Health Informatics And Implementation Science
Elisabeth Chair for the Dean of Medicine
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
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.
Potential Rotation Projects 1. 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. Cocaine's Synaptic Actions at the Dopamine Transporter. Synaptic models. (A) Dopamine released into the extracellular space is rapidly cleared by the dopamine transporter (purple), thereby limiting the postsynaptic dopamine signal. (B) Cocaine binds to and blocks the dopamine transporter, allowing dopamine to accumulate extracellularly and enhancing the postsynaptic signal.
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.
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.
Dr. Henninger is a vascular neurologist with research interest in the neurobiology of axonal injury associated with traumatic brain injury and its contribution to functional outcome.
UMass Chan Medical School Chair in Biomedical Research
A postdoctoral position is available to study in this laboratory. Contact Dr. Rock for additional details.
Potential Rotation Projects <p >Rotations are available in Dr. Rock’s laboratory for graduate students in the GSBS program. The rotation projects will explore various aspects of how the immune system carries out surveillance to detect viral infections and cancers. Among the potential areas of research are: (1) The alarm signals that alert the immune system to potential danger; (2) The initial innate immune and inflammatory response to infection or other dangerous situations; (3) The biology of the sentinel cells (e.g. dendritic cells) that sense danger and report it the adaptive immune system; (4) The mechanisms by which sentinel cells (e.g. dendritic cells) acquire and display antigens to T cells; and, (5) The antigen presentation pathways by which virally infected or cancer cells display a sampling of their expressed gene products to the activated T cells. Specific rotation projects are chosen based on the student’s interests and state/availability of the various projects in the laboratory. The goals of rotations are for the student to gain knowledge in immunology, to learn how to approach experimental problems, to learn new techniques and methods, and to actually generate data that moves our knowledge forward. In addition, the rotation provides the student the opportunity to evaluate the laboratory as a possible place to conduct their thesis research in the future.
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.
Arthur F. and Helen P. Koskinas Professor in Biochemistry and Molecular Biotechnology
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.
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.
Richard M. Haidack Professor in Medicine
Population and Quantitative Health Sciences
Biochemistry and Molecular Biotechnology
Family Medicine at UMass Chan - Baystate
Healthcare Delivery and Population Sciences at UMass Chan - Baystate
Joseph D. Early Chair in Biomedical Research
Dr. Wilcox trained in EM at the Harvard Affiliated EM Residency, then completed an Anesthesia Critical Care fellowship. In addition to the ED, she has attended in Surgical, Medical, and Cardiac ICUs. She joined Lahey Hospital in 2022 as the Medical Director of the 5C Medical ICU. She is Vice Chair for Academic Affairs and a Professor of Medicine. She is the Associate CMO for Boston MedFlight.
David Lawrence Burns MD, CNSP, FACG, FASPEN
EMCrit 181 – Pulmonary Hypertension and Right Ventricular Failure with Susan Wilcox
HarvardX: Mechanical Ventilation for COVID-19
CritCases 7 Pulmonary Hypertension – A Fine Balance
Academic Life in Emergency Medicine: The Myth of Vasopressors and Ischemia
ACEP COVID-19 Field Guide: ICU Care in the Emergency Department
Podcast summary of articles from the June 2021 edition of the Journal of Emergency Medicine