Proposals for Next Classification Schema of Myeloid Neoplasms
Endowed Chair in Biochemistry and Molecular Biotechnology I
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.
Blood Cancers Today: Therapy-Related CHIP
All-Oral Regimen for Newly Diagnosed AML
Psychology Department and Center for Neuroendocrin
School of Public Health and Health Sciences
College of Social and Behavioral Sciences
Psychology Department And Center for Neuroendocrin
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.
Elisabeth Chair for the Dean of Medicine
Our Danny Cancer Fund Chair in Biomedical Research I
A postdoctoral position is available to study in this laboratory. Contact Dr. Kelliher for additional details.
Please visit the Kelliher Lab website at: http://labs.umassmed.edu/kelliherlab/ to learn more about our current research areas. 1. Identify genes/pathways that mediate leukemia-initiating cell survival 2. Understand the molecular basis of glucocorticoid resistance in leukemia 3. Examine contribution of RIPK1 kinase in inflammatory and autoimmune disease mouse models. 4. Reveal tissue-specific roles for RIPK1 in cell death and inflammation. Use conditional Ripk1 allele to investigate effects of Ripk1 deletion in liver, pancreas and antigen presenting cells.
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.
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.
An entry level postdoctoral position is open immediately in the laboratory of Dr. Susan L. Swain to study the factors that control the development and survival of CD4 and CD8 T cell memory. Graduate student experience with tissue culture, in vitro assay, flow cytometry, experience in mouse models on infectious disease and a knowledge of cellular and molecular immunology are all strongly desired.
<p >Rotations: Projects in the following areas <p >CD4 T cell memory. We can generate in vitro CD4 T cells that are for all extents and purposes identical to the memory CD4 T cells observed in vivo. In situ memory CD4 T cells persist at very low frequency and in most instances it is difficult to analyze them thoroughly using tetramer or multimer reagents both because of their low frequency and the relatively low specific affinity of the Class II reagents for the TcR. Being able to generate “recent” memory cells in vitro gives us the opportunity to analyze in detail the mechanisms by which memory CD4 T cells may contribute to secondary immunity and immune protection. Once identified. will determine if particular pathways are relevant in situ. We have discovered that memory CD4 T cells are superior in protection to those from the primary response and that they display pleitropic functions that have not been previously identified. <p > Cytotoxic CD4 Effectors. One unexpected function of CD4 T cells we identified is robust, perforin-dependent cytotoxic activity (7, 16). Cytotoxic activity by CD4 T cells has been reported in response to several infections, but its significance has not heretofore been established. We find that “Th1 polarized” CD4 effectors and more relevantly the CD4 effectors found in the lung following influenza infection, are able to kill infected or peptide-pulsed Class II-bearing targets and we find that this perforin dependent activity can work together with antibody to provide protection against lethal influenza challenge in otherwise unprimed mice (17). We also will determine when memory CD4 T cells re-express cytotoxic activity following in vivo challenge and how cytotoxic killing contributes to the memory cell mediated protection. We want to analyze how the program of cytotoxicity is induced in these “ThCTL”. <p > Memory CD4 Cells Enhance an Innate Response. Memory cells can act by becoming secondary effectors but they are best characterized by their ability respond rapidly even to low antigen doses, by producing cytokines and chemokines and it is assumed that these initial abilities are key to memory cell activity. However this assumption has not been directly demonstrated and the mechanisms involved and how they might contribute to immunity have not been elucidated. We find that restimulation of memory CD4 T cells leads to a markedly enhanced early innate response to influenza infection both in the lung and systemically (17). This response peaks 2-3 days after infection and is transient. We see enhanced production of IL-6 locally and systemically and enhanced production a broad spectrum of innate inflammatory mediators in the lung. We hope to determine in detail the pathways leading to optimum memory T cell-induced innate responses. We suggest a concurrent activation of CD4 memory cells may be an effective adjuvant for vaccination and will be testing this hypothesis as well as mechanisms that lead to viral control over the next couple of years. <p >Aging and Immunity: The study of the impact of aging on CD4 T cell function at the naïve and memory stages has lead us to better understanding of fundamental aspects of T cell behavior in addition to providing important information about what vaccine approaches are most likely to be successful for the aged. Nature of CD4 Aging “Defects”. We have identified multiple levels at which aged naïve CD4 T cells are defective including initial early response to TcR triggering, IL-2 production, expansion and effector generation. The defects in helper function and in the 20 response of memory cells generated from aged naïve CD4 T cells are particularly dramatic. In recent studies we have recapitulated memory age-associated defects in recently generated memory cells in vitro (23). In vitro aged memory cells are markedly defective in production of particular cytokines, IL-4, IL-5 and IL-2, while others are little affected (IFNg, IL-10, TNF), suggesting the aging “defect” may be restricted to loss of potential to make certain CD4 T cell subsets, such as those responsible for help to B cells .We will pursue this hypothesis both in vitro and in vivo. <p >We have found that aged naïve CD4 T cells are in fact longer-lived than their naïve counterparts (23). We find that reduced expression of Bim, a proapoptotic protein, is responsible for this increase in lifespan and that the increase in lifespan is required for the development of aging defects. We are now investigating the factors that regulate Bim expression. <p >Enhancement by Inflammatory Cytokines. We have shown that the defective effector generation responses of naïve CD4 T cells from aged animals can be overcome by IL-2 and by proinflammatory cytokines, in particular a mix of IL-1, IL-6 and TNF (20,21). We want to determine the extent to which the inflammatory cytokines can reverse the heritable aging defects and restore functional memory generation. We have developed in vitro models to test the generation of effectors and memory. In these models we are evaluating TLR agonists for their ability to restore aged naïve CD4 responses to peptide-pulsed derived dendritic cells (DC). Pre-incubation of DC with many TLR agonists, enhances expansion of the responding aged naïve CD4 T cells via a mechanism dependent on IL-6 that acts in part by increasing survival of the developing effector population. We plan to use this model to identify the extent of the rescue and what pathways and mechanisms contribute with the ultimate goal of evaluating whether specific TLR stimulation or stimulation of specific pathways might improve the response of the elderly to vaccines. We want to see if we can reproduce this model with human naïve CD4 T cells and DC derived from peripheral blood and if TLR agonists can also enhance those responses. <p >
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.
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 Postdoctoral position is available in the Trivedi lab to study roles of novel chromatin and epigenetic modifications during cardiovascular development and disease (for details of our research: The Journal of Clinical Investigation, Science Advances, Journal of Experimental Medicine, ATVB, Human Molecular Genetics, Journal of Biological Chemistry). Candidates with a PhD in Biochemistry, Molecular Biology, Stem Cell Biology or Developmental Biology are encouraged to apply. Previous experience with mice handling and biochemistry-molecular biology-epigenetics related techniques such as ChIP-seq is strongly desired. Candidate will be required to learn new techniques in the area of translational biology to advance their project.
Rotation Projects: Please contact Chinmay Trivedi (chinmay.trivedi@umassmed.edu) for information regarding potential rotation projects (for details - research performed by graduate students in the trivedi lab: The Journal of Clinical Investigation, Science Advances, Journal of Experimental Medicine, JCI Insight, ATVB, Human Molecular Genetics, Journal of Biological Chemistry). We will develop a specific rotation project based on student's interest, background, and goals of the rotation. Students can rotate either for a half- or full-semester.
David J. Freelander Memorial Professor in AIDS Research
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
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.
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.
The Emerson lab investigates skeletal muscle development and disease. Research has focused on defining transcriptional networks and signaling pathways that control the specification and differentiation of skeletal muscle progenitors in the developing embryo.
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.
Neil and Margery Blacklow Chair in Infectious Diseases and Immunology
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.
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.
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.
Herman G. Berkman Chair in Diabetes Care Innovation
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.
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.
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
Emergency Medicine at UMass Chan - Lahey
Joseph D. Early Chair in Biomedical Research
Eleanor Eustis Farrington Chair in Cancer Research
Prevention Strategies for Second Primary Malignancies After CAR-T Therapy
The Darkest Side of AML: The TP53 Mutation
Clonal Hematopoiesis in Clinical Practice: Real-World Insights
Unpacking CHIP: Recent Updates, Remaining Questions
Dr Patel on the Impact of Donor-Engrafted Clonal Hematopoiesis on Outcomes With Auto-/Allo-HSCT
Effects of donor-engrafted clonal hematopoiesis in stem cell transplantation
High-Risk Myelodysplastic Syndrome Findings in the SELECT-MDS-1 Study
Stem Cell Transplantation: How Clonal Hematopoiesis Shapes Patient Outcomes
Olutasidenib as a Breakthrough for R/R mIDH1 AML Patients
The Impact of Mutations in Clonal Hematopoiesis
TP53 in MDS & AML Prognostication & Treatment Strategies
Exploring the Biological Basis of TP53-Aberrant MDS & AML
Improving Outcomes in Blast Phase Chronic Myeloid Leukemia
ASH Clinical News - Practical Solutions Amid Cuts to Federally Funded Research
OncLive with Dr. Patel and Dr. Gerber: p53 Immunohistochemistry
Early Identification of TP53-Mutant MDS and AML Using p53 Immunostaining
Point-of-Care p53 IHC Unveils TP53-Mutant MDS/AML
IHC Enables Rapid Identification of TP53-Mutant MDS/AML
ASH Clinical News: p53 Immunohistochemistry for TP53-Mutant MDS/AML
p53 Immunostain in TP53-Mutant MDS and AML