Research Interests: My lab investigates the role of prostate-specific membrane antigen (PSMA) in prostate cancer tumor growth and metastasis, and I currently have two federally funded projects:
Project 1: Recently, my lab has developed a novel multi-cell type, scaffold-free, 3D bioprinted prostatic tumor model that accurately represents the human PSMA (+) primary tumor vasculature and the primary tumor microenvironment. This model provides the laboratory with a unique system for interrogating novel PSMA small molecule inhibitors on multiple tumorigenic endpoints.
Project 2: We are investigating if germ-line SNPs within specific components of the PSMA signaling pathway might contribute to the increased risk of prostate cancer in African American men vs. that of men of European descent. Investigation into these molecular mechanisms not only has the potential to improve the outcomes of all men with lethal prostate cancer but also can reduce prostate cancer disparities by improving detection, morbidity, and mortality of lethal prostate cancer in African American and other at-risk populations through the identification of unique, tailored treatment and prevention strategies for each patient.
Research Interests: Breast cancer recurrence and subsequent metastasis is the cause of the majority of breast cancer related deaths. When and why breast cancer recurrence occurs also remains poorly understood. Examining the mechanisms of survival under long-term stress can provide information as to how to target these dormant cells.
Research Interests: My research focuses on defining the intracellular communication networks that promote specificity in signal transduction. In particular, we work on A-kinase-anchoring proteins (AKAPs) that target the camp-dependent protein kinase, as well as other signaling enzymes, into discrete signaling complexes in order to regulate the phosphorylation of target proteins. In particular, we are concentrating on AKAP complexes in the heart, and how they regulate cardiac physiology.
Research Interests: Research in the Epstein laboratory centers on second messengers and signal transduction. Particular focus has been on cyclic nucleotide metabolism and protein phosphorylation, with emphasis on analysis of cyclic nucleotide phosphodiesterases (PDEs). It has become apparent, in recent years, that PDE is a superfamily of enzymes encoded by 21 different genes, grouped into 11 gene families, based on sequence similarity, mode of regulation and preference for cAMP or cGMP as substrate. With the existence of multiple transcription initiation sites, as well as alternatively spliced forms of many of these genes, more than 100 different forms of PDE have been identified and cloned to date, and many of these PDE forms are localized to different cells and different subcellular compartments as part of complexes or signalosomes composed of scaffolding proteins, cAMP effectors, and distinct PDEs, thus achieving targeted cAMP degradation and the creation of localized intracellular cAMP gradients and allowing the control of specific cellular functions by specific PDE isoforms during cellular signaling. Hence, by inhibiting or altering the expression of specific forms of PDE, cAMP levels in specific cell types can be altered, and fundamental physiological processes in one cell type can be changed, without affecting others. Thus, a main research goal in this laboratory is to examine the tissue distribution of different forms of PDE and regulation of their expression during development and in different pathophysiological states so that specific PDE isoforms can be targeted to treat a number of different diseases. The focus of our research has been to identify and inhibit specific PDE isoforms as novel treatment methods for leukemia, breast cancer and autoimmune and inflammatory illnesses.
Research Interests: Angiogenesis, or growth of blood vessels, is often suboptimal in many injured tissues such as ischemic tissues following heart attack or diabetic wounds. The healing and regeneration of such tissues critically depend on proper angiogenesis. On the other hand, uncontrolled neovascularization underlies many diseases such as tumor growth, diabetic retinopathy (DR), and age-related macular degeneration (AMD). In addition, capillary destruction is a significant pathological contributor to such diseases as bronchopulmonary dysplasia (BPD) and retinopathy of the prematurity (ROP). At the current state of the knowledge, the molecular mechanisms controlling angiogenesis and vascular integrity are only partially understood, which handicaps efforts to develop effective therapies. In our laboratory, we use both developmental and disease models to understand how these processes are controlled, and explore potential therapeutic approaches.
Research Interests: The overall goal of the Han Laboratory is to utilize newly developed proteomic technologies to uncover cellular signaling networks and pathways that govern mechanisms of programmed cell death/apoptosis. Toward the overall goal, we have made significant level of commitment to improve currently available technologies and apply proteomic technologies to uncover novel biological insights.
- Apoptotic Signaling Networks in Vascular Inflammation and Atherosclerosis
- Mechanisms of Apoptotic Cell Engulfment
- Modeling Genomics and Proteomics Datasets by Developing Novel Bioinformatics Approaches
- Implementation of Proteomics and Mass Spectrometry Technologies for Protein Identification and Quantification
Research Interests: Asymmetric stem cell division is a mechanism that balances stem cell self-renewal and differentiation through the production of one stem cell and one differentiating cell. It is a simple way of maintaining the stem cell population without increasing it and is thus thought to be a vital mechanism for tissue homeostasis and tumor suppression. My research goal is to elucidate the molecular mechanism as to how two daughter cells of different fates are made after only one cell division. My lab primarily uses Drosophila gonads, in which we can monitor asymmetric division in vivo. Owning to the simple anatomy and abundant imaging tools, this system allows us to discover previously unrecognized regulatory mechanisms Our research findings should lead to the development of new therapeutic approaches for cancers and degenerative diseases.
Research Interests: Research in the Jaffe lab concerns the physiological mechanisms that regulate the oocyte cell cycle and fertilization. Currently, our studies are focused on regulation of meiosis in mammalian ovarian follicles by cyclic nucleotides.
Board of Trustees Distinguished Professor
Center for Cell Analysis and Modeling
Research Interests: My lab is focused on the development of new experimental and computational technologies to help us understand the mechanisms underlying cell function. We have a longstanding effort aimed at developing and characterizing fluorescent probes of membrane potential. This effort is continuing, using organic chemical design and synthesis to develop better more sensitive voltage indicators. This work has led to a continual interest in the organization of signaling pathways along the cell membrane and within the cytoplasm. We are interested in the very general question of how the intricate spatial organization of molecules in cells is used to control cell function. This is especially true of neuronal cells and we are actively investigating the cell biology of dendritic spines in brain tissue. This motivated us to develop a very general computational modeling software platform called the “Virtual Cell”, in which we have created a framework for using computer simulation to explore cell biological mechanisms. The models are built naturally from experimental images of cellular and subcellular structures combined with biochemical and electrophysiological data. We have used the “Virtual Cell” system to explain the pattern of electrical and signaling activity in neuronal and non-neuronal cells. Most recently, we have developed new software called SpringSaLaD that can model molecular interactions at the sub-cellular scale. This allows us to explore how the shape of individual molecules control their interactions, leading ultimately to cell-level responses.
Research Interests: Our lab is interested in elucidating cytoplasmic changes that occur in the mammalian oocyte that are important for the egg to become developmentally competent, as well as the mechanisms that cause these cytoplasmic changes to occur. A complete understanding of these events will contribute to improving methods for maturing oocytes in vitro.
Research Interests: My research is in the area of computational systems biology, which aims to better understand biological systems through the use of computer models. My active areas of research include the development of modeling and simulation software as the author of the popular simulator Gepasi and leader of the COPASI simulator (with U. Kummer) and have been actively involved in the development of SBML, the systems biology markup language, and the MIRIAM proposal for model annotation. My group also constructs biochemical models, currently, this involves models of iron metabolism, eukaryotic translation, and microbial central metabolism. Through this work, I have pioneered the application of numerical global optimization in biochemical kinetic modeling and I am interested in using formal systems identification techniques in systems biology, particularly for reverse engineering models from data. My research requires a broad interdisciplinary approach and I work with people from most areas of science, either in my own research group or as collaborators.
Center for Cell Analysis and Modeling
Research Interests: My general research relates to the theoretical understanding of cellular processes, and developing tools for mathematical modeling in cell biology. Current work focuses on interfacing pathway/logic models and –omics data with kinetic quantitative models and dynamic simulations, both on new technology developments and the application to complex modeling of signaling pathways in normal and malignant cells. I am also the current lead developer of the Virtual Cell software platform for mathematical modeling and direct development of both the user interface and computational infrastructure. In addition, my interest in model reproducibility has led to a powerful new web platform that provides a central portal for simulating a broad range of models of biological systems. I have been involved in community standards for a long time, contributing to the development of both Systems Biology Markup Language (SBML) and Simulation Experiment Description Markup Language (SED-ML).
Research Interests: Our research focuses on endothelial cells lining the vasculature, aiming to better understand the critical role of these cells in mediating inflammatory and immune responses. Our work has revealed post-transcriptional regulation by alternative splicing in the response to inmate immune cell recruitment.
Research Interests: Blood-forming hematopoietic stem cells (HSCs) maintain the entire blood/immune system throughout life and are the functional units of bone marrow transplantation. The Oguro laboratory investigates the mechanisms that regulate HSC development, self-renewal, mobilization, and malignant transformation using mouse models, patient samples, and human induced pluripotent stem cells (hiPSCs). Our laboratory currently focuses on: 1) understanding how HSCs proliferate and mobilize in response to acute hematopoietic demands; 2) understanding how normal mechanisms that activate HSCs are exploited in hematologic malignancies; 3) understanding the HSC developmental process to generate long-term engraftable HSCs from hiPSCs. Our findings could lead to novel therapies for diseases caused by insufficient hematopoiesis or hematologic malignancies.
Research Interests: How we sense and react to our environment is communicated in the cell by vast networks of highly dynamic, interacting proteins. These interactions are regulated in both space and time, and it is this tight regulation that allows signals from outside of the cell to be rapidly and precisely transmitted to the nucleus leading to the appropriate, and healthy, cellular response. We integrate structural biology, cell biology, genetics and biochemistry in order to understand how these signals in both prokaryotes and eukaryotes are communicated in the cell at atomic resolution.
Center for Cell Analysis and Modeling
Research Interests: Research in my laboratory is focused on molecular mechanisms of intracellular transport and the organization of microtubule cytoskeleton. Melanophores, pigment cells of lower vertebrates, are large cells that synchronously transport thousands of membrane-bounded pigment granules either rapidly to the cell center to form a tight aggregate or to disperse uniformly throughout the cytoplasm. During aggregation, granules move along microtubules using cytoplasmic dynein, but dispersion involves both initial microtubule-dependent transport to the periphery by Kinesin II and then slow diffusion-like movement along randomly arranged actin filaments. Transport is regulated by a Protein Kinase A (PKA) signaling cascade and thus provides a unique system for studying the role of the cytoskeleton in intracellular transport, mechanisms of switching between the two major transport systems, and regulation of activity of motor molecules by signal transduction mechanisms. We use molecular biology and biochemistry along with live cell fluorescence microscopy, photobleaching, photoactivation, and microinjection of motor-specific probes to understand the molecular mechanisms underlying the regulation of intracellular transport.
Research Interests: High density lipoprotein cholesterol (HDL-C) levels are thought to protect against cardiovascular disease. This may or may not be true in certain populations. The Rodriguez-Oquendo lab is studying the genetic link between healthy HDL cholesterol, heart disease, and infertility in women. This work suggests that variations within the SCARB1 (scavenger receptor class B type I) gene, connected to increased HDL levels, are associated with heart disease risk as well as hormonal and fertility problems in women. The goal of the research discoveries is the development of methods to diagnose and, ultimately, treat heart disease and improve a woman’s ability to conceive.
Research Interests: Research in the Shapiro Laboratory is focused on understanding the physiological and pathological regulation and function of two M1 family cell surface peptidases CD13/aminopeptidase N and PSMA/glutamate carboxy-peptidase II. This interest is the result of the striking upregulation of numerous cell surface peptidases on endothelial cells in response to both angiogenic land inflammatory signals, leading to the hypothesis that these may functionally cooperate in enzymatic cascades to regulate angiogenesis, inflammation and endothelial cell function. While the angiogenic significance of proteases that cleave large proteins (such as the matrix metalloproteases) is well documented, increasing evidence supports a role for peptidases (metAP2, CD13, APA, PSMA) as angiogenic regulators as well. The fact that these enzymes metabolize small peptide substrates suggests that small molecule regulators of angiogenesis exist which have yet to be identified and whose mechanisms are unknown. Indeed, we have shown that CD13 and PSMA are potent regulators of angiogenesis individually and our investigation of their regulatory mechanisms and their possible interaction is a current focus of the laboratory. However, our investigations have identified a variety of additional functions for these multifunctional molecules, leading our studies into the areas of molecular biology, immunology, cell biology, nephrology, transplant biology, stem cell biology, biomarkers and oncology in addition to angiogenesis using mouse models of myocardial infarction, peripheral artery disease, stroke, peritonitis, diabetic nephropathy, ureteropelvic junction obstruction and prostate cancer. Our strong relationship with clinician-scientists from the Connecticut Children’s Medical Center Departments of Surgery, Urology and Nephrology has fostered a high degree of translational research by providing clinical insights and remarkable access to patient samples, allowing us to identify, investigate and potentially treat truly clinically relevant questions.
- Use of heavy-atom nanoparticles for tumor imaging, vascular imaging and as a radiation enhancer for tumor therapy.
- Use of iron and gold nanoparticles for tumor hyperthermia
- Development of novel brain tumor therapies for experimental, advanced, imminently lethal intracerebral malignant gliomas and melanomas in rats and mice using a combination of radiation therapy and immunotherapy.
- Tumor dormancy
- Novel biomarkers in human breast cancer.
- Use of heavy atom nanoparticles to study vulnerable plaque in mouse models of atherosclerosis
Research Interests: I have a long interest in the 3D organization of the endoplasmic reticulum, and more recently have started to work on 3D organization of cells and related structures in tissues. My lab uses microtomes to physically cut serial sections of varying thicknesses then images the sections by electron microscopy or fluorescence microscopy. Recent morphology projects include the tubular ER network in axons, the capillary network of the glomerulus, filopodial distribution in the mouse ovarian follicle, and the first myelin paranode at the axon initial segment of spinal motor neurons.
Research Interests: Our research is at the intersection of computational systems medicine and systems biology, mathematical biology, and bioinformatics. We work on the design, software development, and application of mathematical algorithms for the modeling, simulation, and control of biological systems. In molecular biology, the systems of our interest include gene regulatory networks and intracellular signaling networks where we aim to understand and control the cells’ intricate regulatory programs. We are focused on Cancer research (cancer reversion mechanisms and reversion of chemotherapy resistance) in breast cancer and leukemia.
Research Interests: Calcium is the most common signal transduction element in virtually all cells ranging from bacteria to neurons. Recent studies have demonstrated the importance of transient receptor potential (TRP) channels in mediating calcium signals. The mammalian TRP channel superfamily consists of a diverse group of calcium permeable nonselective cation channels that may play a role in pain transduction, thermo-sensation, mechanotransduction, tumor suppression, vasodilatation, and neurodegenerative disorder. Twenty-eight mammalian TRP channel genes have been cloned since the first TRP channel protein was identified in Drosophila, yet their physiological functions are to be revealed.
In Residence Faculty
- Corey Acker, Assistant Professor, Center for Cell Analysis and Modeling
- Iman M. Al-Naggar, Assistant Professor, Center on Aging
- Jeremy Egbert, Assistant Professor
- Mallika Ghosh, Assistant Professor, Center for Vascular Biology
- Yvonne Grimm-Jorgensen, Assistant Professor
- Yida Jiang, Instructor
- Katie Lowther, Instructor and Assistant Director, Center for Mouse Genome Modification
- Rachael Norris, Assistant Professor and Assistant director, Central Electron Microscopy Facility
- Sathya Srinivasan, Assistant Professor
- Boris Slepchenko, Associate Professor, Center for Cell Analysis and Modeling
- James Watras, Associate Professor
- Ping Yan, Assistant Professor, Center for Cell Analysis and Modeling
- Siu-Pok Yee, Associate Professor and Director, Center for Mouse Genome Modification
Joint, Adjunct and Affiliated Appointments
- Alison Bartolucci, Department of Obstetrics and Gynecology and CARS
- Molly Brewer, Department of Obstetrics and Gynecology
- Caroline Dealy, Department of Reconstructive Sciences
- Ahmed Elmokadem, Metrum Research Group, Tariffville, Ct
- Stephen Falk
- Sherli Koshy-Chenthittayil, Touro University, Las Vegas, NV
- Kshitiz, Biomedical Engineering
Office Staff (E6036)
Business Services Manager
Department of Cell Biology
Administrative Program Coordinator
Department of Cell Biology
Administrative Program Coordinator
Department of Cell Biology