Department Name

Kevin E. Behrns M.D.

RESEARCH INTERESTS:
Dr. Behrns, a gastrointestinal surgical scientist with a focus on hepatobiliary and pancreatic
diseases, investigates the role of chronic inflammation and resistance to apoptosis in the liver and pancreas.  In the liver, chronic disease results in cirrhosis with loss hepatocyte function and fibrosis.  Frequently, patients with cirrhosis develop hepatocellular carcinoma suggesting altered growth control mechanisms such as apoptosis or programmed cell death.  We hypothesized and discovered that chronic liver injury inhibits hepatocyte apoptosis through a reactive oxygen species-dependent mechanism.  In addition to innate changes in hepatocyte function, the abundant extracellular matrix that accumulates in cirrhosis may alter hepatocyte growth regulation.  These areas of investigation are the core of Dr. Behrns NIH-funded R01 award.  In addition to studying the role of chronic inflammation in the liver, Dr. Behrns and colleagues are creating a mouse model of chronic pancreatic inflammation so that changes in growth control in pancreatic tissue may be examined.  In both the liver and pancreas, chronic inflammation is associated with increased expression of transforming growth factor beta (TGFb).  Dr. Behrns laboratory has thoroughly examined and continues to explore the TGFb signaling pathway in normal and cirrhotic hepatocytes.  Regulation of this pathway may be important in developing new therapies in chronic inflammatory diseases of the liver and pancreas.  The mission of the laboratory is to identify mechanisms that regulate growth control of parenchymal cells in the liver and pancreas and to bridge these findings to novel therapies.

Support:
 

National Institutes of Health, Mentored Clinical Scientist Development Award (K08), Growth Control of Normal and Cirrhotic Hepatocytes, 1999-2004

American Digestive Health Foundation, Industry Research
Scholar Award, Mechanisms of Apoptosis Resistance in Hepatocytes, 1999-2002 

National Institutes of Health, Small Grant Program for K08 Recipients (R03), Growth Control of Normal and Cirrhotic Hepatocytes, 2002-2004

National Institutes of Health, National Institutes of Diabetes & Digestive Diseases & Kidney, Growth Control of Normal and Cirrhotic Hepatocytes (R01), September 1, 2005-August 30, 2010.

National Institutes of Health, National Cancer Institute, SPORE in Gastrointestinal Cancer:  Mechanisms of Apoptosis Resistance in Hepatocellular Carcinoma, Career Development Award, August 1, 2004-July 31, 2005.

Publications:

1. Iimuro Y, Nishiura T, Hellerbrand C, Behrns KE, Shoonhoven R, Grisham JW, Brenner DA. NFKB prevents apoptosis and liver failure during liver regeneration.  J Clin Investigation, 101:802-811, 1998.

2. Behrns KE, Shaheen NJ, Grimm IS. Type I choledochal cyst in association with familial adenomatous polyposis. Am J Gastroenterology, 93:1377-1379, 1998.

3. Jobin C, Behrns KE, Brenner DA.  Molecular and cellular biology of the small intestine.Current Opinion in Gastroenterology, 15:103-107, 1999.

4. Behrns KE, Schrum LW, Que F.  Apoptosis:  Cell Death by Proteolytic Scalpel.  Surgery,  126:463-468, 1999.

5. Heider TR, Meyer AA, Galanko J, Behrns KE.  Percutaneous drainage of pancreatic pseudocysts is associated with a higher failure rate than surgical treatment.  Annals of Surgery, 229:781-789, 1999.

6. Behrns KE, Kircher A, Brownstein M, Koruda MJ.  A prospective, randomized trial of early initiation and hospital discharge on a liquid diet following elective intestinal surgery.  J Gasrointestinal Surgery, 4:217-221, 2000.

7. Schrum LW, Rippe RA, Black DM, Brenner DA, Behrns KE. c-Jun does not mediate hepatocyte apoptosis following NFB inhibition and partial hepatectomy. J Surg Research, 88:142-149, 2000.

8. Heider TR, Warshauer DM, Behrns KE. Inverted Meckel's diverticulum as a source of chronic gastrointestinal blood loss. Surgery, 128: 107-108, 2000.

9. Jenkins JT, Taylor AJ, Behrns, KE. Secondary Causes of Intestinal Obstruction: Rigorous Preoperative Evaluation is Required. American Surgeon, 66:7, 662-666, 2000

10. Schrum LW, Bird MA, Salcher O, Burchardt ER, Grisham JW, Brenner DA, Rippe RA, Behrns KE. Autocrine expression of activated transforming growth factor-beta (1) induces apoptosis in normal rat liver. American Journal of Physiology, 280(1):G139-48, 2001.

11. Heider TR, Farrell TM, Kircher SA, Koruda MJ, Colliver CC, Behrns KE. Complete fundoplication is not associated with increased dysphagia in patients with abnormal esophageal motility. Journal of Gastrointestinal Surgery, 5:1, 36-41, 2001

12. Heider TR, Behrns KE. Pancreatic pseudocysts complicated by splenic parenchymal involvement: results of operative and percutaneous management. Pancreas, 23: 20-25, 2001.

13. Bird MA, Schrum LW, Rippe RA, Behrns KE. Cholestasis induces murine hepatocyte apoptosis and DNA synthesis with preservation of the immediate - early gene response. Surgery, 131:556-563, 2002.

14. Samson CM, Schrum LW, Bird MA, Lange PA, Brenner DA, Rippe RA, Behrns KE.  Transforming growth factor-β1 induces hepatocyte apoptosis by a c-Jun independent mechanism.  Surgery, 132:3, 441-449, 2002.

15. Morton JM, Bowers SP, Lucktong TA, Mattar s, Bradshaw WA, Behrns KE, Koruda MJ, Herbst CA, McCartney W, Halkar RK, Smith CD, Farrell TM.  Gallbladder function before and after fundoplication.  J of Gastrointestinal Surg, 6:6, 806-811, 2002.

16. Heider TR, Behrns KE, Koruda MJ, Shaheen NJ, Lucktong TA, Bradshaw B, Farrell TM.  Fundoplication improves disordered esophageal motility.  J of Gastrointestinal Surg, 7:159-163, 2003.

17. Poole ME, Bernard SA, Churchel MA, Weissler MC, Calvo B, Cance W, Ollila D, Koruda M, Behrns K, Detterbeck FC.  A PhaseI Study of Gencitabine and Docetaxel for Advanced Stage Solid Tumors.  Cancer Investigation, 21:3, 350-354, 2003.

18. Bird MA, Black D, Lange PA, Samson CM, Hayden M, Behrns KE.  NFкB Inhibition Decreases Hepatocyte Proliferation but Does Not Alter Apoptosis in Obstructive Jaundice.  J Surg Research, 114:2, 110-117, 2003.

19. Lange PA, Samson CM, Bird MA, Hayden MA, Behrns KE.  Cirrhotic hepatocytes exhibit decreased TGFβ growth inhibition associated with downregulated Smad protein expression.  Biochem and Biophys Res Commun, 313, 546-551, 2004.

20. Black D, Lyman S, Heider TR, Behrns KE.  Molecular and Cellular Features of Hepatic Regeneration.  J Surg Research, 117(2), 306-315, 2004.

21. Zaré SM, Galanko J, Behrns KE, Koruda MJ, Boyle LM, Farley DR, Evans S RT, Meyer AA, Sheldon GF, Farrell TF.  Psychological well-being of surgery residents before the 80-hour work week:  a multiinstitutional study.  J of Amer College of Surgeons, 198:4, 633-640, 2004.

22. Heider TR, Koruda MJ, Farrell TM, Behrns KE.  Acute vagotomy does not augment the systemic inflammatory response in patients with peptic ulcer disease.  Am Surg, 70(4):342-6, 2004.

23. Black D, Bird MA, Samson CM, Lyman S, Lange PA, Schrum LW, Qian T, Lemasters JJ, Brenner DA, Rippe RA, Behrns KE.  Primary cirrhotic hepatocytes resist TGFb-induced apoptosis through a ROS-dependent mechanism.  J Hepatology, 40:942-951, 2004.

24. Heider TR, Azeem S, Galanko JA, Behrns KE.  The natural history of pancreatitis-induced splenic vein thrombosis.  Ann Surg, 239(6), 876-882, 2004.

25. Morton JM, Baker C, Farrell T, Yohe M, Kimple RJ, Herman D, Galanko J, Behrns K, Meyer A.  What do surgery residents do on their call nights?  Am J Surg, 188(3), 225-229, 2004.

26. Black D, Bird MA, Hayden M, Schrum LW, Lange P, Samson C, Hatano E, Rippe RA, Brenner DA, Behrns KE.  TNFa-induced hepatocyte apoptosis is associated with alterations of the cell cycle and decreased stem loop binding protein.  Surgery, 135:619-628, 2004.

27. Morton JM, Brown A, Galanko JA, Norton JA, Grimm IS, Behrns KE.  A national comparison of surgical versus percutaneous drainage of pancreatic pseudocysts:  1997-2001.  J Gastrointest Surg, 9(1):15-21, 2005.