- Lauren E. Ball, Ph.D.
- Joe B. Blumer, Ph.D.
- Warren Davis Jr., Ph.D.
- Scott Eblen, Ph.D.
- Perry V. Halushka, M.D., Ph.D.
- John D. Hildebrandt, Ph.D.
- Jennifer S. Isaacs, Ph.D.
- Daniel R. Knapp, Ph.D.
- David T. Kurtz, Ph.D.
- Stephen M. Lanier, Ph.D.
- Carola A. Neumann, M.D.
- John E. Oatis, Ph.D.
- Steven A. Rosenzweig, Ph.D.
- Kevin L. Schey, Ph.D.
- Kenneth D. Tew, Ph.D., D.Sc.
- Thomas Walle, Ph.D.
- Michael J. Wargovich, Ph.D.
- Jerry G. Webb, Ph.D.
Carola Neumann, M.D.Assistant Professor
Cell and Molecular PharmacologyMember, Experimental Therapeutics Program
Hollings Cancer Center
M.D., Ludwig-Maximilians University, 1997
neumannc@musc.edu
Tel: 843-792-8367
Fax: 843-792-9588
Role of the reactive oxygen species (ROS) and the antioxidant peroxiredoxin1 (Prdx1) in tumor initiation
Oxidative stress: Free radicals, reactive oxygen species (ROS) and reactive nitrogen species (RNS), are molecules with one or more unpaired electrons. An important feature of free radical reactions with non-radicals is that they result in new radicals, which leads to chain reactions. Electron acceptors such as molecular oxygen react easily with free radicals, to become radicals themselves, called reactive oxygen species (ROS). This explains why, in aerobic life, where molecular oxygen is ubiquitous, ROS become the primary mediators of cellular free radical reactions.
At high concentrations, free radicals and radical-derived species are hazardous for living organisms and damage all major cellular components. At moderate concentrations, however, nitric oxide (NO), superoxide anion (O2-), and related reactive oxygen species (ROS), play an important role as regulatory mediators in signaling processes. Maintaining the “redox homeostasis” (see Fig.1) is therefore crucial for cellular wellbeing. An imbalance of the homeostasis with elevated reactive oxygen species (ROS) is the basis of aging and diseases such as atherosclerosis, autoimmune disorders, neuronal degeneration, and especially cancer (Tab.1).
Fig. 1
Tab. 1
Peroxiredoxin1 (Prdx1) acts as a tumor suppressor: Peroxiredoxins (Prdx), a family of small antioxidant proteins, currently consists of six members in mammals. Prdxs are distributed in the cytosol, mitochondria, peroxisomes, and plasma, all of which are potential sites of ROS production. Prdxs share a common reactive cysteine residue in the N-terminal region, and are capable of serving as peroxidases.
I created Prdx1-deficient mice, which die prematurely of hemolytic anemia and multiple malignancies. The malignancies include lymphomas, sarcomas, and carcinomas. Tumors from heterozygotes are frequently accompanied by loss of Prdx1 protein expression, suggesting a tumor suppressor-like function. Cells from Prdx1-deficient mice exhibit a slower population doubling time, increased intracellular H2O2 levels and elevated oxidized guanine residues (8-OxoG). Moreover, NK cells from young Prdx1-deficient mice, had a significantly lower cytotoxic lytic activity than NK cells from wild type animals.
Lab-interests: The lab currently focuses on the molecular details of Prdx1 in its tumor suppressive roles. We use in vitro and in vivo transformation assays to identify molecules regulated by Prdx1. Being part of a strong drug-development community here at MUSC we are investigating new therapeutic approaches in tumor prevention of ROS-induced malignancies. Furthermore, we are in the process of creating new mouse tumor models to study the impact of ROS and the role of Prdx1 in tumor development.
Who is “the lab”: Jennifer Schulte, who is an extremely experienced Research Specialist II, and Dr. Quan Fang, a postdoctoral fellow from USF, who is experienced in tumor biology. I was trained as an MD in Munich, Ludwig Maximilians University and rotated through several hospitals in Boston. My postdoctoral training in cancer biology includes work at the CBR Institute for Biomedical Research, HMS and the Dana Farber Cancer Institute, HMS, in Boston, MA.
Position Open: graduate student
Selected Publications | Additional Publications
Neumann CA and Fang Q. Are peroxiredoxins tumor suppressors? Curr Opin Pharmacol, epub ahead of print, July 4, 2007.
Carthon BC, Neumann CA, Armour S, Li T, Geng Y, Sicinski S. Genetic replacement of cyclin D1 function in mouse development by cyclin D2. Mol Cell Biol 25(3):1081-8, 2005.
Roumiantsev S, Krause, DS, Neumann CA, Dimitri C, Asiedu F, Daley G, Cross NCP, and VanEtten RA. Distinct stem cell myeloproliferative/T-lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations. Cancer Cell 5(3):287-98, 2004.
Neumann CA, Krause DS, Abraham J, Carman CV, Das S, Dubey D, Bronson RT, Fujiwara Y, Orkin SH, and Van Etten RA. Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defense and tumor suppression. Nature 424:561-5, 2003.
Hallek M, Neumann CA, Schaeffer M, Danhauser-Riedl S, von Bubnoff N, de Vos G, Druker B, Yasukawa K, Griffin J, and Emmerich B. Signal transduction of interleukin-6 involves tyrosine phosphorylation of multiple cytosolic proteins and activation of SRC- family kinases Fyn, Hck, and Lyn in multiple myeloma cell lines. Exp Hematology 25:1367-1377, 1997.
Neumann CA, Zehentmeier G, Danhauser-Riedl S, Druker B, Emmerich B, Hallek M. Interleukin 6 induces tyrosine phosphorylation of the ras activating protein SHC, and its complex formation with GRB2 in the multiple myeloma cell line LP-1. Eur J Immunology 26:379-384, 1996.
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