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------------------------------------------------------------------------------------------------- Curriculum Vitae B.S., Massachusetts Institute of Technology 1991 ------------------------------------------------------------------------------------------------- Research Interests The overall aim of my research is to understand the mechanisms regulating tissue homeostasis in order to apply such knowledge to the prevention and treatment of human disease. Recently I have focused upon the roles of several Transforming Growth Factor-ß superfamily members, including GDF-15, GDF-11 and myostatin in normal and pathological conditions. Growth/Differentiation Factor-15 (GDF-15) is an immediate early gene highly induced in various organs following surgical, acute toxic injury and carcinogen exposures to intestine, lung, kidney, liver and bile duct. GDF-15 expression is modulated in tissues during the progression and metastasis of colon, breast, lung, and prostate cancers. Mice over-expressing GDF-15 show reduced intestinal tumorigenesis, but also profound growth and body composition abnormalities. Work in tissue culture systems suggests that GDF-15 may influence tumorigenesis directly by inhibiting cell proliferation, inducing cancer cell apoptosis and potentially by modulating the inflammatory response. We have generated Gdf15 null mice and are examining rates and progression of genetic or toxin-induced colon cancer, efficacy of NSAID chemoprevention and the immune response to tumors in these mice. GDF-11 is required for normal kidney development, but its role in adult kidney function and disease is a mystery. We observed that GDF-11 is highly expressed in adult kidney and was induced in mouse models of acute and chronic kidney injury. Excess GDF-11 led to kidney dysfunction, including reduced filtration, diabetes insipidus, tubular cell wasting and interstitial fibrosis, ultimately progressing to renal failure and cachexia. These effects may be mediated through proliferation and de-differentiation of tubular epithelial cells and proliferation and activation of interstitial fibroblasts. Genetic and pharmacologic inhibition of GDF-11 resulted in reduced fibrosis after ureteric obstruction. Currently we are using in vitro systems and genetically modified mice to further dissect the role of the GDF-11 pathway in acute and chronic renal disease. Myostatin is a highly conserved gene expressed at high levels in skeletal muscle. Animals lacking myostatin function develop skeletal muscle hypertrophy and hyperplasia. We have shown that over-expression of myostatin in mice produces a wasting syndrome similar to the cachexia that complicates many chronic diseases such as cancer, AIDS, and organ failure. We now are using genetic and pharmacological approaches to inhibit myostatin activity in mouse models of cachexia, including burn, sepsis and cancer-related wasting. The laboratory also has funding through an American Cancer Society Research Scholar Grant to Dr. Zimmers for understanding the molecular mechanisms downstream of inflammatory cytokines regulating muscle wasting in cancer cachexia. Contributors and collaborators: The Department of Surgery at University of Miami is committed to fostering basic research into mechanisms of disease. The Zimmers lab is part of the research effort in the Division of Surgical Oncology and works closely with the laboratory of Dr. Leonidas G. Koniaris, a surgical oncologist. The lab also has an active collaboration with the Division of Burns and its chief, Dr. Nicholas Namias. Graduate students, postdoctoral fellows, surgical residents and fellows as well as scientific staff, clinical and research faculty collaborate to drive the research mission forward. ------------------------------------------------------------------------------------------------- Selected Publications—Basic Science Jin X, Zhang Z, Beer-Stolz D, Zimmers TA, Koniaris LG. (2007) IL-6 inhibits oxidative injury and necrosis following extreme liver resection. Hepatology, Aug 1. [Epub ahead of print] Ozeramu U, Byrne MM, Gutierrez JC, Zimmers TA, Koniaris LG. (2007) How important is the contribution of surgical specialties to a medical school’s NIH funding? J Surg Res , 141(1):16-21. Zimmers TA , Gutierrez JC, Koniaris LG. (2007) NAG-1/GDF-15: No evidence for an inhibitory role in colon cancer? Gastroenterology , 132(3):1204-5. Jin XL, Zimmers TA, Perez EA, Zhang ZX, Pierce RH, Koniaris LG. (2006) Paradoxical Effects of Short and Long-Term Interleukin-6 Exposure on Liver Injury and Repair. Hepatology 43:474-484. Zimmers TA , Jin XL, Hsiao EC, Pierce RH, Chavin KD, Koniaris LG. (2005) p53 and TNF regulation of Growth Differentiation Factor-15 in liver injury. J Surg Res, 130:45-51. Epub 2005 Sep 12. Zimmers TA , Jin X, Hsiao EC, Esquela AF, McGrath SM, Koniaris LG. (2005) Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury. Shock, 23(6):543-548. Zimmers TA , Pierce RH, McKillop IH, Koniaris LG. (2003) Resolving the role of IL-6 in liver regeneration. Hepatology, 38:1590-1591. Klover PJ, Zimmers TA, Koniaris LG, Mooney RA. (2003) Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes, 52:2784-2789. Zimmers TA , McKillop I, Yoo J-Y, Murtha-Riel P, Koniaris LG. (2003) Massive liver growth in mice induced by systemic interleukin-6 administration. Hepatology, 38:326-334. Koniaris LG, McKillop IH, Schwartz S, Zimmers TA. (2003) Liver Regeneration. J Am Coll Surg. 197:634-659. Senn JJ, Klover PJ, Nowak,IA, Zimmers TA, Koniaris LG, Furlanetto RW, Mooney RA. (2003) Suppressor of cytokine signaling-3: a potential mediator of interleukin-6 dependent insulin resistance in hepatocytes. J Biol Chem, 278:13740-13746. Zimmers TA , Davies MV, Koniaris LG, Haynes P, Tomkinson KN, McPherron AC, Wolfman NM, Lee S-J. (2002) Cachexia Induced by Systemic Myostatin Administration in Mice. Science, 296:1486-1488. Koniaris LG, Zimmers-Koniaris T, Hsiao E, Sitzmann JV, Farber JM. (2000) Crg2/IP-10 expression in multiple models of liver and bile duct injury suggests a role in tissue regeneration. J Immunol, 167(1):399-406. Hsaio E, Koniaris LG, Zimmers-Koniaris TA, Sebald SA, Hyuhn T, Lee S-J. (2000) Growth/Differentiation Factor-15, a new TGF-ß family member expressed after liver injury. Mol Cell Biol, 20: 3742-3751. Esquela AF*, Zimmers TA*, Koniaris LG, Sitzmann JV, Lee S-J. (1997) Transient down-regulation of Inhibin-ßC following partial hepatectomy. Biochem Biophys Res Commun,235:553-6. (*shared first authorship) Williams DM, Zimmers TA, Pierce JH, Pharr PN, Schechter AN, Sawyer ST, Ruscetti SK, Spivak JL, Hankins WD. (1994) The expression and role of human erythropoietin receptor in erythroid and non-erythroid cells. Ann N Y Acad Sci,718:232-43. Yoshimura A, Zimmers T, Neumann D, Longmore G, Yoshimura Y, Lodish HF. (1992) Mutations in the Trp-Ser-X-Trp-Ser motif of the erythropoietin receptor abolish processing, ligand binding, and activation of the receptor. J Biol Chem, 267(16):11619-25. Other Scholarly Activities Recently in collaboration with colleagues at the University of Miami and elsewhere, we have published a series of papers examining the drug protocols and practices in lethal injection for execution in the United States. Through this work we seek to inform the public and legal debates over lethal injection here and abroad. Zimmers TA, Sheldon J, Lubarsky DA, Lopez-Munoz F, Waterman L, Weisman R, Koniaris LG. (2007) Lethal injection for execution: chemical asphyxiation? PLoS Medicine, 4:e156. Zimmers TA , Lubarsky DA. (2007) Physician participation in lethal injection executions. Current Opinion in Anesthesiology, 20:147-151. Koniaris LG, Sheldon JP, Zimmers TA. (2007) Can lethal injection for execution really be “fixed”? (Invited comment) Lancet 369:352-3. Zimmers TA , Lubarsky DA, Sheldon JS, Koniaris LG. (2005) Inadequate anesthesia in lethal injection for execution. Author reply. Lancet, 366:1074-1076. Koniaris LG*, Zimmers TA*, Lubarsky DA, Sheldon JS. (2005) Inadequate anesthesia in lethal injection for execution. Lancet, 365:1412-1414. (*shared first authorship) ------------------------------------------------------------------------------------------------- |
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