Rotation projects include development of nanobodies for prevention and treatment of mucosal disease (viral and bacteria).
Endowed Chair in Biochemistry and Molecular Biotechnology I
Molly McGovern Chair in Biomedical Research
There are a variety of rotation projects that use a variety of imaging and biochemical techniques to assess microglial function in the CNS. The main projects are highlighted below. 1. Dissecting novel molecular mechanisms underlying microglial function at synapses. 2. Exploring new roles for microglia in the spread of neuroinflammation in neurological disease. 3. Identifying novel ways microglia regulate other glial cell populations (astrocytes and oligodendrocytes) in the CNS.
School of Public Health and Health Sciences
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
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.
A postdoc position is available to study in Dr. Ceol's lab.Click here to apply.
<p >Postdoctoral Research Associate Position available to work on topics related to the molecular mechanisms involved in theactivation and differentiation of both murine and human autoreactive Bcells. The lab is particularlyinterested in innate sensors of cell damage, including members of the Toll-likereceptor and Pyhin receptor gene families.
<p >Rotation position open to work on topics related to the molecular mechanisms involved in theactivation and differentiation of both murine and human autoreactive Bcells. The lab is particularlyinterested in innate sensors of cell damage, including members of the Toll-likereceptor and Pyhin receptor gene families.
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.
Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Kensuke Futai for additional details.
Rotation Projects The Futai laboratory seeks highly motivated graduate students who have interest in the roles of risk genes of neuropsychiatric diseases, such as autism and schizophrenia, on neuronal function.Rotation students will typically work side-by-side with Kenny Futai or Postdoctoral Fellows, and give one laboratory meeting presentation at the conclusion of their rotation project. Rotation projects The roles of the risk genes of neuropsychiatric diseases on neuronal structure and synaptic function The roles of the scaffold molecules in synapse maturation, synaptic transmission and synaptic plasticity Characterization of gultamate receptors which express in interneruon
Please contact the Human Resources at UMass for openings in Dr. Bergmann's lab.
A postdoc position is available to study circadian rhythms in Drosophila. Contact Patrick Emery (patrick.emery@umassmed.edu).
Biological clocks play an essential role in the temporal organization of animal physiology and behavior. We combine the powerful genetics of Drosophila with molecular, cell culture and behavioral approaches to obtain a comprehensive view of the mechanisms regulating circadian clocks and one of their critical output: sleep. We also now study the mechanisms enabling marine organisms to anticipate tides. Indeed, we have developed a model organism to study circatidal rhythms: Parhyale hawaiensis. Rotation projects could for example focus on characterizing new candudate post-transcriptional regulators of circadian rhythms, the role of glial genes in the control of sleep, or studying the molecular mechanisms of circatidal clocks.
A postdoctoral position is available to study in this laboratory. Contact Dr. Theurkauf for additional details.
Rotation Projects Proper control of cell division and accurate chromosome segregation are fundamental to cell function and normal development. Chromosome segregation errors lead to birth defects, and abnormal cell division control is associated with essentially all cancers. A major aim of research in the laboratory is to understand cell cycle control and chromosome segregation mechanisms. We use a combination of classical and molecular genetics, high-resolution in vivo imaging, and biochemical techniques to define pathways that control the cell cycle and chromosome segregation in response to environmental insult (DNA damaging agents) and developmental queues. Rotation projects focus on the role of cell cycle checkpoint and tumor suppressor pathways during the earliest stages of embryogenesis, and cell cycle control of actin and microtubule reorganization during mitosis. Through these projects, students gain exposure of the art in vivo imaging and genetic and molecular manipulations of gene function to define pathways controlling cell division and chromosome segregation. Embryonic Patterning Essentially all cells are asymmetric, with structurally distinct surfaces and polarized internal organization. This asymmetry is essential to the specialized functions cells serve within complex multi-cellular organisms . A second area of interest focuses on the mechanisms that establish cellular asymmetry. In Drosophila, the embryonic axes are specified during oogenesis through the asymmetric localization of key morphogenetic molecules within the developing oocyte. We use axis specification in the fly as a model for the processes that establish cellular asymmetry. An intact microtubule network is essential to axis specification in the fly oocyte and to polarization of somatic. We hope to define the molecular functions for microtubules in establishing cellular asymmetry. We are currently using in vivo imaging techniques to directly characterize the microtubule dependent mRNA transport processes that differentiate the anterior and posterior poles of the developing oocyte. In addition, classical genetic and biochemical techniques are used to identify the microtubule motors and associated proteins that mediate mRNA movements to the oocyte poles.
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.
Focus: Developmental regulation of V(D)J recombination and B cell development
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.
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.
Rotation Projects Please contact me if you are interested in hearing more about current lab projects and potential rotation projects: ann.rittenhouse@umassmed.edu.
Focus: Voltage-Gated Calcium channels and neuronal plasticity
Arthur F. Koskinas Chair in Neuroscience
Many rotation projects are available so please inquire.
Postdoctoral Fellow Applications are being accepted for one position. A position is available to develop Cys2His2 zinc finger proteins (ZFPs) for the treatment of monogenic disorders. This project will focus on the creation of ZFPs with novel DNA-binding specificity to recognize sequence elements within genomic loci of therapeutic interest. In collaboration with other laboratories, we will evaluate the activity of these ZFP-based gene therapy reagents in vitro and in vivo in relevant disease models. Applicants will also have the opportunity to learn to apply Cas9 and Cas12a editing systems in vivo.
Potential Rotation Projects Improving the Precision of CRISPR/Cas9 nucleases for gene therapy applications: We are working to improve the precision of the CRISPR/Cas9 system to generate nucleases that will cleave at only a single site in the genome. These engineering efforts focus on increasing the DNA-editing precision of Cas9 and using protein engineering to introduce new properties into the nuclease. Much of this work is now transitioning to the use of Cas9 (and Cas12a) protein-RNA complexes. These modified nucleases will then be applied to patient derived cell-culture systems for the targeted repair or inactivation of disease-causing alleles. With the eventual goal of creating therapeutics for Sickle Cell Disease, beta-Thalassemia, HIV, Limb Girdle Muscular Dystrophy, Hermansky Pudlak Syndrome and other monogenic disorders. ex vivo genome editing in CD34+ HSPCs: We are developing improved Cas9 proteins for delivery ex vivo into CD34+ HSPCs for therapeutic application to sickle cell disease and beta-thalassemia. The goal is to modify the hematopoietic stem cells of a patient to complement the loss of function of the beta-globin gene and then return these cells to the patient through an autologous transplant. Development of Cys2His2 Zinc fingers proteins (ZFPs) as targeted therapeutics: We are developing artificial ZFPs for the regulation of target genes to change their gene expression profiles for therapeutic applications.
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.
A postdoctoral position is available to study in this laboratory. Contact Dr. Budnik for additional details.
Postdoctoral Positions are available in this laboratory. Contact Dr. ZhuGe for additional details at ronghua.zhuge@umassmed.edu
Rotation projects are available to study (1) the pathophysiology of Cl- channel TMEM16A in smooth muscle, (2) molecular mechanisms by which bitter tasting compounds relax smooth muscle, and (3) the role of bitter taste receptors in the pathogenesis of smooth muscle disorders.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p>
Focus: The ZhuGe lab studies the molecular mechanisms by which Ca2+ signals and ion channels control neurotransmitter release and smooth muscle contractility. We also exploit new physiological functions of bitter taste receptors in extra-oral tissues and organs. We aim to find novel molecular targets for new therapies to manage asthma, fecal incontinence, preterm labor, and adenomyosis.
Herman G. Berkman Chair in Diabetes Care Innovation
Potential Rotation Projects Drugs of abuse: Loose patch clamping of organ cultures from whole brain in order to determine what ion channels are affected by opioids and other drugs of abuse. Determining specific calcium channel subtypes and localization in relationship to release sites using confocal imaging techniques. Molecular mechanisms of synaptic transmission: Bi-layers/Tip dipping: recording single channels reconstituted from posterior pituitary nerve terminals using patch clamp techniques. Reconstitute Ca2+-dependent exocytosis in vitro by a combination of amperometric and molecular biological techniques. Endogenous Feedback regulation of neuropeptide release: Determine different synaptic neurotransmitter (ATP) and opioid receptor subtypes and localization on oxytocin vs. vasopressin releasing nerve terminals using immunohistochemistry and deconvolution techniques.
A postdoctoral position is available to study in this laboratory. Contact Dr. Craig for additional details.
Potential Rotation Projects Project #1: Lipid-Layer Protein Crystallization for Electron Microscopy.While individual protein molecules can be readily visualized by EM, structural information is greatly enhanced if the molecules can by crystallized into 2-dimensional ordered arrays. Methods for achieving this are well established, making use of lipid monolayers at an air-water interface. Follow literature methods to crystallize "standard" proteins using the lipid-layer method. Observe results by electron microscopy following negative staining. If time permits, carry out preliminary image processing of micrographs and/or crystallization of unknown proteins. Techniques to be learned: lipid layer crystallization methods; grid preparation; use of electron microscope; image processing.
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
Biochemistry and Molecular Biotechnology
Worcester Foundation for Biomedical Research Chair I