The Aroian Group is actively recruiting graduate students to: 1. use microbiology and genetics to develop new methods for delivery of protein therapies (anthelmintics) to the GI tract 2. discovery and mechanism of action studies of new anthelmintics to control soil-transmitted helminths 3. study how vertebrate hosts and their immune system interact with intestinal nematodes, with the particular goal of controlling autoimmune disease 4. study innate immune mechanisms that protect animals against pore-forming toxin attack
Endowed Chair in Biochemistry and Molecular Biotechnology I
Blais University Chair in Molecular Medicine
Potential Rotation Projects: There are numerous potential rotation project available in the Mello lab: Projects include: Investigation of RNAi and related mechanisms, including Piwi Argonaute pathways and their affects on fertility and epigenetic inheritance; Investigation of germline determination and cell-fate specification during embryogenesis; the exploration of CRISPR mediated genome editing tools for C. elegans and other organisms; and finally the use of CRISPR to generate C. elegans models for human genetic disease.
Elisabeth Chair for the Dean of Medicine
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.
Lab rotations are currently available in this lab. Please contact Dr. Kim.
My research for almost 30 years has focused on obesity, insulin resistance, and type 2 diabetes and explores the molecular link between inflammation and insulin resistance using transgenic mice with elegant in vivo metabolic experiments and molecular approaches. My research also investigates the role of inflammation and altered metabolism in diabetic heart disease.
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.
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.
Please contact the Human Resources at UMass for openings in Dr. Bergmann's lab.
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.
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.
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.
LAB ROTATION PROJECTS AVAILABLE -- PLEASE CONTACT SAM BEHAR FOR MORE INFORMATION
Focus: We seek to understand how the causative agent of tuberculosis, namely the bacterium Mycobacterium tuberculosis evades host immunity, and how different components of the immune response work together to contain infection. Our ultimate goal is to inform vaccine development and the design of host directed therapy.
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.
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
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.
Herman G. Berkman Chair in Diabetes Care Innovation
Potential Rotation Projects Rotation projects in my laboratory will involve questions of how cilia are assembled and the function these organelles play in mammals. Projects vary depending on ongoing work in the laboratory and interests of the rotation student. Rotations in my laboratory can give students exposure to a range of techniques from mouse breeding and histological analysis of mouse tissues to mammalian cell culture and other cell biological techniques.
A postdoctoral position is available to study in this laboratory. Contact Dr. Kang for additional details.
<!-- [if gte mso 9]><xml> <o:DocumentProperties> <o:Template>Normal</o:Template> <o:Revision>0</o:Revision> <o:TotalTime>0</o:TotalTime> <o:Pages>1</o:Pages> <o:Words>109</o:Words> <o:Characters>624</o:Characters> <o:Company>UMass Medical School</o:Company> <o:Lines>5</o:Lines> <o:Paragraphs>1</o:Paragraphs> <o:CharactersWithSpaces>766</o:CharactersWithSpaces> <o:Version>11.1282</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!-- [if gte mso 9]><xml> <w:WordDocument> <w:Zoom>0</w:Zoom> <w:DoNotShowRevisions/> <w:DoNotPrintRevisions/> <w:DisplayHorizontalDrawingGridEvery>0</w:DisplayHorizontalDrawingGridEvery> <w:DisplayVerticalDrawingGridEvery>0</w:DisplayVerticalDrawingGridEvery> <w:UseMarginsForDrawingGridOrigin/> </w:WordDocument></xml><![endif]--> <!-- [if gte mso 9]><xml> <o:DocumentProperties> <o:Template>Normal</o:Template> <o:Revision>0</o:Revision> <o:TotalTime>0</o:TotalTime> <o:Pages>1</o:Pages> <o:Words>130</o:Words> <o:Characters>743</o:Characters> <o:Company>UMass Medical School</o:Company> <o:Lines>6</o:Lines> <o:Paragraphs>1</o:Paragraphs> <o:CharactersWithSpaces>912</o:CharactersWithSpaces> <o:Version>11.1282</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!-- [if gte mso 9]><xml> <w:WordDocument> <w:Zoom>0</w:Zoom> <w:DoNotShowRevisions/> <w:DoNotPrintRevisions/> <w:DisplayHorizontalDrawingGridEvery>0</w:DisplayHorizontalDrawingGridEvery> <w:DisplayVerticalDrawingGridEvery>0</w:DisplayVerticalDrawingGridEvery> <w:UseMarginsForDrawingGridOrigin/> </w:WordDocument></xml><![endif]--> Postdoctoral positionsstarting in March 2019 for studies of the gene regulatory networks underpinning the hematopoietic system (ImmGen.org), self- or tumor-reactive T cell trafficking to tissues in organ-specific autoimmunity and tumor surveillance, respectively. Applicants must have a record of accomplishment in immunology or developmentalbiology with technical fluency in molecular biology, animal model generationand analysis, gene expression analysis and/or intravital imaging. Send a letterof interest, CV and names of three references to: Joonsoo Kang, Ph. D., E-mail (preferred): joonsoo.kang@ umassmed.edu. Dept. of Pathology, The Albert ShermanCenter (http://www.umassmed.edu/shermancenter/index.aspx)at Univ. of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA01655.
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.
Potential Rotation Projects Several rotation projects are available in structural biology of immune receptors, antigen presentation pathways, T-cell activation, and development of novel T-cell detection reagents. Please see Prof. Stern for details.
Positions for postdoctoral fellows are available in the laboratory of Dr. Gang Han at the Department of Biochemistry and Molecular Pharmacology of The University of Massachusetts- Medical School. Research will focus on developing novel small molecule/ nanoparticle approaches for translational biomedical sciences and molecular imaging. Qualifications: Candidates have a Ph.D degree in (1)Organic Chemistry/polymer synthesis , (2) Molecular cell biology , (3) Biophysics or (4) Biochemistry. A solid training and substantial organic synthesis, animal experiments, spectroscopy and microscopy are desired. Candidates need to have strong work ethic, creativity, and enthusiasm with proven ability to work independently and collaboratively. To apply: Applicants should submit their CV including a full publication list and sources of three reference letters by email to gang.han@umassmed.edu
Rotation projects <p >(1) Specific cell membrane component labeling using bioconjugated nanoparticles <p >(2) To develop tools for targeted and traceable siRNA delivery <p >(3) To synthesize functional nanomaterials for detecting biomarkers in biological fluids
Rotation Projects Please contact Nathan Lawson (nathan.lawson@umassmed.edu) for information regarding potential rotation projects. For information concerning recent research in the lab, please see:lawsonlab.umassmed.edu/research.html
Rotation Projects <p >We have identified a number of bacterial pathways that are required for bacterial viability or virulence. We are particularly interested in: Phosphosignaling systems that regulate cell wall synthesis Metabolic regulatory mechanisms that trigger the “dormancy” response observed during infection. <p >A variety of genetic, biochemical, and informatic methods will be used to define the functions of these genes and the role played by each during infection. <p >
Postdoctoral positions are available in the Miller laboratory to investigate and extend the scope of bioluminescence imaging. Lab projects range from molecular-level studies of the mechanism of luciferases, to non-invasive imaging of specific biological processes and disease states in live animals. Motivated and inherently curious critical thinkers with backgrounds in biology, chemistry, or both are encouraged to apply.
Rotation Projects Work in our lab uses optical imaging to study live cells and organisms. This multi-disciplinary approach brings together the areas of synthetic organic chemistry, molecular biology, biochemistry and cell biology, with translation into mouse models of disease. 1) Broadening the scope of bioluminescence: Bioluminescence results from the chemical generation of light that occurs when a luciferase enzyme oxidizes its small molecule luciferin substrate. We have synthesized a wide variety of novel luciferin substrates designed to improve the ability to detect bioluminescence signals. In parallel, we have mutated luciferases to best accommodate these substrates, and have also found that a homologous protein in the fruit fly can act as a luciferase. Projects in the lab range from basic molecular-level biochemical, chemical, and evolutionary studies of luciferases and luciferins, to powerful applications such as imaging of enzyme activity and drug action in the brains of live mice. 2) Fluorescent probes beyond the visible range: Fluorescent sensors of enzymatic activity, metal ions, and small molecules allow the optical detection of biologically-important molecules. However, most of these sensors are based on visible-wavelength fluorophores that suffer from photoxicity and high background. These probes thus have limited utility in live cells, and are generally unusable in live organisms such as mice. We are designing and constructing sensors that fluoresce in the near-IR, beyond the visible range, which is most suitable for non-invasive optical imaging of the physiological state of live cells and organisms.
Biochemistry and Molecular Biotechnology
National Mouse Metabolic Phenotyping Center
Worcester Foundation for Biomedical Research Chair I