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Home > Directory > Primary Faculty > Carola Neumann, MD

Carola Neumann, MD

Associate Professor & Vice Chair for Precision and Translational Pharmacology
A408 MWRI
can44@pitt.edu
Phone: 412-641-7725

Education

MTA (comparable to baccalaureate degree) as Medical Technical Research Assistant, Naturwissenschaftliches Technikum Landau, i.d. Pfalz, Germany, 1989

MD, Ludwig-Maximilian's University, Medical School, Munich, Germany, 1997
Headshot of Carola Neumann, MD

 The main interest of the Neumann laboratory is to expand our knowledge of cell signaling that is in part mediated by oxidation and reducing (redox) reactions as reactive oxygen species (ROS) deregulate the redox homeostasis and promote tumor formation by initiating an aberrant induction of signaling networks that cause tumorigenesis, including breast cancer. To investigate the specific mechanisms underlying redox-induced tumorigenesis, the Neumann laboratory focuses on the redox-induced posttranslational modifications (PTM) of protein cysteines, which are essential in cell signaling. Peroxiredoxin 1 (PRDX1) is a peroxidase that has emerged as a critical protein in cell signaling as it scavenges the second messenger H2O2, binds to and regulates signaling proteins, and when knocked out in mice, causes a variety of cancers, including breast cancer. 

Using this system, we have identified protein cysteines modified by ROS, contributing to breast cancer initiation and progression. For example, we have discovered that a previously unknown functionally essential cysteine in the recombinase RAD51 is vital for its function in homologous recombination-mediated DNA repair. Based on these findings, we have developed a reversible, non-toxic covalent inhibitor that targets this functionally essential RAD51 cysteine, thus inhibiting RAD51 function and, significantly, sensitizing triple-negative breast cancer cells to DNA-damaging therapies. Current work in the laboratory is geared towards successfully IND-labeling the inhibitor and further discovering other functional protein cysteine targets that can be exploited as anti-cancer therapies.

Other projects include investigating redox signaling pathways in the breast cancer microenvironment with a focus on mammary associated fibroblasts utilizing mouse models and patient-derived tissues. 

 

Journal Articles

Hopkins B, Nadler M, Skoko J, Bertomeu T, Pelosi A, Mousavi Shafaei P, Levine K, Schempf A, Pennarun B, Yang B, Datta D, Oesterreich S, Yang D, Rizzo M, Khosravi-Far R and Neumann CA. A PRDX1-specific redox regulation of the novel FOXO3 miRNA target let-7. Antioxidants and Redox Signaling 28:62-77, 2018.
Turner-Ivey B, Manevich Y Schulte J, Kistner-Griffin E, Jezierska-Drutel A, Yusen L and Neumann CA. A role for Prdx1 in specific redox-regulation of signaling in breast cancer-associated senescence. Oncogene 32:5302-5314, 2013.
Jezierska-Drutel A, Rosenzweig S and Neumann CA.  Role of oxidative stress and microenvironment in breast cancer development and progression.  Advances in Cancer Research 119:107-125, 2013.
Rani V, Neumann CA, Schulte, J. Shao C and Tischfield JA. Prdx1 deficiency in mice promotes tissue specific loss of heterozygosity mediated by deficiency in DNA repair and increased oxidative stress. Mutation Research 735:39-45, 2012.
Neumann CA, Cao J and Manevich Y. Peroxiredoxin 1 and its role in cell signaling. Cell Cycle 8: 4072-4078, 2009.
Cao J, Schulte J, Knight A, Leslie NR, Zagozdzon A, Bronson R, Manevich Y, Beeson C and Neumann CA. Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity. EMBO J 28: 1505-1517, 2009.
Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH and Van Etten RA. Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature 424:561-565, 2003.

Sponsored Research

Characterizing nitro-fatty acids as Rad51 inhibitors as co-treatment in triple negative breast cancer - 2/1/2019 - 1/31/2022
DOD - BC1804671P1