22657-Koniaris, Leonidas
Faculty

Leonidas G. Koniaris, MD

Professor of Surgery

Address
EH 511
SGEN
IN
Indianapolis, IN

Bio

Dr. Leonidas Koniaris is a general surgeon with advanced training in cancer surgery, particularly of the gastrointestinal tract, liver, and pancreas. In addition, he has developed advanced experience in the management of soft tissue sarcomas. Dr. Koniaris is a professor of surgery and also serves as vice chair for research.

Dr. Koniaris is a graduate of The John Hopkins University School of Medicine. He did his surgical training and two advance fellowships at The John Hopkins Hospital in Baltimore. He has also presented and published many of the largest surgical series in the world for treating these cancers. Overall, Dr. Koniaris has published almost 200 peer-reviewed articles in the field of surgery and cancer.

Key Publications

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.

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.

Titles & Appointments

  • Professor of Surgery
  • Education
    1991 MD Johns Hopkins University
    1986 BS University of Massachusetts
  • Research

    Our laboratory concentrates on the mechanism of growth control and dysregulation of tissue growth in vivo. We concentrate our studies particularly on the 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 a 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 diseases, 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 injury, massive small bowel resection, and administration of the chemotherapeutic drug, 5-Fluorouracil. These studies have led to an 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 live, colorectal, breast and prostate cancers.

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