Yale School of Medicine

Internal Medicine

Internal Medicine, Yale School of Medicine

Internal Medicine
333 Cedar Street
Room LMP-1072
P.O. Box 208056
New Haven, CT 06520-8056

E. Scott Swenson M.D., Ph.D.

E. Scott Swenson M.D., Ph.D.

Instructor
Section of Digestive Diseases

Research Interests

I am investigating the role of stem and progenitor cells in the liver during normal development and in response to liver injury. The liver's remarkable capacity for regeneration after injury suggests that a better understanding of these phenomena will lead to novel cell therapy and regenerative medicine approaches to acute and chronic liver disease. Under some conditions, cells arising from the bone marrow may also contribute to liver regeneration.


Male marrow-derived hepatocytes in a female recipient mouse, six months after sex-mismatched bone marrow transplantation and in vivo metabolic selection

The Y chromosome (pink dots) colocalizes with HNF-1 (green nuclei). Nuclei are counterstained with DAPI (blue). The recipient mouse had a homozygous targeted mutation in the Fumaryl acetoacetate hydrolase (FAH) gene, which models the human liver disease, Hereditary Tyrosinemia. Transplantation of normal bone marrow results in extensive repopulation of normal hepatocytes in the tyrosinemic liver. The presence of two or more Y chromosomes in some hepatocytes is consistent with the normal phenomenon of hepatocyte polyploidy.

Ongoing studies will address the issue of whether stable in vivo fusion of cells of hematopoietic origin, such as Kupffer cells, with injured hepatocytes always accounts for the apparent developmental "plasticity" of bone marrow-derived cells.

Selected Publications

  • Whole body leucine, phenylalanine, and tyrosine kinetics in end-stage liver disease before and after transplantation (1987). RLK Shanbhogue, BR Bistrian, K Lakshman, L Crosby, S Swenson, D Wagner, RL Jenkins, and GL Blackburn. Metabolism 36: 1047-1053.
  • Twenty-four hour urinary creatinine: A simple technique for estimating resting energy expenditure in normal population and in the hospitalised patients (1987). RLK Shanbhogue, BR Bistrian, S Swenson, and GL Blackburn. Clinical Nutrition 6: 221-225.
  • Effect of structured lipid-enriched total parenteral nutrition in rats bearing Yoshida sarcoma (1990). LE Crosby, ES Swenson, VK Babayan, GL Blackburn, and BR Bistrian. J. Nutr. Biochem. 1: 41-47.
  • Metabolic effects of medium chain triglyceride-enriched total parenteral total parenteral nutrition in rats bearing Yoshida sarcoma (1990). ES Swenson, LE Crosby, VK Babayan, GL Blackburn, and BR Bistrian. J. Nutr. Biochem 1: 462-470.
  • Persistence of metabolic effects after long term oral feeding of a structured triglyceride derived from medium chain triglyceride and fish oil in burned and normal rats (1991). ES Swenson, KM Selleck, VK Babayan, GL Blackburn, and BR Bistrian. Metabolism 40: 484-490.
  • Dietary fat as determinant of protein-sparing actions of structured triglycerides (1992). CJ Gollaher, ES Swenson, EA Mascioli, VK Babayan, GL Blackburn, and BR Bistrian. Nutrition 8: 348-353.
  • Intestinal permeability enhancement for proteins, peptides, and other polar drugs: Mechanisms and potential toxicity (1992). ES Swenson and WJ Curatolo. Adv. Drug Deliv. Rev. 8: 39-92.
  • Intestinal permeability enhancement: Efficacy, acute local toxicity, and reversibility (1994). ES Swenson, WB Milisen, and W Curatolo. Pharm. Res. 11: 1132-1142.
  • Intestinal permeability enhancement: Structure-activity relationships for nonylphenoxy-polyoxyethylene surfactant permeability enhancers (1994). ES Swenson, WB Milisen, and W Curatolo. Pharm. Res. 11: 1501-1504.
  • The guanylin/STa receptor is expressed in crypts and apical epithelium throughout the mouse intestine (1996). ES Swenson, EA Mann, ML Jump, DP Witte, and RA Giannella. Biochem. Biophys. Res. Comm. 225: 1009-1014.
  • Localization of guanylyl cyclase C gene to mouse chromosome 6 and human chromosome 12p12. EA Mann, ES Swenson, NG Copeland, DJ Gilbert, NA Jenkins, T Taguchi, JR Testa, and RA Giannella (1996). Genomics 34: 265-267.
  • Hepatocyte nuclear factor 4 regulates intestinal expression of guanylyl cyclase C, the guanylin/heat-stable enterotoxin receptor (1999). ES Swenson, EA Mann, ML Jump, and RA Giannella. Am. J. Physiol. 276: G728-G736.
  • Thyroid transcription factor-1, thyroglobulin, cytokeratin y, and cytokeratin 2 in thyroid neoplasms (2000). PA Bejerano, YE Nikiforov, ES Swenson, and PW Biddinger. Appl. Immunohistochem. Mol. Morph 8: 189-194.
  • Smads 2 and 3 are differentially activated by TGF-beta in quiescent and activated hepatic stellate cells: Constitutive nuclear localization of smads in activated cells is TGF-beta independent (2003). C Liu, MD Gaca, ES Swenson, VF Velluci, M Reiss, and RG Wells. J. Biol. Chem. 278(13): 11721-11728.
  • Cirrhosis and portal hypertension (2004). Chap. 45 in Field Guide to Internal Medicine. ES Swenson. Lippincott, Williams and Wilkins, Philadelphia, PA.
  • Dose and time-dependent oval cell reaction in acetaminophen-induced murine liver injury (2005). AV Kofman, G Morgan, A Kirschenbaum, J Osbeck, M Hussain, S Swenson and ND Theise. Hepatology 41(6): 1252-126.
  • Smad2 and smad3 play different roles in rat hepatic stellate cell function and alpha-smooth muscle actin organization (2005). M Uemura, ES Swenson, MDA Gaca, FJ Giordano, M Reiss, RG Wells. Mol. Biol. Cell. 16:4214-4224.
  • JS Van Arnam, E Herzog, J Grove, E Bruscia, E Ziegler, S Swenson, DS Krause. Engraftment of bone marrow derived epithelial cells. Stem Cell Reviews 2005;1:21-28.

Contact

Campus Address
Department of Internal Medicine
333 Cedar Street (LMP 1080)
New Haven, CT 06520

E-mail
scott.swenson@yale.edu

Office Phone
(203) 785-7054

Fax
(203) 785-7095