Meet Eugenie Kleinerman, M.D.
Eugenie S. Kleinerman, M.D.
Department of Pediatrics, Division of Pediatrics
About Dr. Kleinerman
Eugenie S. Kleinerman, MD is Professor of the Division of Pediatrics, and Director of the Adolescent and Young Adult Cancer Program. She is board certified in pediatrics, holds the Mary V. and John A. Reilly Distinguished Chair and is also a Professor of Cancer Biology. A native of Cleveland, OH, Dr. Kleinerman received her BA degree from Washington University in St. Louis, her medical degree from Duke University, then completed her pediatric residency at the Children’s National Medical Center in Washington, DC and her fellowship at the National Cancer Institute in Bethesda, MD. She was a Senior Investigator at the NCI-Frederick Cancer Research facility for 3 years before being recruited to MD Anderson in 1984. Dr. Kleinerman rose through the ranks from Assistant Professor to Professor. She served as Division Head of the Division of Pediatrics from 2001 to February 9, 2015,the first women Division Head at MD Anderson.
Dr. Kleinerman is internationally recognized for her scientific and clinical expertise in sarcomas, particularly osteosarcoma (OS). She pioneered the use of a unique immunotherapy agent liposome-encapsulated MTP-PE, for children with unresponsive relapsed osteosarcoma lung metastases. Her phase II clinical trials done at MD Anderson demonstrated that liposomal MTP-PE therapy activated the tumoricidal properties of macrophages, prolonged disease-free survival and could be combined with chemotherapy. The success of these trials led to a national phase III trial sponsored by the Children’s Oncology Group. Newly diagnosed osteosarcoma patients treated with liposomal MTP-PE plus chemotherapy has a 30% reduction in mortality rate compared to the patients that received chemotherapy alone. This demonstration of efficacy led to the approval of liposomal MTP-PE by the European Medicine Agency, which is now part of the Standard of care in the U.L., Italy, Israel and Turkey. MTP-PE is available in 27 countries in the European Union. Dr. Kleinerman’s pioneering use of this immunotherapeutic agent in children with osteosarcoma resulted in the first improvement in long term survival of children with this disease in over 25 years.
Dr. Kleinerman’s laboratory research has also focused on understanding the mechanisms involved in osteosarcoma metastasis to the lung. Her investigations demonstrate that tumor Fas expression and the Fas/FasL pathway play a critical role in the metastatic potential of osteosarcoma cells and that this pathway can be targeted for therapeutic benefit. She is the first to show that a unique micro-RNA controls fas expression in OS cells. She is also the first to show that Ewing ’s tumor vessels are formed by both local endothelial cells and bone marrow cells that have migrated to the tumor and differentiated into endothelial cells and pericytes. She is the first to show that DLL4 and the NOTCH signaling pathway controls this differentiation process. Most recently her research has focused on using NK cell therapy with aerosol IL-2 against OS lung metastases. Dr. Kleinerman’s research program has been funded by the NCI for over 22 years.
Dr. Kleinerman has served on numerous NCI study sections and was a prior member of an FDA advisory panel. She has authored >170 articles and 21 book chapters. She is the editor of the book "Current Advances in Osteosarcoma" published in 2014.She has mentored numerous graduate students, postdoctoral fellows, MD/PhD students, and physician-scientists. She has worked to promote women and women’s issues in academic medicine. In 2006, her achievements were recognized by her alma mater, Duke University Medical Center, where she received the Distinguished Medical Alumnus Award. She was the recipient of the MD Anderson's Faculty Achievement Award in Clinical Research in 2009; the Distinguished Alumni Award from Washington University in 2010; the Outstanding Women in Texas Government Award in 2010 and inducted into the Greater Houston Women's Hall of Fame in 2011.
Present Title & Affiliation
Primary Appointment
Professor, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX
Mary V. and John A. Reilly Distinguished Chair, The University of Texas MD Anderson Cancer Center, Houston, TX
Dual/Joint/Adjunct Appointment
Professor, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Faculty Member, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX
Research Interests
My major interest is to develop novel ways to treat sarcoma patients by identifying new therapeutic targets in my laboratory and translating these ideas into clinical practice. I generated several investigator-initiated protocols based on my bench research including the use of either liposome-encapsulated MTP-PE, or ImmTher (2 immune therapies) in combination with traditional chemotherapy, and IL-1 a, or IFN a in combination with VP-16. L-MTP-PE alone or with ifosfamide significantly improved the disease-free survival of relapsed osteosarcoma (OS) patients. In a phase III trial adding L-MTP-PE to combination chemotherapy reduced the mortality rate of newly diagnosed OS patients by 30%.
Mouse models were developed (for OS and Ewing ’s sarcoma) to study the properties that influence metastases and to evaluate therapeutic strategies. We determined that Fas expression influences the metastatic potential of OS cells. We demonstrated the in vivo efficacy of aerosol Liposomal 9-nitrocamptothecin and gemcitabine against OS lung metastases. These agents upregulate the expression of Fas on the tumor cell surface, which results in the elimination of tumor cells by the constitutive FasL expressed in the lung.
Another focus is understanding how tumor vessels are formed in Ewing ’s sarcoma. New vessel development is a key component in supporting the growth of solid tumors. We demonstrated that bone marrow (BM) cells are involved in the vascular development and that vasculogenesis, in addition to angiogenesis, plays a role in Ewing ’s sarcoma growth and development. NOTCH signaling and DLL4 play a critical role as does VEGF 165.
Education & Training
Degree-Granting Education
1974 | Duke University, Durham, NC, USA, MD, Medicine |
1971 | Washington University, St. Louis, MO, USA, BA, Biology |
Experience & Service
Administrative Appointments/Responsibilities
Director, Department of Adolescent and Young Adult Cancer Program, The University of Texas MD Anderson Cancer Center, Houston, TX, 2015 - 2015
Endowed Positions
Mosbacher Pediatrics Chair, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, 2005 - 2013
Honors & Awards
2016 | Fellow, American Association for the Advancement of Science (AAAS) |
2014 | Women in Health & Medical Science Hearts of Gold Award |
2010 | Distinguished Alumni Award, Washington University |
2009 | The Otis W. and Pearl L. Walters Faculty Achievement Award in Clinical Research, The University of Texas MD Anderson Cancer Center |
2006 | Distinguished Medical Alumni Award, Duke University |
1999 | Business Professional Women of Texas Award |
1984 | Young Investigator Award in RES Research, Presented at the 21st National Meeting of the Reticuloendothelial Society |
1975 | Sandoz Award, Duke University |
1975 | Sheard-Sanford Award |
Selected Publications
Peer-Reviewed Articles
- Santiago-O'Farrill JM, Kleinerman ES, Hollomon MG, Livingston A, Wang WL, Tsai JW, Gordon NB. Phosphorylated heat shock protein 27 as a potential biomarker to predict the role of chemotherapy-induced autophagy in osteosarcoma response to therapy. Oncotarget 9(2):1602-1616, 2018. e-Pub 2017. PMID: 29416717.
- Hu J, Bernatchez C, Zhang L, Xia X, Kleinerman ES, Hung MC, Hwu P, Li S. Induction of NKG2D Ligands on Solid Tumors Requires Tumor-Specific CD8+ T cells and Histone Acetyltransferases. Cancer Immunol Res 5(4):300-311, 2017. e-Pub 2017. PMID: 28223282.
- Dibra D, Mitra A, Newman M, Xia X, Cutrera JJ, Gagea M, Kleinerman ES, Lozano G, Li S. Lack of immunomodulatory Interleukin-27 enhances oncogenic properties of mutant p53 in vivo. Clin Cancer Res 22(15):3876-83, 2016. e-Pub 2016. PMID: 26979394.
- Corrales-Medina FF, Herzog CE, Hess KR, Egas Bejar DE, Hong D, Falchook G, Anderson P, Nunez CA, Huh W, Naing A, Tsimberidou AM, Wheler JJ, Paul SP, Janku F, Kleinerman ES, Kurzrock R, Subbaih V. Clinical Characteristics and Outcomes of Pediatric Oncology Patients with Aggressive Biology Enrolled in Phase I Clinical Trials Designed for Adults: The University of Texas MD Anderson Cancer Center Experience. Oncoscience 1(7):522-30, 2014. PMID: 25587555.
- Piha-Paul SA, Shin SJ, Vats T, Guha-Thakurta N, Aaron J, Rytting M, Kleinerman E, Kurzrock R. Pediatric patients with refractory central nervous system tumors: experiences on a clinical trial combining the VEGF inhibitor bevacizumab and the mTOR inhibitor temsirolimus. Anticancer Res 34(4):1939-45, 2014. PMID: 24692729.
- Reddy K, Zhou Z, Schadler K, Jia SF, Kleinerman ES. Bone marrow subsets differentiate into endothelial cells and pericytes contributing to Ewing's tumor vessels. Mol Cancer Res 6(6):929-36, 2008. PMID: 18567797.
- Meyers PA, Schwartz CL, Krailo MD, Healey JH, Bernstein ML, Betcher D, Ferguson WS, Gebhardt MC, Goorin AM, Harris M, Kleinerman E, Link MP, Nadel H, Nieder M, Siegal GP, Weiner MA, Wells RJ, Womer RB, Grier HE, Children's Oncology Group. Osteosarcoma: The addition of muramyl tripeptide to chemotherapy improves overall survival. A Report from the Children's Oncology Group. J Clin Oncol 26(4):633-638, 2008. PMID: 18235123.
- Reddy K, Cao Y, Zhou Z, Yu L, Jia SF, Kleinerman ES. VEGF(165) expression in the tumor microenvironment influences the differentiation of bone marrow-derived pericytes that contribute to the Ewing's sarcoma vasculature. Angiogenesis 11(3):257-67, 2008. PMID: 18344025.
- Gordon, N, Koshkina NV, Jia SF, Khanna C, Mendoza Arnulfo, Worth, LL, Kleinerman ES. Corruption of the Fas pathway delays the pulmonary clearance of murine osteosarcoma cells, enhances their metastatic potential and reduces the effect of aerosol gemcitabine. Clin Cancer Res 13:4503-4510, 2007.
- Lee TH, Bolontrade MF, Worth LL, Guan H, Ellis LM, Kleinerman ES. 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 119(4):839-46, 2006. PMID: 16557578.
- Guan H, Jia SF, Zhou Z, Stewart J, Kleinerman ES. Herceptin down-regulates HER-2/neu and vascular endothelial growth factor expression and enhances taxol-induced cytotoxicity of human Ewing's sarcoma cells in vitro and in vivo. Clin Cancer Res 11(5):2008-17, 2005. PMID: 15756027.
- Cao Y, Zhou Z, de Crombrugghe B, Nakashima K, Guan H, Duan X, Jia SF, Kleinerman ES. Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in murine osteosarcoma. Cancer Res 65(4):1124-8, 2005. PMID: 15734992.
- Lafleur EA, Koshkina NV, Stewart J, Jia SF, Worth LL, Duan X, Kleinerman ES. Increased Fas expression reduces the metastatic potential of human osteosarcoma cells. Clin Cancer Res 10(23):8114-9, 2004. PMID: 15585647.
- Jia SF, Worth LL, Densmore CL, Xu B, Duan X, Kleinerman ES. Aerosol gene therapy with PEI: IL-12 eradicates osteosarcoma lung metastases. Clin Cancer Res 9(9):3462-8, 2003. PMID: 12960138.
- Bolontrade MF, Zhou RR, Kleinerman ES. Vasculogenesis Plays a Role in the Growth of Ewing's Sarcoma in Vivo. Clin Cancer Res 8(11):3622-7, 2002. PMID: 12429654.
Book Chapters
- Huang G, Nishimoto K, Yang Y, Kleinerman ES. Participation of the Fas/FasL Signaling Pathway and the Lung Microenvironment in the Development of Osteosarcoma Lung Metastases. In: Adv Exp Med Biol, 203-17, 2014.
Grant & Contract Support
Title: | The Future of Cancer Research: Training Program for Basic and Translational Scientists |
Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
Role: | Mentor |
Title: | The Future of Cancer Research: Training Program for Basic and Translational Scientists |
Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
Role: | Mentor |
Title: | Preclinical Evaluation of ERBB Family Members as Therapeutic Targets in Osteosarcoma |
Funding Source: | NIH/NCI |
Role: | Principal Investigator |