Michael A. Pack, M.D.
Professor of Medicine
Attending Physician, Hospital of the University of Pennsylvania
Associate Professor of Cell and Developmental Biology, (Secondary) University of Pennsylvania Perelman School of Medicine
Department: Medicine
Graduate Group Affiliations
Contact information
GI Division, Department of Medicine
University of Pennsylvania
School of Medicine
Rm. 1212, BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104
University of Pennsylvania
School of Medicine
Rm. 1212, BRB II/III
421 Curie Blvd.
Philadelphia, PA 19104
Office: (215)573-4145
Email:
mpack@mail.med.upenn.edu
mpack@mail.med.upenn.edu
Publications
Education:
B.A.
State University of New York at Binghamton, 1980.
M.D.
Washington University, 1984.
B.A.
State University of New York at Binghamton, 1980.
M.D.
Washington University, 1984.
Post-Graduate Training
Intern in Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, 1984-1985.
Resident in Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, 1985-1987.
Research Fellow, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, 1987-1989.
Chief Medical Resident, Thomas Jefferson University Hospital, Philadelphia, PA, 1989-1990.
Clinical and Research Fellow in Medicine, Massachusetts General Hospital, Boston, MA., 1990-1996.
Permanent linkIntern in Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, 1984-1985.
Resident in Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, 1985-1987.
Research Fellow, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, 1987-1989.
Chief Medical Resident, Thomas Jefferson University Hospital, Philadelphia, PA, 1989-1990.
Clinical and Research Fellow in Medicine, Massachusetts General Hospital, Boston, MA., 1990-1996.
Description of Research Expertise
Research interests: Research in my laboratory is geared towards studying medically relevant aspects of digestive organ development.Keywords: Zebrafish and mouse genetics, developmental biology, cancer, chemical genetics
Research details: Using the zebrafish system, we have applied genetics, gene targeting methodologies and pharmacological analyses to questions pertaining to growth, differentiation and survival of progenitor cells in the intestine, liver and pancreas. Through the positional cloning of zebrafish mutants our studies have led us in a number of directions. A major project in the lab concerns the role of epithelial-mesenchymal interactions in the maintenance of tissue architecture in the intestine and other epithelial organs. This work has direct relevance to cancer invasion and metastases. Another major project examines how nucleoporins, proteins within the nuclear pore complex, regulate DNA repair independently of nuclear trafficking. A third project examines mechanisms of bile duct development and their connection to diseases such as biliary atresia. Our zebrafish studies have also led us to examine how diverse cellular processes such as endosomal and golgi trafficking, RNA metabolism and methionine metabolism affect organ development and what implications these effects may have for studying human disease. Most recently we have begun to translate our findings from the zebrafish into mouse models. A new emphasis in the lab concerns the use of zebrafish chemical genetic screens to identify compounds that may be developed into drugs to treat cancer and lipid disorders.
Rotation projects for all of these research areas are available.
Current lab personnel: Kristin Lorent, PhD; Weilong Gong, PhD; Christoph Seiler, PhD; Gangarao Davuluri, Ph.D; Joshua Abrams (CAMB graduate student); Jie He, M.D., Mani Muthumani (research specialist).
Description of Clinical Expertise
Gastroenterology and Hepatology.Selected Publications
Matthews RP, Lorent K, Mañoral-Mobias R, Huang Y, Gong W, Murray IV, Blair IA, Pack M.: TNFalpha-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafish S-adenosylhomocysteine hydrolase. Development 136(5): 865-75, 2009.Davuluri G, Gong W, Yusuff S, Lorent K, Muthumani M, Dolan AC and Pack M.: Mutation of the Zebrafish Nucleoporin elys Sensitizes Tissue Progenitors to Replication Stress. PLoS Genetics 4(10), 2008.
Yee NS, Gong W, Huang Y, Lorent K, Dolan AC, Maraia RJ and Pack M: 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 5(11): e312, 2007.
Ho SY, Lorent K, Pack M* and Farber S. : Zebrafish fat-free, a gene required for intestinal lipid absorption, is essential for Golgi apparatus structure and vesicle recycling. Cell Metabolism 3(4): 289-300, 2006 Notes: * Co-Senior and co-communicating author.
Wallace KN, Dolan AC, Seiler C, Smith EM, Yusuff S, Chaille-Arnold L, Judson B, Sierk R, Yengo C, Sweeney HL and Pack M: Mutation of smooth muscle myosin causes epithelial invasion and cystic expansion of the zebrafish intestine. Developmental Cell 8(5): 717-726, 2005.
Farber SA, Pack M*, Ho SY, Johnson SD, Wagner DS, Dosch R, Mullins MC, Hendrickson HS, Hendrickson EK and Halpern ME: Genetic Analysis of Digestive Physiology Using Fluorescent Phospholipid Reporters. Science 292: 1385-88, 2001 Notes: * Co-first and co-communicating author.
Matthews R, Lorent K and Pack M : The transcription factor onecut3 regulates intrahepatic biliary development in zebrafish. Developmental Dynamics 237(1): 124-31, 2008.
Wallace KN, Akhter S, Smith EN, Lorent K and Pack M. : Intestinal Growth and Differentiation in Zebrafish. Mechanisms of Development 122(2): 157-173, 2005.
Lorent K, Yeo SY, Oda T, Chandrasekharappa S, Chitnis A and Pack M. : Inhibition of Jagged-mediated Notch signaling disrupts zebrafish biliary development and generates multi-organ defects compatible with an Alagille syndrome phenocopy. Development 131(22): 5753-66. 2004
Matthews R, Lorent K and Pack M. : 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): 5295-5306, 2005.
