Dr. Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research
Veterinary & Animal Sciences; Pioneer Valley Life
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.
<p >Rotation Projects: Characterization of gene which influences survival in sporadic ALS patients. Characterization of 2 newly identified familial ALS genes. Development of a new mouse model for familial ALS. Positional cloning of novel genes which cause familial ALS.
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.
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
<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
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.
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 >
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.
If you are interesting in applying computational methods to biological problems please contact me. Potential projects in my lab are Modeling of transcription factor gene expression control in innate immune cells Evolutionary analysis of gene transcription factor networks in mammals Epigenetics inheritance in mice: From male sperm to phenotypic effect in grandchildren Application of genome and exome sequencing to newborn screening Development of computational methods for analysis of RNA-protein interactions
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
Dr. King is a computational biologist with research interests in algorithm development and the analysis of high-throughput datasets. His current research projects involve facioscapulohumeral muscular dystrophy (FSHD), amyotrophic lateral sclerosis (ALS), and other disorders.
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.
Postdoctoral positions are available to study the relationship(s) between the Rb/E2F proliferation pathway and p53-dependent apoptosis. Areas of investigation include understanding why E2F1 is unique among the E2F family in its strong apoptosis signaling ability and determining the pathways that lead from E2F1 activation to cell death. Fellows will be associated with a highly motivated and interactive group of researchers studying aspects of cell cycle, apoptosis signaling and cancer using cell culture, virology and animal models. If interested, please contact: Timothy Kowalik Department of Molecular Genetics and Microbiology University of Massachusetts Medical School 55 Lake Avenue North Worcester, MA 01655 The University of Massachusetts Medical School is an Affirmative Action / Equal Opportunity Employer.
Rotation Projects Identify the region on E2F1 responsible for p53-mediated apoptosis. We know that a transcriptionally functional E2F1 is required for apoptosis signaling. We also know that E2F2 does not induce apoptosis in our system. Therefore, domains on E2F1 and E2F2 will be swapped to determine which E2F1 domain is responsible for apoptosis signaling. Role of nuclear kinases in E2F1 mediated apoptosis. Our recent efforts have revealed that E2F1 expression leads to the phosphorylation of p53 and this modification correlates with apoptosis. There are several candidate kinases that need to be analyzed for their contribution to p53 phosphorylation. A dominant negative approach will be used in this project to identify which kinase(s) contribute to the E2F1 signal to p53. Role of CMV IE proteins in proliferation. We have found that both IE1 and IE2 target different Rb family members. IE2 binds to Rb and IE1 interacts with p107. We now know that IE2 is a strong inducer of S phase but IE1 can only significantly modulate proliferation in cells lacking p53. We are interested in knowing why p53 can prevent IE1 from inducing S phase. Mechanism of p53 accumulation by CMV. It has recently been shown that CMV infection results in an accumulation of p53. We have recently found that IE1 expression also leads to p53 accumulation. We wish to determine the steps leading to p53 accumulation and the consequences of this event.
Focus: Cellular and organismal studies of viral infections
Rotation Projects Determine the mechanism of PrPCtm production by constructing PrP mutants with N-terminal glycosylation sites and analyzing their modification in yeast and in vitro. Test the role of PrPCtm in prion pathology by determining the effects of changing the charged topogenic signals in PrP on transmembrane insertion and pathogenicity. Isolate new pio mutants and determine their effects on normal yeast TM proteins.
Arthur F. and Helen P. Koskinas Professor in Biochemistry and Molecular Biotechnology
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.
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.
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 >
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.
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
We are looking for rotation students to visit our lab and participate in one of our ongoing research projects. Different aspects of the projects require different toolsets ranging from experimental biology to quantitative biology and mathematical modeling. Rotation students will have a chance to acquire new skill-sets and develop expertise required for implementing a quantitative approach for understanding cell regulation, signaling and evolution. Interested students should email Amir directly and briefly describe their academic background, future plans and interest in the lab. Current rotation projects: Investigating bacterial response to host-targeted drugs: As part of our research into the tumor-microbiome (tumor assosiated bacteria), we are testing how bacterial growth is inhibited by cytotoxic drugs that target cancer cells. Rotation students will run genetic screens in bacteria to identify bacterial toxicity and resistance mechanisms. In addition the students will test if bacteria can rapidly become drug resistance by evolutionary adaptation. Monitoring recovery dynamcis of melanoma cells in response to targeted therapy: The project involves examining and quantifying different aspects of cell behavior, population dynamics and adaptive resistance to targeted therapy. Rotation students will examine cellular behavior of established cell-lines and will clone and engineer new live-cell reporters for microscopy based assays.
Biochemistry and Molecular Biotechnology
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Joseph D. Early Chair in Biomedical Research