Veterinary & Animal Sciences; Pioneer Valley Life
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
A postdoctoral position is available to study in this laboratory. Clickhereto apply.
<p >Rotations <p >Potential rotations <p >1. To examine how TCR affinity and specificity for MHC + peptide influences the development and activation of CD4 T cells. <p >2. To assess the impact of self tolerance on the specificity, affinity and pathogenic potential of T cells reactive to proteins expressed in the central nervous system and b-islet cells of the pancreas.
Elisabeth Chair for the Dean of Medicine
Our Danny Cancer Fund Chair in Biomedical Research II
Postdoctoral positions are available for this lab. Please contact Eric Baehrecke directly, 508-856-6733 or via email, Eric.Baehrecke@umassmed.edu
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.
The project aims to develop computational algorithms and software programs for analyzing high-throughput sequence data such as ChIP-Seq RNA-Seq small RNA sequencing data. PhD required. A strong background in computational biology especially experience with analyzing high-throughput sequencing data is highly desirable. Excellent communication and writing skills and the ability to work with experimental and computational collaborators are essential. To apply please forward CV cover letter and three references to: Zhiping.Weng@umassmed.edu
Please contact Dr. Weng for information on rotations that are available in her lab.
Rotations <p >Project 1: Genetic screens for proteins that modify or regulate the activity of microRNAs in C. elegans.
Postdoctoral positions are available for this lab. Please contact Junhao Mao directly, 508-856-4149 or via email, Junhao.Mao@umassmed.edu
Lab rotations are currently available in this lab. Please contact Dr. Kim.
My research for almost 30 years has focused on obesity, insulin resistance, and type 2 diabetes and explores the molecular link between inflammation and insulin resistance using transgenic mice with elegant in vivo metabolic experiments and molecular approaches. My research also investigates the role of inflammation and altered metabolism in diabetic heart disease.
Rotation Projects for graduate students: Examining the role of cross-reactive CD8 memory T cells in mediating the EBV-induced infectious mononucleosis syndrome in humans. Examining the role of cross-reactive CD8 memory T cells and cytokines in murine models of viral infection. Examining the mechanisms used by these memory T cells to unrelated infections to modulate disease outcome either for the bad or the good.
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 >
Governor Paul Cellucci Chair in Neuroscience Research
Project 1: Dervelop RNA-based therapies for frontotemporal dementia (FTD) and related disroders. Project 2: Study pathogenic mechanisms of FTD and related disorders in mouse models.
Our lab uses a combination of molecular, cellular, genetic, and behavioral approaches to further dissect the pathogenic mechanisms of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis with a focus on mutant CHMP2B, progranulin and C9ORF72. We will identify common underlying pathways as potential targets for therapeutic interventions.
Please contact the Human Resources at UMass for openings in Dr. Bergmann's lab.
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.
Isadore and Fannie Foxman Chair in Medical Research
A postdoctoral position is available to study in this laboratory. Contact Dr. Czech for additional details.
Mentoring……………………………………………………………………………………………………… The Czech laboratory is active in mentoring graduate students and postdoctoral fellows. Many former student and postdoctoral trainees of the Czech laboratory are now internationally recognized professors at major universities and medical schools. These former lab members include: Paul Pilch, Professor of Biochemistry, Boston University School of Medicine Jeffrey Pessin, Professor and Director of the Diabetes Center, Einstein College of Medicine Joan Massague, Director, Sloan Kettering Institute Roger Davis, HHMI investigator and Professor of Molecular Medicine, UMASS Medical School Silvia Corvera, Professor of Molecular Medicine, Co-Director of the MD/PhD Program, UMASS Medical School Carla Greenbaum, Vice Chair and Director of Clinical Research, Benaroya Research Institute Jes Klarlund, Professor of Ophthalmology, University of Pittsburgh Medical Center Rob Lewis, Professor of Biochemistry and Molecular Biology, Eppley Cancer Institute, University of Nebraska Medical Center Richard MacDonald, Professor of Biochemistry and Molecular Biology, Eppley Cancer Institute, University of Nebraska Medical Center Assia Shisheva, Professor of Physiology, Wayne State School of Medicine. Mark Sleeman, Professor of Physiology, Monash University, Australia John Harris, Associate Professor of Medicine, UMASS Medical School Zhen Jiang, Associate Professor of Pharmacology and Medicine, Boston University Vishu Puri, Professor of Biomedical Sciences, Ohio University Olga Gupta, Assistant Professor of Pediatrics and Medicine, University of Texas Southwestern Medical Center Tim Fitzgibbons, Assistant Professor of Medicine, UMASS Medical School Myriam Aouadi, Assistant Professor, Integrated Cardio Metabolic Centre, Karolinska Institute Adilson Guilherme, Associate Professor, University of Massachusetts Medical School Our laboratory currently offers graduate student Rotation Projects (examples below and others available) and Thesis Research Projects for students following a rotation: Developing CRISPR technology for gene editing in adipocytes: Adipocytes function as master regulators of whole body metabolism and deletions of specific adipocyte genes in knockout mice promote dramatic improvements in glucose tolerance and insulin sensitivity in diabetic models. Thus the ability to direct gene editing in adipocytes in vivo has great potential in developing therapeutic strategies for obesity, type 2 diabetes and cardiovascular complications. Alternatively, an ex vivo approach is also feasible since adipose cells can be genetically altered in vitro prior to implantation into mice with beneficial effects. Such projects are designed to be performed in collaboration with other Czech lab members with the goal of specifically deleting or editing genes in adipose depots that drive increases in fatty acid oxidation, energy expenditure and systemic metabolic activity. Exciting preliminary data at the “proof of principle” stage has been achieved and this project is designed to focus on specific genes of high interest for therapeutics. Signaling by the lipogenesis pathway through Acetyl CoA: A major function of adipocytes is to store calories as triglyceride, in part through the process of fatty acid synthesis (lipogenesis). This metabolic pathway involves a number of metabolites including Acetyl CoA, which is also a substrate for acetylation reactions that modify proteins such as histones. Thus metabolic flux through adipocyte lipogenesis may also function as a signaling pathway to the nucleus to modulate transcription via levels of Acetyl CoA that accumulate during this process. This rotation project is designed to test this idea at the molecular level by monitoring histone acetylations and resultant transcriptional events during changes in Acetyl CoA levels caused by altering physiological conditions such as exercise, obesity and diabetes. If this concept is correct, the project could lead to developing therapeutic strategies for metabolic disease based on targeting lipogenic enzymes.
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.
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.
Background for Student Rotation Projects <p >See Politz, Hogan and Pederson (2009) and Politz et al. (2005) in the above list. The novel microRNA work may be the most suitable for student rotations. Potential Rotation Projects <p >Are the nucleolar microRNAs pri-, pre- or mature? <p >Are they complexed with other nucleolar RNAs? <p >Do the cell cycle related proteins in the nucleolus exist as heterotypic complexes? <p >Does the nucleolus of human embryonic stem cells also share these features (which we have so far looked for, and found, only in transformed human cell lines)? <p >Can vanadium tagging be used to detect specific proteins by electron microscopy, perhaps exceeding the limitations of immuno-EM?
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/
Lambi and Sarah Adams Chair in Genetic Research
Rotations: Targeting the IFN-?-chemokine axis for treatment of vitiligo: We are using our newly developed mouse model and human tissues from patients with vitiligo to identify the cytokines and chemokines that are expressed within the depigmenting skin and which skin cells produce them. We are using genetically modified mouse strains (knockouts, conditional knockouts, fluorescent reporter strains), and cytokine and chemokine neutralizing antibodies to identify the key proteins required for disease. This data will permit us to rationally develop and test new therapeutic agents. Understanding the proinflammatory signals generated by melanocytes under cellular stress. Melanocytes from vitiligo patients have intrinsic abnormalities, including cellular stress evidenced by increased production of reactive oxygen species (ROS) and activation of the unfolded protein response (UPR). The immune system has evolved to recognize this stress as damage-associated molecular patterns (DAMPs), which activate innate immunity. We are using human cells and tissues to determine how cellular stress, innate immunity, and adaptive immunity cooperate to initiate and perpetuate depigmentation in vitiligo. Developing a humanized mouse model of immune-skin interactions to serve as a pre-clinical bridge to clinical studies: We are developing a humanized mouse model of skin disease that consists of an immunodeficient mouse strain as a host for an autologous human skin graft and immune reconstitution in order to study mechanisms of inflammation in the skin, including allergic contact dermatitis, response to infection, tumor immunotherapy, and autoimmunity, all within a fully human environment. This model system will act as a pre-clinical bridge between mouse models and human clinical trials, providing an opportunity to test new treatments on human cells and tissues prior to initiating trials on patients. Tracking real-time autoreactive T cell migration and interactions within the skin: We are using fluorescently/bioluminescently tagged CD8 T cells to track their movements and interactions within the skin in live mice, using real-time confocal microscopy and bioluminescent imaging. Initial studies will focus on the role of cytokines and chemokines in T cell migration within the skin. Clinical trial to test a novel treatment for vitiligo: We are in the early stages of developing a clinical trial based on insights developed from our animal data to test a novel drug for its ability to treat vitiligo.
Rotations: Targeting the IFN-g-chemokine axis for treatment of vitiligo: We are using our newly developed mouse model and human tissues from patients with vitiligo to identify the cytokines and chemokines that are expressed within the depigmenting skin and which skin cells produce them. We are using genetically modified mouse strains (knockouts, conditional knockouts, fluorescent reporter strains), and cytokine and chemokine neutralizing antibodies to identify the key proteins required for disease. This data will permit us to rationally develop and test new therapeutic agents. Understanding the proinflammatory signals generated by melanocytes under cellular stress. Melanocytes from vitiligo patients have intrinsic abnormalities, including cellular stress evidenced by increased production of reactive oxygen species (ROS) and activation of the unfolded protein response (UPR). The immune system has evolved to recognize this stress as damage-associated molecular patterns (DAMPs), which activate innate immunity. We are using human cells and tissues to determine how cellular stress, innate immunity, and adaptive immunity cooperate to initiate and perpetuate depigmentation in vitiligo. Developing a humanized mouse model of immune-skin interactions to serve as a pre-clinical bridge to clinical studies: We are developing a humanized mouse model of skin disease that consists of an immunodeficient mouse strain as a host for an autologous human skin graft and immune reconstitution in order to study mechanisms of inflammation in the skin, including allergic contact dermatitis, response to infection, tumor immunotherapy, and autoimmunity, all within a fully human environment. This model system will act as a pre-clinical bridge between mouse models and human clinical trials, providing an opportunity to test new treatments on human cells and tissues prior to initiating trials on patients. Tracking autoreactive T cell interactions within the skin: We are using fluorescently tagged CD8 T cells to track their cellular interactions within the skin using confocal microscopy. Future studies will adapt this model to investigate real-time migration and other movements of these cells within compartments of the skin. Clinical trial to test a novel treatment for vitiligo: We recently completed a clinical trial based on insights developed from our animal data to test a novel drug for its ability to treat vitiligo.
Interests: Vitiligo, autoimmunity, immunology, translational research
Arthur F. Koskinas Chair in Neuroscience
Many rotation projects are available so please inquire.
A postdoctoral position is available to study in this laboratory. Contact Dr. Ip for additional details.
Rotation Projects Project #1: Mechanistic study of isolated mutants that show abnormal intestinal stem cell division phenotypes. Project #2:Perform transgenic RNAi-based genetic screen for genes required for intestinal stem cell response to tissue damage.
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.
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.
Rotation Projects Please contact Nathan Lawson (nathan.lawson@umassmed.edu) for information regarding potential rotation projects. For information concerning recent research in the lab, please see:lawsonlab.umassmed.edu/research.html
<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
We are seeking a post-doctoral fellow to study toll/interleukin 1 receptors and their role in inflammatory disease pathogenesis using human cells and mouse models. Candidates should have a Ph.D. or M.D. degree, or have completed degree requirements. Experience in immunology, molecular biology and/or biochemistry and publication of papers in the areas of cytokine biology, receptor biochemistry and/or cell signaling required.
Potential Rotation Projects Expression of Toll-like receptors: Patterns of TLR expression in normal cells. Control of TLR receptor expression by environmental factors and cytokines. TLR expression in diseased tissues. Role of TLRs in disease pathogenesis: Use of knockout and genetically defined animals to study the role of TLRs in the control of bacterial or viral diseases. Structure-function studies of TLR signaling: Assessing the signaling activity of wild type and mutant TLRs (altered by site-directed mutageneis) using transient transfection and luciferase reporter gene analysis.
Biochemistry and Molecular Biotechnology
National Mouse Metabolic Phenotyping Center
Jack M. Wilson Chair in Biomedical Research
Joseph D. Early Chair in Biomedical Research