Rotation projects include development of nanobodies for prevention and treatment of mucosal disease (viral and bacteria).
Health Informatics And Implementation Science
Focus: Mycobacterial cell wall synthesis, mycobacterial genetic manipulation
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.
Donna M. and Robert J. Manning Chair in Neurosciences
Dr. Brown’s laboratory has focused on the identification of gene defects that elucidate the molecular pathogenesis of selected neuromuscular diseases including amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease), muscular dystrophy, adrenoleukodystrophy, hereditary neuropathy and hyperkalemic periodic paralysis.
The lab is currently looking for motivated postdoctoral scholars with backgrounds in genomics and computational biology. Please email the PI.
Rotation projects are available related to malaria and Burkitt lymphoma. Our projects range from genetic epidemiology to directed genomics studying human, parasite and tumor.
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 >
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
Rotation Projects Study the interaction of the ssDNA annealing protein Bet and its cognate exonuclease with dsDNA ends. Compare wild type Bet with one or mutant Bet proteins. Use both genetic and biochemical studies to answer the question of how this annealase binds to ssDNA and promotes recombination. Develop recombineering technologies for M. tuberculosis involving the electroporation of oligos containing clinically relevant single nucleotide polymorphisms (SNPs). Generate a recombineering system for Pseudomonas aeruginosa via the electroporation of PCR substrates into electrocompetent cells containing PA phage Red-like recombination systems.
Focus: DNA Mismatch repair mechanisms in M. smegmatis; recombineering technology for gene replacement in bacterial pathogens, M. tuberculosis drug discovery.
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
A postdoctoral position is available to study in this laboratory. Contact Dr. Rogaev for additional 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 <p >We have identified a number of bacterial pathways that are required for bacterial viability or virulence. We are particularly interested in: Phosphosignaling systems that regulate cell wall synthesis Metabolic regulatory mechanisms that trigger the “dormancy” response observed during infection. <p >A variety of genetic, biochemical, and informatic methods will be used to define the functions of these genes and the role played by each during infection. <p >
Richard M. Haidack Professor in Medicine
Teresita del Nino Jesus Padilla-Benavides PhD
Claudia A. Vilchis Nestor. Visiting Scholar from CINVESTAV-IPN, MEXICO
Interests: Autoimmunity, Immunology, Fibrosis, Translational Research, Lupus
Focus: Director of the Sanderson Center for Optics Experimentation (SCOPE)
Population and Quantitative Health Sciences
Focus: Host-microbiome interaction, computational biology, synthetic biology
Biochemistry and Molecular Biotechnology
Healthcare Delivery and Population Sciences at UMass Chan - Baystate
Dr. Mustafa Barbhuiya is currently the Medical Director of Clinical Chemistry and Point of Care Testing at the Department of Pathology, Baystate Medical Center, Springfield, MA. His basic and translational research interests include liver and biliary tract cancer biomarkers. He also conducts research on the role of essential diagnostics list in health care delivery and population health.
Joseph D. Early Chair in Biomedical Research