Rotation projects include development of nanobodies for prevention and treatment of mucosal disease (viral and bacteria).
School of Public Health and Health Sciences
Health Informatics And Implementation Science
Biostatistics And Health Services Research
Fiocruz-Minas Caroline Junqueira, PhD - Staff Scientist Camila Brabosa, PhD student - Mapping of CD8 T cell-specifc Epitopes from Malaria Blood Stage Gregorio Almeida, DVM, PhD - Immunology of Asymptomatic Malaria Guilherme Maia, PhD - Innate Lymphocytes in Malaria Isabella Hirako, PhD - Monocyte-Derived Dendritic Cells in Malaria Júlia Castro, MSc student - Chagas Disease Vaccine Larissa Pereira, MSc student - Inflammatory Caspases in Malaria Kely Mateucci, PhD - Monocyte-Derived Dendritic Cells Metabolism in Malaria Milton Pereira, PhD - Caspases and inflammasomes in Malaria and Chagas Disease Natalia Satchiko Souza, PhD - CD8+ T cells in malaria UMASS Danielle Durso, PhD - IRAKs and Myddosomes in host resistance to T. gondii Patricia Assis, PhD - Host Clock genes and Malaria Ogooluwa Ojelabi, PhD - Glucose Metabolism and Malaria
Additional information about lab rotations within the CPHR program can be found athttp://www.umassmed.edu/cphr/program/rotations.aspx
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 >
Rotation Projects Rotation projects are available in support of our research. See the research description section of this page.
David J. Freelander Memorial Professor in AIDS Research
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
Potential Rotation Projects Proteostasis regulators, HSF1, HSP70 and HSP90 in liver disease: Determine the expression and function in different cell types of the liver during acute and chronic liver injury using in vivo and in vitro models. Subsequently, we will test the relevance of the expression of these proteins in activation of intracellular signaling molecules involved in induction of fatty liver, inflammation and fibrosis. Role of chemokines in liver disease: CC-chemokines particularly CCL2/MCP-1, is significantly increased in serum as well as in the liver parenchyma in patients with alcoholic hepatitis. We test the role of MCP-1 in induction of fatty acid synthesis or metabolism and inflammation in the alcoholic liver. Our studies will also investigate the role of MCP-1 directed migration of immune cells in the liver contributing to injury.
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.
LAB ROTATION PROJECTS AVAILABLE -- PLEASE CONTACT SAM BEHAR FOR MORE INFORMATION
Focus: We seek to understand how the causative agent of tuberculosis, namely the bacterium Mycobacterium tuberculosis evades host immunity, and how different components of the immune response work together to contain infection. Our ultimate goal is to inform vaccine development and the design of host directed therapy.
Neil and Margery Blacklow Chair in Infectious Diseases and Immunology
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.
Potential Rotation Projects Contact Dr. Sullivan for more project details.
A postdoctoral position is available to study in this laboratory. Contact Dr. Rogaev for additional details.
Arthur F. and Helen P. Koskinas Professor in Biochemistry and Molecular Biotechnology
Herman G. Berkman Chair in Diabetes Care Innovation
UMass Memorial Health Care Chair in Biomedical Research
Potential Rotation Projects: Contact Dr. Luzuriaga for project details.
A postdoctoral position is available to study in this laboratory. Contact Dr. Kang for additional details.
<!-- [if gte mso 9]><xml> <o:DocumentProperties> <o:Template>Normal</o:Template> <o:Revision>0</o:Revision> <o:TotalTime>0</o:TotalTime> <o:Pages>1</o:Pages> <o:Words>109</o:Words> <o:Characters>624</o:Characters> <o:Company>UMass Medical School</o:Company> <o:Lines>5</o:Lines> <o:Paragraphs>1</o:Paragraphs> <o:CharactersWithSpaces>766</o:CharactersWithSpaces> <o:Version>11.1282</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!-- [if gte mso 9]><xml> <w:WordDocument> <w:Zoom>0</w:Zoom> <w:DoNotShowRevisions/> <w:DoNotPrintRevisions/> <w:DisplayHorizontalDrawingGridEvery>0</w:DisplayHorizontalDrawingGridEvery> <w:DisplayVerticalDrawingGridEvery>0</w:DisplayVerticalDrawingGridEvery> <w:UseMarginsForDrawingGridOrigin/> </w:WordDocument></xml><![endif]--> <!-- [if gte mso 9]><xml> <o:DocumentProperties> <o:Template>Normal</o:Template> <o:Revision>0</o:Revision> <o:TotalTime>0</o:TotalTime> <o:Pages>1</o:Pages> <o:Words>130</o:Words> <o:Characters>743</o:Characters> <o:Company>UMass Medical School</o:Company> <o:Lines>6</o:Lines> <o:Paragraphs>1</o:Paragraphs> <o:CharactersWithSpaces>912</o:CharactersWithSpaces> <o:Version>11.1282</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!-- [if gte mso 9]><xml> <w:WordDocument> <w:Zoom>0</w:Zoom> <w:DoNotShowRevisions/> <w:DoNotPrintRevisions/> <w:DisplayHorizontalDrawingGridEvery>0</w:DisplayHorizontalDrawingGridEvery> <w:DisplayVerticalDrawingGridEvery>0</w:DisplayVerticalDrawingGridEvery> <w:UseMarginsForDrawingGridOrigin/> </w:WordDocument></xml><![endif]--> Postdoctoral positionsstarting in March 2019 for studies of the gene regulatory networks underpinning the hematopoietic system (ImmGen.org), self- or tumor-reactive T cell trafficking to tissues in organ-specific autoimmunity and tumor surveillance, respectively. Applicants must have a record of accomplishment in immunology or developmentalbiology with technical fluency in molecular biology, animal model generationand analysis, gene expression analysis and/or intravital imaging. Send a letterof interest, CV and names of three references to: Joonsoo Kang, Ph. D., E-mail (preferred): joonsoo.kang@ umassmed.edu. Dept. of Pathology, The Albert ShermanCenter (http://www.umassmed.edu/shermancenter/index.aspx)at Univ. of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA01655.
Potential Rotation Projects <p >1. SOX proteins in the maintenance of mucosal tissue integrity and innate immunity. There are ~20 Sox genes in mammals. Although the prototypic SOX-related proteins, SRY (Sex-determining gene on Y chromosome) and TCF/LEF are reasonably well characterized, very little is known about the relevance of SOX proteins in lymphocyte development and function. We have discovered that some SOX proteins can regulate the WNT/Wingless signaling cascade, a central morphogenetic pathways specifying cell fate in all organisms whose aberrant activity leads to tumourigenesis. Importantly, expression of specific combinations of Sox genes is lymphocyte subset-specific, temporally and spatially. Our results so far strongly indicate that Sox genes are important regulators of multiple lymphocyte subsets, in part by opposing WNT signaling. An impediment to advances in understanding Sox gene functions has been that they are critical for embryonic development and mutations lead to early lethality. We have therefore embarked on generating conditional KO mice of various Sox genes and their cofactors that we postulate are centrally involved in lymphocyte differentiation and function. A few rotation projects are available to analyze these newly derived mouse models, both at the level of cellular and molecular analysis of lymphocyte development and single-cell tracking of specific Sox gene expressing cells in vivo. These mice have defects in mucosal tissue barrier functions and often exhibit aberrant inflammatory responses in the skin that can model human skin diseases such as psoriasis and dermatitis. <p >a. analysis of Sox13 reporter mice <p >b. analysis of Sox4-deficient mice for innate lymphocyte developmental defects <p >c. analysis of spontaneous skin inflammation in mice lacking dermal innate IL-17 producers <p >d. analysis of global chromatin docking of HMG TFs in ex vivo T cells <p >e. comparative analysis of global gene regulation and gene networks across all hematopoietic cells <p > <p >2. Testing small molecule compounds to treat organ-specific T cell-mediated autoimmunity in mice (e.g. Type I Diabetes, colitis and the mouse model of multiple sclerosis). <p >3. Analysis of mice with novel mutations in TGFb signaling to investigate the role of TGFb in regulating self-destructive T cells.
Potential Rotation Projects Several rotation projects are available in structural biology of immune receptors, antigen presentation pathways, T-cell activation, and development of novel T-cell detection reagents. Please see Prof. Stern for details.
A postdoctoral position is available to study in this laboratory. Contact Dr. Gottlinger for additional details.
Potential Rotation Projects 1.The identification of novel binding partners for cellular proteins required for HIV-1 budding using a double tag immunoaffinity purification approach. 2.The characterization of mutant ESCRT-III components that block HIV-1 budding with regard to subcellular localization and their ability to interact with certain phosphoinositol lipids and with other proteins involved in late endosomal sorting. 3.The mapping of binding sites for cellular proteins that we have identified as specific components of HIV-1 using GST pulldown, yeast two-hybrid, and co-immunoprecipitation approaches. 4.The generation and functional characterization of mutant viral Gag proteins that fail to interact with specific cellular partners.
Population and Quantitative Health Sciences
Focus: The Munro laboratory develops and applies quantitative biophysical approaches to visualize virus replication, and probe the functions of the proteins and RNAs involved.
Focus: Viral entry, antibodies & vaccines, single molecule techniques
Biochemistry and Molecular Biotechnology
Life Time Achievement Award Lecture, OTS
Jack M. Wilson Chair in Biomedical Research
Joseph D. Early Chair in Biomedical Research
Advisory links alcohol consumption to cancers: Here's how Worcester feels about the report