people in the lab, Karl Landsteiner Institute for Cytokine and Tumormicroenvironment

Josef D. Schwarzmeier

Medhat Shehata

Martin Hilgarth

Rainer Hubmann

Susanne Schnabl

Medical School: University Vienna and Paris. Internship and Residency at the First Department of Medicine, University of Vienna.

Research Fellow: Dept.Hematology, Univ.Tübingen (erythrocyte metabolism); Dept.Physiology, Univ.Freiburg and Aachen (purine metabolism); Dept.Int. Medicine, Univ.Cologne (cell cycle synchronisation); Dept. Pharmacology, Univ.Virginia (cAMP, cell fusion, signal transduction, G-proteins, Prof. A.Gilman-Nobel Price 1994).

Clinical training: Memorial Sloan Kettering Institute, New York; Baltimore Cancer Res.Ctr., Baltimore; Dept.Haematology, Royal Free Hospital, London; Dept.Hematology/Oncology, Univ.Hospital, Chicago.

Present research activities: Studies on the biology of chronic leukemias in association with cytokines and chemokines. Elucidation of the mechanism of action of Interferon-alpha in Hairy Cell Leukemia (involvement of hematopoietic growth factors, basic fibroblast growth factor, transforming growth factor-ß, etc.). Defining molecular genetic abnormalities in B-cell chronic lymphocytic leukemia (upregulation of CD23, overexpression of Notch-2, disturbance of signal transduction pathways, in vitro culture models and drug testing, effect of proteasome inhibitors, etc.). - Investigation of the effect of Bisphosphonates on malignant cell lines. - Studies on the effect of Radon on the production of inflammatory cytokines and TGF-ß in patients with chronic rheumatoid diseases and Bechterew's disease.

Professional activities: Senior physician, including patient care at the Department of Hematology as well as teaching and examining medical students at the Clinic of Internal Medicine. - Head of the L.Boltzmann Institute of Cytokine Research. - Reviewer of scientific journals, preparation of expert testimonials for various academic commissions, organizing international scientific conferences on cytokines, etc.

Active memberships: Societies of Hematology (American, Austrian, Germany, Int.) Soc. Intern. Med.(Austria), Society of Physicians Vienna (board member), Medical Council of the Austrian Ministry of Health (board member), Fellinger-Cancer Res.Foundation (president), New York Academy of Sciences, European School of Oncology (board member), EORTC-NDDG (board member), Int.Cytokine Soc. and Int.Soc.Interferon and Cytokine Res. (ICS/ISICR, member scientific commitee).

Dr. Medhat Shehata

Dr. Shehata studied medicine in Alexandria and Vienna. He had his postdoctoral fellowship in Universities of London, Liverpool and Edinburgh and Vienna in internal medicine and tropical medicine together with participation in several research activities. In 1993, he joined L. Boltzmann Institute f. Cytokine Research in the Department of Internal Medicine I in Vienna University to explore the mechanism of action of alpha-interferon and the molecular mechanisms of bone marrow fibrosis in hairy cell leukaemia. Having a wide range of clinical experience together with extensive engagement in basic research and cell biology allowed him to merge basic research into clinical application. He received several research awards from national and international institution, such as the Austrian Society of Haematology and Oncology (ÖGHO), Aventis prise, “Erste Bank Preis/Ärztekammer f. Wien” and MSG prise/MSD USA and he is an active member of several international scientific organizations such as “EHA”, “ÖGHO“, “IBMS, “AuSBMR” and “ ECTS”.

Translating basic research into clinical application particularly in human neoplasia and cancer-related disorders. This includes dissecting the molecular mechanisms of disease initiation and progression, exploration of the mechanism of action of drugs, synthetic and naturally occurring compounds, cytokines and biological modifiers, aiming at identification of new and safe application of these compounds in therapy of human diseases. Current activities:

* Molecular mechanism of action of cytokine and growth factors in pathogenesis and therapy of human neoplasia. For instance, the therapeutic effect of IFN-a and the pathological role of TGF-ß1 in bone marrow fibrosis in hairy cell leukaemia.

*In vitro models which mimic the in vivo situation in lymphoid tissue to study signal transduction events involved in the inhibition of apoptosis of B-CLL cells and the role of CD23 and PI3-K/Akt pathway in prolonging survival of the leukaemia cells.

* Anti-tumour effect of bisphosphonate compounds and molecular mechanisms of apoptosis in neoplastic cells, including breast, prostate, lung carcinoma, osteosarcoma, malignant melanoma and multiple myeloma. In cooperation with MSD laboratories (USA) and Novartis Pharma (Basel).

-Shehata M, Schwarzmeier J.D., Hilgarth M., Hubmann R., Duechler M., Gisslinger H. Transforming Growth factor beta1 induces bone marrow fibrosis in hairy cell leukaemia. J. Clin. Invest. 113:676-685 (2004).

- Medhat Shehata, Joesef D. Schwarzmeier, Son Tho Nguyen, Martin Hilgarth, Rudolf Berger, Rainer Hubmann, Sonja Kichmaier, and Thomas Decker. Reconstitution of Endogenous Interferon a by Recombinant Interferon in hairy Cell Leukemia. Cancer Research, 60, October 1, 2000.

- Josef Schwarzmeier, Martin Hilgarth, Medhat Shehata, Son T. Nguyen, Gerhard Gruber et al. Inadequate Production of Hematopoietic Growth factors in Hairy Cell Leukemia: Up-regulation by Interleukin 6 by recombinant IFN-a in vitro. Cancer Research. 56: 4679-4685, 1996.

- Gerhard Gruber, Josef D. Schwarzmeier, Medhat Shehata, Martin Hilgarth, Rudolf Berger. Basic Fibroblast Growth Factor in Expressed by CD19/CD11c-Positive Cell in Hairy Cell Leukemia. Blood. 94,3: 1077-1085, 1999.

- Schwarzmeier JD, Shehata M, Hilgarth M, Marschitz I, Louda N, Hubmann R, Greil R. "The role of soluble CD23 in distinguishing stable and progressive forms of B-chronic

- Derhaschnig U, Shehata M, Herkner H, Bur A, Woisetschläger C, Laggner AN and Hirschl MM. "Increased Levels of Transforming Growth Factor-ß1 in Essential Hypertension." American Journal of Hypertension 2002 Mar;15(3):207-11.

- Filipic B, Shehata M, Toth S, Schwarzmeier JD, Koren S. "Novel serum replacement based on bovine ocular fluid: a useful tool for cultivation of different animal cells in vitro."
ALTEX. 2002;19(1):15-20.

- Hubmann R, Schwarzmeier, Shehata M, Hilgarth M, Duechler M, Dettke M, and Berger R. "Notch2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic leukemia." Blood 2002 May 15;99(10):3742-7.

- Schwarzmeier JD, Shehata M, Ackermann J., Hilgarth M., Kaufmann H., Drach J. simaltaneous occurance of chronic myeloid leukemia and multiple myeloma: Evaluation by FISH analysis and in vitro expansion of bone marrow cells. Leukemia, 2003, 17, 1426-1428.

- Shehata M, Schwarzmeier JD, Hilgarth M, Strommer S, Hoelbl A, Wressnigg N, Hubmann R, Duechler M. "Human Stromal Fibroblasts Inhibit Apoptosis of B-CLL Cells through a Mechanism Involving Phosphatidylinositol 3-Kinase Pathway." Blood 100:1479, 2002.

- Shehata M, Schwarzmeier JD, Hilgarth M, Hubmann R. "Zoledronic Acid Inhibits Focal Adhesion Assembly and Induces Apoptosis in Several Tumour Cell Types." Bone 30;3:37S-57S, B29, 2002.

- Shehata M, Schwarzmeier JD, Hilgarth M, Hubmann R. "Bisphosphonates induce apoptosis in tumour cells by inactivation of RhoA GTPase and disruption of actin cytoskeleton. Eur J Cancer 2001:37, Suppl 3, S109

Graduation from Higher Technical Education School "Vienna's Rosensteingasse", 1990

Since June 1991 working in the research laboratory of Dr. Schwarzmeier at the University of Vienna, Faculty of Medicine, Haematology Department, Waehringer Guertel 18-20, 1090 Vienna.

currently: lab management, flowcytometry, ELISA, RNA/DNA isolation, PCR, Northern-, Southern-Blot, cell culture, datamanagement with MS-Office, webdesign, . . .

Innovation/Exploration

Isolation of the first D-type cyclin in higher plants; Identification of Notch2 as being responsible for the overexpression of CD23 in B-CLL cells.

M. Dahl,.I. Meskiene, L. Bogre, D.T. Ha, I. Swoboda, R. Hubmann, H. Hirt, E. Heberle-Bors. The D-type alfalfa cyclin gene cycMs4 complements G1 cyclin-deficient yeast and is induced in the G1 phase of the cell cycle. Plant Cell. 1995 Nov;7(11):1847-57.

R. Hubmann, J.D. Schwarzmeier, M. Shehata, M. Hilgarth, K. Lechner, R. Berger:Deregulation of Notch2 signaling in B-CLL. Blood 94/10:540, 1999 (Abstract).

M. Shehata, J.D. Schwarzmeier JD, S.T. Nguyen, M. Hilgarth, R. Berger, R. Hubmann, S. Kickmaier, T. Decker. Reconstitution of endogenous interferon a by recombinant interferon in hairy cell leukemia. Cancer Res. 2000 Oct 1;60(19):5420-6.

Hubmann R, Schwarzmeier JD, Shehata M, Hilgarth M, Duechler M, Dettke M, Berger R: NOTCH2 IS INVOLVED IN THE OVEREXPRESSION OF CD23 In B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA Blood May 15, 2002; 99 (10) (in press).