Michael Pack
Associate Professor of Medicine and Cell and Developmental Biology
Director, Department of Medicine Physician Scientist Training Program

Developmental Biology Program

State University of New York, B.A. (Chemistry) 1980

Washington University (St. Louis), M.D. 1984

Research Interests

• Development of the vertebrate digestive system
• Biology and physiology of digestive epithelia and cancers
• High throughput small molecule drug screens

Key words: development, zebrafish, intestine, liver, pancreas, biliary, cancer, invasion, metastases, DNA repair, lipid metabolism, high throughput screening.

Search PubMed for articles

Description of Research

The organs of the vertebrate digestive system (esophagus, stomach, liver, pancreas and intestine) arise from the primitive gut tube, a simple epithelial structure that forms during early development. Work in my laboratory is focused on using the zebrafish to identify genes that regulate this process, particularly the later stages of organ development, when organ anlagen begin their differentiation programs. Through participation in several collaborative mutagenesis screens we have identified and molecularly characterized numerous mutations that disrupt organ development and physiology. Our long-term goal is to apply knowledge gained from these studies to clinically relevant basic research projects. Examples include the establishment and maintenance of epithelial architecture, the role of DNA repair in the biology of tissue progenitor cells, biliary development and hepatic lipid metabolism, and RNA metabolism and cancer. Most recently, through participation in the NIH funded Penn Center for Molecular Discovery (Director, Zebrafish Core), we have initiated high throughput screens of small molecule chemical libraries using the zebrafish system.. Through these studies, we hope to identify lead compounds for drugs to treat human diseases.

Recent Publications

Yee NS, Gong W, Huang Y, Lorent K, Dolan AC, Maraia, RJ and Pack M. (In Press) Mutation of RNA polymerase III subunit rpc2.polr3b leads to deficiency of the RNA cleavage subunit, Rpc11/Polr3k, and disrupts zebrafish digestive system development. PLOS Biology

Ho SY, Lorent K, Pack M*, Farber SA. Zebrafish fat-free is required for intestinal lipid absorption and Golgi apparatus structure. (2006) Cell Metab. 3(4):289-300. * Co-corresponding and Co-senior author

Wallace KN, Dolan AC, Seiler C, Smith EM, Yusuff S, Chaille-Arnold L, Judson B, Sierk R, Yengo C, Sweeney HL, Pack M. (2005) Mutation of smooth muscle myosin causes epithelial invasion and cystic expansion of the zebrafish intestine. Dev Cell. 8(5):717-26.

Matthews RP, Plumb-Rudewiez N, Lorent K, Gissen P, Johnson CA, Lemaigre F, Pack M. (2005) Zebrafish vps33b, an ortholog of the gene responsible for human arthrogryposis-renal dysfunction-cholestasis syndrome, regulates biliary development downstream of the onecut transcription factor hnf6. Development. 132(23):5295-306.

Yee NS, Lorent K, Pack M. (2005) Exocrine pancreas development in zebrafish. Dev Biol. 284(1):84-101

Lab

Rotation Projects

Projects include the phenotypic and molecular characterization of zebrafish intestinal, liver and pancreas mutants, biliary and pancreatic duct development, the design of assays for use in small molecule screens.

Lab personnel:

Christoph Seiler, Postdoctoral Fellow
Gangarao Davuluri, Postdoctoral Fellow
Clifton Justin David, Postdoctoral Fellow
Kristin Lorent, Senior Research Investigator
Weilong Gong, Senior Research Specialist
Manimegalai Muthumani, Research Specialist
Jie He, Research Specialist