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Health Science Campus, Mail Stop #1010
3000 Arlington Avenue
Toledo, OH 43614
Steve Patrick, Ph.D.
The major focus of the lab lies in understanding the mechanisms of cisplatin DNA repair.
Cisplatin is a chemotherapeutic drug that is used in the treatment of testicular and
ovarian cancers, as well as other cancer types. Many chemotherapeutic drugs, including
cisplatin, target DNA and inhibit cells from dividing which ultimately leads to cell
death. The problem with cisplatin is that after treatment and remission of the cancer,
recurrence and resistance often occurs. The main mechanism of resistance is enhanced
DNA repair or the ability of the cancer cells to remove the damaged DNA such that
cell division can continue. Research using cisplatin and the clinically ineffective
transplatin, have suggested that the DNA adducts alone may not be responsible for
the cancer killing activity of these drugs, but more likely involves the interplay
of proteins within the cell that can bind to and alter the metabolism and repair of
these DNA adducts. It has been suggested that the longer a cisplatin lesion remains
on the DNA, the better cancers respond to drug treatment. Our focus specifically,
is on the cisplatin interstrand cross-links (ICLs) and proteins that play a role in
the ICL DNA repair pathway. This includes the proteins that bind and initiate the
ICL DNA repair pathway. By understanding the mechanism of cisplatin ICL DNA damage
recognition and the proteins that play a role in the cisplatin ICL DNA repair process,
the improvement and development of new cancer treatment is possible. This is significant
with respect to drug resistant cancers and cancers that are typically non-responsive
to cisplatin treatment. We have begun a separate project to screen and identify inhibitors
of the XPF-ERCC1 DNA repair endonuclease. Preliminary data suggest that inhibitors
of this DNA repair complex will enhance the efficacy of cisplatin.
Member of the mentoring faculty for the Biomedical Sciences Graduate Program (Cancer Biology Track).
1999 Ph.D. Wright State University, Dayton, OH
1994 B.S. Urbana University, Urbana, OH
|Jan 2011 - present||Associate Professor, Department of Bichemistry & Cancer Biology, University of Toledo College of Medicine, Toledo, OH|
|Sept 2006 - Dec 2010||Assistant Professor, Department of Biochemistry & Cancer Biology, University of Toledo College of Medicine, Toledo, OH|
|Sept 2002 - Aug 2006||Assistant Professor, School of Medicine, Biochemistry & Mol. Biol. Dept., Wright State University, Dayton, OH|
|1999 - Aug. 2002||Postdoctoral Fellow, John J. Turchi’s Lab, Department of Biochemistry and Molecular Biology, Wright State University|
Kaliyaperumal, S., Patrick, S.M., and Williams, K.J. (2011) Phosphorylated hMSH6: DNA mismatch versus DNA damage recognition. Mutat Res 706:36-45.
Kothandapani, A., Dangeti, V.S.M.N., Brown, A.R., Banze, L.A., Wang, W-H., Sobol, R.W., and Patrick, S.M. (2011) Novel role of base excision repair in mediating cisplatin cytotoxicity. J Biol Chem 286:14564-14574.
Arora, S., Kothandapani, A., Tillison, K., Kalman-Maltese, V., and Patrick, S.M. (2010) Downregulation of XPF-ERCC1 enhances cisplatin efficacy in cancer cells. DNA Repair 9:745-753.
G.G. Oakley and Patrick, S.M. (2010) Replication protein A: Directing traffic at the intersection of replication and repair (Invited Review) Frontiers in Bioscience 15:883-900.
G.G. Oakley, K. Tillison, S.A. Opiyo, J.G. Glanzer, J.M. Horn, and Patrick, S.M. (2009) Physical interaction between replication protein A (RPA) and MRN: Involvement of RPA2 phosphorylatin and the N-terminus of RPA1. Biochemistry 48:7473-7481.
A. Schroering, A. Kothandapani, S.M. Patrick, S. Kaliyaperumal, V.P. Sharma, and K.J. Williams (2009) Prolonged cell cycle response of HeLa cells to low-level alkylation exposure. Cancer Res. 69:6307-6314.
S.M. Patrick, K. Tillison, and J.M. Horn (2008) Recognition of cisplatin-DNA interstrand cross-links by replication protein A. Biochemistry 47(38):10188-10196.
S.M. Patrick, G. Oakley, K. Dixon and J.J. Turchi (2005) DNA Damage Induced Hyper-Phosphorylation of Replication Protein A. 2. Characterization of DNA binding activity, protein interactions and activity in DNA replication and repair. Biochemistry 44(23):8438-8448.
J.E. Nuss, S.M. Patrick, G.G. Oakley, G.M. Alter, J.G. Robison, K. Dixon, and J.J.
Turchi (2005) DNA Damage Induced Hyper-Phosphorylation of Replication Protein A. 1. Identification
of novel sites of phosphorylation in response to DNA damage. Biochemistry 44(23):8428-8437.
L-M. Zhou, Q. Chai, J. Parrish, D. Xue, S.M. Patrick, J.J. Turchi, S. Yannone, D. Chen and B. Shen (2005) Novel function of the flap endonuclease-1 complex in processing DNA replication forks. EMBO Reports 6(1):83-89.
S.M. Patrick, G. Oakley, J. Yao, M.P. Carty, J.J. Turchi and K. Dixon (2003) RPA Phosphorylation in Mitosis Alters DNA Binding and Protein-Protein Interactions. Biochemistry 42:3255-3264.
S. Tornaletti, S.M. Patrick, J.J. Turchi and P.C. Hanawalt (2003) Behavior of T7 RNA polymerase and mammalian RNA polymerase II at site-specific cisplatin adducts in the template DNA. J Biol Chem 278:35791-35797.
S.M. Patrick and J.J. Turchi (2002) Xeroderma Pigmentosum Group A protein (XPA) Modulates RPA-DNA Interactions via Enhanced
Complex Stability and Inhibition of Strand Separation Activity. J Biol Chem 277:16096-16101.
J.J. Turchi and S.M. Patrick (2011) Targeting the Nucleotide Excision Repair Pathway for Therapeutic Applications. In: DNA Repair in Cancer Therapy, Chapt. 6, 109-117.