Molecular Cell and Developmental Biology : Faculty Detail

Teresa A. Zimmers, Ph.D.

Research Assistant Professor, Dewitt Daughtry Family Department of Surgery, Division of Surgical Oncology, Cell Biology & Anatomy, Sylvester Comprehensive Cancer Center

(305) 243-1685 (office)

(305) 243-7083 (fax)

Lab address: Surgical Oncology Research Laboratory, R.M.S.B. 1038 Office address: R.M.S.B. 1044

tzimmers@med.miami.edu

Curriculum Vitae

B.S., Massachusetts Institute of Technology 1991
Ph.D., Johns Hopkins University School of Medicine, 2001
Postdoctoral Fellow, University of Rochester, 2001-2003
Research Assistant Professor, University of Miami, 2003-present
Member, Molecular Therapeutics Program, Sylvester Comprehensive Cancer Center
Member, Graduate Faculty, Molecular Cell and Developmental Biology Program
Member, Graduate Faculty, Cancer Biology Program

Research Interests

The laboratory focuses upon the role of growth factors and cytokines in disease and organ regeneration.

Molecular mechanisms regulating muscle growth and wasting.

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 the Transforming Growth Factor-ß superfamily member, myostatin, in regulation of skeletal muscle and fat mass. Mice and cattle lacking myostatin function develop skeletal muscle hypertrophy and hyperplasia. We have shown that overexpression of myostatin in mice produces hypoglycemia along with a wasting syndrome similar to the cachexia that complicates many chronic diseases such as cancer, AIDS, and organ failure. Concomitant over-expression of the myostatin binding proteins, follistatin and myostatin propeptide, inhibits this wasting, suggesting a means of interfering with endogenous myostatin signaling in animals and patients. My current research focuses upon the following questions:

Is dysregulation of the myostatin signaling pathway involved in the etiology of muscle wasting due to cancer, AIDS, congestive heart failure, burn, or sepsis?

How does myostatin regulate muscle and fat mass in vivo?

What are the target genes induced by myostatin signaling?

How does myostatin-induced wasting differ from that induced by cytokines such as interleukin-6 (IL-6) or Tumor Necrosis Factor (TNF)?

Our recent data suggest that myostatin may regulate skeletal muscle mass on several levels, including by altering proteolysis, cell proliferation and apoptosis, and cell energetics/metabolism. As well, using gene expression profiling of myostatin and cytokine induced cachexia, I have identified a number of candidate genes that might control skeletal muscle regulation in normal development and disease.

In addition to myostatin, my laboratory is actively engaged in deciphering the mechanisms by which Interleukin-6, signaling through STAT3, affects muscle growth regulation in disease and how the same pathway can influence liver mass, function and regeneration, both in normal physiology as well as in pathological conditions. Our research on this pathway is funded by an American Cancer Society Research Scholar Grant “Manipulating STAT3 for muscle preservation in cancer cachexia.” Other research efforts are currently or formerly supported by: the Women's Cancer Association of the University of Miami, the Wendy Will Case Foundation, the Stanley J. Glaser Foundation, the Papanicoulau Corps for Cancer Research, and the United States Department of Defense.

Recent Publications

Yang R, Cheung MC, Hurley J, Byrne MM, Huang Y, Zimmers TA, Koniaris LG. (2009) A comprehensive evaluation of outcomes for inflammatory breast cancer. Breast Cancer Res Treat, Jan 24 (Epub ahead of print.)

Jin X, Zimmers TA, Zhang Z, Pierce RH, Koniaris LG. (2009) Interleukin-6 is an important in vivo inhibitor of intestinal epithelial cell death in mice. Gut, Feb 3 (Epub ahead of print).

Cheung MC, Spalding PB, Namias N, Koniaris LG, Zimmers TA. (2009) The skeletal muscle myostatin/ACVR2B pathway is essential for recovery from burn injury. J Surg Res 151(2):291.

Cheung MC, Spalding PB, Namias N, Koniaris LG, Zimmers TA. (2009) A murine model of chronic muscle wasting induced by burn injury. J Surg Res 151(2):291.

Link M, Aydogdu T, Guo S, Koniaris LG, Zimmers TA. (2008) Genetic and Pharmacologic Inhibition of Myostatin for Muscle Preservation in Cancer Cachexia. J Surg Res 144(2):307.

Koniaris L, Aydogdu T, Guo S, Zhang Z, Jin X, Puzis L, Perez EC, Zimmers TA. (2008) STAT3 regulation of muscle wasting in cancer cachexia. In: Proceedings of the 99th Annual Meeting of the American Association for Cancer Research; 2008 Apr 12-16; San Diego, CA. Philadelphia (PA):AACR; 2008.

Cheung MC, Spalding P, Balkan W, Namias N, Koniaris LG, Zimmers TA. (2008) Body surface area prediction in normal, hypermuscular and obese mice. J Surg Res, 153(2):326-31. Epub 2008 Jun 4.

Koniaris LG, Goodman KW, Ozomaro O, Sugarman J, Sheldon J, Zimmers TA. (2008) Ethical Implications of Modifying Lethal Injection Protocols. PLoS Medicine, 5(6):e126.

Housri N, Cheung MC, Gutierrez JC, Koniaris LG, Zimmers TA. (2008) Scientific Impact of Women in Academic Surgery. J Surg Res, 148(1):13-6. Epub 2008 Mar 13.

Housri N, Cheung MC, Gutierrez JC, Zimmers TA, Koniaris LG. (2008) SUS/AAS abstracts: what is the scientific impact? Surgery, 144(2):322-31.

Zimmers TA, Jin X, Gutierrez JC, Acosta CA, Pierce RH, Koniaris LG. (2008) Effect of in vivo loss of GDF-15 on hepatocellular carcinogenesis. J Cancer Res and Clin Oncol 2008 Jan 22; [Epub ahead of print].

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.

Jin X, Zhang Z, Beer-Stolz D, Zimmers TA, Koniaris LG. (2007) IL-6 inhibits oxidative injury and necrosis following extreme liver resection. Hepatology, 46:802-12.

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, 141:16-21.

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, X., Zimmers, T.A., Perez, E.A., Pierce, R.H., Zhang, Z., and Koniaris, L.G. 2006. Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair. Hepatology 43:474-484.

Zimmers, T.A., Jin, X., Hsiao, E.C., Perez, E.A., Pierce, R.H., Chavin, K.D., and Koniaris, L.G. 2006. Growth differentiation factor-15: induction in liver injury through p53 and tumor necrosis factor-independent mechanisms. J Surg Res 130:45-51.

Zimmers, T.A., Jin, X., Hsiao, E.C., McGrath, S.A., Esquela, A.F., and Koniaris, L.G. 2005. Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury. Shock 23:543-548.

Klover, P.J., Zimmers, T.A., Koniaris, L.G., and Mooney, R.A. 2003. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes 52:2784-2789.

Koniaris, L.G., McKillop, I.H., Schwartz, S.I., and Zimmers, T.A. 2003. Liver regeneration. J Am Coll Surg 197:634-659.

Senn, J.J., Klover, P.J., Nowak, I.A., Zimmers, T.A., Koniaris, L.G., Furlanetto, R.W., and Mooney, R.A. 2003. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 278:13740-13746.

Zimmers, T.A., McKillop, I.H., Pierce, R.H., Yoo, J.Y., and Koniaris, L.G. 2003. Massive liver growth in mice induced by systemic interleukin 6 administration. Hepatology 38:326-334.

Zimmers, T.A., Pierce, R.H., McKillop, I.H., and Koniaris, L.G. 2003. Resolving the role of IL-6 in liver regeneration. Hepatology 38:1590-1591

Zimmers, T.A., Davies, M.V., Koniaris, L.G., Haynes, P., Esquela, A.F., Tomkinson, K.N., McPherron, A.C., Wolfman, N.M., and Lee, S.J. 2002. Induction of cachexia in mice by systemically administered myostatin. Science 296:1486-1488.

Koniaris, L.G., Zimmers-Koniaris, T., Hsiao, E.C., Chavin, K., Sitzmann, J.V., and Farber, J.M. 2001. Cytokine-responsive gene-2/IFN-inducible protein-10 expression in multiple models of liver and bile duct injury suggests a role in tissue regeneration. J Immunol 167:399-406.

Hsiao, E.C., Koniaris, L.G., Zimmers-Koniaris, T., Sebald, S.M., Huynh, T.V., and Lee, S.J. 2000. Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury. Mol Cell Biol 20:3742-3751.

Esquela, A.F., Zimmers, T.A., Koniaris, L.G., Sitzmann, J.V., and Lee, S.J. 1997. Transient down-regulation of inhibin-betaC expression following partial hepatectomy. Biochem Biophys Res Commun 235:553-556.

Williams, D.M., Zimmers, T.A., Pierce, J.H., Pharr, P.N., Schechter, A.N., Sawyer, S.T., Ruscetti, S.K., Spivak, J.L., and Hankins, W.D. 1994. The expression and role of human erythropoietin receptor in erythroid and nonerythroid cells. Ann N Y Acad Sci 718:232-243; discussion 243-234.

Yoshimura, A., Zimmers, T., Neumann, D., Longmore, G., Yoshimura, Y., and Lodish, H.F. 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 267:11619-11625.

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, T.A., Sheldon, J., Lubarsky, D.A., Lopez-Munoz, F., Waterman, L., Weisman, R., and Koniaris, L.G. 2007. Lethal injection for execution: chemical asphyxiation? PLoS Med 4:e156.

**Accompanying editorial and international media coverage. Referenced by name during oral arguments in Baze v. Rees by Supreme Court of the United States Justice Stephen Breyer.

Zimmers, T.A., and Lubarsky, D.A. 2007. Physician participation in lethal injection executions. Curr Opin Anaesthesiol 20:147-151.

Koniaris LG, Sheldon JP, Zimmers TA. (2007) Can lethal injection for execution really be “fixed”? (Invited comment) Lancet 369:352-3. **Accompanying editorial.

Koniaris, L.G., Zimmers, T.A., Lubarsky, D.A., and Sheldon, J.P. 2005. Inadequate anaesthesia in lethal injection for execution. Lancet 365:1412-1414.

**Accompanying editorial, international media coverage, and referred to by name during oral arguments before the Supreme Court of the United States in Baez v. Rees by Justice Stephen Breyer and in the resulting opinion by Justices Roberts, Alito and Breyer.

Law Review Article:

Koniaris LG, Zimmers TA. (2008) Problems with the implementation of lethal injection for execution. Fordham Urban Law Journal, in press.

Book chapter:

Zimmers-Koniaris T. (March 2001) Northern blotting and RNA detection. In: Nature Encyclopedia of Life Sciences, London: Nature Publishing Group. http://www.els.net/ [doi:10,1038/npg.els.0000997].

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