Six students make the transition from students to scientists as they begin their dissertation research.
Our lab has recently shown that the Promyelocytic Leukemia Zinc Finger (PLZF) gene, a BTB-zinc finger family member, is necessary for the differentiation and function of Natural Killer T (NKT) cells. Like NKT cells, γδ T cells are categorized as “innate-like” unconventional T cells, as both share several phenotypic and functional characteristics. In order to improve our understanding of γδ T cell lineage program, we propose to investigate the role of PLZF in γδ T cell development. We hypothesize that these studies will reveal an important role for PLZF in γδ T cell differentiation and function, while potentially establishing a common link in the development of distinct unconventional T cells.
Meiotic recombination is initiated by DNA double-strand breaks (DSBs) catalyzed by the Spo11 protein. Nine other proteins are required for this process in budding yeast; however, so far, few have been identified in higher eukaryotes. My project attempts to identify other proteins required for meiotic DSB formation in the mouse by screening for Spo11 interacting partners. Biochemical and genetic analysis will be used to determine whether these proteins play a role in meiosis.
Although at least eight protein kinases are necessary to maintain the spindle assembly checkpoint, a cell cycle brake that protects against aneuploidy by preventing premature anaphase onset, their role has been unexplored and their relevant targets remain obscure. In order to gain insight into the role of these kinases, we will use small molecule inhibition, chemical genetics, and mass spectrometry to detect spindle checkpoint-dependent phosphates on the mitotic checkpoint complex, a transient, spindle checkpoint effector. In addition, we are using chemical genetics to model the effects of spindle checkpoint inactivation on tumorigenesis in the mouse.
The majority of the work done on cell signaling in mammalian development has focused on the roles of signaling networks in directing cell fate through the control of transcription factors. However, much less is known about how the cellular architecture of the embryo is established. My long-term goal is to define the cell biology that underlies the elongation of the mammalian neural plate, with the objective of determining what aspects of this morphogenic process are perturbed in embryos mutant for genes in the planar cell polarity pathway. This work is significant to human disease as these cellular processes may underlie defects in neural tube closure, a congenital malformation affecting one in every 1,000 births.
Breast cancer metastasis is the ultimate cause of mortality of patients with the disease. The ability of cancer cells to migrate away from the primary tumor and into the surrounding tissues requires dramatic cytoskeletal rearrangements, which are controlled by Rho family GTPases. These molecular switches are activated and inactivated by GEF and GAP proteins and are thought to confer specificity of signal regulation to various cellular processes related to migration and invasion. Systematic analysis of all Rho GTPase GEFs/GAPs and targets should reveal how the GTPases regulate cell migration in breast cancer cells.
An effective anti-cancer T cell-mediated immune response depends on the proper selection and presentation of peptides on MHC by a targeted tumor cell. My overall objective is to identify new MYCN-derived T cell epitopes and subsequently assess their heterogeneity within and among tumors using HLA-restricted, peptide-specific antibodies. Since MYCN amplification strongly predicts adverse outcome in neuroblastoma, identifying and visualizing T cell epitopes derived from this transcription factor could ultimately lead to advances in T cell-mediated immunotherapy.
Our Growing Community
The School has welcomed six new faculty members since January 1:
Research Interest: How the genome dictates development, with C. elegans as our models
Ross L. Levine
Human Oncology and Pathogenesis
Research Interest: Investigation of genetic basis of hematopoietic malignancies
Jason S. Lewis
Molecular Pharmacology and Chemistry
Research Interest: Development of radiopharmaceuticals for the imaging and therapy of cancer
Ingo K. Mellinghoff
Human Oncology and Pathogenesis
Research Interest: Molecular determinants in drug response and growth factor signaling
Research Interest: Theoretical evolutionary biology of cancer initiation and progression, treatment, and resistance
Meng-Fu Bryan Tsou
Research Interest: Cell cycle control of centrosome duplication and degeneration
Gerstner Sloan Kettering is proud to announce that 11 new PhD students will begin their studies on July 28, and 19 undergraduate students will begin their summer studies on June 2.
Students and Staff Support a Worthy Cause
A Gerstner Sloan Kettering team of students and staff participated in the May 3 Revlon Walk/Run. The event raises funds for research and treatment of women’s cancers, as well as for support services for women affected by cancer.