hka full cv 4-21-2015
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CURRICULUM VITÆ Date Prepared: April 21, 2015 Name: Hava Karsenty Avraham, Ph.D Office Address: Northeastern University Center for Drug Discovery
116 Mugar Hall 360 Huntington Avenue Boston, MA 02115
Home Address: 22 Heath Hill Road Brookline, MA 02445 Work Phone: 617-373-4218 Cell Phone: 617-775-0697 Work E-mail: [email protected] Private email: [email protected] EDUCATION 1977 B.S. Biology, High Honors Science Faculty Hebrew
University Jerusalem, Israel
1982 Ph.D. General & Tumor Immunology, High Honors
Hebrew University, Jerusalem, Israel
POSTDOCTORAL TRAINING 1982-1985 Postdoctoral Fellow Molecular Biology and
Immunology Weizmann Institute of Science, Rehovot, Israel
1985-1988 Postdoctoral Fellow Molecular Biology Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA
FACULTY ACADEMIC APPOINTMENTS
1982 Senior Assistant Microbiology and Basic Immunology
The Hebrew University, Jerusalem, Israel
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1989-1990 Instructor Medicine Harvard Medical School, Boston, MA
1991-1995 Assistant Professor Medicine Harvard Medical School, Boston, MA
1995-2014 Associate Professor Medicine Harvard Medical School, Boston, MA
2014-Present Adjunct Professor Biology Northeastern University, Center for Drug Discovery, Boston, MA
APPOINTMENTS AT HOSPITAL/AFFILIATED INSTITUTIONS
1989-1989 Scientific Associate Medicine, Division of Experimental Medicine
New England Deaconess Hospital, Boston, MA
1989-1996 Senior Scientist Hematology/Oncology New England Deaconess Hospital, Boston, MA
1996-7/2014 Senior Scientist Hematology/Oncology Beth Israel Deaconess Medical Center, Boston, MA
1/2011-7/2014 Principal Faculty Stem Cell Research Harvard Stem Cell Institute, Cambridge, MA
MAJOR ADMINISTRATIVE LEADERSHIP POSITIONS
2001-7/2005 Associate Chief Experimental Medicine Beth Israel Deaconess Medical Center, Boston, MA
11/2007-7/2014 Associate Chief Experimental Medicine Beth Israel Deaconess Medical Center, Boston, MA
COMMITTEE SERVICE Local
1990-Present Masters and Doctoral Theses Committee, Biological Sciences
Harvard Medical School
1990-2014 Member National
2003-2005 Research Committee on Scientific Sessions Program
American Heart Association
2003-2005 Member
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2014-Present U54 Program Steering
Committee University of California, San Diego Moores Cancer Center
2014-Present Member PROFESSIONAL SOCIETIES
1990- American Society of Hematology 1990-Present Member 1993- American Society of Hematology 1993-Present Member 1997- American Association for
Cancer Research (AACR)
1997-Present Member 2002- International Society for Stem Cell Research 2002-Present Member GRANT REVIEW ACTIVITIES
1996 Medical Biochemistry Study Section
National Institutes of Health
1996 Reviewer 1996 Hematology Study Section National Institutes of Health 1996 Reviewer 1997-1998 Hematopoiesis Research &
Development U.S. Department of Veterans Affairs
1997-1998 Reviewer 1999 Hematology Study Section National Institutes of Health 1999 Reviewer 1999-2002 National Molecular Signaling
Committee American Heart Association
1999-2002 Reviewer 2000-2003 Cell Biology, Breast Research
Program U.S. Army Medical Research and Materiel Command/Congressionally Directed Medical Research Programs
2000-2003 Reviewer 2002 Basic & Clinical National
Cancer Institute Initial Review Group
National Institutes of Health
2002 Reviewer 2003 Hematology Subcommittee 1
(HEM-1) National Institutes of Health
2003 Reviewer 2003-2005 Hemostasis and Thrombosis
Study Section (HT) National Institutes of Health
2003-2005 Reviewer 2004 Basic and Preclinical Studies,
Subcommittee C National Cancer Institute
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2004 Reviewer 2004 Neurogenesis and Cell Fate
Study Section National Institutes of Health
2004 Reviewer 2004 Stem Cells in Aging National Institutes of Health 2004 Reviewer 2004 Cancer Research Fellowship
Study Section, Oncological Science
National Institutes of Health
2004 Reviewer 2004 Physical and Engineering
Sciences Grant Committee National Science Foundation (NSF)
2004 Reviewer 2004-2005 Lung and Blood Institute
(NHLBI) Program National Institutes of Health
2004-2005 Reviewer 2005 3rd Annual Meeting of the
International Society for Stem Cell Research
International Society for Stem Cell Research
2005 Reviewer 2005 Centers of Biomedical Research
Excellence Review Panel National Institutes of Health
2005 Reviewer 2005 Grant Committee International Society for Stem Cell
Research 2005 Reviewer 2008 Hematopoiesis Special
Emphasis Panel, ZRG1 HEME-D (NHLBI)
National Institutes of Health
2008 Reviewer 2008 Translational Breast Cancer
Research Grant Committee American Association for Cancer Research (AACR)
2008 Reviewer 2009 Grant Committee California Breast Cancer Research
Program 2009 Reviewer 2009 RFA OD-09-003 Challenge
Grant Panel 6 National Institutes of Health
2009 Reviewer 2009 Molecular Oncogenesis
(MONC) Study Section National Institutes of Health
2009 Reviewer 2010-2012 Grants Committee United States—Israel Binational Science
Foundation (BSF) 2010-2012 Reviewer
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2010 Systems Biology Committee Netherlands Genomic Initiative 2010 Reviewer 2010 CCNE Special Emphasis Panel,
Nanotechnology National Institutes of Health
2010 Reviewer 2010 Review Panel 6.5 Academy of Finland, Cancer Research 2010 Reviewer 2010 Tumor Biology Panel California Brest Cancer Research
Program 2010 Reviewer 2010 Grants Committee Cancer Research UK 2010 Reviewer 2010 Grants Committee, Stem Cells Israel-Japan Scientific Research
Cooperation 2010 Reviewer 2011-2013 Grants Reviewer Florida Department of Health, Bankhead
Coley Cancer Research Program 2011-2013 Reviewer 2011 Tumor Biology Panel California Breast Cancer Research
Program 2011 Reviewer 2011 Cancer Health Disparities and
Diversity in Basic Cancer Research Panel (ZRG1 OBT-A)
National Institutes of Health/National Cancer Institute
2011 Reviewer 2011-2012 Grants Committee Italian Ministry of Health, Department of
Public Health and Innovation 2011-2012 Reviewer 2013 Grants Committee Center for the Advancement of Science
in Space (CASIS) 2013 Reviewer
EDITORIAL ACTIVITIES Ad hoc Reviewer
American Journal of Pathology Journal of Biochemistry Journal of Biological Chemistry Breast Cancer Research British Journal of Haematology Cancer Research Clinical Medicine Insights: Therapeutics Gene Regulation and Systems Biology Journal of Immunology Journal of Clinical Investigation Libertas Academica Molecular Biology of the Cell
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Other Editorial Roles
1997-2002 Editorial Board Member Blood 2009-2011 Editor-in-Chief Journal of Breast Cancer: Targets
and Therapy 2011-2014 Editorial Board Member ISRN Biochemistry 2011-2013 Associate Editor PLoS ONE HONORS AND PRIZES
1983-1984 Israel Cancer Research Fellowship
Cancer Research Foundation
1984 Leah and Dr. Arthur Felix Academic Achievement Award
Hebrew University Jerusalem, Israel
Excellence in academic achievement
1985 Fulbright-Hays Faculty Research Abroad Fellowship
U.S. Department of Education
1986-1988 Rothschild Fellowship
Yad Hanadiv Foundation, Israel
Fellowship to help young scholars of outstanding academic merit and potential to advance in their respective fields
1991 William F. Milton Fund
Harvard Medical School Supports research conducted by Harvard University Faculty
2000-2001 Breast Cancer Research Program Postdoctoral Fellowship Award
U.S. Department of Defense
Supports the training of exceptionally talented doctoral or medical graduates
1999-2002 National Established Investigator Award
American Heart Association
Supports mid-career investigators with unusual promise and an established record of accomplishments
2003-2005 Career Enhancement Award for Stem Cell Research (K18)
National Institutes of Health
Encourages investigators to obtain the training and career development they need to appropriately use stem cells in their research
REPORT ON FUNDED PROJECTS Costs given are per year amounts.
1992-1997 Hematopoiesis and Megakaryocytopoiesis Genentech, Inc.
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Co-PI (Total direct costs/5 years shared between 2 co-PIs) 1994-1999 Studies of a Novel Tyrosine Kinase in Megakaryocytes NIH - 1R01 HL51456 PI (Direct: $202,124, Indirect: $146.539, Total: $348,663) 1996-2001 Studies of a Related Adhesion Kinase in Megakaryocytes NIH - 1R01 HL55445 Co-PI (Direct: $204,436, Indirect: $148,216, Total: $352,652) 1998-2001 Regulation of ErbB-2 and Src Signaling by CHK and Csk Tyrosine
Kinases in Breast Cancer U.S. Department of Defense - BC972668 PI (Direct: $65,305, Indirect: $48,325, Total: $113,630) 1998-2002 CHK: a Novel Signaling Molecule in Breast Cancer NIH - 1R01 CA76226-01 PI (Direct: $162,653, Indirect: $120,363, Total: $283,016) 1999-2002 Studies of RAFTK Tyrosine Kinase in Platelets American Heart Association - 9940133N PI (Direct: $68,131, Indirect: $6,813, Total: $74,944) 1999-2002 Studies of Vascular Endothelial Growth Factor (VEGF) Signaling in Breast
Cancer Cells U.S. Department of Defense – BC980169 PI (Direct: $70,000, Indirect: $49,000, Total: $119,000) 2000-2001 Role of BRCA1 in Sporadic Breast Cancer Commonwealth of Massachusetts – Experienced Breast Cancer Grant PI (Direct: $20,000, Indirect: $0, Total: $20,000) 2000-2001 Role of BRCA1 in Sporadic Breast Cancer Milheim Foundation PI (Direct: $17,100, Indirect: $0, Total: $17,100) 2000-2002 Regulation of BRCA1 Signaling and Function by Heregulin NIH/NCI - 1R21 CA87290-0 PI (Direct: $75,000, Indirect: $48,125, Total: $123,125) 2001-2002 Regulation of BRCA1 function by AKT Kinase in Breast Cancer Cells Massachusetts Department of Public Health PI (Direct: $20,000, Indirect: $0, Total: $20,000) 2001-2002 Studies of CHK Kinase in Pancreatic Cancer Cells Lustgarten Foundation, Inc. PI (Direct: $100,000, Indirect: $25,000, Total: $125,000) 2002-2005 Effects of Csk Homologous Kinase Overexpression on HER2 U.S. Department of Defense Co-PI (Direct: $50,000, Indirect: $35,000, Total: $85,000 2003-2005 Career Enhancement Award for Stem Cell Research NIH - K18 PI (Direct: $250,000, Indirect: $175,000, Total: $425,000) 2003-2005 Role of CXCR4 Milheim Award for Excellence in Cancer Research, Milheim Foundation Co-PI (Direct: $17,100, Indirect: $0, Total: $17,100) 2003-2004 Evaluation of CHK-Based Treatment in Brain Cancer
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American Brain Tumor Society Co-PI (Direct: $50,000, Indirect: $0, Total: $50,000) 2003-2010 Studies of a Novel BRCA1 Tricomplex in Breast Cancer NIH - 1RO1 CA96805 PI (Direct: $225,000, Indirect: $157,500, Total: $382,500) 2004-2005 Targeting RNA Stabilization to Reduce Growth Factor Expression in
Breast Cancer Cells U.S. Department of Defense – BC033037 PI (Direct: $75,000, Indirect: $52,500, Total: $127,500) 2004-2005 CD133 (AC133) as a Marker for Breast Cancer Stem Cells in Human
Breast Tumors U.S. Department of Defense – BC033433 PI (Direct: $75,000, Indirect: $52,500, Total: $127,500) 2004-2005 The Role of Mammary Stem Cells in Neu/ErbB-2 Mediated
Carcinogenesis U.S. Department of Defense – BC033433 PI (Direct: $75,000, Indirect: $52,500, Total: $127,500) 2004-2007 Program in Blood Coagulation and Vascular Biology NIH/NHLBI – T32 Supervisor (PI: Elvis Tiburu) 2005 Summer Fellowship Aid for Cancer Research Supervisor (PI: Sunshine Dwojak) 2005 UICC Cancer Technology Transfer Union for International Cancer Control (UICC) Supervisor (PI: Anna Asenko) 2005-2006 Japan Foundation Fellowship Japan Foundation Supervisor (PI: Masayuki Sekine) 2005-2007 Studies on the Role of CHK Kinase in Neuroblastoma Children’s Neuroblastoma Cancer Foundation Co-PI (Direct: $25,000, Indirect: $0, Total: $25,000) 2006-2007 Detection of the Dynamics, Structure, and Orientation of the
Transmembrane Segment of ErbB2 in Model Membranes Using Solid-State NMR Spectroscopy
U.S. Department of Defense Supervisor (PI: Elvis Tiburu) 2008-2009 Cannabinoid Compounds Induce Hematopoietic Stem Cell Mobilization National Blood Foundation PI (Direct: $65,000, Indirect: $6,500, Total: $71,500) 2009-2010 Substance P Increases Breast Cancer metastasis to the Brain U.S. Department of Defense – BC086391 Supervisor (PI: Shuxian Jiang) 2009-2010 Regulation of Breast Cancer Stem Cell Trafficking and Metastasis by Brain
Originated Signals U.S. Department of Defense – BC086398
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Supervisor (PI: Shuxian Jiang) 2009-2011 BRCA1 Sporadic Breast Cancer NIH/NCI - 5R21 CA135226-02 PI (Direct: $88,000, Indirect: $61,600, Total: $149,600) 2010-2012 New Mechanisms for Breast Cancer Transmigration across the Blood Brain
Barrier U.S. Department of Defense - BC094909, W81XWH-10-0648 PI (Direct: $183,718, Indirect: $135,032, Total: $318,750) 2011-2013 Oxidative Stress Increases the Blood-Brain Barrier Permeability, Resulting
in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers U.S. Department of Defense - BC102246, W91ZSQ0289N649 PI (Direct: $187,500, Indirect: $138,750, Total: $326,250)
REPORT OF LOCAL TEACHING AND TRAINING No presentations listed below were sponsored by outside entities. Local Invited Presentations
1988 The Rho Gene Family Experimental Medicine, Deaconess Hospital 1992 Regulation of Megakaryocytopoiesis by Stem Cell Factor Cellular and Molecular Biology Laboratory, Deaconess Hospital 1993 Molecular Studies of Megakaryocytopoiesis Hematology/Oncology, Dana-Farber/Deaconess Hospital 1994-1998 Basic Science Teaching Conference Hematology/Oncology, Deaconess Hospital 1999 Cancer Biology Seminar Series / Grand Rounds, Oncology Immunology, Orthopedics, Neurology, Radiology, Deaconess Hospital 2002 Cancer Biology Seminar Hematology/Oncology, Beth Israel Deaconess Medical Center 2003-2004 Vascular Biology Hematology, Beth Israel Deaconess Medical Center/Harvard Medical School 2006 Vascular Biology Hematology, Beth Israel Deaconess Medical Center/Harvard Medical School 2006 Vascular Biology Biochemistry, Boston University School of Medicine 2007 Vascular Biology Center for Drug Discovery, Northeastern University 2007 The Endocannabinoid System in Stem Cells Center for Drug Discovery, Northeastern University 2008 The Role of the Endocannabinoid System in Bone Marrow Recovery following
Irradiation Center for Drug Discovery, Northeastern University 2009 Vascular Biology Hematology/Bone Marrow Transplant, Beth Israel Deaconess Medical Center 2009 The Protective effects of the CB2 Cannabinoid Agonists and the
Endocannabinoids on HIV-1 Gp120 Mediated Damage on Neural Progenitor Cells
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Using in vitro and in vivo Studies Center for Drug Discovery, Northeastern University 2009 Protective Effects of Cannabinoids on Substance P and HIV-1 Gp120 Mediated
Insult to the Blood Brain Barrier and Neural Progenitor Cells Pharmacology & Experimental Therapeutics, Boston University School of
Medicine 2010 Pharmacologic Intervention in Inflammatory Responses: Inflammation and Breast
Cancer Pharmacology & Experimental Therapeutics, Boston University School of
Medicine 2010 Approaches for Drug Discovery in Breast Cancer Metastasis in the Brain Bouvé College of Health Sciences, School of Pharmacy, Northeastern University 2010 Cannabinoids and Stem Cell Research Center for Drug Discovery, Northeastern University 2010-2012 Oncopharmacology Pharmacology & Experimental Therapeutics, Boston University School of
Medicine 2011 Cannabinoid Modulation of the Blood-Brain Barrier Integrity in the Presence of
HIV Proteins Center for Drug Discovery, Northeastern University 2011 Cancer Systems Biology: Tumor Dormancy Center for Cancer Systems Biology, St. Elizabeth's Medical Center 2011 Substance P/NK-1R and VEGF/Angiopoietin-2 as Molecular Determinants in
Breast Cancer Metastasis to the Brain 2012 Alteration In COX-2 Signaling in Triple Negative (ER-/PR-/Her2) Breast Cancer
Cells and its Potential Application to Breast Cancer Disparity Monthly Scientific Meeting, Dana-Farber Cancer Institute 2014 Cannabinoid Receptor Type2 Agonists Targeting Neurotoxicity and
Neuroinflamation in HIV-1 Mouse Model of HIV-Neurotoxicity Center for Drug Discovery, Northeastern University
2014 CB2 Cannabinoid Receptor Agonists for the Treatment of HIV Associated Neurological Disease (HAND)
Center for Drug Discovery, Northeastern University Formally Supervised Trainees and Faculty
1989-1993 Sherry Chi, Ph.D. / Scientist, Genzyme, Cambridge, MA 1990-1993 Sally Cowley, Ph.D. / Head of James Martin Stem Cell Facility, School of
Pathology, Oxford University, U.K. 1991-1996 Naheed Banu, Ph.D. / Research Scientist II, Celgene, Summit, NJ 1991-2012 Yigong Fu, B.S. 1992-1996 Sandhya Raja, Ph.D. / Scientist, Biogen Idec, Cambridge, MA 1992-2013 Shuxian Jiang, B.S. 1993-1999 Roanna London, M.A. / Associate Director, Pfizer Research, Cambridge,
MA 1994-1999 Bijia Deng, Ph.D. / Senior Associate Scientist, Bioanalytical Sciences,
Biogen Idec, Cambridge, MA
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1995-1996 Junzhi Li, Ph.D. / Instructor, Massachusetts General Hospital, Boston, MA
1995-1997 Dan Hiregowdara, Ph.D. / Deceased 1995-1997 Byung H. Jhun, Ph.D. / Assistant Professor, Pusan National University,
South Korea 1995-1997 Setsuo Ota, Ph.D. / Assistant Professor, Chiba University, Japan 1995-2001 Dan Price, Ph.D. / BioSource-Tech, Houston, TX 1997-1999 Sheila Zrihan-Licht, Ph.D. / Scientist, Prochon Biotech, Ltd, Israel 1997-1999 Gina McShan, Ph.D. / Post-doc Fellow, Fox Chase Cancer Center,
Philadelphia, PA 1997 Martin Ellis, M.D. / Physician, Meir Hospital, Israel 1998 Julio J. Hajdenberg, M.D. / Physician, MD Anderson Cancer Center,
Orlando, FL 1998-1999 Yoshitaka Taniguchi, Ph.D. / Assistant Professor, Toray Research Center,
Japan 1998-1999 Hiroshi Yamashita, Ph.D. / Assistant Professor, Hiroshima University,
Japan 1998-2002 Cecile Bougeret, Ph.D. / Research Associate, Pasteur Institution, France 1999 Tihomir Miralem, Ph.D. / Scientist, University of Rochester, NY 1999 Xia Bu, Ph.D. / Post-doc Fellow, Harvard Medical School 1999-2000 Jakob Golab, Ph.D. / Research Associate, University of Warsaw, Poland 1999-2000 Katarzyna Koziak, Ph.D. / Research Associate, University of Warsaw,
Poland 1999-2001 Hitesh Jindal, Ph.D. / Assistant Professor, Alpert Medical School of
Brown University, RI 1999-2011 Huchun Li, Ph.D. 2000-2001 Joo-Won Suh, Ph.D. 2000-2001 Soyoun Kim, Ph.D. / Post-doc Fellow, University of Southern California,
CA 2000-2002 Hideki Kawai, M.D. / Physician, Fujita Health University, Japan 2000-2005 Byeong-Chel Lee, Ph.D. / Assistant Professor, University of Pittsburgh,
School of Medicine, PA 2000-2006 Iha Park, Ph.D. / Research Scientist, Korea 2000-2008 Radoslaw Zagozdzon, M.D., Ph.D. / Leader of Bioinformatics,
Department of Immunology, Medical University of Warsaw, Poland 2001-2002 Sun-Ok Kim, Ph.D. / Scientist, South Korea 2001-2005 Tae-Hee Lee, Ph.D. / Scientist, South Korea 2002-2004 Rafal Kaminski, M.D., Ph.D. / Physician-scientist, Poland 2004-2008 Elvis Tuburu, Ph.D. / Assistant Professor, Northeastern University,
Boston, MA 2005 Massimilliano Cerletti, Ph.D. / Post-doc Felow 2005-2007 Masayuki Sekine, M.D., Ph.D. / Physician-scientist, Japan 2006-2008 Cimona Hinton, M.D., Ph.D. / Assistant Professor, Clark Atlanta
University, GA 2007-2008 Jayone Ki, M.D. / Physician 2008-2010 Pedro L. Rodriguez, Ph.D. / Scientist, Roche Inc., Branchburg, NJ
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2009-2010 Farheen Saddiqui 2010 Jinhua Quan, Ph.D. / Post-doc Fellow, Dana-Farber Cancer Institute 2010 Christopher Sy, B.S. 2010-2012 Lili Wang, B.S. / Master of Science in Biomedical Sciences Candidate,
Rutgers Graduate School of Biomedical Sciences, NJ Research Students
7/1996-8/1999 Geertrui Spaepen Lior Avraham 5/1997-6/2000 Sarah Rosner 6/1997-9/1998 Anupam Raychaudhuri Edward Rhee 5/1999-8/1999 Jamal Misleh 6/2000-7/2000 Angell Shieh 5/2002-7/2002 Istok Miralem 6/2003-8/2003 Shy Steinberger 6/2004-8/2004 Akivah Steinberger 6/2005-8/2005 Noam Kimelman 6/2006-8/2006 Shiri Avraham Rachel Weiss 5/2007-8/2007 Gabby Katz 5/2008-8/2008 Gabby Katz 5/2009-8/2009 Or-El Avraham Gabby Bressler 5/2009-8/2010 Shiri Avraham Benjamin Chen Yehuda Stuchins Lili Wang 5/2011-8/2011 Yehuda Stuchins 7/2013 Evan Cohen REPORT OF REGIONAL, NATIONAL, AND INTERNATIONAL TEACHING AND PRESENTATIONS No presentations listed below were sponsored by outside entities. National
1992 Interaction of Human Bone Marrow Fibroblasts with Megakaryocytes: Role of the c-kit Ligand
Cleveland, OH (American Society of Hematology) 1992 Megakaryocytopoiesis and Platelet Production / Workshop Bethesda, MD (National Institutes of Health) 1993 Identification and Characterization of a Novel Tyrosine Kinase from
Megakaryocytes Cleveland, OH (American Society of Hematology) 1994 Modulation of Megakaryocytopoiesis by Human c-mpl Ligand Cleveland, OH (American Society of Hematology) 1994 Structural and Functional Studies of the Intracellular Tyrosine Kinase
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MATK Gene and its Translated Product Cleveland, OH (American Society of Hematology) 1994 Tyrosine Kinases in Megakaryocytopoiesis Keystone, CO (Keystone Symposia) 1995 Identification and Characterization of a Novel Related Adhesion Focal
Tyrosine Kinase (RAFTK) From Megakaryocytes and Brain Cleveland, OH (American Society of Hematology) 1995 Characterization of Interaction of the Megakaryocyte-Associated Tyrosine
Kinase, MATK, with the c-kit Receptor Cleveland, OH (American Society of Hematology) 1996 An Integrin (GpIIb/IIIa) Independent Phosphorylation of a Novel Related
Adhesion Focal Tyrosine Kinase (RAFTK) in Platelets Cleveland, OH (American Society of Hematology) 1999 Functional Characterization of CHK as a Novel Negative Growth
Regulator of Human Breast Cancer Philadelphia, PA (American Association for Cancer Research) 2000 Overexpression of the CSK Homologous (CHK) Inhibits Human Breast
Tumor Cell Growth Philadelphia, PA (American Association for Cancer Research) 2000 VEGF Stimulation of Signaling in T-47D Breast Cancer Cells Philadelphia, PA (American Association for Cancer Research) 2000 RAFTK/Pyk2 Tyrosine Kinase Mediates the Association of p190
RhoGAP with RasGAP in Breast Cancer Cells Philadelphia, PA (American Association for Cancer Research) 2001 Functional analysis of Csk and CHK kinases in Breast Cancer Cells New Orleans, LA (American Association for Cancer Research) 2001 Extracellular matrix enhances heregulin-dependent BRCA1
phosphorylation and suppresses BRCA1 expression through its C-terminus in breast cancer cells
New Orleans, LA (American Association for Cancer Research) 2001 A novel BTB/POZ domain and kelch motif protein, Mayven, induces c-
jun/AP-1 activity and promotes cell cycle progression in human breast cancer cells
New Orleans, LA (American Association for Cancer Research) 2001 A novel tricomplex of BRCA1, Nmi and c-Myc inhibits c-Myc induced
hTERT promoter activity in breast cancer New Orleans, LA (American Association for Cancer Research) 2002 Breast Cancer Biology Orlando, FL (Era of Hope, U.S. Department of Defense) 2004 Graduate Biology Lecture New York, NY (Columbia University) 2005 Cardiology and Vascular Biology Lecture San Diego, CA (San Diego State University) 2006 Barriers of the CNS Gordon Research Conference (Tilton, NH) 2007 Angiogenic and Cell Survival Functions of VEGF and VEGFR-1 in
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Breast Cancer Cells: Application to Anti-Angiogenesis Therapy Baltimore, MD (National Institute on Aging, Gerontology Research
Center) 2007 Angiogenic and Cell Survival Functions of VEGF and VEGFR-1 in
Breast Cancer Cells Indianapolis, IN (Indiana University-Purdue University Indianapolis) 2007 Angiogenic and Cell Survival Functions of VEGF and VEGFR-1 in
Breast Cancer Cells Bethesda, MD (National Cancer Institute, Division of Cancer Biology) 2008 BRCA1 Regulates activation of beta-catenin/FOXO pathway During
Oxidative stress responses East Lansing, MI (Michigan State University, Carcinogenesis Laboratory) 2008 Hematology Seminar San Francisco, CA (American Society of Hematology) 2009 The Endocannabinoid System and HIV Bethesda, MD (National Institute on Drug Abuse, National Institutes of
Health) 2010 The Interplay of Risk Factors, BRCA1 and Environment in Breast Cancer Bethesda, MD (National Center on Minority Health and Health
Disparities, National Institutes of Health) 2010 The Interplay of Risk Factors, BRCA1 and Environment in Breast Cancer New York, NY (Department of Environmental Medicine, NYU Langone
Medical Center) 2010 Role of BRCA1 in Oxidative Stress Mediated Responses West Hollywood, CA (Cedars-Sinai Medical Center) 2012 Circulating Breast Tumor Cells Breaching the Blood-Brain Barrier and
Forming Tumor Colonies in Brain Newark, NJ (Child Health Institute of New Jersey, Rutgers New Jersey
Medical School) 2012 Circulating breast tumor cells beaching the blood-brain barrier and
forming tumor colonies in brain Summit, NJ (Celgene Corportation) 2012 Circulating breast tumor cells beaching the blood-brain barrier and
forming tumor colonies in brain Augusta, GA (Georgia Health Sciences University Cancer Center) 2013 Role of Angiopoietin-2 in Breaching of the Blood-Brain Barrier by
Circulating Breast Tumor Cells Stevenson, Washington (19th Annual Blood-Brain Barrier Consortium
Meeting) 2013 Ang-2 As a Molecular Determinant in Triple Negative Breast Cancer Cell
Colonization in Brain Norfolk, VA (College of Health Sciences, Old Dominion University) 2013 Breast Cancer and Breast Cancer Metastasis to Brain: Signaling Gone
Awry Mt Pleasant, MI (Central Michigan University)
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2013 Blood-Brain Barrier Impairment and Colonization of Triple Negative Breast Cancer Cells in Brain
Mt Pleasant, MI (Central Michigan University) International
2002 Oncology Lecture Crete, Greece (7th World Congress on Advances in Oncology and 5th
International Symposium on Molecular Medicine) 2006 Vascular and Cancer Biology Lecture Jerusalem, Israel (Hadassah Medical School) 2011 Mechanisms for cannabinoid-mediated protective effects on HIV-1
Gp120 induced insult on brain endothelium St. Charles, IL (International Cannabinoid Research Society) REPORT OF TECHNOLOGICAL AND OTHER SCIENTIFIC INNOVATIONS
Differentiated megakaryocyte line producing novel megakaryocyte differentiation factor
US Patent: 5,686,576, filed 6/6/1994 / patft.uspto.gov
Differentiated megakaryocytes produced by introducing an activated oncogene into blast-megakaryocytes is disclosed. Also disclosed are novel megakaryocyte differentiation factors and platelets obtained from the differentiated megakaryocytes.
Neural cell protein marker RR/B and DNA encoding same
US Patent: 5,863,744, filed 10/3/1994 / patft.uspto.gov
The invention contemplates the novel neural cell protein marker RR/B, cDNA encoding RR/B, nucleic acid probes for detection of mRNA encoding RR/B, synthetic polypeptides whose sequences correspond to a portion of RR/B and have a molecular weight equal to less than that of RR/B, and methods for detection of RR/B.
Neural cell protein marker RR/B and DNA encoding the same
US Patent: 6,066,451, filed 10/3/1994 / patft.uspto.gov
The invention contemplates the novel neural cell protein marker RR/B, cDNA encoding RR/B, nucleic acid probes for detection of mRNA encoding RR/B, synthetic polypeptides whose sequences correspond to a portion of RR/B and have a molecular weight equal to less than that of RR/B antibodies specific for RR/B, and methods for detection of RR/B.
Methods and kits using macrophage stimulating protein
US Patent: 5,696,086, filed 11/3/1994 / patft.uspto.gov
The invention provides methods for stimulating megakaryocyte maturation and thrombocyte production using macrophage stimulating protein
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("MSP"). In the methods, an effective amount of MSP can be administered in vivo, or alternatively, be used to stimulate maturation of megakaryocytes and produce thrombocytes in vitro. Methods for treating thrombocytopenia in a mammal with MSP are also provided. Kits and articles of manufacture which include MSP are further provided.
Methods of detection and treatment of breast cancer
US Patent: 5,981,201, filed 6/16/1997 / patft.uspto.gov
Novel methods of detecting and treating breast cancer are described.
Agonist murine monoclonal antibody as a stimulant for megakaryocytopoiesis
US Patent: 5,980,893, filed 7/17/1997 / patft.uspto.gov
A class of murine monoclonal antibodies that is capable of stimulating megakaryocytopoiesis in vitro has been raised against human megakaryocytic cells. The monoclonal antibody BAH-1 specifically recognizes and demonstrates agonist activity against the c-Mpl receptor on the megakaryocytic cell surface. In therapeutic applications, the BAH-1 and M4 monoclonal antibodies identified to date and similar antibodies (or active portions and chimeric combinations thereof) can stimulate proliferation of primary bone marrow megakaryocytes. Thus, the antibodies of the invention can be used to prepare a composition for treating, e.g., thrombocytopenia. A typical composition comprises a therapeutically effective amount of the BAH-1 monoclonal antibody in association with a pharmaceutically acceptable carrier vehicle.
Methods of detection and treatment of breast cancer
US Patent: 6,638,769, filed 5/20/1999 / patft.uspto.gov
Novel methods of detecting and treating breast cancer are described.
REPORT OF SCHOLARSHIP Peer-Reviewed Publications in Print Research Investigations 1. Avraham, H., D.T. Spira, Y. Gorsky, and D. Sulitzeanu, A solid-phase antibody binding-
inhibition test, for the assay of Plasmodium berghei antigen and antibodies, using radioiodinated protein A. J Immunol Methods, 1980. 32(2): p. 151-155.
2. Avraham, H., J. Golenser, D.T. Spira, and D. Sulitzeanu, Plasmodium falciparum: assay of antigens and antibodies by means of a solid phase radioimmunoassay with radioiodinated staphylococcal protein A. Trans R Soc Trop Med Hyg, 1981. 75(3): p. 421-425.
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3. Ronai, Z., H. Avraham, and D. Sulitzeanu, Autoantibodies to red blood cells in rats infected with Plasmodium berghei. J Parasitol, 1981. 67(3): p. 351-354.
4. Avraham, H., J. Golenser, Y. Gazitt, D.T. Spira, and D. Sulitzeanu, A highly sensitive solid-phase radioimmunoassay for the assay of Plasmodium falciparum antigens and antibodies. J Immunol Methods, 1982. 53(1): p. 61-68.
5. Avraham, H., D.T. Spira, and D. Sulitzeanu, Inhibition of antibody-binding as a radioimmunoassay for Plasmodium berghei infection in rats. J Parasitol, 1982. 68(2): p. 177-184.
6. Avraham, H., J. Golenser, D. Bunnag, P. Suntharasamai, S. Tharavanij, K.T. Harinasuta, D.T. Sira, and D. Sulitzeanu, Preliminary field trial of a radioimmunoassay for the diagnosis of malaria. Am J Trop Med Hyg, 1983. 32(1): p. 11-18.
7. El-On, J., U. Zehavi, H. Avraham, and C.L. Greenblatt, Leishmania tropica and Leishmania donovani: solid phase radioimmunoassay using leishmanial excreted factor. Exp Parasitol, 1983. 55(3): p. 270-279.
8. Golenser, J., J. Miller, H. Avraham, and D.T. Spira, The inhibitory effect of human immune sera upon the in vitro development of Plasmodium falciparum. Trop Geogr Med, 1983. 35(1): p. 15-20.
9. Berrebi, A., Z. Eshhar, S. Linder, L. Guedj, and H. Avraham, RAB-1: a new monoclonal antibody to leukemic hairy cells. Leuk Res, 1986. 10(9): p. 1071-1078.
10. Livneh, A., H. Avraham, D. Elias, J. Sack, I.R. Cohen, and Z. Eshhar, A human monoclonal antibody to insulin. Diabetes, 1986. 35(1): p. 68-73.
11. Avraham, H., S. Avraham, and S.C. Bernstein, A rapid procedure for cell colony hybridization using DNA probes. Anal Biochem, 1989. 179(2): p. 217-221.
12. Avraham, H. and R.A. Weinberg, Characterization and expression of the human rhoH12 gene product. Mol Cell Biol, 1989. 9(5): p. 2058-2066.
13. Avraham, H., rho gene amplification and malignant transformation. Biochem Biophys Res Commun, 1990. 168(1): p. 114-124.
14. Livneh, A., H. Avraham, T. Bistritzer, L. Weisglass, R. Theodor, and J. Sack, Deleterious effect of anti-insulin antibodies on diabetes control. Isr J Med Sci, 1990. 26(1): p. 11-15.
15. Avraham, H., E. Vannier, S.Y. Chi, C.A. Dinarello, and J.E. Groopman, Cytokine gene expression and synthesis by human megakaryocytic cells. Int J Cell Cloning, 1992. 10(2): p. 70-79.
16. Avraham, H., E. Vannier, S. Cowley, S.X. Jiang, S. Chi, C.A. Dinarello, K.M. Zsebo, and J.E. Groopman, Effects of the stem cell factor, c-kit ligand, on human megakaryocytic cells. Blood, 1992. 79(2): p. 365-371.
17. Avraham, S., H. Avraham, K.F. Austen, and R.L. Stevens, Negative and positive cis-acting elements in the promoter of the mouse gene that encodes the serine/glycine-rich peptide core of secretory granule proteoglycans. J Biol Chem, 1992. 267(1): p. 610-617.
18. Cowley, S.A., J.E. Groopman, and H. Avraham, Effects of transforming growth factor beta on megakaryocytic cell fusion and endomitosis. Int J Cell Cloning, 1992. 10(4): p. 223-231.
19. Avraham, H., S. Cowley, S.Y. Chi, S. Jiang, and J.E. Groopman, Characterization of adhesive interactions between human endothelial cells and megakaryocytes. J Clin Invest, 1993. 91(6): p. 2378-2384.
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20. Hauser, C., S. Avraham, and H. Avraham, Association of rho proteins with the mitochondria organelle. Int J Oncol, 1993. 3(6): p. 1103-1110.
21. Avraham, H., N. Banu, D.T. Scadden, J. Abraham, and J.E. Groopman, Modulation of megakaryocytopoiesis by human basic fibroblast growth factor. Blood, 1994. 83(8): p. 2126-2132.
22. Avraham, H., G. Erdos, and Y. Gazitt, Differential expression and subcellular-localization of protein-kinase-C, alpha, gamma, delta, xi and zeta isoforms in agf T-cells - modification during pma-induced differentiation. Int J Oncol, 1994. 5(2): p. 237-241.
23. Bennett, B.D., S. Cowley, S. Jiang, R. London, B. Deng, J. Grabarek, J.E. Groopman, D.V. Goeddel, and H. Avraham, Identification and characterization of a novel tyrosine kinase from megakaryocytes. J Biol Chem, 1994. 269(2): p. 1068-1074.
24. Grabarek, J., J.E. Groopman, Y.R. Lyles, S. Jiang, L. Bennett, K. Zsebo, and H. Avraham, Human kit ligand (stem cell factor) modulates platelet activation in vitro. J Biol Chem, 1994. 269(34): p. 21718-21724.
25. Jiang, S., J.D. Levine, Y. Fu, B. Deng, R. London, J.E. Groopman, and H. Avraham, Cytokine production by primary bone marrow megakaryocytes. Blood, 1994. 84(12): p. 4151-4156.
26. Avraham, H., M.H. Ellis, B.H. Jhun, S. Raja, D. Chalasani, and S. Avraham, Tyrosine kinases in megakaryocytopoiesis. Stem Cells, 1995. 13(4): p. 380-392.
27. Avraham, S., S. Jiang, S. Ota, Y. Fu, B. Deng, L.L. Dowler, R.A. White, and H. Avraham, Structural and functional studies of the intracellular tyrosine kinase MATK gene and its translated product. J Biol Chem, 1995. 270(4): p. 1833-1842.
28. Avraham, S., R. London, Y. Fu, S. Ota, D. Hiregowdara, J. Li, S. Jiang, L.M. Pasztor, R.A. White, J.E. Groopman, and H. Avraham, Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain. J Biol Chem, 1995. 270(46): p. 27742-27751.
29. Banu, N., J.F. Wang, B. Deng, J.E. Groopman, and H. Avraham, Modulation of megakaryocytopoiesis by thrombopoietin: the c-Mpl ligand. Blood, 1995. 86(4): p. 1331-1338.
30. Jhun, B.H., B. Rivnay, D. Price, and H. Avraham, The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit. J Biol Chem, 1995. 270(16): p. 9661-9666.
31. Lee, J., A. Gray, J. Yuan, S.M. Luoh, H. Avraham, and W.I. Wood, Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. Proc Natl Acad Sci U S A, 1996. 93(5): p. 1988-1992.
32. Li, J., H. Avraham, R.A. Rogers, S. Raja, and S. Avraham, Characterization of RAFTK, a novel focal adhesion kinase, and its integrin-dependent phosphorylation and activation in megakaryocytes. Blood, 1996. 88(2): p. 417-428.
33. Nimer, S., J. Zhang, H. Avraham, and Y. Miyazaki, Transcriptional regulation of interleukin-3 expression in megakaryocytes. Blood, 1996. 88(1): p. 66-74.
34. Salgia, R., S. Avraham, E. Pisick, J.L. Li, S. Raja, E.A. Greenfield, M. Sattler, H. Avraham, and J.D. Griffin, The related adhesion focal tyrosine kinase forms a complex with paxillin in hematopoietic cells. J Biol Chem, 1996. 271(49): p. 31222-31226.
35. Astier, A., H. Avraham, S.N. Manie, J. Groopman, T. Canty, S. Avraham, and A.S. Freedman, The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after
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beta1-integrin stimulation in B cells and binds to p130cas. J Biol Chem, 1997. 272(1): p. 228-232.
36. Astier, A., S.N. Manie, H. Avraham, H. Hirai, S.F. Law, Y. Zhang, E.A. Golemis, Y. Fu, B.J. Druker, N. Haghayeghi, A.S. Freedman, and S. Avraham, The related adhesion focal tyrosine kinase differentially phosphorylates p130Cas and the Cas-like protein, p105HEF1. J Biol Chem, 1997. 272(32): p. 19719-19724.
37. Avraham, S., R. London, G.A. Tulloch, M. Ellis, Y. Fu, S. Jiang, R.A. White, C. Painter, A.A. Steinberger, and H. Avraham, Characterization and chromosomal localization of PTPRO, a novel receptor protein tyrosine phosphatase, expressed in hematopoietic stem cells. Gene, 1997. 204(1-2): p. 5-16.
38. Ganju, R.K., W.C. Hatch, H. Avraham, M.A. Ona, B. Druker, S. Avraham, and J.E. Groopman, RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes. J Exp Med, 1997. 185(6): p. 1055-1063.
39. Hiregowdara, D., H. Avraham, Y. Fu, R. London, and S. Avraham, Tyrosine phosphorylation of the related adhesion focal tyrosine kinase in megakaryocytes upon stem cell factor and phorbol myristate acetate stimulation and its association with paxillin. J Biol Chem, 1997. 272(16): p. 10804-10810.
40. Manie, S.N., A.R. Beck, A. Astier, S.F. Law, T. Canty, H. Hirai, B.J. Druker, H. Avraham, N. Haghayeghi, M. Sattler, R. Salgia, J.D. Griffin, E.A. Golemis, and A.S. Freedman, Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells. J Biol Chem, 1997. 272(7): p. 4230-4236.
41. Price, D.J., B. Rivnay, Y. Fu, S. Jiang, S. Avraham, and H. Avraham, Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes. J Biol Chem, 1997. 272(9): p. 5915-5920.
42. Raja, S., S. Avraham, and H. Avraham, Tyrosine phosphorylation of the novel protein-tyrosine kinase RAFTK during an early phase of platelet activation by an integrin glycoprotein IIb-IIIa-independent mechanism. J Biol Chem, 1997. 272(16): p. 10941-10947.
43. Wang, J.F., R.K. Ganju, Z.Y. Liu, H. Avraham, S. Avraham, and J.E. Groopman, Signal transduction in human hematopoietic cells by vascular endothelial growth factor related protein, a novel ligand for the FLT4 receptor. Blood, 1997. 90(9): p. 3507-3515.
44. Zrihan-Licht, S., J. Lim, I. Keydar, M.X. Sliwkowski, J.E. Groopman, and H. Avraham, Association of csk-homologous kinase (CHK) (formerly MATK) with HER-2/ErbB-2 in breast cancer cells. J Biol Chem, 1997. 272(3): p. 1856-1863.
45. Deng, B., N. Banu, B. Malloy, P. Hass, J.F. Wang, L. Cavacini, D. Eaton, and H. Avraham, An agonist murine monoclonal antibody to the human c-Mpl receptor stimulates megakaryocytopoiesis. Blood, 1998. 92(6): p. 1981-1988.
46. Jiang, S., A.G. Tulloch, T.A. Kim, Y. Fu, R. Rogers, A. Gaskell, R.A. White, H. Avraham, and S. Avraham, Characterization and chromosomal localization of PTP-NP-2, a new isoform of protein tyrosine phosphatase-like receptor, expressed on synaptic boutons. Gene, 1998. 215(2): p. 345-359.
47. Kim, T.A., J. Lim, S. Ota, S. Raja, R. Rogers, B. Rivnay, H. Avraham, and S. Avraham, NRP/B, a novel nuclear matrix protein, associates with p110(RB) and is involved in neuronal differentiation. J Cell Biol, 1998. 141(3): p. 553-566.
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48. Sato, T., A. Fuse, H. Niimi, P.J. Fielder, and H. Avraham, Binding and regulation of thrombopoietin to human megakaryocytes. Br J Haematol, 1998. 100(4): p. 704-711.
49. Soltoff, S.P., H. Avraham, S. Avraham, and L.C. Cantley, Activation of P2Y2 receptors by UTP and ATP stimulates mitogen-activated kinase activity through a pathway that involves related adhesion focal tyrosine kinase and protein kinase C. J Biol Chem, 1998. 273(5): p. 2653-2660.
50. Zhang, Z., H. Avraham, and D.M. Cohen, Urea and NaCl differentially regulate FAK and RAFTK/PYK2 in mIMCD3 renal medullary cells. Am J Physiol, 1998. 275(3 Pt 2): p. 447-451.
51. Zrihan-Licht, S., B. Deng, Y. Yarden, G. McShan, I. Keydar, and H. Avraham, Csk homologous kinase, a novel signaling molecule, directly associates with the activated ErbB-2 receptor in breast cancer cells and inhibits their proliferation. J Biol Chem, 1998. 273(7): p. 4065-4072.
52. Altiok, S., D. Batt, N. Altiok, A. Papautsky, J. Downward, T.M. Roberts, and H. Avraham, Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells. J Biol Chem, 1999. 274(45): p. 32274-32278.
53. H. Avraham, and D.J. Price, Regulation of megakaryocytopoiesis and platelet production by tyrosine kinases and tyrosine phosphatases. Methods, 1999. 17(3): p. 250-264.
54. Banu, N., B. Deng, S.D. Lyman, and H. Avraham, Modulation of haematopoietic progenitor development by FLT-3 ligand. Cytokine, 1999. 11(9): p. 679-688.
55. Gerwin, N., J.A. Gonzalo, C. Lloyd, A.J. Coyle, Y. Reiss, N. Banu, B. Wang, H. Xu, H. Avraham, B. Engelhardt, T.A. Springer, and J.C. Gutierrez-Ramos, Prolonged eosinophil accumulation in allergic lung interstitium of ICAM-2 deficient mice results in extended hyperresponsiveness. Immunity, 1999. 10(1): p. 9-19.
56. Pandey, P., S. Avraham, S. Kumar, A. Nakazawa, A. Place, L. Ghanem, A. Rana, V. Kumar, P.K. Majumder, H. Avraham, R.J. Davis, and S. Kharbanda, Activation of p38 mitogen-activated protein kinase by PYK2/related adhesion focal tyrosine kinase-dependent mechanism. J Biol Chem, 1999. 274(15): p. 10140-10144.
57. Price, D.J., B. Rivnay, and H. Avraham, CHK down-regulates SCF/KL-activated Lyn kinase activity in Mo7e megakaryocytic cells. Biochem Biophys Res Commun, 1999. 259(3): p. 611-616.
58. Soltysik-Espanola, M., R.A. Rogers, S. Jiang, T.A. Kim, R. Gaedigk, R.A. White, H. Avraham, and S. Avraham, Characterization of Mayven, a novel actin-binding protein predominantly expressed in brain. Mol Biol Cell, 1999. 10(7): p. 2361-2375.
59. Taniguchi, Y., R. London, K. Schinkmann, S. Jiang, and H. Avraham, The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during megakaryocyte differentiation and Is associated with the c-Kit receptor. Blood, 1999. 94(2): p. 539-549.
60. van Os, R., H. Avraham, N. Banu, P.M. Mauch, J. Whater, Y. Yang, and B. Du, Recombinant adeno-associated virus-based vectors provide short-term rather than long-term transduction of primitive hematopoietic stem cells. Stem Cells, 1999. 17(2): p. 117-120.
61. Yamashita, H., S. Avraham, S. Jiang, I. Dikic, and H. Avraham, The Csk homologous kinase associates with TrkA receptors and is involved in neurite outgrowth of PC12 cells. J Biol Chem, 1999. 274(21): p. 15059-15065.
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62. Yamashita, H., S. Avraham, S. Jiang, R. London, P.P. Van Veldhoven, S. Subramani, R.A. Rogers, and H. Avraham, Characterization of human and murine PMP20 peroxisomal proteins that exhibit antioxidant activity in vitro. J Biol Chem, 1999. 274(42): p. 29897-29904.
63. Avraham, H., S. Avraham, and Y. Taniguchi, Receptor protein tyrosine phosphatases in hematopoietic cells. J Hematother Stem Cell Res, 2000. 9(4): p. 425-432.
64. Avraham, H., S.Y. Park, K. Schinkmann, and S. Avraham, RAFTK/Pyk2-mediated cellular signalling. Cell Signal, 2000. 12(3): p. 123-133.
65. Park, S.Y., H. Avraham, and S. Avraham, Characterization of the tyrosine kinases RAFTK/Pyk2 and FAK in nerve growth factor-induced neuronal differentiation. J Biol Chem, 2000. 275(26): p. 19768-19777.
66. Radisavljevic, Z., H. Avraham, and S. Avraham, Vascular endothelial growth factor up-regulates ICAM-1 expression via the phosphatidylinositol 3 OH-kinase/AKT/Nitric oxide pathway and modulates migration of brain microvascular endothelial cells. J Biol Chem, 2000. 275(27): p. 20770-20774.
67. Zrihan-Licht, S., Y. Fu, J. Settleman, K. Schinkmann, L. Shaw, I. Keydar, S. Avraham, and H. Avraham, RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion. Oncogene, 2000. 19(10): p. 1318-1328.
68. Bougeret, C., S. Jiang, I. Keydar, and H. Avraham, Functional analysis of Csk and CHK kinases in breast cancer cells. J Biol Chem, 2001. 276(36): p. 33711-33720.
69. Koziak, K., E. Kaczmarek, S.Y. Park, Y. Fu, S. Avraham, and H. Avraham, RAFTK/Pyk2 involvement in platelet activation is mediated by phosphoinositide 3-kinase. Br J Haematol, 2001. 114(1): p. 134-140.
70. Miralem, T., R. Steinberg, D. Price, and H. Avraham, VEGF(165) requires extracellular matrix components to induce mitogenic effects and migratory response in breast cancer cells. Oncogene, 2001. 20(39): p. 5511-5524.
71. Price, D.J., T. Miralem, S. Jiang, R. Steinberg, and H. Avraham, Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ, 2001. 12(3): p. 129-135.
72. Banu, N., S. Avraham, and H.K. Avraham, P-selectin, and not E-selectin, negatively regulates murine megakaryocytopoiesis. J Immunol, 2002. 169(8): p. 4579-4585.
73. Kawai, H., H. Li, P. Chun, S. Avraham, and H.K. Avraham, Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells. Oncogene, 2002. 21(50): p. 7730-7739.
74. Kim, S., R. Zagozdzon, A. Meisler, J.D. Baleja, Y. Fu, S. Avraham, and H. Avraham, Csk homologous kinase (CHK) and ErbB-2 interactions are directly coupled with CHK negative growth regulatory function in breast cancer. J Biol Chem, 2002. 277(39): p. 36465-36470.
75. Lee, T.-H., H. Avraham, S.-H. Lee, and S. Avraham, Vascular endothelial growth factor modulates neutrophil transendothelial migration via up-regulation of interleukin-8 in human brain microvascular endothelial cells. J Biol Chem, 2002. 277(12): p. 10445-10451.
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76. Li, H., T.-H. Lee, and H. Avraham, A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer. J Biol Chem, 2002. 277(23): p. 20965-20973.
77. Li, X., X. Bu, B. Lu, H. Avraham, R.A. Flavell, and B. Lim, The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function. Mol Cell Biol, 2002. 22(4): p. 1158-1171.
78. McShan, G.D., R. Zagozdzon, S.-Y. Park, S. Zrihan-Licht, Y. Fu, S. Avraham, and H. Avraham, Csk homologous kinase associates with RAFTK/Pyk2 in breast cancer cells and negatively regulates its activation and breast cancer cell migration. Int J Oncol, 2002. 21(1): p. 197-205.
79. Melendez, J., S. Welch, E. Schaefer, C.S. Moravec, S. Avraham, H. Avraham, and M.A. Sussman, Activation of pyk2/related focal adhesion tyrosine kinase and focal adhesion kinase in cardiac remodeling. J Biol Chem, 2002. 277(47): p. 45203-45210.
80. Nakamura, T., H. Yamashita, Y. Nagano, T. Takahashi, S. Avraham, H. Avraham, M. Matsumoto, and S. Nakamura, Activation of Pyk2/RAFTK induces tyrosine phosphorylation of alpha-synuclein via Src-family kinases. FEBS Lett, 2002. 521(1-3): p. 190-194.
81. Price, D.J., S. Avraham, J. Feuerstein, Y. Fu, and H.K. Avraham, The invasive phenotype in HMT-3522 cells requires increased EGF receptor signaling through both PI 3-kinase and ERK 1,2 pathways. Cell Commun Adhes, 2002. 9(2): p. 87-8102.
82. Zagozdzon, R., C. Bougeret, Y. Fu, and H.K. Avraham, Overexpression of the Csk homologous kinase facilitates phosphorylation of Akt/PKB in MCF-7 cells. Int J Oncol, 2002. 21(6): p. 1347-1352.
83. Avraham, H.K., T.-H. Lee, Y. Koh, T.-A. Kim, S. Jiang, M. Sussman, A.M. Samarel, and S. Avraham, Vascular endothelial growth factor regulates focal adhesion assembly in human brain microvascular endothelial cells through activation of the focal adhesion kinase and related adhesion focal tyrosine kinase. J Biol Chem, 2003. 278(38): p. 36661-36668.
84. Kawai, H., H. Li, S. Avraham, S. Jiang, and H.K. Avraham, Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor alpha. Int J Cancer, 2003. 107(3): p. 353-358.
85. Kim, T.-A., H.K. Avraham, Y.-H. Koh, S. Jiang, I.-W. Park, and S. Avraham, HIV-1 Tat-mediated apoptosis in human brain microvascular endothelial cells. J Immunol, 2003. 170(5): p. 2629-2637.
86. Miralem, T. and H.K. Avraham, Extracellular matrix enhances heregulin-dependent BRCA1 phosphorylation and suppresses BRCA1 expression through its C terminus. Mol Cell Biol, 2003. 23(2): p. 579-593.
87. Price, D., I. Park, and H. Avraham, Methods for the study of protein-protein interactions in cancer cell biology. Methods Mol Biol, 2003. 218: p. 255-267.
88. Takahashi, T., H. Yamashita, Y. Nagano, T. Nakamura, H. Ohmori, H. Avraham, S. Avraham, M. Yasuda, and M. Matsumoto, Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation. J Biol Chem, 2003. 278(43): p. 42225-42233.
89. Avraham, H.K., S. Jiang, T.-H. Lee, O. Prakash, and S. Avraham, HIV-1 Tat-mediated effects on focal adhesion assembly and permeability in brain microvascular endothelial cells. J Immunol, 2004. 173(10): p. 6228-6233.
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90. Kim, S.-O., S. Avraham, S. Jiang, R. Zagozdzon, Y. Fu, and H.K. Avraham, Differential expression of Csk homologous kinase (CHK) in normal brain and brain tumors. Cancer, 2004. 101(5): p. 1018-1027.
91. Lee, B.-C., K. Cha, S. Avraham, and H.K. Avraham, Microarray analysis of differentially expressed genes associated with human ovarian cancer. Int J Oncol, 2004. 24(4): p. 847-851.
92. Lee, B.-C., T.-H. Lee, S. Avraham, and H.K. Avraham, Involvement of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1alpha in breast cancer cell migration through human brain microvascular endothelial cells. Mol Cancer Res, 2004. 2(6): p. 327-338.
93. Liang, X.-Q., H.K. Avraham, S. Jiang, and S. Avraham, Genetic alterations of the NRP/B gene are associated with human brain tumors. Oncogene, 2004. 23(35): p. 5890-5900.
94. Melendez, J., C. Turner, H. Avraham, S.F. Steinberg, E. Schaefer, and M.A. Sussman, Cardiomyocyte apoptosis triggered by RAFTK/pyk2 via Src kinase is antagonized by paxillin. J Biol Chem, 2004. 279(51): p. 53516-53523.
95. Park, S.-Y., H.K. Avraham, and S. Avraham, RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a Src-independent manner. J Biol Chem, 2004. 279(32): p. 33315-33322.
96. Price, D.J., S. Avraham, S. Jiang, Y. Fu, and H.K. Avraham, Role of the aging vasculature and Erb B-2 signaling in epidermal growth factor-dependent intravasion of breast carcinoma cells. Cancer, 2004. 101(1): p. 198-205.
97. Zrihan-Licht, S., S. Avraham, S. Jiang, Y. Fu, and H.K. Avraham, Coupling of RAFTK/Pyk2 kinase with c-Abl and their role in the migration of breast cancer cells. Int J Oncol, 2004. 24(1): p. 153-159.
98. Bu, X., H.K. Avraham, X. Li, B. Lim, S. Jiang, Y. Fu, R.G. Pestell, and S. Avraham, Mayven induces c-Jun expression and cyclin D1 activation in breast cancer cells. Oncogene, 2005. 24(14): p. 2398-2409.
99. Jiang, S., H.K. Avraham, S.-Y. Park, T.-A. Kim, X. Bu, S. Seng, and S. Avraham, Process elongation of oligodendrocytes is promoted by the Kelch-related actin-binding protein Mayven. J Neurochem, 2005. 92(5): p. 1191-1203.
100. Kim, T.-A., S. Jiang, S. Seng, K. Cha, H.K. Avraham, and S. Avraham, The BTB domain of the nuclear matrix protein NRP/B is required for neurite outgrowth. J Cell Sci, 2005. 118(Pt 23): p. 5537-5548.
101. Lee, B.-C., T.-H. Lee, R. Zagozdzon, S. Avraham, A. Usheva, and H.K. Avraham, Carboxyl-terminal Src kinase homologous kinase negatively regulates the chemokine receptor CXCR4 through YY1 and impairs CXCR4/CXCL12 (SDF-1alpha)-mediated breast cancer cell migration. Cancer Res, 2005. 65(7): p. 2840-2845.
102. Zhang, J., J. Zhu, X. Bu, M. Cushion, T.B. Kinane, H. Avraham, and H. Koziel, Cdc42 and RhoB activation are required for mannose receptor-mediated phagocytosis by human alveolar macrophages. Mol Biol Cell, 2005. 16(2): p. 824-834.
103. Fu, Y., R. Zagozdzon, R. Avraham, and H.K. Avraham, CHK negatively regulates Lyn kinase and suppresses pancreatic cancer cell invasion. Int J Oncol, 2006. 29(6): p. 1453-1458.
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104. Jiang, S., H.K. Avraham, T.-A. Kim, R.A. Rogers, and S. Avraham, Receptor-type PTP-NP inhibition of Dynamin-1 GTPase activity is associated with neuronal depolarization. Cell Signal, 2006. 18(9): p. 1439-1446.
105. Kaminski, R., R. Zagozdzon, Y. Fu, P. Mroz, W. Fu, S. Seng, S. Avraham, and H.K. Avraham, Role of SRC kinases in Neu-induced tumorigenesis: challenging the paradigm using Csk homologous kinase transgenic mice. Cancer Res, 2006. 66(11): p. 5757-5762.
106. Klein, B.Y., S.D. Tachado, H. Koziel, and H.K. Avraham, Protein changes typical for therapy-resistant cancer cells appear in MCF7 breast cancer cultures as early as one doubling time after chemical treatment. Int J Canc Res, 2006. 2(2): p. 161-175.
107. Lee, B.-C., S. Avraham, A. Imamoto, and H.K. Avraham, Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice. Blood, 2006. 108(3): p. 904-907.
108. Lee, T.-H., S. Seng, H. Li, S.J. Kennel, H.K. Avraham, and S. Avraham, Integrin regulation by vascular endothelial growth factor in human brain microvascular endothelial cells: role of alpha6beta1 integrin in angiogenesis. J Biol Chem, 2006. 281(52): p. 40450-40460.
109. Park, I. and H.K. Avraham, Cell cycle-dependent DNA damage signaling induced by ICRF-193 involves ATM, ATR, CHK2, and BRCA1. Exp Cell Res, 2006. 312(11): p. 1996-2008.
110. Seng, S., H.K. Avraham, S. Jiang, S. Venkatesh, and S. Avraham, KLHL1/MRP2 mediates neurite outgrowth in a glycogen synthase kinase 3beta-dependent manner. Mol Cell Biol, 2006. 26(22): p. 8371-8384.
111. Tiburu, E.K., E.S. Karp, G. Birrane, J.O. Struppe, S. Chu, G.A. Lorigan, S. Avraham, and H.K. Avraham, 31P and 2H relaxation studies of helix VII and the cytoplasmic helix of the human cannabinoid receptors utilizing solid-state NMR techniques. Biochemistry, 2006. 45(23): p. 7356-7365.
112. Zagozdzon, R., R. Kaminski, Y. Fu, W. Fu, C. Bougeret, and H.K. Avraham, Csk homologous kinase (CHK), unlike Csk, enhances MAPK activation via Ras-mediated signaling in a Src-independent manner. Cell Signal, 2006. 18(6): p. 871-881.
113. Avraham, S., S. Seng, S. Jiang, and H.K. Avraham, ENC1 (ectodermal-neural cortex (with BTB-like domain)). Atlas Genet Cytogenet Oncol Haematol, 2007.
114. Jiang, S., Y. Fu, J. Williams, J. Wood, L. Pandarinathan, S. Avraham, A. Makriyannis, S. Avraham, and H.K. Avraham, Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells. PLoS One, 2007. 2(7).
115. Jiang, S., S. Seng, H.K. Avraham, Y. Fu, and S. Avraham, Process elongation of oligodendrocytes is promoted by the Kelch-related protein MRP2/KLHL1. J Biol Chem, 2007. 282(16): p. 12319-12329.
116. Lee, T.-H., S. Seng, M. Sekine, C. Hinton, Y. Fu, H.K. Avraham, and S. Avraham, Vascular endothelial growth factor mediates intracrine survival in human breast carcinoma cells through internally expressed VEGFR1/FLT1. PLoS Med, 2007. 4(6).
117. Seng, S., H.K. Avraham, S. Jiang, S. Yang, M. Sekine, N. Kimelman, H. Li, and S. Avraham, The nuclear matrix protein, NRP/B, enhances Nrf2-mediated oxidative stress responses in breast cancer cells. Cancer Res, 2007. 67(18): p. 8596-8604.
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118. Tiburu, E.K., C.E. Bass, J.O. Struppe, G.A. Lorigan, S. Avraham, and H.K. Avraham, Structural divergence among cannabinoids influences membrane dynamics: a 2H solid-state NMR analysis. Biochim Biophys Acta, 2007. 1768(9): p. 2049-2059.
119. Hinton, C.V., S. Avraham, and H.K. Avraham, Contributions of integrin-linked kinase to breast cancer metastasis and tumourigenesis. J Cell Mol Med, 2008. 12(5A): p. 1517-1526.
120. Lu, T.-S., H.K. Avraham, S. Seng, S.D. Tachado, H. Koziel, A. Makriyannis, and S. Avraham, Cannabinoids inhibit HIV-1 Gp120-mediated insults in brain microvascular endothelial cells. J Immunol, 2008. 181(9): p. 6406-6416.
121. Zagozdzon, R., Y. Fu, and H.K. Avraham, Csk homologous kinase inhibits CXCL12-CXCR4 signaling in neuroblastoma. Int J Oncol, 2008. 32(3): p. 619-623.
122. Alberich Jorda M, J.S., Zagozdzon R, Parmar K, Mauch P, Fu Y, Makriyannis A, Zvonok AM, Tenen DG, Avraham S, Groopman JE, Avraham HK, The peripheral cannabinoid receptor regulates human and mouse hematopoiesis, bone marrow recovery, and hematopoietic stem and progenitor cell mobilization, in Haematologica. 2009. p. 208.
123. Li, H., M. Sekine, S. Seng, S. Avraham, and H.K. Avraham, BRCA1 interacts with Smad3 and regulates Smad3-mediated TGF-beta signaling during oxidative stress responses. PLoS One, 2009. 4(9).
124. Seng, S., H.K. Avraham, G. Birrane, S. Jiang, H. Li, G. Katz, C.E. Bass, R. Zagozdzon, and S. Avraham, NRP/B mutations impair Nrf2-dependent NQO1 induction in human primary brain tumors. Oncogene, 2009. 28(3): p. 378-389.
125. Tiburu, E.K., A.L. Bowman, J.O. Struppe, D.R. Janero, H.K. Avraham, and A. Makriyannis, Solid-state NMR and molecular dynamics characterization of cannabinoid receptor-1 (CB1) helix 7 conformational plasticity in model membranes. Biochim Biophys Acta, 2009. 1788(5): p. 1159-1167.
126. Arshad, F., L. Wang, C. Sy, S. Avraham, and H.K. Avraham, Blood-brain barrier integrity and breast cancer metastasis to the brain. Patholog Res Int, 2010. 2011: p. 920509-920509.
127. Hinton, C.V., S. Avraham, and H.K. Avraham, Role of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain. Clin Exp Metastasis, 2010. 27(2): p. 97-9105.
128. Jiang, S., B.C. Lee, Y. Fu, S. Avraham, B. Lim, and H.K. Avraham, Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation. PLoS One, 2010. 5(3): p. e9707.
129. Li, H., M. Sekine, N. Tung, and H.K. Avraham, Wild-type BRCA1, but not mutated BRCA1, regulates the expression of the nuclear form of beta-catenin. Mol Cancer Res, 2010. 8(3): p. 407-420.
130. Seng, S., H.K. Avraham, G. Birrane, S. Jiang, and S. Avraham, Nuclear matrix protein (NRP/B) modulates the nuclear factor (Erythroid-derived 2)-related 2 (NRF2)-dependent oxidative stress response. J Biol Chem, 2010. 285(34): p. 26190-26198.
131. Jiang, S., Y. Fu, and H.K. Avraham, Regulation of hematopoietic stem cell trafficking and mobilization by the endocannabinoid system. Transfusion, 2011. 51 Suppl 4: p. 71.
132. Li, H., J.T. Wood, K.M. Whitten, S.K. Vadivel, S. Seng, A. Makriyannis, and H.K. Avraham, Inhibition of fatty acid amide hydrolase activates Nrf2 signalling and induces heme oxygenase 1 transcription in breast cancer cells. Br J Pharmacol, 2013. 170(3): p. 489-505.
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133. Avraham, H.K., S. Jiang, Y. Fu, H. Nakshatri, H. Ovadia, and S. Avraham, Angiopoietin-2 mediates blood-brain barrier impairment and colonization of triple-negative breast cancer cells in brain. J Pathol, 2014. 232(3): p. 369-381.
134. Avraham, H.K., S. Jiang, Y. Fu, E. Rockenstein, A. Makriyannis, A. Zvonok, E. Masliah, and S. Avraham, The cannabinoid CB₂ receptor agonist AM1241 enhances neurogenesis in GFAP/Gp120 transgenic mice displaying deficits in neurogenesis. Br J Pharmacol, 2014. 171(2): p. 468-479.
135. Rodriguez, P.L., S. Jiang, Y. Fu, S. Avraham, and H.K. Avraham, The proinflammatory peptide substance P promotes blood-brain barrier breaching by breast cancer cells through changes in microvascular endothelial cell tight junctions. Int J Cancer, 2014. 134(5): p. 1034-1044.
136. Avraham, H.K., S. Jiang, Y. Fu, E. Rockenstein, A. Makriyannis, J. Wood, L. Wang, E. Masliah, and S. Avraham, Impaired Neurogenesis by HIV-1-Gp120 is Rescued by genetic deletion of Fatty Acid Amide Hydrolase Enzyme. Br J Pharmacol, Feb 26, 2014.
Other Peer-Reviewed Publications 1. Avraham, H., M.H. Ellis, B.H. Jhun, S. Raja, D. Chalasani, and S. Avraham, Tyrosine
kinases in megakaryocytopoiesis. Stem Cells, 1995. 13(4): p. 380-92. 2. Ellis, M.H., H. Avraham, and J.E. Groopman, The regulation of megakaryocytopoiesis.
Blood Rev, 1995. 9(1): p. 1-6. 3. Avraham, S. and H. Avraham, Characterization of the novel focal adhesion kinase
RAFTK in hematopoietic cells. Leuk Lymphoma, 1997. 27(3-4): p. 247-56. 4. Avraham, H., S. Avraham, and Y. Taniguchi, Receptor protein tyrosine phosphatases in
hematopoietic cells. J Hematother Stem Cell Res, 2000. 9(4): p. 425-32. 5. Avraham, H., S.Y. Park, K. Schinkmann, and S. Avraham, RAFTK/Pyk2-mediated
cellular signalling. Cell Signal, 2000. 12(3): p. 123-33. 6. Avraham, H., S. Avraham, and R. Zagozdzon, Use of Antisense Oligonucleotide
Technology to Investigate Signaling Pathways in Megakaryocytes, in Platelets and Megakaryocytes, J.M. Gibbins and M.P. Mahaut-Smith, Editors. 2004, Humana Press: Totowa, NJ.
7. Jiang, S., Y. Fu, and H.K. Avraham, Regulation of hematopoietic stem cell trafficking and mobilization by the endocannabinoid system. Transfusion, 2011. 51 Suppl 4: p. 65S-71S.
Professional Education Materials or Reports in Print or Other Media 1. Avraham, H. and S. Avraham, Human Rho Gene Family, in Current Perspectives on
Molecular and Cellular Oncology: A Research Mannual, D.A. Spandidos, Editor. 1992, JAI Press Limited: London. p. 197-209.
2. Price, D.J., Groopman, J.E., and H. Avraham, Megakaryocyte Signaling, in Hematopoiesis: A Developmental Approach, L.I. Zon, Editor. 2001, Oxford University Press: NY.
3. Avraham, H., S. Avraham, and R. Zagozdzon, Use of Antisense Oligonucleotide Technology to Investigate Signaling Pathways in Megakaryocytes, in Platelets and Megakaryocytes, J.M. Gibbins and M.P. Mahaut-Smith, Editors. 2002, Humana Press: Totowa, NJ.
4. Avraham, H., S. Avraham, and R. Zagozdzon, Use of Antisense Oligonucleotide
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Technology to Investigate Signaling Pathways in Megakaryocytes, in Platelets and Megakaryocytes, J.M. Gibbins and M.P. Mahaut-Smith, Editors. 2004, Humana Press: Totowa, NJ.
5. Avraham, H., Park, I., and D.J. Price, Protein Interactions, in Cancer Cell Signaling: Methods and Protocols, D. Terrian and S.G. Pandalai, Editors. 2002, Humana Press: Totowa, NJ. p. 255-268.
6. Park, S.Y., Avraham, H., and S. Avraham, Functional Aspects of RAFTK-Pyk2 in the Nervous System, in Recent Research Developments in Neurochemistry, S.G. Pandalai, Editor. 2002, Research Signpost: Kerala, India. p. 125-142.
7. Park, S.Y., Avraham, H., and S. Avraham, The Superfamily of Proteins Containing Kelch and/or BTB Domains: from Cytoskeleton Dynamics to Transcriptional Regulation, in Recent Research Developments in Neurochemistry, S.G. Pandalai, Editor. 2002, Research Signpost: Kerala, India. p. 231-254.
8. Avraham, H., Hinton, C.V., Seng, S., Jiang, S., Avraham, R., and S. Avraham, Mechanisms of VEGF-mediated Survival of Breast Cancer Cells, in Cancer Metastasis: Recent Developments in Cancer, P. Rameshwar, Editor. 2007, Research Signpost: Kerala, India.
9. Avraham, S., and H. Avraham, The Blood-Brain Barrier, in Encyclopedia of Cancer, M. Schwab, Editor. 2007, Springer: NY.
10. Avraham, H., Hinton, C.V., Seng, S., Jiang, S., Avraham, R., and S. Avraham, Mechanisms of VEGF-mediated Survival of Breast Cancer Cells, in Cancer Metastasis: Recent Developments in Cancer, P. Rameshwar, Editor. 2010, Transworld Research Network: Kerala, India.
11. Avraham, H.K., Jiang, S., Avraham, S., and A. Makriyannis, Regulation of Stem Cells by the Endocannabinoid System, in Therapeutic Applications in Disease and Injury: Stem Cells and Cancer Stem Cells, M.A. Hayat, Editor. 2012, Springer: NY.
12. Avraham, H.K., Jiang, S., Wang, L., Fu, Y., and S. Avraham, Cellular and Molecular Mechanisms Involved in Breaching of the Blood-Brain Barrier by Circulating Breast Cancer Cells, in Breast Cancer Metastasis and Drug Resistance: Challenges and Progress, A. Ahmad, Editor. 2012, Springer: NY.
13. Avraham, S., Jiang, S., Wang, L., Fu, Y., and H.K. Avraham, VEGF-mediated Effects on Brain Microvascular Endothelial Tight Junctions and Transmigration of Breast Cancer Cells across the Blood-Brain Barrier, in Tight Junctions in Cancer Metastasis (Cancer Metastasis - Biology and Treatment), T.A. Martin and W.G. Jiang, Editors. 2013, Springer: NY. p. 247-261.
14. Avraham, H.K., Byeong-Chel, L., and S. Avraham, Colony-forming Unit Assay, in Encyclopedic Reference of Immunotoxicology, H. Vohr, Editor. 2013, Springer: NY.
Thesis Avraham, H.K., Development of a Radioimmunoassay for the Diagnosis of Malaria. 1983, Hebrew University of Jerusalem: Israel. NARRATIVE REPORT References cited are located under Report of Scholarship. The major goals of my early career had been to conduct basic research to identify novel genes and pathways regulating hematopoiesis. During the past 25 years, my focus has
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been to determine the role of these genes in pathways in malignancy. My research is in the area of signaling mechanisms that are essential for normal tissue growth and development, but are perturbed in cancer. Specifically, my lab has focused on signaling pathways of tyrosine kinases, such as CSK, CHK, SRC, FAK, RAFTK/Pyk2, ErbB-2 and VEGF receptors in breast cancer cells and the identification of molecular mechanisms important in breast cancer tumorigenesis and breast cancer metastasis to the brain. In addition, my recent focus has been to study the molecular mechanisms for the disproportionate incidence of triple-negative breast cancer (TNBC), characterized by a lack of expression of the estrogen receptor, progesterone receptor and Her2/ErbB2, which is more prevalent in African American (AA) and Hispanic women, as compared to Caucasian women. Elucidation of novel mechanisms, and identification of novel biomarkers, endogenous risk factors, and their targets that may contribute to the increased mortality of AA women with breast cancer, is of high importance for reducing racial disparities in breast cancer. Specifically, we have investigated the prostanoid signaling pathways in TNBC tumor cells from AA and Caucasian women. The main topics studied at my lab include:
I. Molecular mechanisms for breast cancer metastases to the brain II. Role of BRCA1 and oxidative stress in sporadic and inherited breast cancer
III. Signal transduction pathways mediated by ErbB kinases, VEGF receptors, Src kinases, Csk/CHK kinases and FAK/RAFTK/Pyk2 kinases in breast cancer cells and their role in tumorigenesis and breast cancer metastasis
IV. VEGF-VEGFR 1 autocrine survival system and its role in chemotherapy resistance
I, also, received a NIH-K18 award on stem cells. Therefore, during the last several years, I have investigated new pathways that are important in hematopoietic and neural stem cell survival and self-renewal, specifically focusing on the endocannabinoid system. SUMMARY OF MAJOR ACTIVITIES AND RESEARCH ACHEIVEMENTS My lab has made several seminal discoveries in the field of hematopoiesis and signaling by tyrosine kinases and tyrosine phosphatases. Following my post-doctoral training at the Weizmann Institute in Rehovot, Israel and the Whitehead Institute at the Massachusetts Institute of Technology in Boston, I joined the Deaconess Hospital/Harvard Medical School in 1989. My initial work was to characterize cytokine gene expression and synthesis by human megakaryocytic cells. My laboratory, a pioneer group, was one of the first to demonstrate the role of the c-kit ligand in the interaction of human bone marrow fibroblasts with megakaryocytes [16,19]. In addition, we elucidated the effects of transforming growth factor beta, SCF/c-kit ligand and thrombopoietin on megakaryocytes and platelet formation. Next, I focused my efforts on new gene discovery. We have been successful not only in identifying new genes but also in characterizing their functions. Some of our most important discoveries were:
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I. The protein tyrosine kinases CHK [23,27,30] and RAFTK [28,32]
II. The protein tyrosine phosphatases PTP-NP-2 [47,63, 104] and PTP-RO [37,59] III. Identification of Flt-4 [31] IV. The novel Kelch-related proteins: NRP/B, Mayven, and MRP2, which were
studies performed in collaboration with Dr. Shalom Avraham) [48,58,98,100,110,116]
These were all novel genes expressed in hematopoietic cells and/or brain, and were shown to be important molecules in cell signaling pathways. CHK The Csk homologous kinase (CHK) was cloned first by our group. CHK expression is restricted to hematopoietic cells and the nervous system. We demonstrated that CHK phosphorylates the inhibitory C-terminal tyrosine of several Src-family kinases in vitro, and importantly interacts with c-kit in megakaryocytes. Recently, we identified MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice [107]. Interestingly, we also discovered that CHK is a unique negative regulator of breast cancer cell growth and that it associates with ErbB-2 upon heregulin stimulation in breast cancer cells. This project has been supported significantly by the NIH, the Department of Defense, and the Commonwealth of Massachusetts. In summary, we found that CHK binds specifically to the cytoplasmic tail of ErbB-2, the overexpressed oncogene that is a major target in breast cancer therapeutics [45,52,68]. We demonstrated that CHK has an anti-oncogene activity of blocking growth signaling by heregulin (the ligand for ErbB-2). The NMR structure of CHK with the tail of ErbB-2 was also solved [74]. This structural information allows the design of small molecules to mimic the activity of CHK and block breast cancer growth by shutting down ErbB-2 signaling. Lastly, we generated CHK transgenic mice and showed the role of Src kinases in Neu-induced tumorigenesis. Our data, using CHK as a physiologic inhibitor of Src activity, showed that blocking of Neu-induced Src activity without altering Src expression levels had no significant effects on Neu-mediated mammary tumorigenesis in vivo [105]. This contradicts the current paradigm that activation of Src kinases is essential for Neu-induced oncogenesis. This study was the first to distinguish between the kinase-dependent and kinase-independent actions of Src and showed that its kinase-dependent properties are not requisite for Neu-induced tumorigenesis. We also found that CHK in brain modulates the signaling of the Trk-A receptor following nerve growth factor (NGF) stimulation [61]. Our discovery on CHK showed differential expression of CHK in normal brain and brain tumors [90]. RAFTK/Pyk2 Our lab was central in the cloning and identification of RAFTK/Pyk2, a signaling molecule that coordinates cytokine, chemokine and integrin-mediated signaling in megakaryocytes, platelets and other blood cells. Of note, RAFTK appears to be a target of HIV in T-cells and macrophages. RAFTK serves as a critical “platform kinase” upon
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which a variety of signaling molecules interact, including adaptor proteins, Src kinase, phosphatases, and cytoskeletal elements. RAFTK was shown to play critical signaling roles in a variety of essential cell functions like chemotaxis, cell adhesion, and apoptosis [28,32,34,35,36,39,43,63,64]. In addition, we have demonstrated that RAFTK is involved in breast cancer invasion [65,97]. My lab also showed that vascular endothelial growth factor regulated focal adhesion assembly in human brain microvascular endothelial cells through activation of RAFTK/Pyk2 [83]. MOLECULAR MECHANISMS FOR BREAST CANCER CELL INVASION AND MIGRATION While investigating the molecular mechanisms of breast cancer cell invasion and metastasis, we discovered unique roles of VEGF and the CXCR4/CXCL12 axis in breast cancer cell invasion and migration. We reported that vascular endothelial growth factor modulates the transendothelial migration of MDA-MB-231 breast cancer cells through regulation of brain microvascular endothelial cell permeability [75]. We reported the involvement of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1alpha in breast cancer cell migration through human brain microvascular endothelial cells [92]. We also discovered a unique role of CHK kinase in negatively regulating the chemokine receptor CXCR4 through YY1 and impaired CXCR4/CXCL12 (SDF-1alpha)-mediated breast cancer cell migration [101]. ROLE OF BRCA1 IN SPORADIC AND INHERITED BREAST CANCER We also investigated several aspects of BRCA1, the breast cancer susceptibility gene. Our studies showed that BRCA1 is modulated through heregulin binding to the ErbB-2 receptor via the PI-3 kinase/AKT pathway [52]. We also identified novel proteins associated with BRCA1 genes using the yeast two-hybrid system. BRCA1 encodes a nuclear phosphoprotein that acts as a tumor suppressor, while activation of the ErbB receptors by heregulin (HRG) promotes cell growth in breast epithelial cells. The possibility that ErbB-2 receptor activation by heregulin can modulate BRCA1 function presents a new approach and a novel mechanism for understanding breast cancer biology. In addition, we have shown that BRCA1 forms a novel complex with Nmi and c-Myc and inhibits c-Myc induced Telomerase activity [76]. We also discovered that the extracellular matrix enhances heregulin-dependent BRCA1 phosphorylation and suppresses BRCA1 expression through its C-terminus [86]. We next showed that cell cycle-dependent DNA damage signaling induced by ICRF-193 involves ATM, ATR, CHK2, and BRCA1. The DNA damage signaling induced by ICRF-193 was mediated by ATM and ATR and was restricted to cells in specific cell cycle stages such as S, G2, and mitosis including late and early G1 phases. Downstream signaling of ATM and ATR involved the phosphorylation of CHK2 and BRCA1 [109]. Effects of Cannabinoids on Profiling and Pathways of Neural Stem Cell Niches in NeuroAIDS/HIV:
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Neural progenitor cells (NPCs) are critical for brain development and response to injury and inflammation. Emerging reports suggest that NPCs are involved in the neuropathogenesis of HAD and are targeted in HIV-mediated toxicity. However, it is not known how HIV-1 and HIV-1 viral proteins (such as Gp120) cause damage to NPCs. We hypothesize that cognitive dysfunction in the setting of HIV infection is related to alterations in hippocampal neurogenesis, resulting in molecular changes of adult neurogenesis; Further, since cannabinoids were reported to have neuroprotective effects, we suggest that HIV-1 mediated toxicity of NPCs is inhibited by endocannabinoids by increasing NPC survival and proliferation, resulting in increased neurogenesis. In this project we aim to determine the pathways and molecular profiling by which HIV-1 mediates damage to NPC niches in NeuroAIDS/HIV. Using novel in vivo mice models for HAD and autopsy samples from brain of patients with HAD, proteomic modeling and three-dimensional whole mounts, confocal microscopy, and automated computer-based image quantification, will be employed to examine the NPCs within their adult subventricular zone niches following exposure to HIV-1 Gp120 and HIV-1 infection. In addition, we aim to examine the protective effects of endocannabinoids in inhibiting HIV-1 mediated injury on neurogenesis using in vivo mice models.
Understanding of how HIV affects both molecular and cellular aspects of neurogenesis should lead to the development of more effective therapeutic interventions for HAD and for the eradication of HIV reservoirs in brain.