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.
Biostatistics And Health Services Research
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
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 Position Available A postdoctoral position is available to study in this laboratory. Contact Kensuke Futai for additional details.
Rotation Projects The Futai laboratory seeks highly motivated graduate students who have interest in the roles of risk genes of neuropsychiatric diseases, such as autism and schizophrenia, on neuronal function.Rotation students will typically work side-by-side with Kenny Futai or Postdoctoral Fellows, and give one laboratory meeting presentation at the conclusion of their rotation project. Rotation projects The roles of the risk genes of neuropsychiatric diseases on neuronal structure and synaptic function The roles of the scaffold molecules in synapse maturation, synaptic transmission and synaptic plasticity Characterization of gultamate receptors which express in interneruon
Rotations We always welcome rotation students who are interested in learning more about the eye and the techniques the lab utilizes. Most rotation projects can be integrated into a Ph.D. thesis afterwards if the candidate desires to continue with this line of research. In my lab we use molecular biology, genetics, histology, virology and surgical procedures on mice to conduct our research. You will be working in an environment that is focused on translational research and gaining basic science knowledge on disease that affect vision in order to develop better therapeutic strategies to the currently available strategies. The goal of the lab is to move as quickly as possible from a basic science discovery to a therapeutic application. The basic science research the lab is conducting focuses around the role of metabolism and the Insulin/mTOR pathway in photoreceptors. Interested in a rotation? Email Dr. Punzo and ask if a project is currently available.
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.
Focus: AAV vector technology and AAV-mediated miRNA therapeutics
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.
POSTDOCTORAL POSITION A Postdoctoral Position is available immediately in the Department of Cell and Developmental Biology to study the regulation of RNA processing and export by signal transduction pathways. So far in this project we have found that the assembly of mRNA export complexes in live cells is regulated by the PI3 kinase/AKT signal transduction pathway and that, for a subset of mRNAs, nuclear export is AKT regulated. The experimental approach for this project integrates molecular techniques and microscopy, especially live cell microscopy. The postdoc in this position could also be involved in studies of the role of nuclear architecture in regulating gene expression and in studying the role of chromatin remodeling enzymes in breast cancer. Candidates with a strong background in cell biology, biochemistry, or molecular biology are especially desirable. Quaresma, A.J., Sievert, R. & Nickerson, J.A. Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway. Mol Biol Cell 24, 1208-1221 (2013). The University of Massachusetts Medical School is located in Worcester, at the western edge of the Boston Metropolitan Area. The Department of Cell and Developmental Biology has especially strong research programs in nuclear and chromatin structure, cytoskeletal function, and mitotic architecture. Interested candidates should contact: Jeffrey A. Nickerson, Ph.D. Department of Cell and Developmental Biology S7-214 University of Massachusetts Medical School 55 Lake Avenue North Worcester, MA 01655 (508) 856-2312 jeffrey.nickerson@umassmed.edu
Potential Rotation Projects Identify the AKT phosphorylation sites on mRNA export proteins. Determine the effect that point mutation of those sites has on mRNA export complex assembly and on the export of specific mRNAs. Investigate the role of chromatin remodeling in driving the important metabolic changes occurring during breast tumorigenesis.
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
Postdoctoral Fellow Applications are being accepted for one position. A position is available to develop Cys2His2 zinc finger proteins (ZFPs) for the treatment of monogenic disorders. This project will focus on the creation of ZFPs with novel DNA-binding specificity to recognize sequence elements within genomic loci of therapeutic interest. In collaboration with other laboratories, we will evaluate the activity of these ZFP-based gene therapy reagents in vitro and in vivo in relevant disease models. Applicants will also have the opportunity to learn to apply Cas9 and Cas12a editing systems in vivo.
Potential Rotation Projects Improving the Precision of CRISPR/Cas9 nucleases for gene therapy applications: We are working to improve the precision of the CRISPR/Cas9 system to generate nucleases that will cleave at only a single site in the genome. These engineering efforts focus on increasing the DNA-editing precision of Cas9 and using protein engineering to introduce new properties into the nuclease. Much of this work is now transitioning to the use of Cas9 (and Cas12a) protein-RNA complexes. These modified nucleases will then be applied to patient derived cell-culture systems for the targeted repair or inactivation of disease-causing alleles. With the eventual goal of creating therapeutics for Sickle Cell Disease, beta-Thalassemia, HIV, Limb Girdle Muscular Dystrophy, Hermansky Pudlak Syndrome and other monogenic disorders. ex vivo genome editing in CD34+ HSPCs: We are developing improved Cas9 proteins for delivery ex vivo into CD34+ HSPCs for therapeutic application to sickle cell disease and beta-thalassemia. The goal is to modify the hematopoietic stem cells of a patient to complement the loss of function of the beta-globin gene and then return these cells to the patient through an autologous transplant. Development of Cys2His2 Zinc fingers proteins (ZFPs) as targeted therapeutics: We are developing artificial ZFPs for the regulation of target genes to change their gene expression profiles for therapeutic applications.
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.
A postdoctoral position is available to study in this laboratory. Contact Dr. Brodsky for additional details.
Potential Rotation Projects We are utilizing a variety of technologies to study p53 regulation and function in Drosophila. These include genetic screens, molecular biology, fluorescence and scanning electron microscopy, tissue culture, RNAi, homologous recombination, and others. Rotation projects in this lab will be determined based on a combination of the student's and PI's interests. Possible projects are listed below: Project 1: A genetic screen for new regulators of Drosophila p53. Project 2: Using RNAi and homologous recombination to study regulators of p53. Project 3: Characterization of p53 activation in Drosophila tissue culture cells by flurescence microscopy, Real-Time PCR, and RNAi. Project 4: Genetic analysis of Drosophila p53 targets identified in microarray experiments.
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.
Anesthesiology and Perioperative Medicine
Focus: Virology and vectorology of adeno-associated viruses
A postdoctoral position is available to study in this laboratory. Contact Dr. Pai for additional details.
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
Population and Quantitative Health Sciences
Post-doc positions are available, please contact me via email.
Rotation projects are designed to aim to train students in both computational genetics/genomics and experimental technologies such as brain organoids. Please contact me via email to discuss.
Biochemistry and Molecular Biotechnology