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Glycobiology and Lipid Biology

Research into the biological functions of sugars and lipids.

Labs in This Area

 Hossein Ardehali Lab

Role of mitochondria and metabolic processes in cancer growth, cardiac disease and immunological processes

 

Research Description

Our lab focuses on three major areas of research:

Role of hexokinase enzymes in immune function, cancer growth and stem cell differentiation

Hexokinase (HK) enzymes phosphorylate glucose to trap it inside the cell. There are 5 mammalian HKs (named HK1-5), with two of them having a hydrophobic region at their N-terminus that allows them to bind to the mitochondria. We have made mouse models and developed in vitro systems to allow us to study the role of mitochondrial binding of HKs in glucose metabolism. We have determined that HK1 binding to the mitochondria determines whether glucose is used for anabolic processes (ie, pentose-phosphate pathway) or catabolism (ie, glycolysis). Thus, the non-enzymatic function of this protein and its subcellular location determines the fate of glucose. We are now studying this process in T-cells, vascular cells and cancer cells. We are also in the process of generating several mouse models of hexokinase enzymes, including HK2 without the mitochondrial binding domain and HK3 knockout mice. We will study these models in different disease and physiological conditions.

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 through epigenetic changes, 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.

Role of mRNA-binding proteins 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.

For more information, see Dr. Ardehali's faculty profile.

Publications

See Dr. Ardehali's publications in PubMed.

Contact

Dr. Ardehali

 Bruce Bochner Lab

The Bochner lab studies cells and siglec receptors (especially Siglec-8 and Siglec-F) involved in allergic inflammation, focusing mainly on eosinophils, mast cells and basophils in humans and mice.

Our primary research interests are in eosinophil- and mast cell-associated diseases, including asthma, hypereosinophilic syndromes and systemic mastocytosis. We have a particular interest and focus on understanding the function of Siglec-8, an inhibitory and sometimes pro-apoptotic receptor expressed on human eosinophils, basophils and mast cells and how it can be targeted for clinical benefit. Animal models are used to study its closest counterparts, such as Siglec-F. In studies involving carbohydrate biochemistry and glycoproteomics, the lab is isolating and characterizing potential glycan ligands for Siglec-F and Siglec-8. Finally, we are interested in food allergy and anaphylaxis and are exploring new ways to prevent allergic reactions in vitro and in vivo. 


Publications

View lab publications via PubMed

For more information, please see Dr. Bochner's faculty profile or view more information regarding our NHLBI-funded work.

Contact Us

Email Dr. Bochner
Phone 312-503-0068 or the Bochner Lab at 312-503-1396.

Lab Staff

Melanie C. Dispenza, MD, PhD
Postdoctoral Fellow
312-503-0066

Piper Robida, PhD
Postdoctoral Fellow
312-503-0066

Krishan Chhiba, BS
MD/PhD Candidate
312-503-8032

Yun Cao, MS
Research Lab Manager 1
312-503-1396

Rebecca Krier, MS
Research Lab Manager 1
312-503-8032

Jeremy O’Sullivan, PhD
Research Assistant Professor
312-503-0066

Soon Cheon Shin, PhD
Research Associate
312-503-1131

 Richard Green Lab

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.  

Publications

See Dr. Green's publications in PubMed.

For more information, please see Dr. Green's faculty profile.

Contact

Contact Dr. Green at 312-503-1812 or the Green Lab at 312-503-0089

 Thomas Hope Lab

Studying the posttranscriptional regulation of intronless viral messages

Research Description

We study the posttranscriptional regulation of intronless viral messages. Intronless messages must be efficiently processed in the absence of splicing. Therefore, intronless messages must uncouple RNA processing and export from the splicing process making a simpler model system. We are currently focused on the posttranscriptional regulatory element (PRE) of the Hepadnaviruses, including hepatitis B virus (HBV) and woodchuck hepatitis virus (WPRE). Our goal is to understand the novel mechanism of the stimulation of heterologous gene expression by the WPRE. Understanding WPRE function will allow the development of even more efficient gene expression for a variety of applications from gene therapy to large scale protein production.

Although much is known about the molecular biology of HIV, little is known about the details of interactions between the virus and cellular components such as the cytoskeleton. To gain insights into these processes we are combining the disciplines of virology and cell biology to develop the field of cellular virology. We are especially excited by new methods we have developed – such as time-lapse analysis and fluorescent tagging – that allow for HIV to be visualized in living cells.

For lab information and more, see Dr. Hope's faculty profile and lab website.

Publications

See Dr. Hope's publications on PubMed.

Contact

Contact Dr. Hope at 312-503-1360.

Lab Staff

Research Faculty

Ann Carias, Gianguido Cianci, Katarina Kotnik Halavaty, Joao Mamede, Danijela Maric

Postdoctoral Fellows

Muhammad Shoaib Arif, Koree Wee Ahn, Yanille Scott, Tahmina Sultana, Roslyn Taylor, Yanique Thomas

Lab Manager

Michael McRaven

Graduate Student

Faisal Nuhu

Technical Staff

Edward Allen, Meegan Anderson, Lisette Corbin, Flora Engelmann, Joseph Griffin, Megan Halkett, Jared Schooley, Divya Thakkar, Sixia Xiao

Program Staff

Debra Walker

Temporary Staff

Bryan Luna, Ewa Tfaily

 Geoff Kansas Lab

T helper cell differentiation and trafficking.

Research Description

My laboratory is interested in signaling mechanisms which control T helper cell differentiation and traffic. We are currently focused on two areas: functions of p38 MAP kinases (MAPK) and the role of a transcription factor KLF2 in these processes. Toward this end, we have produced novel mouse models which will allow us to test the role of the different isoforms of p38 (of which there are 4) in T helper differentiation and expression of key leukocyte adhesion molecules; and to determine the role of KLF2 downregulation in T helper biology generally.

For lab information and more, see Dr. Kansas's faculty profile.

Publications

See Dr. Kansas's publications on PubMed.

Contact

Contact Dr. Kansas at 312-908-3237 or the lab at 312-908-3752.

Lab Staff

Technical Staff

Caroline Patel

 Edward Thorp Lab

The Thorp laboratory studies how immune cells coordinate tissue repair and regeneration under low oxygen, such as after a heart attack.

Research Interests

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.

Publications

For additional information, visit the Thorp Lab site or view the faculty profile of Edward B Thorp, PhD.

View Dr. Thorp's publications at PubMed

Contact

Contact the Thorp lab at 312-503-3140.

Lab Staff

Shuang Zhang
PhD student
312-503-3140

Xin-Yi Yeap, MS
Lab Manager and Microsurgery
312-503-3140

 Ming Zhao Lab

The Zhao lab develops diagnostic markers and investigates pathogenic mechanisms of human diseases based on changes in cellular membranes.

Research Description

Major research areas in the Zhao lab include:

  1. Apoptosis imaging technology development. Programmed cell death (apoptosis) plays a significant role in degenerative diseases. There is currently no clinical tool for assessing apoptosis in pathological conditions. Our research focuses on the development of optimal agents that combine sophisticated binding activities and favorable clearance kinetics for clinical translation.
  2. Assessing systemic toxicity in anticancer therapies. The outcome of chemotherapies hinges on the balance between tumor toxicity and patient tolerance. With the ability to noninvasively detect tissue apoptosis, we propose to assess anticancer therapies in a whole-body approach by monitoring tumor cell killing simultaneously with systemic tissue injury in response to chemotherapeutic agents. This is a transformative approach in oncology in terms of optimizing therapies on an individualized basis.
  3. Detecting myocardial injury in ischemic heart disease. Non-infarct myocardial injury in ischemic heart disease is of particular interest because this type of cardiac injury is not well understood in terms of its pathophysiological characteristics and its roles in long-term adverse cardiac events. Our research in this area focuses on the diagnosis of non-infarct myocardial injury, which in turn, will help address a significant gap in identifying patients at risk.
  4. Investigating the pathogenesis of antiphospholipid syndromes. The presence of circulating antibodies against phosphatidylethanolamine (PE) is positively correlated with clinical manifestations of antiphospholipid syndromes. However, the underlying pathogenic mechanism of anti-PE autoimmunity remains unknown. We have a major interest in investigating the cellular susceptibility to PE-binding agents, which in turn, will shed light on the potential pathogenic mechanism of aPE.

Publications

View publications by Ming Zhao in PubMed.

For more information, visit Dr. Zhao's Faculty Profile page

Contact

Contact Dr. Zhao at 312-503-3226.

Lab Staff

Songwang Hou, PhD
Research Associate

Steven E. Johnson
Graduate Student

Ke Ke, PhD
Research Associate

Kaixi Ren, MD
Graduate Student

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