Endowed Chair in Biochemistry and Molecular Biotechnology I
Dr. Owegi specializes in neuromuscular disorders such as ALS, myasthenia gravis, muscular dystrophy (FSHD, OPMD, Myotonic Dystrophy), myopathy & peripheral neuropathy. Clinical research focus is on ALS clinical trials. Dr. Owegi completed medical school at Kansas City University of Medicine and Biosciences. Neurology residency & neuromuscular fellowship were completed at Johns Hopkins Hospital.
Health Informatics And Implementation Science
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
Cutler Chair in Vascular and Endovascular Surgery
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
<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.
Paul J. DiMare Chair in Neurodegenerative Disease
Rotation Projects: See our lab webpage for more information on Research Projects: https://www.umassmed.edu/boscolab
Elucidating the factors involved in sporadic ALS and investigating protein misfunction associated with neurodegenerative 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.
Dr. Esteves is a neuroscientist with interest in gene therapy to help treat neurodegenerative diseases.
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.
Focus: Post-transcriptional gene regulation in eukaryotes
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.
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.
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.
Arthur F. and Helen P. Koskinas Professor in Biochemistry and Molecular Biotechnology
Motor Neuron Disease Mechanisms; Hyperkalemic Periodic Paralysis: a Muscle Ion Channel Disorder.
Potential Rotation Projects One of the five most common structural classes of proteins is the (b/a)8 barrel motif. These proteins have eight parallel b strands arranged in a cylindrical fashion in the hydrophobic core and a corresponding number of amphipathic a-helices that dock on the surface of this cylinder. Equilibrium and kinetic studies of the folding reaction of one representative of this class, the subunit of tryptophan synthase, have shown that this single, symmetrical domain is formed by the progressive development of structure and stability in two partially folded forms. We are currently exploring the folding mechanisms of other (b/a)8 barrel proteins. Our goal for comparing the folding mechanisms of different members of the (b/a)8 barrel family is to learn how sequence relates to folding mechanism. The laboratory rotation would involve studying the equilibrium folding properties of another member of this structural class. Experiences that would be gained include expertise in protein expression and purification, and the collection and analysis of data acquired by spectroscopic techniques such as circular dichroism and fluorescence. Understanding the mechanism of folding and assembly of oligomeric peptides and proteins will provide important insights into a process that is essential for all forms of life. One model system that we have been using to study multimeric folding events is the homodimeric leucine zipper peptide, GCN4-p1. Mutational studies have yielded insights into the roles of helix propensity, salt bridges and buried polar residues in the transition state for folding. We are currently extending these studies to explore the folding and assembly of heterodimeric and heterotrimeric coiled coils. This rotation will provide training in peptide synthesis, HPLC purification, ultracentrifugation, circular dichroism spectroscopy, fluorescence resonance energy transfer experiments, and data analysis. The mechanism by which natural proteins fold to their functional forms has been evolutionarily selected to be relevant on a biological time scale. Synthetic proteins, while designed to achieve stable native forms, have not had evolutionary pressures applied to remove kinetic traps in their folding mechanisms and may have complicated access routes to their native states. By studying the folding of five synthetic ßa-repeat proteins, we will test the proposition that the design principles not only achieve the native state but do so via relatively smooth energy landscapes (Baker lab, Nature 2013). The project will involve the expression and purification of the synthetic proteins and their biophysical characterization, with a focus on the early folding events<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p>
One postdoctoral position is available to study the mechanism and treatment of motor neuron disease. Experience in molecular biology and neuroscience is preferred. Contact Dr. Xu for additional details.
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.
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.
Richard M. Haidack Professor in Medicine
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.
Dr. John Meyers Professor in Primary Care Medicine
Population and Quantitative Health Sciences
Biochemistry and Molecular Biotechnology
Tweets by @DrSherryPagoto
Healthcare Delivery and Population Sciences at UMass Chan - Baystate
Preventing Osteoarthritis After an ACL Injury
Preventing Osteoarthritis After an ACL Injury Playing the Long Game: Consensus for Preventing OA
Preventing Osteoarthritis After an ACL Injury Playing the Long Game: Consensus for Preventing OA Characteristics of Accelerated Hand Osteoarthritis
Joseph D. Early Chair in Biomedical Research