Section: Research

Postdoctoral Position Available

Michael Czech, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Program in Molecular Medicine

Joint Faculty In:
   Biochemistry and Molecular Pharmacology

Other Affiliation(s):
   Center for AIDS Research
   Interdisciplinary Graduate Program

RNAi-based therapeutic strategies for inflammatory and metabolic diseases

Many major human diseases such as diabetes, atherosclerosis and rheumatoid arthritis are promoted by dysfunctions in inflammatory pathways. Macrophages are central players in such diseases based on their ability to express antigenic peptides on their cell surfaces and secrete cytokines that attract and activate immune cells. Experiments in our laboratory are currently devoted to 1.) applying RNAi-based approaches to identify target genes in macrophages, adipocytes and other cells that promote these diseases, and 2.) developing strategies for therapeutic application of RNAi against these targets.

Unlike small molecule drugs, RNAi can target human genes without regard to the nature of the protein structure of the gene product. As a consequence, all genes become potential targets for RNAi based therapies.  However, there is one over-riding roadblock to the general use of siRNA as a medicine for human disease: safe, effective delivery to specific target tissues or cell types in vivo.  Achieving the goal of an oral delivery system for synthetic siRNA, in particular, could potentially transform the practice of medicine.

Our laboratory is engaged in collaborative experiments with Dr. Gary Ostroff’s group to achieve orally delivered siRNA as an effective therapeutic strategy for inflammatory pathways. We are employing unique encapsulation technology that both protects siRNA through the digestive tract and directs its uptake by macrophages and dendritic cells where it silences genes involved in pathogenic inflammation.

Other projects in our laboratory address the underlying mechanisms whereby inflammation and other processes impair insulin signaling in obesity and type 2 diabetes. We are investigating the roles of lipid droplet proteins in regulating adipocyte metabolism and whole body glucose tolerance using mouse knockout models and adipose samples from human subjects. Our studies are also directed towards understanding the signaling pathways whereby the protein kinase Map4k4 acts to cause insulin resistance. Finally, we are using high resolution ultrafast TIRF microscopy to study the cellular trafficking pathways whereby insulin controls the glucose transporter protein (GLUT4) that mediates glucose disposal in skeletal muscle and adipose tissue.

Office: Suite 100
Phone: 508-856-2254
Fax: 508-856-1617
E-mail: Michael.Czech@umassmed.edu
Keywords: Signal Transduction, Cell Biology, Biochemistry

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Czech for additional details.