Имя: Ховав Нехуштан

Образование:

• 1984 – степень бакалавра биологии – Еврейский университет Иерусалима, с отличием
• 1991 – профессорская степень в биохимии  – медицинская школа “Хадассы”, “Регулирование гена фосфоэнолпируваткарбоксиназы в жировой ткани” под руководством профессора Л. Решеф
• 1996 – доктор медицины – Еврейский университет медицинская школа “Хадассы”
• 1995-1996 – Стажировка в больнице “Хадасса Эйн Керем”, Иерусалим.
• 1996-2002 – Клиническая ординатура по онкологии в больнице “Хадасса”
• 2002-2005 – Исследование иммунологии опухоли в лаборатории профессора J.D.Rosenblatt ( Университет Майами)

Должность:

• Старший врач в онкологическом отделении, Иерусалим, Израиль
• Старший преподаватель Еврейского университета медицинской школы Эйн-Карем, Иерусалим.

Исследования и профессиональный опыт

• 1989- Работа в течение 4 месяцев в лаборатории R.W.Hanson (Кливленд)
• 1990-1991 Неполная исследования с профессором H. Cedar – кафедра  биохимии Еврейского университета “Хадасса”, медицинская школе в Иерусалиме.
• 1997 – EMBO, краткосрочное сотрудничество (3 месяца) В. А. Тараховский лаборатории Кельнского университета.
• 2005- по настоящее время – лечащий врач онкологического отделения медицинского центра “Хадасса”, Иерусалим, Израиль

Преподавательская деятельность:

• 1987-1991 – ассистент преподавателя
• 1999-2006 – преподаватель
• 2006 – Старший преподаватель
• 2012-  доцент университета Еврейского университета медицинской школы “Хадассы”

Клинические исследования

Cetuximab plus Taxane for triple negative breast cancer patients(PI) 2007- 2010.

Autologus vaccines for RCC patients in combination with sunitinib began 2009 Несколько компаний начали клинические исследования

Список публикаций:

1) Nechushtan, H.,  Benvenisty, N., Brandeis, R & Reshef, L.Glucocorticoids control phosphoenolpyruvate carboxykinase gene expression in a tissue specific manner. Nucleic Acids Res  15: 6405-17, 1987.

2) Benvenisty, N., Nechushtan, H.,  Cohen, H & Reshef, L.  N. Separate cis-regulatory elements confer expression of phosphoenolpyruvate carboxykinase (GTP) gene in different cell lines. Proc Natl Acad Sci U S A   86: 1118-22, 1989

3) Eisenberger, C.L., Nechushtan, H., Cohen, H., Shani, M &  Reshef, L. Differential regulation of the rat phosphoenolpyruvate carboxykinase gene expression in several tissues of transgenic mice. Mol Cell Biol 12: 1396-403, 1992.

( 4) Lewin, I., Nechushtan, H., Qingen, Q and Razin, E.  Regulation of AP-1 expression and activity in antigen-stimulated mast cells: The role played by protein kinase C and the possible involvement of Fos interacting protein. Blood, 82: 3745-51, 1993.

5). Nechushtan, H., Soreq, H.,  Kuperstein, V., Tshori, S  and Razin, E. Murine and Human Mast Cell express Acetylcholinesterase. FEBS letters 379: 1-6, 1996

6) Nechushtan, H and Razin, E. Regulation of mast cell growth. Critical Reviews in Oncology/Hematology,23:131-150, 1996

7). Nechushtan, H., Zhang Z C, and Razin, E.  Microphthalmia (mi) in murine mast cells:  Regulation of its stimuli-mediated expression on the translational level., Blood, 89:2999-3008, 1997.)

8). Ligumsky, M , Kuperstein V , Nechushtan, H.,  Zhang , and Razin,E. Analysis Of Cytokine Profile In Human Colonic Mucosal FceRI- Positive Cells By Single Cell PCR: Inhibition Of IL-3 Expression In Steroid-Treated Patients. FEBS letter 413:436-440,1997.

9) Cassuto H, Olswang Y, Livoff AF, Nechushtan H, Hanson RW, Reshef L. Involvement of HNF-1 in the regulation of phosphoenolpyruvate carboxykinase gene expression in the kidney. FEBS Lett  4;412:597-602, 1997.

10). Zhang Z,  Nechushtan, H,  Jacob-Hirsh, J, Avni D, Meyuhas  O and Razin E. Growth-Dependent And PKC-Mediated Translational Regulation Of The  Upstream Stimulating Factor 2 (USF2) mRNA In Hematopoietic Cells. Oncogene 16:763-769, 1998.

11). Frenkel, S., Kay, G., Nechushtan, H and Razin E. Nuclear translocation of up stream stimulating factor 2 (USF2) in activated mast cells: Possible role in their survival.J. Immunology, 161:2881-2887, 1998.

12). Nechushtan H., Razin, E. Deciphering the mystery of the early response transcription factor networks in mast cells.  Immunology Today, 19:441 1998

13.)  Razin E, Zhang ZC, Nechushtan H, Frenkel S, Lee YN, Arudchandran R, Rivera J. Suppression of microphthalmia transcriptional activity by its association with protein kinase C-interacting protein 1 in mast cells. J Biol Chem.;274:34272-6 1999

14) Nechushtan H., Leitges M. Cohen C, Kay G and Razin E.   Pkc beta deficient mast cells. , Blood. 95:1752-1757. 2000

15).Nechushtan H..,  and Razin E.,. Studies of different aspects of the role of protein kinase c in mast cells. Int Arch Allergy Immunol.;124(1-3):130-2. 2001

16.)Levy c.,Nechushtan H Razin E A new role for the STAT3 inhibitor, PIAS3: A repressor of microphthalmia transcription factor J Biol Chem;277(3):1962-6. . 2002

17) Nechushtan H..,  and Razin E.,.  The function of MITF and associated proteins in mast cells. Mol Immunol. 38:1177  2002

18) Nechushtan H.  and Peretz  T.,. Tamoxifen and breast cancer. Harefuah. 141:718-20 2002

19) Rosenblatt JD, Shin SU, Nechustan H, Yi KH,, Tolba K,. Potential role of chemokines in immune therapy of cancer Isr Med Assoc J  11: 1054-9 2002

20) Cohen-Saidon C, Nechushtan H, Kahlon S,Livni N, Nissim A,, Razin E A novel strategy using single-chain antibody to show the importance of Bcl-2 in mast cell survival. Blood. 2003  102 :2506-12 (first two authors contributed equally to this work)

21) Lee, Y.-N ,Nechushtan, H*,  Figov, N., Razin, E   A novel function of lysyl-tRNA synthetase and diadenosine tetraphosphate (Ap₄A) as a signaling regulator of the activity of microphthalmia transcription factor in FcRI-activated mast cells. Immunity 2004  20:145-151 (first two authors contributed equally to this work)* faculty of 1000 article

22) O. Merimsky, E. Gez, R. Weitzen, H. Nehushtan, R. Rubinov, H. Hayat, T. Peretz M. Ben-Shahar, H. Biran, R. Katsenelson, V. Mermershtein, D. Loven, N. Karminsky, A. Neumann, D. Matcejevsky and M. Inbar. Targeting pulmonary metastases of renal cell carcinoma by inhalation of interleukin-2. Annals of Oncology  15: 610–612 2004

23).Lee YN, Tuckerman J, Nechushtan H, Schutz G, Razin E, Angel P,c-Fos as a regulator of degranulation and cytokine production in FcepsilonRI-activated mast cells J Immunol  2004  15:173:2571-7 2004.

24) Lu X, Nechushtan H, Ding F, Rosado MF, Singal R, Alizadeh AA, Lossos IS.. 2005 Distinct IL-4 induced gene _expression, proliferation and intracellular signaling in germinal center B-cell like and activated B-cell like diffuse large cell lymphomas.: Blood.;105:2924-32) 2005

25) Cho HM, Rosenblatt JD, Kang YS, Iruela-Arispe ML, Morrison SL, Penichet ML, Kwon YG, Kim TW, Webster KA, Nechustan H, Shin SU. Enhanced inhibition of murine tumor and human breast tumor xenografts using targeted delivery of an antibody-endostatin fusion protein.Mol Cancer Ther. 2005 (6):956-67

26) Shah S, Divekar AA, Hilchey SP, Cho HM, Newman CL, Shin SU, Nechustan H, Challita-Eid PM, Segal BM, Yi KH, Rosenblatt JD Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and TH1 cytokine responses by B cells Int. J Cancer 2005 :117574-86.

27) Nechushtan  H  and   Razin E  Mast cells: must they always be different?  Blood 2006 107: 1-2.

28) Levy C, Lee YN, Nechushtan H, Schueler-Furman O, Sonnenblick A, Hacohen S, Razin E.Identifying a common molecular mechanism for inhibition of MITF and STAT3 by PIAS3. Blood. 2006  1;107(7):2839-45

29) Benhamron S, Nechushtan H, Verbovetski I, Krispin A, Abboud-Jarrous G, Zcharia E, Edovitsky E, Nahari E, Peretz T, Vlodavsky I, Mevorach D.Translocation of active heparanase to cell surface regulates degradation of extracellular matrix heparan sulfate upon transmigration of mature monocyte-derived dendritic cells.J Immunol;176 (11):641 2006

30)Tshori, S., Gilon, D., Beeri, R., Nechushtan, H.,Kaluzhny, D., Pikarsky, E.,   and Razin, E. Transcription factor MITF regulates cardiac growth and hypertrophy. J Clin Invest, 116: 2673-2681, 2006

31) Kadouri, L., Hubert, A., Rotenberg, Y., Hamburger, T., Sagi, M., Nechushtan, C., Abeliovich, D., and Peretz, T. Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations. J Med Genet. 44:467-71 2007.

32)Tshori,    S., Sonnenblick A ,Yannay-Cohen N, Kay G  Nechushtan, H  Razin,The Microphthalmia Transcription Factor Isoforms in Mast Cells.   E Mol Cell Biol, 27: 3911-3919, 2007.

33) Yi K H, Nechushtan H,  Bowers  WJ  Walker GW, Zhang Y, Pham  DG,  Podack ER, Federoff H,  Tolba KA, and JD. Rosenblatt1, Adoptively transferred tumor-specific T cells stimulated ex vivo using HSV amplicons encoding 4-1BBL persist in the host and demonstrate anti-tumor activity in vivo  Cancer Research  67 10027-37.2007

34)Nechushtan, H Pham D,  Zhang, Y Morgensztern,D   Yi K.H. , Shin SH,  Federoff H, Bowers W.J , Tolba  KA and .Rosenblatt JD  Augmentation of anti-tumor responses of adoptively  transferred CD8+T    cells in the lymphopenic setting by HSV amplicons.Cancer Immunology and Immunotherapy 57 663-75.2008

35) Katz D, Peretz T, Maly B, Ospovat I, Salim N, Ramu N, Hovav N, Uziely B.Expect the unexpected: peritoneal spread–late relapse presentation of breast cancer.Isr Med Assoc J. 2008 10:310-135

36)Galinsky  D S ,Nechushtan H Mast cells and cancer – no longer just basic science.   Critical Reviews in Oncology / Hematology 2008;68:115-30 37)Yagil Z Kay G; Nechushtan H* Razin E A specific epitope of protein inhibitor of activated STAT3 is responsible for the induction of apoptosis in rat transformed mast cells. Journal of immunology  2009;182 2168-75 * corresponding author 38) Nechushtan H Hamburger T; Mendelson S; Kadouri L; Sharon N Pikarsky E, Peretz T Effects of the single nucleotide polymorphism at MDM2 309 on breast cancer patients with/without BRCA1/2 mutations BMC cancer 2009;9():60. 39)  Nechushtan H; Kim S; Kay G; Razin E Chapter 1: The physiological role of lysyl tRNA synthetase in the immune system.Advances in immunology 2009;103():1-27. 40)Yannay-Cohen N Carmi-Levy  Kay G; Yang CM; Han JM; Kemeny D MKim S; Nechushtan H*; Razin E LysRS serves as a key signaling molecule in the immune response by regulating gene expression.Molecular cell 2009;34:603-11.* corresponding author  41) Sarosiek K  Nechushtan H Lu Xi; Rosenblatt JD; Lossos IS Interleukin-4 distinctively modifies responses of germinal centre-like and activated B-cell-like diffuse large B-cell lymphomas to immuno-chemotherapy. British journal of haematology 2009;147:308-18. 42)Sarosiek KA, Malumbres R, Nechushtan H, Gentles AJ, Avisar E, Lossos ISNovel IL-21 signaling pathway upregulates c-Myc and induces apoptosis of diffuse large B-cell lymphomas.Blood. 2010 115:570-80 43) Nechushtan H. The complexity of the complicity of mast cells in cancer Int J Biochem Cell Biol. 2010  42 :551-4.           44)Yagil Z, Nechushtan H, Kay G, Yang CM, Kemeny DM, Razin E.

The enigma of the role of protein inhibitor of activated STAT3 (PIAS3) in the immune response Trends Immunol. 2010 31:199-204 45)  Nisman B, Yutkin V, Nechushtan H, Gofrit ON, Peretz T, Gronowitz S, Pode D.Circulating Tumor M2 Pyruvate Kinase and Thymidine Kinase 1 Are Potential Predictors for Disease Recurrence in Renal Cell Carcinoma After Nephrectomy Urology. 2010 . [Epub ahead of print) 46) Tshori S and Nechushtan H  Mast cell transcription factors – regulators of cell fate and phenotype accepted for publication in BBA – Molecular Basis of Disease 47) Carmi-Levy I,Motzik A, Ofir-Birin, Ygil Z,Yang C M,Kemeny DM,Han JM,Kim S, Kay G,Nechushtan H,Suzuki R Rivera J and Razin E Importin beta plays an essential role in the regulation of the LysRS2 Ap4A pathway in immunologically activated mast cells. Mol. Cell. Biol .  48) Yagil Z., Erlich H T, Ofir-Birin Y, Tshori S., Kay G,  Yektin Z., Cheng  C^C. Wong WSF^C, Razin E Nechushtan H TFE3, a major regulator of mast cell mediated allergic response. J Allergy Clin Immunnol J Allergy Clin Immunol. 2012 May;129(5):1357-1366. 49) Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz1 M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton G, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z,  Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Ryul Kim H, Park S, Ercan D, Sheehan CE, Ross JF, Cronin MT, Jänne PA and StephensPJ  Identification of recurrent KIF5B-RET gene fusions from lung cancer biopsies Nature Medicine:2012 12;18(3):382-4.50) Breuer  S Nechushtan H Pemetrexed induced Lung toxicity-a case report   Clincal Oncology R Coll Radiol   2012 2 4:76-7

51) Structural switch of lysyl-tRNA synthetase between translation and transcription. Ofir-Birin Y, Fang P, Bennett SP, Zhang HM, Wang J, Rachmin I, Shapiro R, Song J, Dagan A, Pozo J, Kim S, Marshall AG, Schimmel P, Yang XL, Nechushtan H, Razin E, Guo M.Mol Cell. 2013 Jan 10;49(1):30-42

52) Tumor STAT3 tyrosine phosphorylation status, as a predictor of benefit from adjuvant chemotherapy for breast cancer. Sonnenblick A, Uziely B, Nechushtan H, Kadouri L, Galun E, Axelrod JH, Katz D, Daum H, Hamburger T, Maly B, Allweis TM, Peretz T. Breast cancer research and treatment, 1-7

53) Non-canonical roles of lysyl-tRNA synthetase in health and disease A Motzik H Nechushtan SY Foo E Razin Trends in molecular medicine 19 (12), 726-731

54)Mitochondrial STAT3 plays a major role in IgE-antigen-mediated mast cell exocytosis.  Erlich TH, Yagil Z, Kay G, Peretz A, Migalovich-Sheikhet H, Tshori S, Nechushtan H, Levi-Schaffer F, Saada A, Razin E.J Allergy Clin Immunol. 2014 Feb 27. pii: S0091-6749(14)00003-7. doi: 10.1016/j.jaci.2013.12.1075.

56)An ALK translocation positive carcinoma of the lung presenting as          uremia due to bilateral renal obstruction.Rosenberg S, Katz R, Pode D, Gofrit NO, Pizov G, Hovav N.Can Urol Assoc J. 2013 8):E490-4.

57) A phase 1/2 of a combination of Cetuximab and Taxane for “triple negative” breast cancer patients. Nechushtan H, Vainer G, Stainberg H, Salmon AY, Hamburger T, Peretz T.Breast. 2014 (4):435-8

58)Amino-acyl tRNA synthetases generate dinucleotide polyphosphates as second messengers: functional implications.Tshori S, Razin E, Nechushtan H.Top Curr Chem. 2014;344:189-206. doi: 10.1007/128_2013_426.

59)EGFR Mutation Testing Practice in Advanced Non-Small Cell Lung Cancer.Bar J, Cyjon A, Flex D, Sorotsky H, Biran H, Dudnik J, Peylan-Ramu N, Peled N, Nechushtan H, Gips M, Katsnelson R, Rosenberg SK, Merimsky O, Onn A, Gottfried M.Lung. 2014 Jun 26. [Epub ahead of print

60) Serum Thymidine Kinase 1 Activity in the Prognosis and Monitoring of Chemotherapy in Lung Cancer Patients: A Brief Report Nisman B Nechushtan H, Biran H, Gantz Sorotsky  H, Peled N , Gronowitz S, Peretz T

Journal of Thoracic Oncology 9 (10), 1568-1572, 2014

61) A Phase IIb Trial Assessing the Addition of Disulfiram to Chemotherapy for the Treatment of Metastatic Non-Small Cell Lung Cancer H Nechushtan, Y Hamamreh, S Nidal, M Gotfried, A Baron, YI Shalev,  et al…The oncologist 20 (4), 366-367, 2015

62) A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer

V Lazar, E Rubin, S Depil, Y Pawitan et al   2015 Oncotarget

63) FHL switches MITF from activator to repressor of Erbin expression    during cardiac hypertrophy I Rachmin, E Amsalem, E Golomb, R Beeri, D Gilon, P Fang,   International Journal of Cardiology 2015 195 85-94 , 2015

Главы:

1. Nechushtan, H, and Razin, E. cDNA amplification of RNA from single mast cells in Immunology Methods Manual Academic Press 1997 P1430-1433

2. Nechushtan, H, and Razin, E. Early response genes in mast cell activation. In Ehud Razin, and Juan Rivera , Signal transduction in the activation of  mast cells.Springer-Verlag, 1999 P323-328.

3. Ligumsky M , Nechushtan H. and Razin E. Single cell RT-PCR for the detection of cytokine  In Methods in molecular medicine vol 60 Interleukin Protocols  E. Oniell LAJ and Bowie A  editors  Humana Press  2001
4.   Nechushtan H, Yannay-Cohen N, Carmi Levy I, Kay G, Razin  E.  MITF and its regulation in mast cells by a pathway involving LysyltRNA synthetase Hint-1 and Ap4A.  In: Van Ree R,  Ring J, Marone G, editors.  Enviromental and genetic factors in allergy and clinical immunology (Proceeding of the 27th Symposium of the Collegium Internationale Allergologicum (CIA).  Pisa, Italy: Pacini Editore Medicine: (published 2010)

departments: онкология

positions: Старший врач в отделении онкологии