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
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.
Dr. Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research
Psychology Department and Center for Neuroendocrin
Department of Psychology; Neuroscience And Behavio
Psychology Department And Center for Neuroendocrin
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.
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.
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.
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.
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.
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
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.
Dr. Henninger is a vascular neurologist with research interest in the neurobiology of axonal injury associated with traumatic brain injury and its contribution to functional outcome.
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. Sluder for additional details.
Potential Rotation Projects We favor having students work independently on defined projects that have promise of completion during the study period. Project #1: Use a frog egg extract that supports multiple rounds of centrosome duplication in vitro to investigate the role of various high interest kinases in the control of centrosome duplication. Also, we can use these extracts to further investigate how various other proteins interact with the centrosome to influence its duplication. Hinchcliffe, E.H., C. Li, E.A. Thompson, J.L. Maller and G. Sluder. 1999. Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extract. Science 283:851-854. Project #2: Use microsurgery and immunofluorescence on BSC-1 cells to further investigate how centrioles influence the interphase progression of the cell cycle. Hinchcliffe, E.H., F.J. Miller, M. Cham, A. Khodjakov and G. Sluder. 2001. Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291: 1547-1550.
A postdoctoral position is available to study in this laboratory. Contact Dr. Rogaev for additional details.
Higgins Family Professor in Neuroscience
Potential Rotation Projects Project #1: Molecular Mechanisms in the Pathogenesis of Neurodegenerative Disease. The student can select projects emphasizing either molecular mechanisms of huntingtin in trafficking in neurons or receptor stimulated effects on gene expression in neurons. Techniques include: Generation of fusion proteins, raising antisera Preparation of organelles Immunocytochemistry, light microscopy and electron microscopy Immunoprecipitation methods PCR Protein separation techniques, gel electrophoresis, immunoblotting Autoradiography
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. Budnik for additional details.
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.
Maroun Semaan Chair in Biomedical Research
A postdoctoral position is available to study in this laboratory. Please contact Dr. Walhout for additional details.
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.
Dr. Almeida focuses on uncovering the molecular mechanisms underlying frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease (AD). Her research leverages patient-derived induced pluripotent stem cell (iPSC) lines to create neuronal models that closely mimic disease conditions.
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).
https://www.umassmed.edu/globalassets/radiology/documents/King-Graduate Student-Training-UpTo-2020.pdf
List of Graduate Students and Post-Doctoral Fellows
Physics Review for Radiology Residents Taking the ABR Exam
Nuclear Medicine Physics Imaging Laboratory
In Living Color: Whole-Nervous-System Cell IDs
Worcester Foundation for Biomedical Research Chair I