We are looking for postdoc candidates with experience in cancer biology, mouse models and genome-engineering. Please email CV and 3 letters of recommendation to Wen.Xue@umassmed.edu.
Our lab uses CRISPR tools to speed up cancer gene discovery and disease gene repair. Rotation projects are available to explore experimental techniques such as molecular cloning of CRISPR plasmids, measuring genome-editing efficiency, dissecting mice, and processing of mouse tumor/tissue for histology.
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.
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.
<p >Our laboratory combines biochemical, biophysical, molecular and cell biological approaches to investigate various aspects of pre-mRNA processing, mRNA metabolism and RNA quality control in eukaryotic cells. Potential rotation projects are available in all areas of the laboratory's interests (see Research section).
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.
Penelope Booth Rockwell Chair in Biomedical Research
Focus: Adeno-associated virus vector mediated gene transfer for gene therapy, gene therapy of inherited neurodegenerative Canavan Disease
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.
Postdoctoral Positions Candidates should have a recent Ph.D. in cell biology, molecular biology, genetics or related area. To apply, send a letter describing your current research activities and future research interests, a CV, and contact information for three references to Jennifer Benanti.
Rotation Projects Several rotation projects are available for current Morningside Graduate School of Biomedical Sciences students. Contact Jennifer Benanti to discuss potential projects.
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.
Rotation projects We apply X-ray crystallography and biochemical methods to understand the mechanisms employed by the ribosome. Potential rotation projects are 1) to understand various aspects of translation via mutagenesis/biochemical assays, 2) to crystallize and work on determining the structures of translation factors and functional ribosome complexes, and 3) to improve computational methods used to determine crystal structures of macromolecules. Feel free to contact the lab for a more detailed discussion.
Focus: Post-transcriptional gene regulation in eukaryotes
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
<p >A postdoctoral research position is available to investigate Amyotrophic LateralSclerosis (ALS) mitochondrial dysfunction. ALS causes motor neurondegeneration, then paralysis and death. An early target in ALS is themitochondrion, whose dysfunction enhances ALS progression. The most commonALS-causing mutations are found in the copper-zinc superoxide dismutase (SOD1)gene. Most wild type (WT) SOD1 protein (SOD1WT) resides in the cytosol and only1% is targeted to the inner mitochondrial space (IMS). In contrast, mutant SOD1protein (SOD1mut) accumulates in the mitochondrial outer membrane and in thematrix, and subsequently impairs mitochondrial function by a mechanism that ispoorly understood. Abnormal SOD1mut accumulation leads to mitochondrialdysfunction found in the early stage of presymptomatic ALS mice, before theonset of motor neuron degeneration. Thus, it is critical to determine the firstevent induced by SOD1mut and devise a strategy to stop or delay it beforemitochondrial damage becomes irreversible. The objective of future studies willbe to determine which step/steps are affected by the SOD1 mutation byidentifying the sequence of events involved in SOD1mut and SOD1WT mitochondrialtargeting, import and IMS-sorting. This project will provide important basicinformation on the mechanisms underlying mitochondrial dysfunction in ALS andwill identify possible targets for future therapies. <p > Applicants must have (or expect toobtain shortly) a Ph.D. in Biochemistry, Cell Biology, Molecular Biology or arelated field and be strongly motivated to conduct research in an excitingresearch environment. <p >
Focus: Mitochondria and the endoplasmic reticulum
Potential Rotation Projects <p >Research in the Munson lab is focused on biochemical/biophysical and cell biological characterization of proteins in the exocyst complex. Potential rotation projects include the following: Cloning of various exocyst protein domains and point mutations. These will be expressed in E. coli for biochemical/structural studies, and their functions tested in yeast. Protein expression and purification. Develop purification strategies for several exocyst proteins and their domains, using chromatography methods such as ion exchange and gel filtration (Fig. 2). Characterization of the purified exocyst proteins. Protein structure, stability, oligomerization state and protein:protein interactions will be monitored by such techniques as circular dichroism, analytical ultracentrifugation and gel filtration (Fig. 3). Crystallography. We have determined the structure of the C-terminal domain of Sec6p (Fig. 4). Crystallization trials ofotherexocyst proteins and their domains are in progress. Design and test functional exocyst mutants in yeast. Mutants will be characterized using a variety of biochemical, cell biological, and microscopic techniques. Identify novel regulators of yeast exocytosis using a genetic screen. Mutants created in these screens are currently being tested and identified (Fig. 5). Their role in exocytosis will be explored <p >
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.
Potential Rotation Projects 1) Coordination of replication and recombination by the S-phase DNA damage checkpoint The replication checkpoint coordinates replication and recombinational repair to allow for the replication of damaged templates, however the mechanism by which the checkpoint regulates recombination is unknown. We have identified a number of potential checkpoint-kinase targets by phosphoproteomics. One possible rotation project would be to create site-directed mutations that would prevent kinase regulation of one or more of the targets. These mutations could be used to validate the role of the target in the checkpoint and to test the importance of checkpoint regulation in S-phase DNA repair. 2) Regulation of replication timing Heterochromatin regulates the timing of replication origin firing, however the mechanism by which it affects origin function is unknown. We have developed a model of how origin timing is regulated in non-heterochromatic chromatin; now we want to test how heterochromatin affects this mechanism. In particular, we want to manipulate the heterochromatic context at specific loci, measure the changes in origin timing and investigate the molecular mechanisms responsible for the change. One possible rotation project would be to establish heterochromatin at a well-characterized origin, measure origin timing, which we presume will be delayed, and then test at which step origin firing is delayed. <p >
A postdoctoral fellow position is available for a highly motivated candidate to join us in the Program in Molecular Medicine at the University of Massachusetts Medical School. Our research interests are focused on understanding how aneuploidy affects cellular physiology and metabolism, and how aneuploidy influences cell evolution leading to further gross genomic alterations.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p> <o:p> </o:p> The Candidates should have a recent Ph.D or M.D/Ph.D degree in Cancer Biology, Genetics, Biochemistry, Cell Biology or related field. The candidates must also have a proven track record of productivity and research experience. They should be highly motivated, have a strong desire to learn and excellent communication skills.<o:p></o:p> <o:p> </o:p> <o:p></o:p>Applicats should send their CV, summary of previous research and the name of three references that may be contacted to Dr. Eduardo Torres, e-mail: Eduardo.torres@umassmed.edu (address: 364 Plantation Street, LRB -523, Worcester, MA 01605-4321
Rotations are available in this laboratory. Please contact Dr. Torres for details.
Gerald L. Haidak, MD, and Zelda S. Haidak Professor in Cell Biology
Rotation Projects <p >Rotation projects generally address specific gene expression issues in yeast, including problems in NMD, general mRNA decay, and translation termination. Methodological approaches depend on time commitment, but could include yeast genetics, individual and genome-wide transcript analysis, in vitro translation, and protein:protein interaction studies.
Focus: Cytoplasmic aspects of post-transcriptional regulation in eukaryotes
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.
Immediate opening! Two postdoctoral positions are available immediately to study cellular andmolecular mechanisms resulting in immunosuppression after alcohol use. Thefocus of this research is the role of monocytes and dendritic cells indecreased antigen-specific T cell activation after alcohol use.Intracellular signalling mechanisms resulting in decreased NF-kBactivation and inflammatory cytokine induction after acute alcoholconsumption are being investigated. Please contact Dr. Szabo for details.
Background for Student Rotation Projects <p >See Politz, Hogan and Pederson (2009) and Politz et al. (2005) in the above list. The novel microRNA work may be the most suitable for student rotations. Potential Rotation Projects <p >Are the nucleolar microRNAs pri-, pre- or mature? <p >Are they complexed with other nucleolar RNAs? <p >Do the cell cycle related proteins in the nucleolus exist as heterotypic complexes? <p >Does the nucleolus of human embryonic stem cells also share these features (which we have so far looked for, and found, only in transformed human cell lines)? <p >Can vanadium tagging be used to detect specific proteins by electron microscopy, perhaps exceeding the limitations of immuno-EM?
Gretchen Stone Cook Chair in Biomedical Sciences
A postdoctoral position is available to study in this laboratory. Contact Dr. Zamore for additional details
Potential Rotation Projects Our laboratory uses a combination of biochemistry, cell biology, and genetics to dissect the RNAi pathway. A rotation project is available to explore the mechanisms that underlie the RNAi phenomenon or the biological pathways in which RNAi enzymes participate in flies, mice and humans.
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
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. McCollum for additional details.
Rotation Projects Analog sensitive LATS kinase: The goal of this project is to use CRISPR based genome modification to make mutations in the endogenous LATS kinase that cause it to be inhibited by a synthetic ATP analog. This will allow LATS kinase activity to be turned on and off using the ATP analog. The analog sensitive cell line will be a valuable tool for studying Hippo pathway responses to various stimuli and will be used to test whether dephosphorylation of LATS substrates is an important regulatory mechanism. This project will also set the stage for future experiments to create mice that have analog sensitive versions of LATS. These mice will be used to test whether LATS inhibition is a viable treatment for regenerative therapies for the heart, gut, pancreas and other organs. TRIP6 and Angiomotin interacting proteins: We know that cells monitor their mechanical environment by sensing F-actin levels and by measuring tension at cell-cell junctions. We have identified angiomotins as sensors for F-actin and the TRIP6 protein as part of a tension sensor at cell-cell junctions. However, to understand how these sensors work, we need know the network of proteins that they each interact with, and how those networks change in response to mechanical perturbations. To do this we will fuse each sensor to the promiscuous biotin ligase protein BirA, and express the fusion proteins in cells under various conditions. The biotin ligase will label proteins in close proximity with biotin. Labeled proteins will be purified and analyzed by mass spectrometry, and the spectrum of interacting partners under different conditions will be compared.
Herman G. Berkman Chair in Diabetes Care Innovation
Rotation Projects Project #1: Signaling in the MAP kinase cascade. Membranerecruitment ofthe kinase cascade "scaffold" protein, Ste5, initiates signaling. But our recent work suggests that membrane localization alsoboosts signaling efficiency through the kinase cascade, and similar findings have been reported in a mammalian pathway. Yet the mechanism explaining this effect is unknown.This project would use molecular genetic approaches to probe thisphenomenon. Project #2: Membrane targeting domains. Our recent work identified a small membrane-binding domain that guides Ste5 to the plasma membrane, but it does so only acting in conjunction with protein-protein interactions. Relatedly, we have recently found similar domains, and their cooperative relationship with protein-protein interactions, in several other plasma membrane-localized signaling proteins. We suspect this may be a very common arrangement, and that multiple weak interactions are advantageous to ensuring dynamic localization that constantly probes the availability of membrane-localized binding partners. This project would involve conducting a small-scale survey of polarized proteins in yeast, searching for small membrane-binding domains that are critical for their normal localization and function.
Rotation Project Background
In yeast cells, protein translocation across the endoplasmic reticulum can occur by cotranslational or posttranslational pathways. The objective of this project is to develop a rapid method to inactivate the posttranslational pathway in vivo in yeast cells by appending the CMV-ribosome stalling sequence to the C-terminus of a typical posttranslational translocation substrate (carboxypeptidase Y). Complexes between the posttranslational translocation channel (SEC complex) and the stalled ribosomes will be purified for structural and functional analysis.
Postdoc position is available. Please contact us.
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.
A post-doctoral position is available immediately to study the role of genes found in a genome-wide RNAi screen to regulate the cellular response to the chemotherapy agent, cisplatin. The goal is to determine whether these genes function as tumor suppressor and/or regulate the mechanism of DNA repair processing. The laboratory is interested in understanding the role of hereditary cancer genes of the BRCA-Fanconi anemia pathway in DNA damage repair and tumor suppression. We seek motivated candidates with a PhD and background in cancer cell biology. Experience in mouse cancer models is desirable. The exceptional training environment within the Department of Cancer Biology at UMASS Medical School offers a rigorous and interactive research environment covering several aspects of tumor biology. Applicants should have excellent communication skills, and ability to conduct research independently and as a team. To apply, please send your CV with bibliography, a brief description of research experience and contact information for at least two references via email.
The laboratory is interested in a range of DNA replication/repair-related topics including (i) Defining biomarkers of “BRCAness” that signifies deficiency in the hereditary breast/ovarian cancer genes, BRCA1 or BRCA2, (ii) Targeting BRCAness as a replication gap vulnerability, (iii) Defining why replication proficiency requires the FANCJ helicase disengage mismatch repair proteins, (iv) Determining if suppressing gaps improves the health of Fanconi anemia patient cells, (v) Hunting down the cancer vulnerability that defines curability, (vi) performing functional genomic screens to uncover mechanisms regulating chemotherapy resistance.
<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
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.
Potential Rotation Projects <p >Our laboratory combines genetic and biochemical approaches to investigate the molecular underpinnings of adaptation. Potential rotation projects are available in two general (and partially overlapping) areas: exploring fitness landscapes through systematic approaches and investigating the molecular mechanism of the Hsp90 chaperone in signal transduction. Please contact the lab to discuss specific rotation projects in more detail.
We are looking for motivated postdoctoral researchers. Send in your application and get in touch today!
- AAV gene therapy for genetic diseases - Therapeutic genome editing - RNA-based approaches to treating genetic diseases - Interactions between AAV vector and host cell - AAV vector capsid engineering
Focus: The Munro laboratory develops and applies quantitative biophysical approaches to visualize virus replication, and probe the functions of the proteins and RNAs involved.
Biochemistry and Molecular Biotechnology
Eleanor Eustis Farrington Chair in Cancer Research