391515.
  28. Napolioni V, Serone E, Iacoacci V, Carpi MC, Giambra V, and Frezza D,
    The functional VNTR of IGH enhancer HS1.2 associates with human longevity and interacts with TNFA promoter diplotype in a population of Central Italy,
    Gene, Aug 28 (2014) - PMID: 25175451.
  29. Jenkins CR, Shevchuk OO, Giambra V, Lam SH, Carboni JM, Gottardis MM, Holzenberger M, Pollak M, Humphries RK, and Weng AP,
    IGF signaling contributes to malignant transformation of hematopoietic progenitors by the MLL-AF9 oncoprotein,
    Exp Hematol, 40, 715-723 (2012) - PMID: 22613471.
  30. Frezza D, Serone E, Lolli S, Cianci R, D’Addabbo P, Mattioli C, Giambra V, Pavlovic N, Djordjevic V, Pandolfi F, and Kostic E,
    Balkan Endemic Nephropathy risk is associated to the HS1.2 Ig enhancer polymorphism,
    Eur. J. Inflamat, 10, 393-403 (2012).
  31. Frezza D, Tolusso B, Giambra V, Gremese E, Nowik M, Mattioli M, Serone E, Canestri S, Petricca L, D’Antona G, Birshtein B K, and Ferraccioli G,
    Polymorphisms of IgH enhancer HS1.2 and risk of Systemic Lupus Erythematosus,
    Ann Rheum Dis, 71, 1309-15 (2012) - PMID: 22294636.

*corresponding author

**contributed equally to this work

Ongoing Research Projects

tart Year: 2020
Expiry: 2025
Funding Entity: Italian Association for Research on Cancer (AIRC)
Project Leader: Dr. Giambra Vincenzo
Principal Investigator: Dr. Giambra Vincenzo

Start Year: 2020
Expiry: 2023
Funding Entity: Worldwide Cancer Research
Project Leader: Dr. Giambra Vincenzo
Principal Investigator: Dr. Giambra Vincenzo

Start Year: 2018
Expiry: 2022
Funding Entity: Italian Ministry of Health
Project Leader: Dr. Giambra Vincenzo
Principal Investigator: Dr. Giambra Vincenzo


Equipe

Dr. Mattia Miroballo, PhD Postdoctoral Fellow
Elisabetta De Santis, Lab Manager/ Research Associate
Mattia Colucci, Msc Graduate Student
Miriana Marino, Msc Graduate Student
Beatrice Totti Research Assistant
Sabrina Pennelli Research Student
Gaja Bruno Research Student
Emanuele Murgo Research Student

Head of lab
Dr. Vincenzo Giambra
Contacts

Tel: +39 0882 416574
Fax: +39 0882 411705
 

 

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