Interdisciplinary groups of Northwestern scientists are new treatment possibilities for diabetes, obesity and metabolic disorders. The prevalence of obesity, often caused by metabolic disorders, in the United States is resulting in skyrocketing healthcare costs. Because of its effects on the body and the host of diseases that are associated with obesity, including diabetes, it threatens to lower the life expectancy of our next generation. Our center members’ investigate this broad area of research from multiple angles, including:
- Type 1 Diabetes: discovering promising strategies to prevent or reverse the onset of type 1 diabetes (juvenile diabetes) in high-risk patients
- Adult-Onset Type 2 Diabetes: focusing on better treat complications from diabetes that occur in the eyes, kidney, nerves and heart, including new strategies to reverse disease even after it occurs in small vessels in these tissues
- Gestational Diabetes: examining how a mother’s obesity and high sugar levels affect the child’s lifelong risk of obesity and his or her overall metabolic health; leading in the study of maternal-child health research, our work has set the standard for how to best treat diabetic women during pregnancy
- Obesity: looking to better understand the condition and its many causes, including social, cultural, biological and psychological
- Metabolism and Metabolic Disorders: understanding the complex network of hormones and enzymes that not only converts food into fuel but also affects how efficiently an individual burns that fuel
Learn more about our current work below.
Labs in This Research Area
Role of mitochondria and metabolic processes in cancer growth, cardiac disease and metabolic disorders
Our lab focuses on three major areas of research:
Role of proteins involved in cellular and systemic metabolism
TTP is a protein that binds to AU-rich regions in the 3’ UTR of mRNA molecules and causes their degradation. It has been studied extensively in the field of inflammation. We recently showed that it also plays a role in cellular iron conservation. We have also shown that TTP is a key mediator of cellular metabolic processes. Our studies have demonstrated that TTP regulates glucose, fatty acid and branched-chain amino acid metabolism in the liver and muscle tissue. We also have evidence that TTP directly regulates mitochondrial electron transport chain (ETC) by targeting specific proteins in the ETC complexes. Finally, recent studies demonstrated that TTP also regulates systemic metabolism by targeting FGF-21 expression. We have both TTP Floxed mice (for the generation of tissue specific TTP knockout mice) and TTP knockout mice in the background of TNF-alpha receptor 1/2 knockout mice (to reduce the inflammatory burden). Current studies include: 1) role of TTP in liver metabolism of fatty acids and glucose, 2) effects of TTP on mitochondrial proteins, 3) mechanism of TTP regulation of branched-chain amino acid levels and 4) role of TTP in cardiac metabolism.
Adult cardiomyocytes regenerate at a very low rate, but neonatal cardiomyocytes grow and replicate at a high rate. We have identified specific tandem zinc-finger (TZF) proteins that bind to mRNAs to regulate cardiac regeneration and cardiac development. Our studies suggest that these proteins may alter DNA repair in response to damage by regulating p53 and helicases. Current projects include: 1) identifying the mechanism by which TZF proteins regulate p53 and DNA damage, 2) characterization of the role of helicases in cellular proliferation and regeneration and 3) role of TZF proteins in cardiac development.
Characterization of cellular and mitochondrial iron regulation
Our lab has identified a novel mitochondrial protein, ATP-Binding Cassette-B8 (ABCB8), which plays a role in mitochondrial iron homeostasis and mitochondrial iron export. Mice with ABCB8 knocked out in the heart develop cardiomyopathy and mitochondrial iron accumulation. In addition, we have shown that a pathway involving mTOR and tristetraprolin, treatment with doxorubicin (an anticancer drug that also causes cardiomyopathy) and SIRT2 protein also impact cellular and/or mitochondrial iron regulation. Current studies in this area include: 1) further characterization of ABCB8 in iron homeostasis in other organs and disorders, 2) characterization of the mechanism for iron regulation by SIRT2, 3) identification of the mechanism by which mTOR is regulated by iron, 4) role of iron in viral infection, particularly HIV, 5) characterization of the effects of iron on mitochondrial dynamics and 6) identification of novel mitochondrial-specific iron chelators.
For more information, see Dr. Ardehali's faculty profile.
See Dr. Ardehali's publications in PubMed.
Transcriptional regulators of inflammation and metabolism
The burgeoning epidemic of obesity and type 2 diabetes mellitus presents a major health and therapeutic challenge. Transcriptional regulation is the fundamental control mechanism for metabolism, but a gap remains in our knowledge of gene regulatory pathways that control lipid and glucose homeostasis. Thus, we seek to identify modulable pathways that may be leveraged to counteract diabetes mellitus and its comorbidities, particularly cardiovascular disease. In this effort, we use a variety of genetic, molecular, next-generation sequencing, biochemical methods and physiological models. Our recent work has helped to reveal the genomic architecture for transcriptional regulation in innate immunity, which plays a key role in both diabetes mellitus and atherosclerosis. Surprisingly, although macrophage regulatory elements are often at significant linear distance from their associated genes, we identified interplay between transcriptional activators and repressors that is highly proximate, occurring at shared nucleosomal domains (Genes & Development, 2010). Moreover, we discovered a powerful role for the BCL6 transcriptional repressor to maintain macrophage quiescence and prevent atherosclerosis (Cell Metabolism, 2012).
Currently, we are exploring the impact of activator–repressor interactions on enhancer function and transcription, the signal-dependent control of repression and the functional impact of transcriptional activators and repressors on inflammatory and metabolic disease. In particular, we strive to further understand the role for B cell lymphoma 6 (BCL6), a C2H2-type zinc finger repressor, in innate immunity and metabolism.
In related work, we are developing new methods for cell-specific isolation of RNA and chromatin from tissues composed of mixed cell populations. These genetic tools will allow us to explore transcriptional regulation in living animals with unprecedented precision and global scope using transcriptome sequencing and ChIP-sequencing. We anticipate that these approaches will identify new candidate regulators and mechanisms underlying cardiovascular and metabolic disease.
For more information, please see Dr. Barish's faculty profile.
See Dr. Barish's publications in PubMed.
Circadian and metabolic gene networks in the development of diabetes and obesity
An epidemic of obesity and diabetes has continued to sweep through the industrialized world, already posing a risk to over one-third of the US population who are overweight or obese. Although both physical inactivity and overnutrition are tied to “diabesity,” recent evidence indicates that disruption of internal circadian clocks and sleep also play a role. The primary research focus in our laboratory is to apply genetic and biochemical approaches to understand the basic mechanisms through which the circadian clock regulates organismal metabolism. We anticipate that a better understanding of clock processes will lead to innovative therapeutics for a spectrum of diseases including diabetes, obesity, autoimmunity and cancer.
Studies of Clock Function in Beta Cell Failure and Metabolic Disease
Glucose homeostasis is a dynamic process subject to rhythmic variation throughout the day and night. Impaired glucose regulation leads to metabolic syndrome and diabetes mellitus, disorders that are also associated with sleep-wake disruption, although the molecular underpinnings of circadian glucose regulation have been unknown. Work from our laboratory first demonstrated an essential role of the intrinsic pancreatic clock in insulin secretion and diabetes mellitus and present efforts focus on dissecting the genomic and cell biologic link between clock function and beta cell failure (Nature, 2010, 2013).
Studies of Clock Regulation of Metabolic Epigenetics
In 2009 we first reported discovery that the circadian system plays a central role in metabolism through regulation of NAD+ biosynthesis (Science, 2009). NAD+ is a precursor of NADP+ and is required for macromolecule biosynthesis, in addition to functioning as an oxidoreductase carrier. NAD+ is also a required cofactor for the class III histone deacetylases (silencer of information regulators, SIRTs), nutrient-responsive epigenetic regulators Biochemical analyses show that SIRT1 deacetylates substrate proteins generating O-acetyl-ADP-ribose and nicotinamide, which is then regenerated to NAD+ by the enzyme nicotinamide phosphoribosyl transferase (NAMPT). We originally showed that CLOCK/BMAL1 directly control the transcription of Nampt and in turn control the activity of SIRT1—identifying a feedback loop composed of CLOCK/BMAL1-NAMPT/SIRT1. More recently, we have identified a role for the clock-NAD+ pathway in mitochondrial respiration (Science, 2013), and our present efforts include the analysis of clock-NAD+ regulation of cellular redox and epigenetic regulation, with the ultimate aim of applying such knowledge to studies of cell growth and stress response.
See Dr. Bass' publications in PubMed.
Focusing on the renin angiotensin system as it relates to the understanding of human diabetic kidney disease and rodent models of diabetic kidney disease and hypertension
Dr. Batlle’s lab currently focuses on the renin angiotensin system as it relates to the understanding of this system in rodent kidney physiology. Of particular focus are the pathways and mechanisms that determine the enzymatic cleavage and degradation of Angiotensin II and other peptides within the system by ACE2-dependent and independent pathways. The lab uses a holistic approach involving ex vivo, in vitro and in vivo studies using various rodent models of diabetic and hypertensive kidney disease.
The lab is also involved in the search for biomarkers of kidney disease progression as part of the NIDDK Consortium on CKD. Other areas of research interest include nocturnal hypertension and the physiology and pathophysiology of electrolyte disorders such as distal renal tubular acidosis.
For more information, please see Dr. Batlle's faculty profile.
See Dr. Batlle's publications in PubMed.
The Chandel Lab studies the mitochondria as a signaling organelle; using reactive oxygen species as the primary signal for metabolic adaptation, differentiation and proliferation.
Historically, reactive oxygen species (ROS) have been thought to be cellular damaging agents, lacking a physiological function. Accumulation of ROS and oxidative damage have been linked to multiple pathologies, including neurodegenerative diseases, diabetes, cancer and premature aging. This guilt by association relationship left a picture of ROS as a necessary evil of oxidative metabolism, a product of an imperfect system. Yet few biological systems possess such flagrant imperfections, thanks to the persistent optimization of evolution. It appears that oxidative metabolism is no different. More and more evidence suggests that low levels of ROS are critical for healthy cellular function. This idea was first proposed in the mid-1990s when low levels of hydrogen peroxide (H2O2) were demonstrated to be important for cellular signaling. Although mitochondria were known to produce H2O2, NADPH oxidases (NOXs) were the subject of early study due to their well-described role as ‘dedicated H2O2 producers’ in phagocytes. We provided early evidence in the late 1990s that mitochondria release H2O2 to regulate the transcription factor hypoxia inducible factor 1 (HIF-1) (i.e. oxygen sensing). Subsequently, we showed that mitochondrial release of H2O2 can activate p53 and NF-κB. We have recently demonstrated that mitochondria-generated H2O2 can regulate other physiological processes including stem cell differentiation, adaptive immunity and replicative life span of mammalian cells. Furthermore, we have shown that cancer cells co-opt mitochondria-generated H2O2 to hyper-activate signaling resulting in tumor cell proliferation. There have been numerous reports from other laboratories in the past decade also highlighting the importance of mitochondrial H2O2-dependent signaling in metabolic adaptation, immunity, differentiation, autophagy and organismal longevity. We propose that mitochondrial release of H2O2 has evolved as a method of communication between mitochondrial function and other cellular processes to maintain homeostasis and promote adaptation to stress.
See Dr. Chandel's publications in PubMed.
Contact Dr. Chandel’s Lab at 312-503-1792
Focusing on the mechanisms underlying neurite degeneration and synapse loss in Alzheimer’s disease and related neurodegenerative disorders
Our work focuses on the mechanisms underlying neurite degeneration and synapse loss in Alzheimer’s disease and related neurodegenerative disorders. We are interested in the relationship between beta-amyloid deposition and the progressive formation of dystrophic neurites and cell death in hippocampal neurons.
Recently, we have determined that the microtubule associated protein tau plays an essential role in beta-amyloid-induced neurite degeneration. These results constitute the first direct evidence of a mechanistic link between beta-amyloid deposition and tau in central neurons. Furthermore, our results indicated that beta-amyloid induces calpain-mediated tau cleavage leading to the generation of a 17 kDa neurotoxic fragment in hippocampal neurons both in culture model systems and in AD human brain samples. Currently, we are analyzing the mechanisms by which this tau fragment mediates beta-amyloid-induced neurite degeneration. These studies are being performed by means of a variety of cell and molecular biology techniques.
See Dr. Ferreira's publications on PubMed.
Contact Dr. Ferreira at 312-503-8250.
The Green Lab investigates the genetics and molecular biology of cholestatic liver diseases and fatty liver disorders. The major current focus is on the role of ER Stress and the Unfolded Protein Response (UPR) in the pathogenesis of these hepatic diseases.
Dr. Green’s laboratory investigates the mechanisms of cholestatic liver injury and the molecular regulation of hepatocellular transport. Current studies are investigating the role of the UPR in the pathogenesis and regulation of hepatic organic anion transport and other liver-specific metabolic functions. We employ genetically modified mice and other in vivo and in vitro models of bile salt liver injury in order to better define the relevant pathways of liver injury and repair; and to identify proteins and genes in these pathways that may serve as therapeutic targets for cholestatic liver disorders.
The laboratory also investigates the mechanisms of liver injury in fatty liver disorders and the molecular regulation of hepatic metabolic pathways. The current focus of these studies includes investigations on the role of the UPR in the pathogenesis of non-alcoholic steatohepatitis and progressive fatty liver disease. We employ several genetically modified mice and other in vivo and in vitro models of fatty liver injury and lipotoxicity. Additional studies include the application of high-throughput techniques and murine Quantitative Trait Locus (QTL) analysis in order to identify novel regulators of the UPR in these disease models.
See Dr. Green's publications in PubMed.
For more information, please see Dr. Green's faculty profile.
Contact Dr. Green at 312-503-1812 or the Green Lab at 312-503-0089
Autophagy in metabolic regulation and pathogenesis of metabolic diseases
The research in my lab is centered on autophagy, a lysosomal degradation pathway essential for nutrient recycling, cellular maintenance and physiological function. Autophagy is induced by various stress conditions and allows cells to adapt to changing nutrient and energy demands through protein catabolism. Malfunction of autophagy is implicated in a variety of diseases such as cancer, neurodegeneration, infection and aging. Our interest focuses on the roles and mechanisms of autophagy in the metabolic regulation of mammals and in the pathogenesis of metabolic disorders in human, including obesity and type 2 diabetes. There are many open questions in this largely unexplored area; our research directions include studies of the functions of autophagy in exercise-induced metabolic benefits and investigation of the molecular mechanism of autophagy and its relationship to other lysosomal degradation pathways in the prevention of metabolic dysregulation.
See Dr. He's publications on PubMed.
Contact Dr. He at 312-503-3094.
The Henkel lab studies hepatic lipid metabolism and mechanisms of liver injury related to fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming a major public health crisis. Hepatic steatosis is currently estimated to affect up to 30% of the US population and the prevalence continues to rise. Currently there is no definitive pharmacologic therapy to prevent or treat NAFLD which is due to the fact that the pathogenesis of this disease is incompletely understood.
The first major area of investigation in our lab is to determine the role of endoplasmic reticulum stress and the ensuing unfolded protein response (UPR) in promoting hepatic lipid accumulation and injury. We use mouse and cell culture models of UPR dysfunction to determine how the balance between pro-survival and pro-apoptotic elements of the UPR mediate the progression of liver disease.
The other major area of investigation is to determine the role of plasminogen activator inhibitor 1 (PAI-1) in the pathogenesis of fatty liver disease. Using genetic and pharmacologic mouse models of PAI-1 depletion we have identified PAI-1 as a potential novel target for pharmacotherapy to treat NAFLD.
For more information, visit the faculty profile page of Anne Henkel, MD.
Contact Dr. Henkel at 312-503-3418 or the Henkel Lab at 312-503-3580
Lab StaffShantel Olivares
Focusing on nitric oxide vascular biology.
Melina R. Kibbe, MD, is a Professor of Surgery at the Northwestern University Feinberg School of Medicine in the Division of Vascular Surgery and is on staff at Northwestern Memorial Hospital and Jesse Brown VA Medical Center, where she serves as director of the Vascular Laboratory and co-chief of the Division of Vascular Surgery. Dr. Kibbe's research interests focus on nitric oxide vascular biology. Specifically, she is studying how nitric oxide inhibits vascular smooth muscle cell proliferation by focusing on the role of nitric oxide in regulating the cell cycle, the ubiquitin-proteasome pathway and apoptosis. She is also developing and evaluating nitric oxide-based pharmacological and bioengineering approaches to inhibit neointimal hyperplasia following vascular interventions, including bypass grafting and peripheral angioplasty/stenting. Her hope is to have a positive effect on patency rates of these procedures, thereby effecting millions of patients that undergo coronary artery or peripheral artery revascularization procedures. In 2010, she received the Presidential Early Career Award for Scientists and Engineers, the highest honor bestowed by the United States Government on young professionals in the early stages of their independent research careers.
Learn more via the Kibbe Lab website.
Considering the societal impact of type 2 diabetes, the overall goal of our lab is to identify, explore and develop novel diabetes treatments
From top, left to right: Medha Priyadarshini-Postdoc, Carrie Pusec-Graduate student, Stephanie Villa-Graduate Student, Marsha Newman-Lab manager, Bottom, left to right. Michael Brodsky-Undergraduate, Anthony Angueira-Undergraduate, Anton Ludvik-Graduate Student, Brian Layden-PI, Miles Fuller-Graduate Student
The insulin resistance observed in obesity leads to pancreatic islets adapting by increasing insulin secretion and production. When this adaptation for more insulin is not met, type 2 diabetes occurs. Identification of the pathways that mediate the response of islets to insulin resistance is needed. We have identified two novel G-protein coupled receptors (GPCRs), free fatty acid receptor-2 and -3 (FFAR2 and FFAR3), that may have a role in this process (see Layden et al., 2010). These two GPCRs have only recently been “deorphanized”, meaning their endogenous ligands have been identified, and, overall, little is known about their biology. Because of this, our focus now is to explore the role of these receptors and their endogenous ligands in diabetes.
The original observation that led to our focus on these receptors was that the expression of these receptors is altered in rodent islets during insulin resistance (see Layden et al., 2010). We therefore further examined their expression in islets, and we have observed that they are expressed in human and rodent pancreatic beta cells. We have also begun to examine their role in islet biology by using global knockout mice for FFAR2 and FFAR3, which we are using to assess their role in glucose homeostasis during insulin resistance states. These data are indicating an important role for both these receptors in glucose homeostasis. Because they are expressed in other tissue besides pancreatic beta cells, including adipocytes and the GI tract, we are developing and using both global and conditional mouse models for both receptors to examine the role of these receptors in pancreatic beta cells.
The ligands for both these receptors are short chain fatty acids (SCFAs). SCFAs are derived from gut fermentation of difficult to digest food (such as fiber) and include molecules such as acetate, propionate and butyrate. Importantly, the role of these molecules in islet biology is largely unknown. Because of this, we are also investigating the role of SCFAs in islet biology and related aspects of metabolism.
In summary, the focus of my research is to understand the role of FFAR2 and FFAR3 and their ligands in obesity and diabetes. These studies are being performed through a variety of mouse models. Overall, the goal of these studies is to uncover the role of a novel class of nutrients (SCFAs) and their receptors in islet biology.
For more information, visit the faculty profile of Brian Layden, MD, PhD.
See Dr. Layden's publications in PubMed.
Contact principal investigator Brian Layden at 312-503-1610.
Genetic determinants of maternal metabolism and fetal growth
A major interest of the Lowe laboratory is genetic determinants of maternal metabolism during pregnancy and the interaction between the intrauterine environment and genetics in determining size at birth. This interest is being addressed using DNA and phenotype information from ~16,000 mothers and their babies who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. A genome wide association study using DNA from mothers and babies from four different ancestry groups has been performed, with several different loci demonstrating genome-wide significant association with maternal and fetal traits. Replication studies have confirmed the identified associations. Studies are now underway now to identify the causal variants and their functional impact. In related studies performed with investigators at Duke, targeted and untargeted metabolomic studies are underway to determine whether metabolic signatures characteristic of maternal obesity and/or hyperglycemia can be identified in mothers and babies. Integration of metabolomic and genomic data is also planned to more fully characterize maternal metabolism during pregnancy and its interaction with fetal growth. Finally, a HAPO Follow-Up Study has been initiated in which a subset of the HAPO mothers and babies (now 8-12 years of age) will be recruited to examine the hypothesis that maternal glucose levels during pregnancy are positively correlated with metabolic measures in childhood, including adiposity, lipidemia, glycemia and blood pressure.
For further information visit Dr. Lowe's faculty profile page
View Dr. Lowe's publications at PubMed
Tolerance mechanisms in autoimmune diabetes and transplantation
1. Tolerance mechanisms for transplantation. We use rodent as well as non-human primate models. These models include allogeneic islet, heart and kidney and xenogeneic islet transplantation. Transplant tolerance is induced by infusion of donor cells treated with the chemical cross-linker ethylcarbodiimide (ECDI). Using a stringent full MHC-mismatched strain combination, we have shown in an allogeneic islet cell transplant model that two infusions of ECDI-treated donor cells prior to and after transplantation led to indefinite graft survival in over 90% of the transplant recipients in the absence of any immunosuppression. This tolerance strategy takes advantage of the tolerogenic recognition of apoptotic donor cells by recipient CD11c dendritic cells and is associated with up-regulation of Tregs and down-regulation of anti-donor T and B cell responses. The same strategy has been applied to allogeneic heart and kidney transplant, as well as xenogeneic islet transplant (rat-to-mouse, pig-to-mouse) with robust tolerance efficacy. We are currently applying the same strategy to monkey-to-monkey (allogeneic) and pig-to-monkey (xenogeneic) islet transplantation. Our ultimate goal is to test this tolerance strategy in human-to-human (allogeneic) and pig-to-human (xenogeneic) solid organ and/or tissue transplantation. Additional ongoing efforts in the lab also focus on: (1) understanding how viral infections at various stages (acute, chronic, latent) can influence tolerance efficacy and stability; (2) collaborating with Shea lab in designing nanoparticle-based cell-free tolerance strategies for allogeneic and xenogeneic transplantation.
2. Proteins with post-translational modifications (PTMs) as neoantigens for autoimmune diabetes. We use the non-obese diabetic (NOD) mouse model to study the role of proteins with PTMs in the pathogenesis of type 1 diabetes. Beta cell secretory proteins are subjected to post-translational modifications such as deamidation and di-sulfide bond formation among others. Such modified proteins/peptides may become neoantigens that can activate endogenous T cells and lead to beta-cell directed autoimmunity. Ongoing efforts in the lab focus on: (1) temporal correlation between the appearance of humoral immunity to proteins/peptides with PTMs and diabetes development; (2) the role of cellular immunity to proteins/peptides with PTMs in the development of diabetes; (3) the role of endogenous enzymatic pathways for the formation of such neoantigens; (4) the role of neoantigens as a diagnostic tool for autoimmune diabetes; (5) the role of neoantigens for more effective tolerance induction strategies for autoimmune diabetes.
3. Circadian Clock regulation in immune cell function and autoimmune diabetes. Disruption of circadian rhythms has been linked to inflammatory diseases, however the precise roles of core clock proteins in the function of immune cells have not been elucidated. Collaborating with the Bass lab, we are investigating the role of BMAL1, one of the core clock proteins, in controlling several fundamental aspects of the immune system. Ongoing efforts in the lab focus on: (1) defining the phenotypic and functional alterations in immune cells caused by disruption of circadian gene regulation; (2) defining the role of circadian gene regulation at the immune cell/beta cell interface and its contribution to the development of autoimmune diabetes; (3) defining the role of circadian gene regulation at the immune cell/transplanted graft interface and its contribution to the development transplant graft rejection.
For more information visit Dr. Luo's faculty profile page
View Dr. Luo's publications at PubMed
Elucidation of mechanisms of pathogenesis and immune regulation of autoimmune disease, allergy and tissue/organ transplantation
The laboratory is interested in understanding the mechanisms underlying the pathogenesis and immunoregulation of T cell-mediated autoimmune diseases, allergic disease and rejection of tissue and organ transplants. In particular, we are studying the therapeutic use of short-term administration of costimulatory molecule agonists/antagonists and specific immune tolerance induced by infusion of antigen-coupled apoptotic cells and PLG nanoparticles for the treatment of animal models of multiple sclerosis and type 1 diabetes, allergic airway disease, as well as using tolerance for specific prevention of rejection of allogeneic and xenogeneic tissue and organ transplants.
Promising Results in Early Trial of Novel MS Treatment: Listen to a Science Friday interview with Dr. Miller regarding the Phase 1 clinical trial in multiple sclerosis patients. Read the article in Science Translational Medicine Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis.
For lab information and more, see Dr. Miller's faculty profile.
See Dr. Miller's publications on PubMed.
Contact Dr. Miller at 312-503-7674 or the lab at 312-503-1449.
The Thorp laboratory studies how immune cells coordinate tissue repair and regeneration under low oxygen, such as after a heart attack.
The Edward Thorp Lab studies the crosstalk between immune cells and the cardiovascular system and, in particular, within tissues characterized by low oxygen tension or associated with dyslipidemia, such as during myocardial infarction. In vivo, the lab interrogates the function of innate immune cell phagocytes, including macrophages, as they interact with other resident parenchymal cells during tissue repair and regeneration. Within the phagocyte, the influence of hypoxia and inflammation on intercellular and intracellular signaling networks and phagocyte function are studied in molecular detail. Taken together, our approach seeks to discover and link basic molecular and physiological networks that causally regulate disease progression and in turn are amenable to strategies for the amelioration of cardiovascular disease.
View Dr. Thorp's publications at PubMed
Contact the Thorp lab at 312-503-3140.
Xin-Yi Yeap, MS
Lab Manager and Microsurgery
Basic, translational and clinical research linking circadian rhythms and sleep to health outcomes and developing innovative treatments for sleep and circadian disorders.
The Sleep and Circadian Rhythms Research Program has a large research portfolio and a history of successful NIH funding of cutting-edge translational research and clinical trials in the area of sleep and circadian medicine. Research projects include basic studies on mechanisms of sleep and circadian rhythms regulation as well as translational and patient oriented studies on the role of sleep and circadian rhythms on neurocognitive function, cardio-metabolic health, neurodegeneration and other neurological disorders. The program also has extensive history collaborating with institutions throughout the country on large-multi site, multi-year studies and trials.
Currently, faculty are Principal Investigators or collaborators on studies to understand the mechanisms linking sleep quality, circadian alignment with neurocognitive impairment, mood, cardiovascular and metabolic risk in populations at risk for sleep and circadian disorders.
Phyllis C Zee, MD, PhD at 312-503-4409.
Faculty and NU Collaborators
Sabra Abbott, MD, PhD
Ravi Allada, MD
Hryar Attarian, MD
Kelly Glazer Baron, PhD, CBSM
Joe Bass, MD, PhD
John Coleman, III, MD
Anna Fishbein, MD
Gokhan Mutlu, MD
Ramadevi Gourineni, MD
William A. Grobman, MD, MBA
Matha Hotz Vitaterna, PhD
Joseph Kang, PhD
Ian Katznelson, MD
Robert Kern, MD
Madhukar Kumar, MD
Kiang Liu, PhD
Donald M Lloyd-Jones, MD
Darius A Loghmanee, MD
Roneil Malkani, MD
Ken Paller, PhD
Frank J. Penedo, PhD
Rishi Raj, MD
Kathryn J. Reid, PhD
Pradip Sethi, MD
Stephen H. Sheldon, DO
Rodolfo Soca, MD
Fred Turek, PhD
Sandra Weintraub, PhD
Lisa F. Wolfe, MD
Post Doctoral Fellows
Giovanni Santostasi, PhD (co-supervised with Prof. Paller)
Meg Kay-Stacey, MD
Minesh Morker, MD
Undergraduate Students & Volunteers
John A. Wilson, IV
Young Jun Lee