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.
Psychology Department and Center for Neuroendocrin
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
Rotations <p >Project 1: Genetic screens for proteins that modify or regulate the activity of microRNAs in C. elegans.
Robert M. and Shirley S. Siff Chair in Autism
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
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.
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.
A postdoctoral position is available to study in this laboratory. Contact Dr. Corvera for additional details.
Rotation Projects Our rotation projects are in the area of diabetes and obesity, and we are interested in basic mechanisms of cell proliferation, differentiation and communication. Diabetes is highly correlated with obesity, but why obesity causes disease in some humans and not others is not understood. Amazingly, we still don’t understand how adipose tissue grows in human adults. A better understanding of this fascinating process can give us insight into basic mechanisms of cell growth, differentiation and communication, as well as mechanisms of disease, not only diabetes but also cancer and developmental defects. During your rotation, you will work on an important piece of a larger project, that has a well-defined outcome. Thus, your successful completion of the rotation project will allow you to be included at the time of publication of the work. Project 1: Adipose tissue is not only formed by adipocytes, but by other cells such as endothelial, mural and immune cells. Also, there are multiple kinds of adipocytes with different functions. We have recently developed conditions to develop adipose tissue from humans in-vitro (adipose tissue “organoids”). From this tissue we have been able to separated single cells, and find that they grow into different kinds of clones. We are now conducting RNAseq on >300 of those clones, to determine how many cell types exist in human adipose tissue, and what their roles are. In this rotation, you will be able to analyze RNAseq data to define what genes characterize these cells, and you will use virus transduction to create immortalized cells for further study. Project 2: Adipose tissue has many functions besides storing and releasing lipids. It also has to coordinate metabolism in the whole body. We have found that human “beige” adipose tissue, which is found in people who are metabolically healthy, expresses genes for secreted factors that communicate with the immune system and the brain. These include IL-33 and enkephalins. In this project you will knockout these genes, and investigate whether this changes the function of adipose tissue when we implant it into immune compromised mice.
Isadore and Fannie Foxman Chair in Medical Research
A postdoctoral position is available to study in this laboratory. Contact Dr. Czech for additional details.
Mentoring……………………………………………………………………………………………………… The Czech laboratory is active in mentoring graduate students and postdoctoral fellows. Many former student and postdoctoral trainees of the Czech laboratory are now internationally recognized professors at major universities and medical schools. These former lab members include: Paul Pilch, Professor of Biochemistry, Boston University School of Medicine Jeffrey Pessin, Professor and Director of the Diabetes Center, Einstein College of Medicine Joan Massague, Director, Sloan Kettering Institute Roger Davis, HHMI investigator and Professor of Molecular Medicine, UMASS Medical School Silvia Corvera, Professor of Molecular Medicine, Co-Director of the MD/PhD Program, UMASS Medical School Carla Greenbaum, Vice Chair and Director of Clinical Research, Benaroya Research Institute Jes Klarlund, Professor of Ophthalmology, University of Pittsburgh Medical Center Rob Lewis, Professor of Biochemistry and Molecular Biology, Eppley Cancer Institute, University of Nebraska Medical Center Richard MacDonald, Professor of Biochemistry and Molecular Biology, Eppley Cancer Institute, University of Nebraska Medical Center Assia Shisheva, Professor of Physiology, Wayne State School of Medicine. Mark Sleeman, Professor of Physiology, Monash University, Australia John Harris, Associate Professor of Medicine, UMASS Medical School Zhen Jiang, Associate Professor of Pharmacology and Medicine, Boston University Vishu Puri, Professor of Biomedical Sciences, Ohio University Olga Gupta, Assistant Professor of Pediatrics and Medicine, University of Texas Southwestern Medical Center Tim Fitzgibbons, Assistant Professor of Medicine, UMASS Medical School Myriam Aouadi, Assistant Professor, Integrated Cardio Metabolic Centre, Karolinska Institute Adilson Guilherme, Associate Professor, University of Massachusetts Medical School Our laboratory currently offers graduate student Rotation Projects (examples below and others available) and Thesis Research Projects for students following a rotation: Developing CRISPR technology for gene editing in adipocytes: Adipocytes function as master regulators of whole body metabolism and deletions of specific adipocyte genes in knockout mice promote dramatic improvements in glucose tolerance and insulin sensitivity in diabetic models. Thus the ability to direct gene editing in adipocytes in vivo has great potential in developing therapeutic strategies for obesity, type 2 diabetes and cardiovascular complications. Alternatively, an ex vivo approach is also feasible since adipose cells can be genetically altered in vitro prior to implantation into mice with beneficial effects. Such projects are designed to be performed in collaboration with other Czech lab members with the goal of specifically deleting or editing genes in adipose depots that drive increases in fatty acid oxidation, energy expenditure and systemic metabolic activity. Exciting preliminary data at the “proof of principle” stage has been achieved and this project is designed to focus on specific genes of high interest for therapeutics. Signaling by the lipogenesis pathway through Acetyl CoA: A major function of adipocytes is to store calories as triglyceride, in part through the process of fatty acid synthesis (lipogenesis). This metabolic pathway involves a number of metabolites including Acetyl CoA, which is also a substrate for acetylation reactions that modify proteins such as histones. Thus metabolic flux through adipocyte lipogenesis may also function as a signaling pathway to the nucleus to modulate transcription via levels of Acetyl CoA that accumulate during this process. This rotation project is designed to test this idea at the molecular level by monitoring histone acetylations and resultant transcriptional events during changes in Acetyl CoA levels caused by altering physiological conditions such as exercise, obesity and diabetes. If this concept is correct, the project could lead to developing therapeutic strategies for metabolic disease based on targeting lipogenic enzymes.
The Melikian Lab seeks a creative and motivated PhD neurobiologist to join our investigative team to study the mechanisms that govern addictive and motivated behaviors, with a focus on circuits that converge on and modulate dopaminergic terminals. We leverage intersectional approaches spanning from molecules to behavior, and utilize mouse genetic, viral, optogenetic and photometric methods. We are seeking postdoctoral applicants with a strong track record of productivity, who will take the lead on a novel project. Applicants will optimally have experience in mouse handling and modern neurobiology approaches (e.g. optogenetics, photometry), but other strong candidates will also be considered. The Neurobiology Department at UMASS Chan Medical School is the hub of a vibrant multidisciplinary neuroscience community, with research strengths in neuropsychiatric disorders, neurodegeneration, neuroinflammation, neuroplasticity, and neurodevelopment. Under the leadership of our recently appointed Chair, Dr. Danny Winder, the department provides an exceptional and interactive training environment that emphasizes team science in a diverse and inclusive space. Interested applicants should submit a CV and names of three references to Dr. Melikian: haley(dot)melikian(at)umassmed(dot)edu.
1. Parkinson's Disease: Signaling Cascades that lead to dopamine neuron degeneration Parkinson's disease (PD) is the 2nd most prevalent neurodegenerative disease and affects >1 million individuals in the U.S., with a 50% higher occurance in males vs. females. Dopamine (DA) is required for movement initiation and PD is the result of DA neuron (DAN) cell death, leading to freezing, gait instability, and resting tremor. Therapy options for PD patients are limited to approaches that replace DA. These are effective in early disease stages, but wane in efficacy as PD progresses. Importantly, none of these treatment strategies target the root cause of PD: DAN cell death. The lack of progress in developing impactful treatments is due, in part, to a lack of understanding the cellular signaling dysfunction that leads to DAN cell death in PD. Moreover, it is completely unknown why males are more susceptible to PD than females. Rit2 (AKA: Ras-like in neurons; Rin) is a small neuronal GTPase that is highly enriched in DANs, and is a PD risk allele. Importantly, a recent single-cell RNA sequencing study from idiopathic PD patients revealed a patient subpopulation in which Rit2 was markedly decreased in DANs. While intriguing, it was yet unknown whether Rit2 losses were simply due to DAN cell death, or actually causative. In collaboration with the UMASS Chan Gene Therapy Center, we recently developed a novel, AAV- and shRNA-mediated approach to silence Rit2 in mouse DANs and found that Rit2 knockdown (Rit2-KD) leads to a significant, striking, and progressive PD phenotype that develops more rapidly in males than females. This new PD mouse model presents a unique opportunity to probe multiple questions regarding Rit2 and PD. What gene expression changes occur downstream of Rit2 loss? Are any of these druggable targets? What are the differences between males and females that make males more susceptible to DAN cell death? Is there an intervention window in which DAN viability can be rescued after Rit2 loss insult? There are 2 rotation projects to tackle these questions. Project 1a. Identify transcriptional changes that occur in DANs downstream of Rit2-KD. Together with the Thomson laboratory (Dept. of Neurobiology), we are performing bulk and single-cell RNA sequencing to identify specific gene expression changes that occur downstream of Rit2-KD in DANs. Students will learn to handle mice and harvest DANs, and to analyze RNA sequencing data. Project 1b: Identify a therapeutic window to rescue motor function in Rit2-KD mice. Students will perform a motor learning assay on control vs. Rit2-KD mice after suppressing Rit2 shRNA expression. In addition, students will design and generate a transgene construct to rescue Rit2 expression and test its efficacy using an in vitro assay.
2. Modulatory glutamate signaling: impact on motor function, novelty, and cocaine addiction Glutamate is the major excitatory neurotransmitter in the brain, but also has a modulatory role by signaling through metabotropic glutamate receptors (mGluRs). Recent work from our laboratory revealed that mGluR5 expression in DA neurons is required for DA signaling and several DA-dependent behaviors including motor learning and cocaine reward. However, the circuit- and mechanistic-specific underpinnings of these processes are unkonwn. Using a novel conditional knockout model, we are leveraging genetically encoded DA sensors to determine how DAergic mGluR5 impacts DA neuron function and DA-dependent behaviors in mice. Rotation students will learn to behaviorally assess cocaine addiction in this mouse model, and will learn immunohistochemical approaches to validate viral expression Cocaine Fails to increase DA in mGluR5-DA-silenced mice. Fiber photometry using genetically-encoded DA sensors during cocaine response. Control or mGluR5-DA-silenced mice were injected with 7.5 mg/kg cocaine and DA signals were recorded in the nucleus accumbens using dLight 1.2 sensor. Control mice: Cocaine caused a significant increase in the total DA signal from 3-5 min post-injection as compared to saline-injections. mGluR5-DA-silenced mice: Cocaine failed to significantly increase DA signals. *p<0.05, paired Student's t test, n=4-5.
3. Nociceptin: A neuropeptide that impacts cocaine sensitivity Nociceptin is an endogenous opiate-like neuropeptide that is implicated in pain and reward motivation. Recent studies suggest that nociceptin has the capacity to block cocaine's initial addictive properties, but the mechanisms underlying nociceptin's actions are largely unknown. Work in our lab has discovered that nociceptin blocks cocaine reward, and does so by acting directly on DA axon terminals in the nucleus accumbens, the brain's "reward center". In addition, our results suggest that nociceptin likely shifts cocaine sensitivity, and does so by controlling reward tone differentially in males vs. females. These exciting results may pave the way towards harnesing nociceptin signaling as a potential addiction therapeutic. However, the mechanisms underlying nociceptin's actions are unknown, nor is it known whether nociceptin specificallly impacts cocaine reward, or other drugs of abuse. There are two possible rotation projects: Project 3a: Impact of nociceptin signaling on other drugs of abuse. Students will conduct addiction behavioral assays while infusing nociceptin directly into the nucleus accumbens in mice. Students will learn mouse handling and stereotaxic surgery, and mouse behavioral assays. Project 3b: Sex-specific differences in nociceptin signalig. Students will use RT-qPCR to test whether males and female mouse midbrain neurons express differing amounts of the nociceptin receptor, NOPR. Students will learn mouse handling skills, brain harvesting, and RT-qPCR. Nociceptin infusion into the nucleus accumbens blocks cocaine preference in females. Conditioned Place Preference Assay (CPP). Wildtype female mice received either saline or 10mg/kg cocaine (I.P.) and were trained for 3 days in a 3-chambered CPP aparatus, while being infused with either vehicle or 500nM nociceptin. Preference scores were determined on test days. Control-infused mice exhibited signifiant preference to the cocaine-paired chamber as compared to the saline-paired chamber (****p<0.001), whereas mice infused with nociceptin failed to establish cocaine preference (p=0.74). Two-way ANOVA with Tukey's multiple comparison test, n=4-10.
4. Dopamine Transporter (DAT) Trafficking in Cocaine Addiction DAT is a membrane protein in dopamine (DA) axon teminals whose primary function is to remove released dopamine and thereby terminate synpatic transmission. Addictive psychostimulants, such as cocaine, block DAT function, which increases extracellular DA and is responsible for cocaine's addictive properties. DAT is not static at the plasma membrane, but is dynamically regulated by membrane traffficking. This project is to determine whether DAT membrane trafficking is required for cocaine addiction. Our lab has developed a novel, AAV-mediated, in vivo molecular replacement strategy, that replaces wildytpe DAT with DAT trafficking dysregulated mutants in adult mice. There are 2 possible rotation projects: Project 1a: Rotation students will assist in behaviorally assessing replacement mice as compared to controls, and will additionally use immumohistochemical approaches to validate mutant protein expression in dopamine neurons in situ. Students will gain experience in mouse behavior, brain dissection, preparation of brain slices, and immunhistochemical techniques in mouse brain. Project 1b: Rotation students will develop a CRISPR/Cas9 guide RNA in order to perform gene editing and mutate DAT in vivo, and will test its efficacy in vitro. Students will learn guide RNA design, and mammalian tissue culture, and genomic sequencing.
A postdoctoral position is available
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.
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
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.
Leo P. and Theresa M. LaChance Chair in Medical Research
Lawrence lab research bridges fundamental questions of developmental epigenetics with translational research into the common problem of chromosome abnormalities, particularly Down syndrome.
Focus: Voltage-Gated Calcium channels and neuronal plasticity
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. Ip for additional details.
Rotation Projects Project #1: Mechanistic study of isolated mutants that show abnormal intestinal stem cell division phenotypes. Project #2:Perform transgenic RNAi-based genetic screen for genes required for intestinal stem cell response to tissue damage.
A postdoctoral position is available to study in this laboratory. Contact Dr. Budnik for additional details.
A rotation project focusing on neuronal processing in alcohol-naive and binge alcohol drinking mice is available
A postdoctoral position is available to study in this laboratory. Contact Dr. Kang for additional details.
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Potential Rotation Projects <p >1. SOX proteins in the maintenance of mucosal tissue integrity and innate immunity. There are ~20 Sox genes in mammals. Although the prototypic SOX-related proteins, SRY (Sex-determining gene on Y chromosome) and TCF/LEF are reasonably well characterized, very little is known about the relevance of SOX proteins in lymphocyte development and function. We have discovered that some SOX proteins can regulate the WNT/Wingless signaling cascade, a central morphogenetic pathways specifying cell fate in all organisms whose aberrant activity leads to tumourigenesis. Importantly, expression of specific combinations of Sox genes is lymphocyte subset-specific, temporally and spatially. Our results so far strongly indicate that Sox genes are important regulators of multiple lymphocyte subsets, in part by opposing WNT signaling. An impediment to advances in understanding Sox gene functions has been that they are critical for embryonic development and mutations lead to early lethality. We have therefore embarked on generating conditional KO mice of various Sox genes and their cofactors that we postulate are centrally involved in lymphocyte differentiation and function. A few rotation projects are available to analyze these newly derived mouse models, both at the level of cellular and molecular analysis of lymphocyte development and single-cell tracking of specific Sox gene expressing cells in vivo. These mice have defects in mucosal tissue barrier functions and often exhibit aberrant inflammatory responses in the skin that can model human skin diseases such as psoriasis and dermatitis. <p >a. analysis of Sox13 reporter mice <p >b. analysis of Sox4-deficient mice for innate lymphocyte developmental defects <p >c. analysis of spontaneous skin inflammation in mice lacking dermal innate IL-17 producers <p >d. analysis of global chromatin docking of HMG TFs in ex vivo T cells <p >e. comparative analysis of global gene regulation and gene networks across all hematopoietic cells <p > <p >2. Testing small molecule compounds to treat organ-specific T cell-mediated autoimmunity in mice (e.g. Type I Diabetes, colitis and the mouse model of multiple sclerosis). <p >3. Analysis of mice with novel mutations in TGFb signaling to investigate the role of TGFb in regulating self-destructive T cells.
Please visit the Socolovsky lab website at: http://labs.umassmed.edu/socolovskylab/ to learn about our current research areas. Rotation and graduate student projects are available in all areas, including: 1. Regulation of the transition from self-renewal to differentiation in erythroid progenitors. Mouse models deleted for one or more of the relevant regulators will be analyzed. 2. understanding the mechanism of global DNA demethylation in erythroid progenitors. Specifically, what is the role of the Tet family of proteins and 5-hydroxymethylcytosine in this process? 3. the regulation of the erythropoietic stress response in vivo.
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
A postdoctoral position is available to study in this laboratory. Contact Dr.Guertin for additional 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.
Teresita del Nino Jesus Padilla-Benavides PhD
Claudia A. Vilchis Nestor. Visiting Scholar from CINVESTAV-IPN, MEXICO
Wet-lab and Bioinformatic postdoctoral fellow positions are available for candidates with recent Ph.D. or M.D./Ph.D. degrees in Molecular Biology, Neuroscience, Genetics, Genomics, Cell Biology, or related fields. They should be highly motivated, have a strong desire to learn, and excellent communication skills. Applicants should send their CV, summary of previous research and the name of three references to Dr. Michael Lodato.
Rotations will revolve around studying somatic mutations in the normal brain, in the diseased brain, and outside of the brain using single-cell genomics. Please contact Dr. Lodato for details.
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).
Mary C. DeFeudis Chair in Biomedical Research
In Living Color: Whole-Nervous-System Cell IDs
Worcester Foundation for Biomedical Research Chair I