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Michael P. Czech is currently the Isadore and Fannie Foxman Chair of Medical Research in the Program in Molecular Medicine at the University of Massachusetts Medical School. He was Chair of the Department of Biochemistry from 1981 to 1989, and was the founding Chair of the Program in Molecular Medicine (1989-2018). Czech earned the PhD degree in biochemistry in 1972 at Brown University under the mentorship of Professor John Fain, and completed postdoctoral study at Duke University Medical Center. He became Assistant Professor at Brown in 1974, rising to the rank of Professor in 1980. His research addresses mechanisms of signal transduction, metabolism and insulin resistance in type 2 diabetes and obesity. Czech’s laboratory has recently applied RNAi and CRISPR techniques to discover novel drug targets and to develop therapeutic strategies for alleviating inflammatory and metabolic diseases.

Czech has served on several editorial boards and NIH Study Sections and is a member of the Scientific Review Board of the Howard Hughes Medical Institute. He has received the Scientific Achievement Award (1982), the Banting Medal (2000) and the Albert Renold Award for mentorship (2004) from the American Diabetes Association; the David Rumbough Scientific Award of the Juvenile Diabetes Foundation (1985); NIH MERIT Awards (1997-2005 and 2012-2022); the Elliot P. Joslin Medal (1998), and the Jacobaeus Prize awarded in Umea, Sweden in 2009.

Czech Lab Research:

Gene editing and deletion to enhance insulin sensitivity in type 2 diabetes and obesity.

Major human diseases such as type 2 diabetes and atherosclerosis are promoted by dysfunctions in adipose tissue and in the interactions between adipocytes, endothelial cells, nerve fibers and immune cells. Adipose tissue remodeling in obesity can also secondarily disrupt liver and skeletal muscle metabolism, causing systemic insulin resistance and glucose intolerance. Our laboratory group is attacking key questions related to these cellular and molecular interactions among metabolic tissues, macrophages, neuronal signals and the vasculature that define both normal and metabolic disease states.

Central questions for our laboratory group are:

 Can we identify molecular mechanisms that disrupt insulin signaling in obesity and type 2 diabetes to develop therapeutic strategies for these diseases?

 Can we identify and modulate molecular mechanisms that switch adipocytes from storing triglyceride to cells that oxidize fat, expend energy and secrete beneficial factors?

 Can we target genes that promote fatty liver and inflammation in obesity and diabetes with therapeutic siRNA to alleviate nonalcoholic steatohepatitis (NASH)?

Many of our projects take advantage of CRISPR and RNA interference (RNAi) to selectively silence normal or disease genes in vivo, providing both powerful research tools and potential approaches to therapies. Experiments in our laboratory are currently devoted to developing CRISPR- and siRNA-based delivery particles that can beneficially alter gene expression in adipocytes, hepatocytes and other cell types. Using these techniques, we have recently shown that gene editing of adipocytes by CRISPR can enhance their energy expenditure and fat oxidation. These efforts are advancing toward therapeutic applications.

Another approach that we have developed in collaboration with the Gary Ostroff laboratory is a method to deliver siRNA in vivo using glucan encapsulation vehicles (GeRPs).  GeRPs can target macrophages in adipose tissue and liver to silence genes and attenuate tissue inflammation and insulin resistance.

 

 

 

 

Rotation Projects

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.

 

 

 

 

 

One or more keywords matched the following items that are connected to Czech, Michael
Item TypeName
Academic Article Fat targets for insulin signaling.
Academic Article Glucose transporter recycling in response to insulin is facilitated by myosin Myo1c.
Academic Article Role of EHD1 and EHBP1 in perinuclear sorting and insulin-regulated GLUT4 recycling in 3T3-L1 adipocytes.
Academic Article RNAi-based analysis of CAP, Cbl, and CrkII function in the regulation of GLUT4 by insulin.
Academic Article An essential role of the JIP1 scaffold protein for JNK activation in adipose tissue.
Academic Article ARNT misbehavin' in diabetic beta cells.
Academic Article Tumor necrosis factor alpha (TNFalpha) stimulates Map4k4 expression through TNFalpha receptor 1 signaling to c-Jun and activating transcription factor 2.
Academic Article Akt substrate TBC1D1 regulates GLUT1 expression through the mTOR pathway in 3T3-L1 adipocytes.
Academic Article A Rictor-Myo1c complex participates in dynamic cortical actin events in 3T3-L1 adipocytes.
Academic Article Paradoxical effect of mitochondrial respiratory chain impairment on insulin signaling and glucose transport in adipose cells.
Academic Article A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation.
Academic Article A phosphatidylinositol 3-kinase-independent insulin signaling pathway to N-WASP/Arp2/3/F-actin required for GLUT4 glucose transporter recycling.
Academic Article Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC.
Academic Article Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity.
Academic Article Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation.
Academic Article C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane.
Academic Article What causes the insulin resistance underlying obesity?
Academic Article Association of common genetic variants in the MAP4K4 locus with prediabetic traits in humans.
Academic Article Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone.
Academic Article CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance.
Academic Article Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes.
Academic Article Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubules.
Academic Article Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing.
Academic Article Insulin's expanding control of forkheads.
Academic Article Unconventional myosin Myo1c promotes membrane fusion in a regulated exocytic pathway.
Academic Article Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.
Academic Article Micromanaging insulin secretion.
Academic Article Identification of WNK1 as a substrate of Akt/protein kinase B and a negative regulator of insulin-stimulated mitogenesis in 3T3-L1 cells.
Academic Article PTEN, but not SHIP2, suppresses insulin signaling through the phosphatidylinositol 3-kinase/Akt pathway in 3T3-L1 adipocytes.
Academic Article The v-SNARE Vti1a regulates insulin-stimulated glucose transport and Acrp30 secretion in 3T3-L1 adipocytes.
Academic Article An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPARgamma, adipogenesis, and insulin-responsive hexose transport.
Academic Article Insulin stimulates membrane fusion and GLUT4 accumulation in clathrin coats on adipocyte plasma membranes.
Academic Article The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation.
Academic Article Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes.
Academic Article Cidea is associated with lipid droplets and insulin sensitivity in humans.
Academic Article A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes.
Academic Article Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity.
Academic Article Tensions rise and blood flows over dysfunctional fat.
Academic Article CD14 deficiency impacts glucose homeostasis in mice through altered adrenal tone.
Academic Article Insulin signalling mechanisms for triacylglycerol storage.
Concept Insulin
Concept Insulin-Like Growth Factor I
Concept Insulin Resistance
Concept Insulin-Secreting Cells
Concept Receptor, Insulin
Academic Article Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: basic mechanisms and clinical associations.
Academic Article Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction.
Academic Article Activated Kupffer cells inhibit insulin sensitivity in obese mice.
Academic Article A major role of insulin in promoting obesity-associated adipose tissue inflammation.
Academic Article Inducible Deletion of Protein Kinase Map4k4 in Obese Mice Improves Insulin Sensitivity in Liver and Adipose Tissues.
Academic Article Emerging evidence for beneficial macrophage functions in atherosclerosis and obesity-induced insulin resistance.
Academic Article Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion.
Academic Article Activation of mTORC1 is essential for ?-adrenergic stimulation of adipose browning.
Academic Article Map4k4 Signaling Nodes in Metabolic and Cardiovascular Diseases.
Academic Article Protein Kinase Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Promotes Obesity-induced Hyperinsulinemia.
Academic Article Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance.
Academic Article Developmental Role of Macrophage Cannabinoid-1 Receptor Signaling in Type 2 Diabetes.
Academic Article Map4k4 impairs energy metabolism in endothelial cells and promotes insulin resistance in obesity.
Academic Article Decreasing CB1 receptor signaling in Kupffer cells improves insulin sensitivity in obese mice.
Academic Article Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance.
Academic Article Insulin action and resistance in obesity and type 2 diabetes.
Academic Article Molecular pathways linking adipose innervation to insulin action in obesity and diabetes mellitus.
Academic Article Mechanisms of insulin resistance related to white, beige, and brown adipocytes.
Academic Article Voices: Insulin and beyond.
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