The Aroian Group is actively recruiting graduate students to: 1. use microbiology and genetics to develop new methods for delivery of protein therapies (anthelmintics) to the GI tract 2. discovery and mechanism of action studies of new anthelmintics to control soil-transmitted helminths 3. study how vertebrate hosts and their immune system interact with intestinal nematodes, with the particular goal of controlling autoimmune disease 4. study innate immune mechanisms that protect animals against pore-forming toxin attack
Endowed Chair in Biochemistry and Molecular Biotechnology I
Blais University Chair in Molecular Medicine
Potential Rotation Projects: There are numerous potential rotation project available in the Mello lab: Projects include: Investigation of RNAi and related mechanisms, including Piwi Argonaute pathways and their affects on fertility and epigenetic inheritance; Investigation of germline determination and cell-fate specification during embryogenesis; the exploration of CRISPR mediated genome editing tools for C. elegans and other organisms; and finally the use of CRISPR to generate C. elegans models for human genetic disease.
A postdoctoral position is available to study in this laboratory. Contact Dr.Francis for additional details.
<p >Potential Rotation Projects <p >The Francis lab studies the regulation of post-synaptic neurotransmitter receptors and how alterations in synaptic transmission lead to changes in behavior. We combine patch-clamp electrophysiology with the powerful genetic techniques available in C. elegans. <p >A variety of potential rotation projects centered around the exploration of synaptic function, mechanisms for receptor localization and analysis of C. elegans movement are available. Students can expect to have access to training in a broad range of techniques including forward and reverse genetic strategies, molecular biology, fluorescent microscopy and electrophysiology. As projects are always evolving, I encourage students to contact the lab directly to discuss your specific interests.
Endowed Chair in Biochemistry and Molecular Biotechnology II
For more information about the Postdoctoral position in Dr. Rando’s lab please use the link provided. Post doc position
Rotation projects are available to study chromatin structure and function. Project 1. Measure histone dynamics in yeast. Histone dynamics play major roles in chromatin metabolism and in the inheritance of chromatin states. To measure histone replacement rates in yeast, we have created yeast strains carrying inducible epitope-tagged histones H3 and H2A. Using microarrays, we will measure histone replacement rates in a variety of mutant yeast to ascertain the role of various chromatin remodeling factors in histone exchange reactions. Project 2. Characterize mechanisms for epigenetic inheritance in yeast. We have identified a variety of genes whose expression state in yeast is epigenetically heritable. We will screen the yeast genome for genes that affect the inheritance of these expression patterns. Project 3. Measure histone dynamics in embryonic stem cells. Embryonic stem cells are pluripotent cells that can give rise to every type of cell in the adult animal. The role of chromatin structure in maintaining this pluripotent state is poorly understood, but it appears that stem cell chromatin is exceptionally labile relative to that in differentiated cells. We will create stem cell lines with inducible tagged histones to measure histone replacement rates across the mouse genome.
Rotation Projects Rotation projects are available to address the following questions: How does the lack of structure in the C-terminal zinc finger of TTP affect the activity of the protein in the cell? In humans, there are three members in the TTP protein family: TTP, TIS11b and TIS11d. Structural studies performed by us and others have shown that while the TZF domain of TTP is partially unstructured in the free state and folds upon binding RNA, those of TIS11d and TIS11b are always folded. We have shown that the degree of structure of the TZF domain affects the activity of the protein in cells and indicates that the protein can modulate its activity through its dynamics. We want to determine whether structural disorder is directly linked to cellular stability or protein localization How do mutations in the RNA-binding domain of TIS11d cause cancer? Several point mutation in TTP and TIS11d have been linked to cancer. In particular, point mutations in the RNA-binding domain of TIS11d are found in leukemia patients. We are currently working on the characterization of the structure, dynamics and biological activity of these mutant proteins to understand their role in the pathogenesis of cancer. How does HuR regulate the stability of its target mRNA? HuR is another protein that, like TTP, binds to AU-rich elements (ARE) in mRNAs and regulate their stability. The detailed mechanisms that determine how HuR regulates transcripts stability are poorly understood. We are investigating how binding or HuR to the 3’UTR of an mRNA leads to its stabilization.
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
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.
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 >
A postdoctoral position is available to study in this laboratory. Please contact Dr. Fazzio for details.
Rotation Projects <p >Rotation projects are available on any of the main topics being studied in the lab. Our recent RNAi screen identifying chromatin regulators necessary for ES cell self-renewal has opened up several new potential projects aimed at identification of the important functions of these regulators in ES cells. Alternatively, projects focusing on the mechanisms of action and regulation of Tip60-p400 complex, or examining the functions of chromatin regulators in cancer stem cells are also possible, depending on the student’s interests. Rotation projects will usually involve some combination of mammalian cell culture, cell and molecular biology, biochemistry, and genomic approaches.
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.
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.
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.
Determine links between SREBPs, SAMe levels and epigenetic regulation Methylation of histones or DNA affects gene expression at local as well as global levels. The major cellular methyl donor, s-adenosylmethionine (SAMe) is produced by the folate or 1-carbon (1C) cycle. 1CC function may be affected by dietary levels of folate, methionine, choline or betaine, genetic polymorphisms, or alcohol intake, linking potential for epigenetic modification in cancer progression to food intake and metabolism. Physiological limitation of 1CC function has multiple deleterious physiological effects from birth defects to the development of hepatosteatosis and has also been linked to hepatic and colon cancer. While many studies have shown that the availability of methyl donors may dramatically affect human disease, the mechanisms governing SAMe production and epigenetic modification are much less clear. We hypothesize that modulation of SBP-1 function affecting sams-1 expression will also alter methyl group levels and subsequently, histone modification, leading to changes in gene expression relevant to overall nutritional homeostasis. We will determine if modulation of SAMe levels through SBP-1 effects histone methylation at nutritionally important promoters and examine how diet quality and dietary supplementation affect SBP-1 activity by evaluating histone methylation, in addition to employing biological assays for epigenetic changes in gene expression. We will also use unbiased assays such as ChIP-Seq to identify genes whose expression levels are linked to epigenetic changes after sbp-1 RNAi, selecting those with roles in metabolism for further study. These studies will provide a basis for understanding how lipid homeostasis and other dietary influences affect SAMe production and how those are linked to increased lipid accumulation in C. elegans. Future studies will extend these models to mammalian systems to investigate how these changes predispose hepatosteatosis, a component of metabolic syndrome in humans.
Determine mechanisms for differential regulation of SREBP-1 and SREBP-2 by PC-based feedback In recent studies, we have found that inactive precursors for SREBP-1 are cleaved, accumulate in the nucleus and activate lipogenic transcription programs when membrane changes linked to low PC levels alter localization of SREBP-activating proteases (see Research Interests). We also found that SREBP-2 was resistant to this regulation (Figure 1), and note that while mouse models of PC depletion are associated with hepatic steatosis, cholesterol levels are not necessarily affected (Jacobs, et al. 2008, JBC). We will determine the mechanisms of this differential regulation which will be important for understanding how lipid or cholesterol synthesis may be inappropriately stimulated in metabolic disease. Figure 1: Depletion of PC biosynthesis enzymes in HepG2 human hepatoma cells causes nuclear localization of SREBP-1, but not SREBP-2. Yellow line shows cell boundary
Identify cellular responses to decreased SAMe production Our studies in C. elegans showed that SREBP transcriptional activators could control expression 1CC genes. These studies are important because they demonstrate that levels of these critical enzymes mRNAa are not controlled as a “housekeeping function” but are instead are coordinated with other cellular processes. We have developed two models for 1CC dysfunction in C. elegans, a genetic model based on loss of function (lof) of sams-1, a SBP-1/SREBP responsive gene encoding the enzyme for producing the methyl donor SAMe and a dietary model in which C. elegans are fed bacteria unable to synthesize folate. In both of these models, transcription of lipogenic genes are highly increased and sams-1(lof) worms accumulate large lipid droplets, mimicking aspects of fatty liver disease in mammals. These models will allow use genetic screens as a tool for identifying 1) other regulatory pathways affecting SAMe production or utilization and 2) cellular responses that limit lipogenesis when methyl donor levels are low.
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.
Remondi Family Chair in Biomedical Research
POSTDOCTORAL POSITION: RNAI PRECLINICAL DEVELOPMENT Excellent training opportunity for a person considering industrial carrier in drug development Oligonucleotides represent a new class of drugs, which have the promise to become a major class of future therapeutics. There are several classes of oligonucleotides which can efficiently silence genes in various tissues with acceptable level of toxicity. There are also new chemistries being developed to further improve oligonucleotide tissue distribution and cellular uptake. The successful candidate will be a key part of an intra-disciplinary team working with biologists and chemists to develop novel types of therapeutics for treatment of neurological disease, liver disease and orphan indications. The work will include compounds identification, screening, characterization, in vivo efficacy and PK/PD studies, novel assays development etc. In addition exposure and training in nucleic acid pre-clinical development, project management etc will be provided. QUALIFICATIONS: Applicants must have (or expect to obtain shortly) a Ph.D. in Chemistry, Organic Chemistry Biochemistry, Cell Biology, Molecular Biology or a related field , be bright, ambitious, independent and collaborative and ideally, have research experience in nucleic acid molecular cell biology or pharmacology.
RNAI MEDICINAL CHEMISTRY/ RNA OLIGONUCLEOTIDE CHEMISTRY Develop and characterize novel RNA chemistries to promote efficient oligonucleotide internalization and tissue distribution. Oligonucleotides represent a new class of drugs, which have the promise to become a major class of future therapeutics. There are several chemistries and formulations developed by us and others that effectively support oligo internalization and favorable PK/PD. In most cases in vivo efficacy is limited by (1) poor PK (2) inefficient tissue distribution (3) compound entrapment in biologically inactive intracellular compartments. The objective of future studies will be development of novel chemistries, which promote receptor mediated cellular internalization and/ or endosomal escape. The successful candidate will be responsible for the design and synthesis of novel RNA precursors, optimization of RNA synthesis and conjugation protocols and interface with the biology part of the lab. In addition, exposure to pre-clinical development programs and oligonucleotide manufacturing will be available. QUALIFICATIONS: Applicants must have (or expect to obtain shortly) a Ph.D. in Chemistry, Organic Chemistry Biochemistry, Cell Biology, Molecular Biology or a related field , be bright, ambitious, independent and collaborative and have previous experience in nucleic acid / oligonucleotide chemistry.
SMALL RNA TRAFFICKING Discover, characterize and adapt mechanisms of small RNA extracellular and intracellular trafficking for development of novel classes of oligonucleotide drugs. A serious limitation in realizing the potential of oligonucleotide based therapies has been the exceedingly inefficient transit of oligonucleotides from outside cells to the intracellular compartments where the biologically relevant activity happens. On the other hand, there are multiple lines of evidence supporting the notion that nature has implemented evolutionarily conserved mechanisms and pathways for efficiently trafficking small RNAs across cellular boundaries. The objective of future studies will be the systematic evaluation of mechanisms of cellular uptake of different classes of oligonucleotides and their comparison to mechanisms of native RNA trafficking using a combination of experimental approaches, including advanced RNA chemistry and high temporal and spatial resolution microscopy in living cells, Mass spectrometry, cell biology and others. The successful candidate will work closely with Victor Ambros and Silvia Corvera labs and the UMASS imaging group and receive training in RNA chemistry, biochemistry, cell biology and pre-clinical development. QUALIFICATIONS:Applicants must have (or expect to obtain shortly) a Ph.D. in Chemistry, Organic Chemistry Biochemistry, Cell Biology, Molecular Biology or a related field , be bright, ambitious, independent and collaborative and ideally, have research experience in nucleic acid molecular and cell biology
Our laboratory uses a combination of nucleic acid and oligonucleotide chemistry, biochemistry, cell biology, and pharmacology and develops and evaluate novel technologies for development of oligonucleotide therapeutics. A rotation project is available to develop and identify chemically modified self-delivering RNAi compounds for treatment of Huntington and other diseases.
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?
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.
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/
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.
Graduate students are encouraged to contact Heidi Tissenbaum to discuss projects available for rotations. Each student has a project tailored for both their abilities and class time commitments.
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
Maroun Semaan Chair in Biomedical Research
A postdoctoral position is available to study in this laboratory. Please contact Dr. Walhout for additional details.
Joseph J. Byrne Chair in Biomedical Research
? Rotation Projects Multiple rotation projects are available in several areas related to long-range gene regulation and higher order chromosome organization. Projects include thorough analyses of the biochemical mechanisms of long-range gene regulation of specific disease-related genes, as well as large-scale analyses of chromosome organization using high-throughput genomics technologies (5C and Hi-C). The lab employs a wide range of experimental approaches, including cell culture, protein biochemistry, microscopy, genomics as well computational approaches such as bioinformatics and modeling. Specific rotation projects are determined dependent on the interest of the student.
<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
A postdoctoral position is available to study in this laboratory. Contact Dr. Mark Alkema for additional details. Contact Information: Mark Alkema, Ph.D. University of Massachusetts Medical School Department of Neurobiology, LRB 717 364 Plantation Street Worcester, MA 01605 USA phone: 508-856-6158 (office) phone: 508-856-8541 (lab) e-mail: mark.alkema@umassmed.edu
Rotation Projects 1) Molecular and neuronal characterization of C. elegans escape behavior Defining sensorimotor circuits requires detailed knowledge of the neural connectivity of the nervous system, and the ability to manipulate the functions of the component neurons and to define and quantify the behavioral outputs. The simplicity and completely defined synaptic connectivity of C. elegans nervous system provides unique opportunity to dissect how neural networks control behavior. 2) Identify genes involved in the processing, expression and subunit composition of voltage-gated calcium channels The release of neurotransmitter from synaptic vesicles is critical for the propagation of signals that generate behavioral outputs. Voltage-gated calcium channels provide the calcium influx essential for synaptic vesicle exocytosis. We are characterizing mutants to identify new genes involved in the proper assembly, expression and trafficking of functional calcium channels. 3) Investigate the evolutionary origins of escape behavior Nematophagous fungi employ a variety of strategies to capture worms. In predator-prey experiments, we have been able to show that the suppression of head movements allows the animal to escape from constricting traps. Further investigation of the neurobiology behind the escape from predation may provide insight into how this behavior evolves. Contact Information: Mark Alkema, Ph.D. University of Massachusetts Medical School Department of Neurobiology, LRB 717 364 Plantation Street Worcester, MA 01605 USA phone: 508-856-6158 (office) phone: 508-856-8541 (lab) e-mail: mark.alkema@umassmed.edu
Potential Rotation Projects A variety of rotation projects are available to study RNP assembly and post-transcriptional regulation during development using quantitative biochemical and modern molecular methods. Project 1: Characterization of the RNA-protein complexes that guide C. elegans early development. Several projects ranging in scope from biochemical characterization of RNA-binding protein complexes to genetic dissection of RNA binding protein function in development are currently available. Contact Sean for more details. Project 2: Post-transcriptional regulation of oligodendrocyte differentiation. Projects are available to monitor changes in gene expression as a function of differentiation with a focus on changes in alternative splicing and mRNA stability. Contact Sean for more details.
A postdoctoral position is available to study in this laboratory. Contact Dr.Guertin for additional details.
Pathogen genetics of the host immune response
How the cholinergic nervous system communicates peroxisomal stress to the whole organism during bacteria infection
Role and regulation of novel innate immune effectors that are conserved across animalia
Focus: Microbiota-gut-brain axis in C. elegans; mucosal innate immunity; staphylococcus aureus; transcriptional regulation of host defense; autophagy; lysosomes; peroxisomes
Biochemistry and Molecular Biotechnology
The Yemini Lab investigates how nervous systems change during development and evolution to generate new behaviors. We use cutting-edge tools and a multiscale systems-biology approach to study the genes, circuitry, and neural activity driving behavioral changes. Our findings provide a foundation to understand normal brain development and brain disorders (e.g., autism and intellectual disabilities).
National Mouse Metabolic Phenotyping Center
In Living Color: Whole-Nervous-System Cell IDs