Dr. Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research
Psychology And Neuroscience & Behavior Program
Health Informatics And Implementation Science
Blais University Chair in Molecular Medicine
Potential Rotation Projects: There are numerous potential rotation project available in the Mello lab: Projects include: Investigation of RNAi and related mechanisms, including Piwi Argonaute pathways and their affects on fertility and epigenetic inheritance; Investigation of germline determination and cell-fate specification during embryogenesis; the exploration of CRISPR mediated genome editing tools for C. elegans and other organisms; and finally the use of CRISPR to generate C. elegans models for human genetic disease.
<p >Our laboratory combines biochemical, biophysical, molecular and cell biological approaches to investigate various aspects of pre-mRNA processing, mRNA metabolism and RNA quality control in eukaryotic cells. Potential rotation projects are available in all areas of the laboratory's interests (see Research section).
Rotation Projects Rotation projects are available to address the following questions: How does the lack of structure in the C-terminal zinc finger of TTP affect the activity of the protein in the cell? In humans, there are three members in the TTP protein family: TTP, TIS11b and TIS11d. Structural studies performed by us and others have shown that while the TZF domain of TTP is partially unstructured in the free state and folds upon binding RNA, those of TIS11d and TIS11b are always folded. We have shown that the degree of structure of the TZF domain affects the activity of the protein in cells and indicates that the protein can modulate its activity through its dynamics. We want to determine whether structural disorder is directly linked to cellular stability or protein localization How do mutations in the RNA-binding domain of TIS11d cause cancer? Several point mutation in TTP and TIS11d have been linked to cancer. In particular, point mutations in the RNA-binding domain of TIS11d are found in leukemia patients. We are currently working on the characterization of the structure, dynamics and biological activity of these mutant proteins to understand their role in the pathogenesis of cancer. How does HuR regulate the stability of its target mRNA? HuR is another protein that, like TTP, binds to AU-rich elements (ARE) in mRNAs and regulate their stability. The detailed mechanisms that determine how HuR regulates transcripts stability are poorly understood. We are investigating how binding or HuR to the 3’UTR of an mRNA leads to its stabilization.
Rotations <p >Project 1: Genetic screens for proteins that modify or regulate the activity of microRNAs in C. elegans.
<p >Potential rotation projects My lab primarily investigates Plasmodium falciparum malaria-induced dysregulation of EBV-specific T cell immunity and its role in the etiology of endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in Equatorial Africa. Within the context of our ongoing studies of healthy Kenyan children with divergent malaria exposure histories (chronic/repeated infections in a holoendemic area versus low infection rates in a nearby highland, malaria hypoendemic area) and by examining children diagnosed with eBL we have established a repository of samples that can be used to address this question. <p >1. One avenue of exploration involves homeostatic cytokine regulation of memory T cells. IL-15 and/or IL-7 responsiveness of EBV-specific memory T cells may be impaired in children with chronic malaria exposure and in children with endemic Burkitt lymphoma (eBL). We would like to investigate IL-15Ra and IL-7Ra surface expression, and CFSE proliferation of EBV-specific T cells in response to cognate antigen with and without IL-15 or IL-7 stimulation and compared children with divergent malaria exposure histories and children diagnosed with eBL. T cell responsiveness to IL-15 and IL-7 can be measured by STAT5 phosphorylation and the specificity of this effect for EBV-specific T cells can be evaluated by comparing IL-15Ra and IL-7Ra expression and responsiveness on other lymphocyte subsets and CMV-specific T cells. <p >2. Another putative mechanism by which malaria may interfere with the development of immunologic memory and influence EBV-specific T cell immunity is through the Programmed death-1 (PD-1) pathway. PD-1 is an immune inhibitory molecule that negatively regulates activated immune cells upon interacting with its ligands, programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2) resulting in down-regulation of immune responses. Previous studies in murine and primate viral and parasitic diseases have reported the up-regulation of PD-1 and soluble PD-1 (sPD-1) but no studies have reported the expression of PD-1 in individuals from areas with divergent malaria transmission dynamics or in children presenting with endemic Burkitt lymphoma (eBL). In addition the PD-1 pathway has been suggested to be involved in the evasion of antitumor immunity by the host immune system. Preliminary studies in my lab suggest that PD-1 expression is significantly increased on CD4, CD8 T cells, B cells and NK cells in those residing in high malaria transmission areas compared to age-matched individuals without a history of malaria exposure. Future studies will explore the kinetics of this effect, the impact of antigen dose and how malaria exploits PD-1 mediated regulation to impair the development of immunologic memory. <p >3. Another area of interest is the role of Th17 cells in pediatric immunity. Because of the naturally delayed production of TH1 mediated pro-inflammatory cytokines (i.e. IL-12 and IFN-g) in utero, neonatal immunity is thought to be Ã¢â‚¬ËœsuppressedÃ¢â‚¬â„¢. However, more recent studies have shown that neonatal monocytes and antigen-presenting cells do express pro-inflammatory and regulatory cytokines (i.e. IL-6, IL-10 and IL-23) and at higher levels than adults. Thus TH17 cells appear to be an early, sequential response to pathogens prior to the induction of a TH1 or TH2 response. TH17 cells are also stimulated with IL-21 and IL-22 in an autocrine and paracrine fashion by natural killer cells. Exploring Th17 cell responses within the context of early-age human infections with malaria and EBV would be an exciting new avenue of investigation in my laboratory.
Focus: Post-transcriptional gene regulation in eukaryotes
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
UMass Chan Medical School Chair in Biomedical Research
A postdoctoral position is available to study in this laboratory. Contact Dr. Rock for additional details.
Potential Rotation Projects <p >Rotations are available in Dr. Rock’s laboratory for graduate students in the GSBS program. The rotation projects will explore various aspects of how the immune system carries out surveillance to detect viral infections and cancers. Among the potential areas of research are: (1) The alarm signals that alert the immune system to potential danger; (2) The initial innate immune and inflammatory response to infection or other dangerous situations; (3) The biology of the sentinel cells (e.g. dendritic cells) that sense danger and report it the adaptive immune system; (4) The mechanisms by which sentinel cells (e.g. dendritic cells) acquire and display antigens to T cells; and, (5) The antigen presentation pathways by which virally infected or cancer cells display a sampling of their expressed gene products to the activated T cells. Specific rotation projects are chosen based on the student’s interests and state/availability of the various projects in the laboratory. The goals of rotations are for the student to gain knowledge in immunology, to learn how to approach experimental problems, to learn new techniques and methods, and to actually generate data that moves our knowledge forward. In addition, the rotation provides the student the opportunity to evaluate the laboratory as a possible place to conduct their thesis research in the future.
Immediate opening! Two postdoctoral positions are available immediately to study cellular andmolecular mechanisms resulting in immunosuppression after alcohol use. Thefocus of this research is the role of monocytes and dendritic cells indecreased antigen-specific T cell activation after alcohol use.Intracellular signalling mechanisms resulting in decreased NF-kBactivation and inflammatory cytokine induction after acute alcoholconsumption are being investigated. Please contact Dr. Szabo for details.
Leo P. and Theresa M. LaChance Chair in Medical Research
Lawrence lab research bridges fundamental questions of developmental epigenetics with translational research into the common problem of chromosome abnormalities, particularly Down syndrome.
Gretchen Stone Cook Chair in Biomedical Sciences
A postdoctoral position is available to study in this laboratory. Contact Dr. Zamore for additional details
Potential Rotation Projects Our laboratory uses a combination of biochemistry, cell biology, and genetics to dissect the RNAi pathway. A rotation project is available to explore the mechanisms that underlie the RNAi phenomenon or the biological pathways in which RNAi enzymes participate in flies, mice and humans.
Please contact Dr. Imbalzano to discuss the possibility of a postdoctoral training.See lab research interests and publications for recent topics of research. http://www.umassmed.edu/imbalzanolab/ http://www.umassmed.edu/imbalzanolab/publications/
Please contact Dr. Imbalzano to discuss the possibility of a rotation project. Rotation projects are generally based on current work and tailored to the interests of the student. See lab research interests and publications for recent topics. http://www.umassmed.edu/imbalzanolab/ http://www.umassmed.edu/imbalzanolab/publications/
Arthur F. Koskinas Chair in Neuroscience
Many rotation projects are available so please inquire.
<p >Rotation Projects <p >Rotation projects are designed to expose students to the molecular cell biology of solid tumors and to provide them with an appreciation for translational cancer research. Specific rotation projects, which are focused on the major themes of the lab, include: <p >Function and Regulation of Integrins (Cell Adhesion Receptors) in Cancer Epigenetic mechanisms that regulate integrin gene expression in human cancers Regulation of integrin expression and function during the EMT Role of specfic microRNAs (miRs) in regulating integrin function and signaling Contribution of integrins to carcinoma progression using mouse models of breast carcinoma <p >Vascular Endothelial Growth Factor (VEGF) Signaling, EMT and Carcinoma Progression Function and expression of VEGF receptors in carcinoma cells Regulation of VEGF transcription in response to EMT stimuli Role of miRs in regulating VEGF receptors and signaling Contribution of VEGF signaling to the behavior of aggressive, de-differentiated carcinomas <p >Nuclear Hormone Receptors and EMT Role of estrogen receptors in regulating the EMT Regulation of VEGF transcription by estrogen receptors
Potential Rotation Projects A variety of rotation projects are available to study RNP assembly and post-transcriptional regulation during development using quantitative biochemical and modern molecular methods. Project 1: Characterization of the RNA-protein complexes that guide C. elegans early development. Several projects ranging in scope from biochemical characterization of RNA-binding protein complexes to genetic dissection of RNA binding protein function in development are currently available. Contact Sean for more details. Project 2: Post-transcriptional regulation of oligodendrocyte differentiation. Projects are available to monitor changes in gene expression as a function of differentiation with a focus on changes in alternative splicing and mRNA stability. Contact Sean for more details.
Richard M. Haidack Professor in Medicine
Population and Quantitative Health Sciences
Biochemistry and Molecular Biotechnology
Healthcare Delivery and Population Sciences at UMass Chan - Baystate
Joseph D. Early Chair in Biomedical Research
Eleanor Eustis Farrington Chair in Cancer Research