The Stem Cells, Differentiation and Cancer Program evolved from the former Cell Growth and Differentiation Control Program with the inclusion of scientists from the former Immuno-oncology program that study B cell biology and lymphoid malignancies. The program was further strengthened by the formation of a Stem Cell Institute at Einstein with the recruitment of four cancer stem cell investigators. There are three major research themes that partially overlap: the myeloid leukemias, lymphoid malignancies and stem cell biology, with a continued emphasis on regulation at the transcriptional level. While there is a focus on hematological malignancies, the stem cell research extends to hepatic, neural, and mammary stem cells. Dr. E. Richard Stanley is leader of this newly configured program. The appointment of Dr. Amit Verma, physician scientist, as Co-Program leader and the establishment of a Hematological Malignancies Working Group has catalyzed translation and increased the number of correlative and therapeutic clinical studies. The goals of this program are: (i) to understand the molecular events that occur during the normal differentiation of stem cell progenitors into their mature counterparts; (ii) to identify the aberrations that occur in transcriptional programming that result in the malignant phenotype with a special, but not sole, focus on the hematopoietic malignancies;(iii) to identify molecules that are novel therapeutic targets, indicators of aggressiveness of disease or reporters of response to treatment;(iv) to translate laboratory research findings into correlative and, ultimately, therapeutic trials and to enhance the effectiveness of clinical regimens with existing and new chemotherapeutics and biologicals;and (v) to encourage those Program members who share a common interest in stem cells, cellular programming, and their relationship to cancer to collaborate with each other and with the members of other programs. Human tissue research has been facilitated by the acquisition of two FACS Sorter Biosafety systems dedicated to this program, a Human Pluripotent Stem Cell Center for the development and analysis of human embryonic and induced pluripotent stem cells that comprises a stem cell preparation unit, a cell sorting and xenotransplantation unit, and a stem cell bioinformatics unit. There are currently 31 program members of whom 30 are primary;nine are new recruits to Einstein. Research is supported by 12 NCI grants ($2.66M DC) and 28 other cancer-relevant peer reviewed grants ($5.35M DC). Since 2008, there have been 364 cancer-relevant publications by members of this program, of which 16% represent intra- and 17% represent inter-programmatic collaborations.

Public Health Relevance

This program seeks to understand the very early changes that occur in the genetic material of cells that makes them cancerous and to develop drugs that will prevent or reverse these changes. There is a particular interest in identifying the most primitive cells (called cancer stem cells) that are affected by these changes. Cancer stem cells may be the most resistant to drugs and radiation and may explain why cancers return after they initially respond to treatment.

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Subcommittee B - Comprehensiveness (NCI)
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Mocholi, Enric; Dowling, Samuel D; Botbol, Yair et al. (2018) Autophagy Is a Tolerance-Avoidance Mechanism that Modulates TCR-Mediated Signaling and Cell Metabolism to Prevent Induction of T Cell Anergy. Cell Rep 24:1136-1150
Mao, Serena P H; Park, Minji; Cabrera, Ramon M et al. (2018) Loss of amphiregulin reduces myoepithelial cell coverage of mammary ducts and alters breast tumor growth. Breast Cancer Res 20:131
Guan, Fangxia; Tabrizian, Tahmineh; Novaj, Ardijana et al. (2018) Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis. Front Nutr 5:37
Yang, Chia-Ping Huang; Wang, Changwei; Ojima, Iwao et al. (2018) Taxol Analogues Exhibit Differential Effects on Photoaffinity Labeling of ?-Tubulin and the Multidrug Resistance Associated P-Glycoprotein. J Nat Prod 81:600-606
Chennamadhavuni, Divya; Saavedra-Avila, Noemi Alejandra; Carreño, Leandro J et al. (2018) Dual Modifications of ?-Galactosylceramide Synergize to Promote Activation of Human Invariant Natural Killer T Cells and Stimulate Anti-tumor Immunity. Cell Chem Biol 25:571-584.e8
Wang, Tao; Hosgood, H Dean; Lan, Qing et al. (2018) The Relationship Between Population Attributable Fraction and Heritability in Genetic Studies. Front Genet 9:352
Rocha, Agostinho G; Franco, Antonietta; Krezel, Andrzej M et al. (2018) MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A. Science 360:336-341
Limi, Saima; Senecal, Adrien; Coleman, Robert et al. (2018) Transcriptional burst fraction and size dynamics during lens fiber cell differentiation and detailed insights into the denucleation process. J Biol Chem 293:13176-13190
Vilchèze, Catherine; Copeland, Jacqueline; Keiser, Tracy L et al. (2018) Rational Design of Biosafety Level 2-Approved, Multidrug-Resistant Strains of Mycobacterium tuberculosis through Nutrient Auxotrophy. MBio 9:
Cabahug-Zuckerman, Pamela; Stout Jr, Randy F; Majeska, Robert J et al. (2018) Potential role for a specialized ?3 integrin-based structure on osteocyte processes in bone mechanosensation. J Orthop Res 36:642-652

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