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------------------------------------------------------------------------------------------------- Curriculum Vitae B.S., University of Massachusetts, Amherst ------------------------------------------------------------------------------------------------- Clinical Interests I am a general surgeon and surgical oncologist with a strong interest and expertise in the management of cancers of the gastrointestinal tract and sarcomas. Research Interests Our laboratory concentrates on mechanism of growth control and dysregulation of tissue growth in vivo. We concentrate our studies particularly on liver and the intestinal tract. Recently we have concentrated our studies on two secreted factors: IL-6 and GDF-15. Interleukin-6 (IL-6) is an inflammatory cytokine essential in normal liver homeostasis. We have demonstrated that it functions as a growth factor for hepatocytes through an apparently direct mechanism that does not involve either activation of cMET or EGF. Subsequent work has demonstrated that this mitogenic response is associated with profound anti-apoptotic activity. Dose and duration of IL-6 signaling are critical determinants of its effects in the liver and other tissue. Acute administration of IL-6 has pro-growth and anti-injury effects, however longer term IL-6 signaling, as in diabetes, obesity or other chronic disease, actually predisposes tissues to injury and death. Manipulating the IL-6 pathway may have important clinical implications, as we have recently shown that IL-6 administration protects mice from massive necrosis following extreme (87%) liver resection. While investigating the effects of IL-6 administration on the liver, we noted profound anti-apoptotic activity in the small and large intestine, resulting in increased small and large bowel mass. We have extended these observations and now show that IL-6 is protective in models of intestinal injury and regeneration, including ischemia-reperfusion in jury, massive small bowel resection, and administration of the chemotherapeutic drug, 5-Fluorouracil. These studies have led to intensive investigation of IL-6 in small bowel repair and colon cancer. GDF-15/MIC-1 is a divergent member of the transforming growth factor- b superfamily of growth and differentiation factors. MIC-1 has been strongly implicated in the pathogenesis of both colorectal and prostate cancers and may play a potent anti-tumor role. We have examined the expression of MIC-1 and found it to be an immediate early response to a variety of organ injuries and exposures to carcinogens. We have generated MIC-1 null mice and are examining their propensity to the development of liver, colorectal, breast and prostate cancers. Contributors and collaborators: The Department of Surgery at University of Miami is committed to fostering basic research into mechanisms of disease. The Koniaris lab is part of the research effort in the Division of Surgical Oncology and works closely with the laboratory of Dr. Teresa Zimmers. ------------------------------------------------------------------------------------------------- Selected Publications— Of over 100 peer-reviewed publications Basic Science Zimmers, T.A., Davies, M., Koniaris, L.G., Haynes, P., McPherron, A.C., Wolfman, N., Lee S.-J. Induction of cachexia in mice by systemically administered myostatin. Science (2002) 296:1486-8. Zimmers, T.A., McKillip, I.H., Pierce, R.H., Yoo, J.-Y., Koniaris, L.G. Massive liver growth induced by systemic administration of interleukin-6. Hepatology (2003) 38(2) 326-34. Senn, J.J., Klover, P.J., Nowak, I.A., Zimmers, T.A., Koniaris, L.G., Furlanetto, R.W., Mooney, R.A. Suppressor of cytokine signaling-3: a potential mediator of interleukin-6 dependent insulin resistence in hepatocytes. J Biol Chem (2003) 18:13740-6. Klover, P.J., Zimmers, T.A., Koniaris, L.G., Mooney, R.A. Chronic exposure to IL-6 causes hepatic insulin resistance in mice. Diabetes (2003) 52:2784-9. Zimmers, T.A,. Pierce, R.H., McKillop, I.H,. Koniaris, L.G. Resolving the role of IL-6 in liver regeneration. Hepatology (2003) 38(6):1590-1. Jin, X, Zimmers, TA, Perez, E, Pierce, RA, Xhou, Z, Koniaris, LG. Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair. Hepatology (2006) 43(3):474-484. Jin, X., Zhang, Z., Beer-Stoltz, D., Zimmers, T., Koniaris, L.G. IL-6 prevents necroapoptosis following extreme hepatic resection. Hepatology (2007) 46:802-812. Clinical Sitzmann, J.V., Koniaris, L.G. Intra-arterial hepatic catheterization and pump placement. Op Tech Gen Surg (2002) 4(1):99-110. Cirillo, R, Koniaris, L.G. Dectecting Blunt Pancreatic Injury. J GI Surg (2002) 6:587-98. Schoeniger LO, Bankey P, Drugas G, Koniaris LG. Optimal closure of the complex abdomen. Arch Surg (letter) (2003) 138: 458. Salloum, R., Koniaris, L.G. Mirizzi’s syndrome mimicking a periampullary malignancy. Arch Surg (2004) 139:449-50. Khanna, A., Koniaris, L.G., Nakeeb, A., Schoeniger, L.O. Laparoscopic distal pancreatectomy. J GI Surg (2005) 9:733-8. Khanna, A., Walker, G.R., Livingstone, A.S., Arheart, K., Koniaris, L.G. Does adjuvant 5-FU prolongs survival following pancreaticoduodenectomy? A meta-analysis. J GI Surg (2006) 10:689-697. Earl, S.A., Perez, E.A., Gutierrez, J., Livingstone, A.S., Franchesci, D., Levi, J.U., Sleeman, D, Koniaris, L.G. Hepatectomy enables prolonged survival in select patients with isolated noncolorectal liver metastasis. J Amer Coll Surg (2006) 203(4):436-46. Perez, E., Franceschi, D., Livingstone, A.S., Gutierrez, J., Specter, S.A., Moffat, F., Levi, J.U., Sleeman, D., Koniaris, L.G. Retroperitoneal and Truncal Sarcomas: Prognosis depends upon type not location. Ann Surg Onc (2007) 14(3):1114-22. Gutierrez, J., Perez, E., Moffit, F.L., Franceschi, D., Livingstone, A.S., Koniaris, L.G. Improved survival for truncal and retroperitoneal sarcomas treated at high volume centers. Ann Surg 2007; 245(6):952-8.View published research articles by Dr. Koniaris in the National Library of Medicine ------------------------------------------------------------------------------------------------- |
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