Endowed Chair in Biochemistry and Molecular Biotechnology I
Health Informatics And Implementation Science
Elisabeth Chair for the Dean of Medicine
Our Danny Cancer Fund Chair in Biomedical Research I
A postdoctoral position is available to study in this laboratory. Contact Dr. Kelliher for additional details.
Please visit the Kelliher Lab website at: http://labs.umassmed.edu/kelliherlab/ to learn more about our current research areas. 1. Identify genes/pathways that mediate leukemia-initiating cell survival 2. Understand the molecular basis of glucocorticoid resistance in leukemia 3. Examine contribution of RIPK1 kinase in inflammatory and autoimmune disease mouse models. 4. Reveal tissue-specific roles for RIPK1 in cell death and inflammation. Use conditional Ripk1 allele to investigate effects of Ripk1 deletion in liver, pancreas and antigen presenting cells.
Penelope Booth Rockwell Chair in Biomedical Research
Focus: Adeno-associated virus vector mediated gene transfer for gene therapy, gene therapy of inherited neurodegenerative Canavan Disease
Postdoctoral positions are available for this lab. Please contact Junhao Mao directly, 508-856-4149 or via email, Junhao.Mao@umassmed.edu
Worcester Foundation for Biomedical Research Chair II
Focus: Mucosal inflammation, host: pathogen interactions, and cancer biology
An entry level postdoctoral position is open immediately in the laboratory of Dr. Susan L. Swain to study the factors that control the development and survival of CD4 and CD8 T cell memory. Graduate student experience with tissue culture, in vitro assay, flow cytometry, experience in mouse models on infectious disease and a knowledge of cellular and molecular immunology are all strongly desired.
<p >Rotations: Projects in the following areas <p >CD4 T cell memory. We can generate in vitro CD4 T cells that are for all extents and purposes identical to the memory CD4 T cells observed in vivo. In situ memory CD4 T cells persist at very low frequency and in most instances it is difficult to analyze them thoroughly using tetramer or multimer reagents both because of their low frequency and the relatively low specific affinity of the Class II reagents for the TcR. Being able to generate “recent” memory cells in vitro gives us the opportunity to analyze in detail the mechanisms by which memory CD4 T cells may contribute to secondary immunity and immune protection. Once identified. will determine if particular pathways are relevant in situ. We have discovered that memory CD4 T cells are superior in protection to those from the primary response and that they display pleitropic functions that have not been previously identified. <p > Cytotoxic CD4 Effectors. One unexpected function of CD4 T cells we identified is robust, perforin-dependent cytotoxic activity (7, 16). Cytotoxic activity by CD4 T cells has been reported in response to several infections, but its significance has not heretofore been established. We find that “Th1 polarized” CD4 effectors and more relevantly the CD4 effectors found in the lung following influenza infection, are able to kill infected or peptide-pulsed Class II-bearing targets and we find that this perforin dependent activity can work together with antibody to provide protection against lethal influenza challenge in otherwise unprimed mice (17). We also will determine when memory CD4 T cells re-express cytotoxic activity following in vivo challenge and how cytotoxic killing contributes to the memory cell mediated protection. We want to analyze how the program of cytotoxicity is induced in these “ThCTL”. <p > Memory CD4 Cells Enhance an Innate Response. Memory cells can act by becoming secondary effectors but they are best characterized by their ability respond rapidly even to low antigen doses, by producing cytokines and chemokines and it is assumed that these initial abilities are key to memory cell activity. However this assumption has not been directly demonstrated and the mechanisms involved and how they might contribute to immunity have not been elucidated. We find that restimulation of memory CD4 T cells leads to a markedly enhanced early innate response to influenza infection both in the lung and systemically (17). This response peaks 2-3 days after infection and is transient. We see enhanced production of IL-6 locally and systemically and enhanced production a broad spectrum of innate inflammatory mediators in the lung. We hope to determine in detail the pathways leading to optimum memory T cell-induced innate responses. We suggest a concurrent activation of CD4 memory cells may be an effective adjuvant for vaccination and will be testing this hypothesis as well as mechanisms that lead to viral control over the next couple of years. <p >Aging and Immunity: The study of the impact of aging on CD4 T cell function at the naïve and memory stages has lead us to better understanding of fundamental aspects of T cell behavior in addition to providing important information about what vaccine approaches are most likely to be successful for the aged. Nature of CD4 Aging “Defects”. We have identified multiple levels at which aged naïve CD4 T cells are defective including initial early response to TcR triggering, IL-2 production, expansion and effector generation. The defects in helper function and in the 20 response of memory cells generated from aged naïve CD4 T cells are particularly dramatic. In recent studies we have recapitulated memory age-associated defects in recently generated memory cells in vitro (23). In vitro aged memory cells are markedly defective in production of particular cytokines, IL-4, IL-5 and IL-2, while others are little affected (IFNg, IL-10, TNF), suggesting the aging “defect” may be restricted to loss of potential to make certain CD4 T cell subsets, such as those responsible for help to B cells .We will pursue this hypothesis both in vitro and in vivo. <p >We have found that aged naïve CD4 T cells are in fact longer-lived than their naïve counterparts (23). We find that reduced expression of Bim, a proapoptotic protein, is responsible for this increase in lifespan and that the increase in lifespan is required for the development of aging defects. We are now investigating the factors that regulate Bim expression. <p >Enhancement by Inflammatory Cytokines. We have shown that the defective effector generation responses of naïve CD4 T cells from aged animals can be overcome by IL-2 and by proinflammatory cytokines, in particular a mix of IL-1, IL-6 and TNF (20,21). We want to determine the extent to which the inflammatory cytokines can reverse the heritable aging defects and restore functional memory generation. We have developed in vitro models to test the generation of effectors and memory. In these models we are evaluating TLR agonists for their ability to restore aged naïve CD4 responses to peptide-pulsed derived dendritic cells (DC). Pre-incubation of DC with many TLR agonists, enhances expansion of the responding aged naïve CD4 T cells via a mechanism dependent on IL-6 that acts in part by increasing survival of the developing effector population. We plan to use this model to identify the extent of the rescue and what pathways and mechanisms contribute with the ultimate goal of evaluating whether specific TLR stimulation or stimulation of specific pathways might improve the response of the elderly to vaccines. We want to see if we can reproduce this model with human naïve CD4 T cells and DC derived from peripheral blood and if TLR agonists can also enhance those responses. <p >
Please contact the Human Resources at UMass for openings in Dr. Bergmann's lab.
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
H. Arthur Smith Chair in Cancer Research
Rotation Projects Laboratory rotations are available to study signal mammalian transduction mechanisms. Several projects are available, including studies of protein kinase cascades, gene expression, the cell cycle, and apoptosis. Targeted gene disruption approaches in mice combined with biochemical and molecular biology studies will be examined.
One rotation student is expected in the lab to characterize the expression and function of Drosophila gustatory receptor 28b (Gr28b) in phototransduction and taste sensation. Please contact Dr. Yang Xiang for details.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p> <o:p> </o:p> Yang Xiang, Ph.D. University of Massachusetts Medical School Department of Neurobiology, LRB 725 364 Plantation Street Worcester, MA 01605 USA phone: 508-856-6816 (office) e-mail: yang.xiang@umassmed.edu<o:p></o:p>
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.
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/
Herman G. Berkman Chair in Diabetes Care Innovation
Potential Rotation Projects Rotation projects in my laboratory will involve questions of how cilia are assembled and the function these organelles play in mammals. Projects vary depending on ongoing work in the laboratory and interests of the rotation student. Rotations in my laboratory can give students exposure to a range of techniques from mouse breeding and histological analysis of mouse tissues to mammalian cell culture and other cell biological techniques.
George F. Booth Chair in the Basic Sciences
<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
Population and Quantitative Health Sciences
Biochemistry and Molecular Biotechnology
Joseph D. Early Chair in Biomedical Research