Principal Investigator/Program Director (Last, First, Middle):		Kleinerman, Eugenie S.
BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.  Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME Eugenie S. Kleinerman		POSITION TITLE Professor and Head, Division of Pediatrics Mosbacher Pediatrics Chair Professor, Department of Cancer Biology
eRA COMMONS USER NAME ekleiner
EDUCATION/TRAINING  (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION	DEGREE (if applicable)		YEAR(s)	FIELD OF STUDY
Washington University, St. Louis, MO	B.A.		1971	Biology
Duke University, Durham, NC	M.D.		1975	Medicine
Children's Hospital National Medical Center			1975-1978	Pediatrics
National Cancer Institute, Bethesda, MD			1978-1981	Allergy-Immunology

 
 

1. Positions:

 
 

1974-1975 Fellow, Rheumatology, Duke University, Durham, NC

1975-1978 PL-1, PL-2, Pl-3 - Children's Hospital National Medical Center, Washington, DC

1978-1981 Clinical Associate, Metabolism Branch, National Cancer Institute, Bethesda, MD

1981-1984 Senior Investigator, Laboratory of Molecular Immunoregulation, Biological Response Modifiers Program, National Cancer Institute, Frederick Cancer Research Facility, Frederick, MD

1984-1987 Assistant Professor, Department of Cell Biology and Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX

1987-1993 Associate Professor, Department of Cell Biology and Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX

1993-Present Professor, Department of Cancer Biology and Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX

2001-Present Professor and Head, Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX

 
 

Honors:

1984. Young Investigator Award in RES Research - Presented at the 21st National Meeting of the Reticuloendothelial Society.

1975 Sandoz Award - Awarded at Medical school graduation

1975 Sheard-Sanford Award - for meritorious original student research in Pathology.

 
 

Committee Memberships:

1998-Present National Institutes Of Health, Cancer Immunobiology Immumotherapy Study Section

1994-1998 Biological Response Modifiers Advisory Committee to the FDA.

2/1994 USAMRDC Breast Cancer Program Grant, Review Committee (Chem 1A)

1987-1991 National Institutes of Health, Experimental Therapeutics-2 Study Section.

 
 

2. Selected Peer-Reviewed Publications:

Lafleur, E.A., Jia, S-F., Worth, L.L., Zhou, Z., Owen-Schuab, L.B., Kleinerman, E.S.  Interleukin (IL)-12 and IL-12 Gene Transfer Up-Regulate Fas Expression in Human Osteosarcoma and Breast Cancer Cells.  Cancer Res. 61:4066-4071, 2001.

Zhou, Z., Jia, S-F., Hung, M.C., Kleinerman, E.S.  E1A sensitizes HER2/neu-overexpressing Ewing’s sarcoma cells to topoisomerase II-targeting anticancer Drugs.  Cancer Res., 61:3394-3398, 2001.

Zhou, Z., Zwelling, L.A., Ganapathi, R., Kleinerman, E.S.  Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase II [Alpha] gene transfer is independent of topoisomerase II [Beta].  British Journal of Cancer  85:747-751, 2001.

Densmore, C.L., Kleinerman, E.S., Gautam, A., Jia, S-F., Xu, B., Worth, L.L., Waldrep, J.C., Fung, Y-K., T’Ang, A., Knight, V.  Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI-p53 complexes.  Cancer Gene Therapy, 8:619-627, 2001.

Worth, L.L., Jeha, S.S., Kleinerman, E.S.  Biologic response modifiers in pediatric cancer.  Hematology-Oncology Clinics of North America, 15:723-740, 2001.

Jia, S.F., Zwelling, L.A., McWatters, A., An, T., Kleinerman, E.S.  Interleukin-1-a increases the cytotoxic activity of etoposide against human osteosarcoma cells.  J. Experimental Therapeutics and Oncol., 2:27-36, 2002.

Jia, S-F., Worth, L.L., Densmore, C.L., Xu, B., Zhou, Z., Kleinerman, E.S.  Eradication of Osteosarcoma Lung Metastases Following Intranasal Interleukin-12 Gene Therapy using a Nonviral Polyethylenimine Vector.  Cancer Gene Therapy, 9:260-266, 2002.

Jia, S-F., Worth, L.L., Turan, M., Duan, X-P., Kleinerman, E.S.  Eradication of Osteosarcoma Lung Metastasis Using Intranasal Gemcitabine.  Anti-Cancer Drugs, 13:155-161, 2002.

Zhou, R-R., Jia, S-F., Zhou, Z., Wang, Y., Bucana, C.D., Kleinerman, E.S.  Adenoivirus-E1A gene therapy enhances the in vivo sensitivity of Ewing’s sarcoma to VP-16.  Cancer Gene Therapy, 9:407-413, 2002.

Bolontrade, M.F., Zhou, R-R., Kleinerman, E.S.  Vasculogenesis plays a role in the growth of Ewing’s sarcoma in vivo.  Clinical Cancer Res., 8:3622-3627, 2002.

Worth, L.L., Lafleur, E.A., Jia, S-F, Kleinerman, E.S.  Fas expression inversely correlates with metastatic potential in osteosarcoma cells.  Oncology Reports, 9:823-827, 2002.

Marco, R.A.W., Diaz-Montero, C.M., Wygant, J.N., Kleinerman, E.S., McIntyre, B.W.  a4 Integrin Increases Anoikis of Human Osteosarcoma Cells.  J. Cellular Biochem., 88:1038-1047, 2003.

Jia, S-F., Worth, L.L., Densmore, C.L., Xu, B., Duan, X., Kleinerman, E.S.  Aerosol Gene Therapy with PEI:IL-12 Eradicates Osteosarcoma Lung Metastases.  Clinical Cancer Res., 9:3462-3468, 2003.

Bolontrade, M.F., Worth, L.L., Zhou, R-R., Marini, F.C., Andreeff, M., Kleinerman, E.S.  Bone Marrow Side Population Cells Contribute to Neovessel Formation in Ewing’s Sarcoma.  Stem Cell and Cellular Therapy, 1:14-20, 2003.

Gorlick, R., Anderson, P., Andrulis, I., Arndt, C., Beardsley, G.P., Bernstein, M., Bridge, J., Cheung, N-K., Dome, J.S., Ebb, D., Gardner, T., Gebhardt, M., Grier, H., Hansen, M., Healey, J., Helman, L., Hock, J., Houghton, J., Houghton, P., Huvos, A., Khanna, C., Kieran, M., Kleinerman, E.S., Ladanyi, M., Lau, C., Malkin, D., Marina, N., Meltzer, P., Meyers, P., Schofield, D., Schwartz, C., Smith, M.A., Toretsky, J., Tsokos, M., Wexler, L., Wigginton, J., Withrow, S., Schoenfeldt, M., and Anderson, B.  Biology of Childhood Osteogenic Sarcoma and Potential Targets for Therapeutic Development: Meeting Summary.  Clinical Cancer Res., 9:5442-5453, 2003.

Gautam, A., Waldrep, J.C., Kleinerman, E.S., Xu, B., Fung, Y.K., T’Ang, A., Densmore, C.L.  Aerosol gene therapy for metastatic lung cancer using PEI-p53 complexes.  Methods in Molecular Medicine, 75:607-618, 2003.

Zhou, Z., Zhou, R-R., Guan, H., Bucana, C.D., Kleinerman, E.S.  E1A gene therapy inhibits angiogenesis in a Ewing’s sarcoma animal model.  Molecular Cancer Therapeutics, 2:1313-1319, 2003.

Duan, X., Zhou, Z., Jia, S-F., Colvin, M., Lafleur, E.A., Kleinerman, E.S.  Interleukin-12 enhances the sensitivity of human osteosarcoma cells to 4-Hydroxperoxycyclophosphamide (4-HC) by a mechanism involving the Fas/Fas-Ligand Pathway.  Clinical Cancer Res., 10:777-783, 2004.

Lafleur, E.A., Koshkina, N.V., Stewart, J., Jia, S-F., Worth, L.L., Duan, X., Kleinerman, E.S.  Increased Fas Expression Reduces the Metastatic Potential of Human Osteosarcoma Cells.  Clinical Cancer Res., 10:8114-8119, 2004.

Guan, H., Jia, S-F., Zhou, Z., Stewart, J., and Kleinerman, E.S.  Herceptin downregulates Her2/neu and VEGF expression and enhances taxol-induced cytotoxicity of human Ewing’s sarcoma cells in vitro and in vivo.  Clinical Cancer Res., 11:2008-2017, 2005.

Guan, H., Zhou, Z., Wang, H., Jia, S-F., Liu, W., and Kleinerman, E.S.  A Small Interfering RNA Targeting Vascular Endothelial Growth Factor Inhibits Ewing’s Sarcoma Growth in a Xenograft Mouse Model.  Clin. Cancer Res., 11:2662-2669, 2005.

Koshkina, N.V. and Kleinerman, E.S.  Aerosol gemcitabine inhibits the growth of primary osteosarcoma and osteosarcoma lung metastases.  Int. J. Cancer, 116:458-463, 2005.

Cao, Y., Zhou, Z., de Crombrugghe, B., Nakashima, K., Guan, H., Duan, X., Jia, S-F., and Kleinerman, E.S.  Oxterix, a Transscription Factor for Osteoblast Differentiation, Mediates Antitumor Activity in Murine Osteosarcoma.  Cancer Res., 65:1124-1128, 2005.

Duan, X., Jia, S-F., Zhou, Z., Langley, R., Bolontrade, M., Fidler, I.J., and Kleinerman, E.S.  Association of a_vb₃ Integrin Expression with the Metastatic Potential and Migratory and Chemotactic Ability of Human Osteosarcoma Cells.  Clin. Exp. Metastasis, 21:747-753, 2005.

Meyers, P.A., Schwartz, C.L., Krailo, M., Kleinerman, E.S., Betcher, D., Bernstein M.L., Conrad, E., Ferguson, W., Gebhardt, M., Goorin, A.M., Harris, M.B., Healey, J., Huvos, A., Link, M., Montebello, J., Nadel, H., Nieder, M., Sato, J., Siegal, G., Weiner, M., Wells, R.J., Wold, L., Womer, R., Grier, H.  Osteosarcoma: A randomized, Prospective Trial of the Addition of Ifosfamide and/or Muramyl Tripeptide to Cisplatin, Doxorubicin, and High-Dose Methotrexate.  J. Clin. Oncol., 23:2004-2011, 2005.

Zhou, Z., Guan, H., and Kleinerman, E.S.  E1A specifically enhances sensitivity to topoisomerase IIa-targeting anticancer Drug by upregulating the promoter activity.  Molecular Cancer Res., 3:271-275, 2005.

Zhou, Z., Guan, H. and Kleinerman E.S.  Zoledronic acid inhibits primary bone tumor growth in Ewing’s sarcoma.  Cancer, 104:1713-1720, 2005.

Zhou, Z., Lafleur, E.A., Koshkina,N.V., Worth,L.L., Lester,M.S., and Kleinerman, E.S.  Interleukin-12 upregulates Fas expression in human osteosarcoma and Ewing's sarcoma cells by enhancing its promoter activity.  Molecular Cancer Res., 3:685-691, 2005.

Gordon, N., Arndt, C.A., Hawkins, D.S., Doherty, D.K., Inwards, C.Y., Munsell, M.F., Stewart, J., Koshkina, N.V., and Kleinerman, E.S.  Fas Expression in Lung Metastasis from Osteosarcoma Patients.  J. Pediatric Hem/Onc., 27:611-615, 2005.

Duan, X., Jia, S-F., Koshkina, N., and Kleinerman, E.S.  Intranasal Interleukin-12 Gene Therapy Enhanced the Activity of Ifosfamide Against Osteosarcoma Lung Metastases.  Cancer, 106:1382-1388, 2006.

Lee, T.H., Bolontrade, M.F., Worth, L.L., Guan, H., Ellis, L.M., and Kleinerman, E.S.  Production of VEGF₁₆₅ by Ewing’s Sarcoma Cells Induces Vasculogenesis and the Incorporation of CD34⁺ Stem Cells Into the Expanding Tumor Vasculature.  Int. J. Cancer, (In Press).

 
 

C. Research Support:

 
 

ONGOING

R01 NCI (CA42992, Years 20-25)  Kleinerman (PI)  01/01/2006 to 12/31/2010  20%

“Liposome and Polycationic Gene Therapy for Osteosarcoma”   $180,000.00 per year

 
 

The major goals of this project are to investigate the efficacy of intranasal and aerosol IL-12 gene therapy, with both viral and non-viral vectors, using a newly developed mouse OS lung metastasis model and determine the mechanism by which IL-12 induces this tumor regression.  The effect of IL-12 gene therapy on tumor vessel development, Fas expression and host production of vascular growth factors in the lung will be determined.

 
 

R01 NCI (CA103986, Years 1-3)  Kleinerman (PI)  07/01/2004 to 06/30/2007  20%

“Vasculogenesis in Ewing’s Sarcoma: Implications for Therapy”  $167,000.00 per year

 
 

The major goals of this project are to define the bone marrow cell subpopulations that contribute to the vasculogenesis process in Ewing’s sarcoma; determine whether cell division of migrated bone marrow cells contributes to vasculogenesis; determine whether tumor VEGF production influences tumor vasculogenesis.

COMPLETED

1RO1 NCI (CA82606, Years 1-3) Kleinerman (PI)  7/1/99 to 6/30/2002

“Chem/Immunotherapy for High-Risk Ewing’s Sarcoma” $100,000.00 per year

 
 

The major goals of this project are to determine (1) whether ImmTher immunotherapy following high-dose VAC can improve the 2-year disease-free survival, to evaluate the immunomodulatory activity of ImmTher and to monitor serum VEGF levels to determine if there is a correlation between VEGF and relapse.

 
 

There is no overlap

 
 

Texas Higher Education Coordinating Board Densmore (PI) 1/1/1999 to 12/31/2002  15%

      Kleinerman (Co-PI)

“Polyethylenimine Gene Therapy by Aerosol:  A Novel Treatment for Pulmonary Metastases”

 
 

The major goals of this project were to perfect a nonviral gene delivery system for aerosol treatment and test the effectiveness of various genes given by aerosol delivery in eradicating pulmonary metastases.  The use of PEI to deliver p53 and a p53-mutant gene by aerosol demonstrated efficacy and the ability of PEI to deliver genes throughout the entire lung.

 
 

No overlap.