Clinical and Experimental Hematology and Immunopathology

Group leader

Principal Investigator

Team members

Ana Helena Santos, MSc

Laboratory Technician

    Ana Mota, PhD

    Integrated PhD researcher

      Beatriz Porto, PhD

      Integrated PhD researcher

        Catarina Lau, MD

        Clinical Researcher

          Cláudia Torres, MSc

          PhD Student

            Esmeralda Cleto, MD

            Clinical Researcher

              Esmeralda Neves, MD

              Laboratory Researcher

                Fernanda Leite, MD, PhD

                Integrated PhD researcher

                  Inês Freitas, MD

                  Laboratory Researcher

                    Iolanda Fernandes, MD

                    Clinical Researcher

                      Ivete Lima, MSc

                      Clinical Researcher

                        João Rodrigues, MSc

                        Laboratory Technician

                          Judite Guimarães, MSc

                          Laboratory Researcher

                            Júlia Vasconcelos, MD

                            Clinical Researcher

                              Laura Marques, MD

                              Clinical Researcher

                                Mª de Lurdes Baptista de Oliveira, BSc

                                Laboratory Technician

                                  Mª Luís Queirós, MSc

                                  Pharmacist Assessor

                                    Magdalena Leander, PhD

                                    Integrated PhD researcher

                                      Marco Sampaio, MD

                                      PhD Student

                                        Marika B. Antunes, MD

                                        Clinical Researcher

                                          Marlene Santos, MSc

                                          Laboratory Technician

                                            Marta Gonçalves, BSc

                                            Laboratory Technician

                                              Mónica Pereira, MSc

                                              Laboratory Researcher

                                                Paula Carneiro, MSc

                                                Laboratory Researcher

                                                  Renata Cabral, MD

                                                  Clinical Researcher

                                                    Rita Coutinho, MD, PhD

                                                    Integrated PhD researcher

                                                      Sara Morais, MD

                                                      Clinical Researcher

                                                        Sónia Fonseca, BSc

                                                        Laboratory Technician


                                                          Introduction

                                                          CLINICAL AND EXPERIMENTAL HEMATOLOGY AND IMMUNOPATHOLOGY (CEHIP)* research group is a multidisciplinary research group dedicated to clinical investigation and educational programs in hematopathology and immunopathology. It integrates health professionals from clinical and laboratory areas, offering a unique opportunity for a successful translation. The principal aim is to combine clinical studies with experimental research, to develop diagnostic and treatment strategies for patients with hematological and immunological disorders. The research programs are devoted to the study of the blood cells and hematopoietic and lymphopoietic organs, as well as the immune system, from a normal and a pathological perspective.

                                                          * Formerly “BLOOD, LYMPHOPOIETIC AND HEMATOPOIETIC DISORDERS (BLHD)” (2006-2013)

                                                          RESEARCH AREAS
                                                          The research programs rely mainly in the domains of the hematopathology and immunopathology, covering different areas.

                                                          Hematopathology:
                                                          • Hematological malignancies, focusing on lymphoproliferative diseases, mainly those arising from T cells and NK cells, as well as on mastocytosis.
                                                          • Hemostasis, concentrating on hereditary hemorrhagic diseases due to coagulation factors defects (e.g. hemophilia) and congenital platelet disorders (e.g. defects of platelet glycoproteins, storage pool diseases), as well as on the role of endothelial cells in thrombosis.
                                                          • Bone marrow failure syndromes, converging on Fanconi Anemia and Paroxysmal Nocturnal Hemoglobinuria.
                                                          • Red blood cell disorders, mainly congenital anemia due to membrane red blood cell defects, such as Hereditary Spherocytosis.
                                                          Immunopathology:
                                                          • Immunodeficiencies, both primary and secondary.
                                                          • Autoimmune diseases.
                                                          • Allergy.
                                                          • Infectious diseases.
                                                          FACILITIES
                                                          Clinical areas (in-patients; out-patients)
                                                          • Hematology consultation (leukemia & lymphoma; bone marrow failure syndromes; red blood cell disorders).
                                                          • Multidisciplinary consultation for cutaneous lymphomas and mastocytosis.
                                                          • Hemostasis consultation (hemophilia, von Willebrand disease & other congenital hemorrhagic disorders; thrombophilia; platelet disorders).
                                                          • Immunodeficiency, autoimmune diseases, infectious diseases and allergy.
                                                          Laboratory areas

                                                          Laboratory areas include, among others: cytology and cytochemistry; flow cytometry and cell immunophenotyping; genetics, hemostasis and immunology. These laboratories have all the equipment needed for contemporary cellular, biochemical and genetic research in the fields of hematology and immunopathology. Facilities comprise automatic cell counters, optical, fluorescence and inverted lens microscopes, benchtop flow cytometers, magnetic cell sorters, laminar flow cabinets, 37°C CO2 humidified incubators, equipment for DNA extraction, PCR and Real time PCR assays and DNA sequencing, radioimmunoassay (RIA) and enzymatic immunoassay (ELISA) and equipment for platelet function and platelet aggregation assays. In addition, there is all the general laboratory equipment such as benchtop centrifuges and microcentrifuges, refrigerators, -70°C and -20°C freezers, water baths, spectrophotometers, ice makers, pH readers, automatic pipettes and dispensers, heater and stirring heater plates and analytical balances.


                                                          Aims

                                                          The specific research goals are:

                                                          • To investigate the molecular pathways involved in the genesis of the lymphoid malignancies originating from T cells and NK cells, to characterize their clinical and biological spectrum, and understand the associated conditions (e.g. cytopenias and autoimmune diseases in patients with large granular lymphocyte leukemia, pruritus in patients with cutaneous T cell lymphomas). To improve the laboratorial procedures for the diagnosis, monitoring and therapeutic management of these conditions.
                                                          • To comprehend the diversity of clinical manifestations observed in patients with mastocytosis (e.g. neuropsychiatric disorders, bone disease, etc.), and to investigate the role of the mast cell mediators.
                                                          • To improve the laboratorial tests for the diagnosis of systemic mastocytosis, monitoring and therapeutic management of patients.
                                                          • To characterize the hematological and genetic abnormalities observed in patients with bone marrow failure syndromes, namely Paroxysmal Nocturnal Hemoglobinuria and Fanconi Anemia; and to understand their predisposition to develop myeloid malignancies (e.g. myelodysplastic syndromes, acute myeloblastic leukemia).
                                                          • To develop, improve and implement in the routine clinical practice, biochemical, molecular genetics and flow-cytometry based tests for the diagnosis of the hereditary blood coagulation factor defects and platelet disorders; and to clarify the molecular mechanisms involved.
                                                          • To study the clinical spectrum and molecular mechanisms involved in immunodeficiencies and autoimmune diseases.

                                                          Highlighted publications

                                                          1. Bárcena P, Jara-Acevedo M, Tabernero MD, López A, Sánchez ML, García-Montero AC, Muñoz-García N, Vidriales MB, Paiva A, Lecrevisse Q, Lima M, Langerak AW, Böttcher S, van Dongen JJ, Orfao A, Almeida J. PHENOTYPIC PROFILE OF EXPANDED NK CELLS IN CHRONIC LYMPHOPROLIFERATIVE DISORDERS: A SURROGATE MARKER FOR NK-CELL CLONALITY. Oncotarget. 2015;6(40):42938-51. [PMID: 26556869] http://dx.doi.org/10.18632/oncotarget.5480
                                                          2. Pagano G, Talamanca AA, Castello G, d’Ischia M, Pallardó FV, Petrović S, Porto B, Tiano L, Zatterale A. FROM CLINICAL DESCRIPTION, TO IN VITRO AND ANIMAL STUDIES, AND BACKWARD TO PATIENTS: OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION IN FANCONI ANEMIA. Free Radic Biol Med. 2013;58:118-25. [PMID: 23376230] https://doi.org/10.1016/j.freeradbiomed.2013.01.015
                                                          3. Kreuz W, Escuriola Ettingshausen C, Vdovin V, Zozulya N, Plyushch O, Svirin P, Andreeva T, Bubanská E, Campos M, Benedik-Dolničar M, Jiménez-Yuste V, Kitanovski L, Klukowska A, Momot A, Osmulskaya N, Prieto M, Šalek SZ, Velasco F, Pavlova A, Oldenburg J, Knaub S, Jansen M, Belyanskaya L, Walter O; ObsITI study group; ObsITI committee. FIRST PROSPECTIVE REPORT ON IMMUNE TOLERANCE IN POOR RISK HAEMOPHILIA A INHIBITOR PATIENTS WITH A SINGLE FACTOR VIII/VON WILLEBRAND FACTOR CONCENTRATE IN AN OBSERVATIONAL IMMUNE TOLERANCE INDUCTION STUDY. Haemophilia. 2016;22(1):87-95. [PMID: 26202305] http://dx.doi.org/10.1111/hae.12774
                                                          4. Jamin C, Le Lann L, Alvarez-Errico D, Barbarroja N, Cantaert T, Ducreux J, Dufour AM, Gerl V, Kniesch K, Neves E, Trombetta E, Alarcón-Riquelme M, Marañon C, Pers JO. MULTI-CENTER HARMONIZATION OF FLOW CYTOMETERS IN THE CONTEXT OF THE EUROPEAN “PRECISESADS” PROJECT. Autoimmun Rev. 2016;15(11):1038-1045. [PMID: 27490203] https://doi.org/10.1016/j.autrev.2016.07.034
                                                          5. Chakraborty PK, Schmitz-Abe K, Kennedy EK, Mamady H, Naas T, Durie D, Campagna DR, Lau A, Sendamarai AK, Wiseman DH, May A, Jolles S, Connor P, Powell C, Heeney MM, Giardina PJ, Klaassen RJ, Kannengiesser C, Thuret I, Thompson AA, Marques L, Hughes S, Bonney DK, Bottomley SS, Wynn RF, Laxer RM, Minniti CP, Moppett J, Bordon V, Geraghty M, Joyce PB, Markianos K, Rudner AD, Holcik M, Fleming MD. MUTATIONS IN TRNT1 CAUSE CONGENITAL SIDEROBLASTIC ANEMIA WITH IMMUNODEFICIENCY, FEVERS, AND DEVELOPMENTAL DELAY (SIFD). Blood. 2014;124(18):2867-71. [PMID: 25193871] https://doi.org/10.1182/blood-2014-08-591370
                                                          6. Aguiar SI, Brito MJ, Horacio AN, Lopes JP, Ramirez M, Melo-Cristino J; Portuguese Group for the Study of Streptococcal Infections. Portuguese Study Group of Invasive Pneumococcal Disease of the Paediatric Infectious Disease Society (Marques L). DECREASING INCIDENCE AND CHANGES IN SEROTYPE DISTRIBUTION OF INVASIVE PNEUMOCOCCAL DISEASE IN PERSONS AGED UNDER 18 YEARS SINCE INTRODUCTION OF 10-VALENT AND 13-VALENT CONJUGATE VACCINES IN PORTUGAL, JULY 2008 TO JUNE 2012. Euro Surveill. 2014;19(12):20750. [PMID: 24698140] https://doi.org/10.2807/1560-7917.ES2014.19.12.20750

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