Stephan Matthew Patrick (fk4300)

University information

Title: Professor
Unit: Oncology
Department: School of Medicine

Contact information

313-576-8335
Karmanos Cancer Institute
4100 John R., HW05AO
HWCRC - 540.2
Detroit, 48201

Cancer Biology Program

Phone: 313-576-8335
Title:

Professor, Co-Director T32 Training Grant, Cancer Biology Graduate Program

Office Address:

4100 John R, HW05A-2
Detroit, MI 48201 

Mentoring:

Jacob Lindquist and Istri Ndoja

Department:

 Oncology

Research Interests:

• DNA Repair pathways and understanding how they mediate cisplatin efficacy
• Assessing the role of APOBEC3 cytidine deaminases in chemotherapy response
• Targeting DNA repair to overcome chemotherapy drug resistance
• Understanding the bystander effect following cisplatin treatment
• Novel combination therapies and mechanistic understanding of drug synergism
 

Research Description:

The major disease focus of my research is understanding how cancer cells respond to chemotherapy, including the pathways that are critical for maintaining drug sensitivity. The development of drug resistance is a major clinical limitation. The platinum-based chemotherapy drugs account for over $3 billion in the medical industry per year. Even though they are widely used, the limitations of these drugs are that they are used for specific cancers and that typically following treatment, cancers develop drug resistance. The projects in the lab all relate to translational approaches for drug discovery that would enhance platinum- based chemotherapeutic efficacy and overcome drug resistance in a variety of cancers. The specific areas of interest include: 1) elucidating mechanisms of drug resistance in specific cancers with DNA repair defects; 2) assessing the role and understanding the mechanism of how APOBEC3 cytidine deaminases can influence platinum based chemotherapy response; 3) targeting DNA repair pathways to enhance platinum-based chemotherapy; 4) elucidating the role of the "bystander effect" in platinum resistance and how DNA damage and the DNA damage response pathway mediate the bystander effect; and 5) identifying novel drug combinations and mechanistic understanding of drug synergism. In recent years, we have identified a protein target, ERCC1-XPF, that when inhibited enhances the efficacy of platinum-based drugs in a variety of cancer cell lines including ovarian, lung and breast cancers. Most importantly, when targeting this protein complex in cisplatin resistant cancer cells, we can reverse the resistant phenotype back to parental sensitive levels. We are currently developing two candidate drugs that inhibit ERCC1-XPF activity in the low nanomolar range, and in cell culture models, enhance platinum-based effects in the low micromolar range. My lab will continue with the development of drugs that inhibit the ERCC1-XPF complex, as well as continue to pursue other pathways that can be targeted to enhance platinum chemotherapy and overcome drug resistance in many cancer types. Refractory cancers remain a major obstacle in the treatment of many adult and childhood cancers and thus, the identification of new targets and the development of new drugs that overcome this critical problem will make a significant contribution to the treatment of these cancers.

Recent Publications:

Kayla L. Conner*, Asra N. Shaik*, Elmira Ekinci*, Seongho Kim, Julie J. Ruterbusch, Michele L. Cote, Steve M. Patrick. HPV induction of APOBEC3 enzymes mediate overall survival and response to cisplatin in head and neck cancer. DNA Repair. 2020;87:102802.

Joshua Heyza*, Wen Lei*, Donovan Watza, Hao Zhang*, Wei Chen, Jessica B. Back, Ann G. Schwartz, Gerold Bepler and Steve M. Patrick. Identification and characterization of synthetic viability with ERCC1 deficiency in response to interstrand crosslinks in lung cancer. Clinical Cancer Research (AACR) 2019;25:2523-36.

Sanjeevani Arora*, Joshua Heyza*, Hoa Ellen Zhang*, Kayla Conner*, Wen Lei*, Ashley Floyd*, Rahul Deshmukh, Jeffrey Sarver, Christopher Trabbic, Paul Erhardt, TakHan Chan, Q. Ping Dou, Steve M. Patrick. Targeting the DNA Repair Endonuclease ERCC1-XPF with Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCG) and Its Prodrug to Enhance Cisplatin Efficacy in Human Cancer Cells. Nutrients. 2018;10:E1644.

Sanjeevani Arora*, Joshua Heyza*, Elaine Chalfin*, RJ Ruch, Steve M. Patrick. Gap Junction Intercellular Communication Positively Regulates Cisplatin Toxicity by Inducing DNA Damage through Bystander Signaling. Cancers (Basel). 2018;10:E368.

Akshada Sawant*, Ashley M. Floyd*, Mohan Dangeti*, Wen Lei*, Robert W. Sobol and Steve M. Patrick. Differential Role of Base Excision Repair Proteins in Mediating Cisplatin Cytotoxicity. DNA Repair. 2017;51:46-59.

 

 

 

 

 

Selected publications:

Sanjeevani Arora*, Joshua Heyza*, Hao Zhang*, Vivian Kalman-Maltese, Kristin Tillison, Ashley M. Floyd*, Elaine M. Chalfin, Gerold Bepler and Steve M. Patrick. Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells. Oncotarget, 2016;7:75104-17.

Akshada Sawant*, Anbarasi Kothandapani*, Anatoly Zhitkovich, Robert W. Sobol and Steve M. Patrick. Role of Mismatch Repair Proteins in the Processing of Cisplatin Interstrand Cross-Links. DNA Repair. 2015;35:126-36.

Anbarasi Kothandapani, Akshada Sawant, Venkata Srinivas Mohan Nimai Dangeti, Robert W. Sobol, and Steve M. Patrick. Epistatic role of base excision repair and mismatch repair pathways in mediating cisplatin cytotoxicity. Nucleic Acids Research. 2013;41:7332-43.

 

Anbarasi Kothandapani and Steve M. Patrick. Evidence For Base Excision Repair Processing of DNA Interstrand Crosslinks. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Invited Review Article. 2013;743-744:44-52.

Moises Serrano, Zhengke Li, Venkata Srinivas Mohan Nimai Dangeti, Phillip Musich, Steve M. Patrick, Marina Roginskaya, Brian Cartwright, and Yue Zou. DNA-PK, ATM and ATR collaboratively regulate p53-RPA interaction to facilitate homologous recombination DNA repair. Oncogene. 2013;32:2452-62.

Anbarasi Kothandapani, Kathirvel Gopalakrishnan, Bhaskar Kahali, David Reisman and Steve M. Patrick. Downregulation of SWI/SNF chromatin remodeling factor subunits modulate cisplatin cytotoxicity. Experimental Cell Research. 2012; 318:1973-86.

Anbarasi Kothandapani, Venkata Srinivas Mohan Nimai Dangeti, Ashley R. Brown, Lauren A. Banze, Xiao-Hong Wang, Robert W. Sobol and Steve M. Patrick. Novel Role of Base Excision Repair (BER) in Mediating Cisplatin Cytotoxicity. Journal of Biological Chemistry. 2011;286:14564-74.

Saravanan Kaliyaperumal, Steve M. Patrick, and Kandace J. Williams. Phosphorylated hMSH6: DNA mismatch versus DNA damage recognition. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2011;706:36-45.

Sanjeevani Arora, Anbarasi Kothandapani, Kristin Tillison Vivian Kalman-Maltese and Steve M. Patrick. Downregulation of the XPF-ERCC1 complex enhances cisplatin efficacy in cancer cells. DNA Repair. 2010;9:745-53.

Greg G. Oakley and Steve M. Patrick. Replication Protein A: Directing the traffic at the intersection of replication and repair. (Invited Review) Frontiers in Bioscience. 2010;15:883-900.

Greg G. Oakley, Kristin Tillison, Stephen A. Opiyo, Jason G. Glanzer, Jeffrey M. Horn, and Steve M. Patrick. Physical Interaction between Replication Protein A (RPA) and MRN: Involvement of RPA2 Phosphorylation and the N-Terminus of RPA1. Biochemistry. 2009;48:7473-81.

Allen G. Schroering, Anbarasi Kothandapani, Steve M. Patrick, Saravanan Kaliyaperumal and Kandace J. Williams. Prolonged cell cycle response of HeLa cells to low-level alkylation exposure. Cancer Research. 2009;69:6307-14.

 

 

 

 

Education/Training:

B.S., 1994, Urbana University, Urbana, OH.
Ph.D., 1999, Wright State University, Dayton, OH.
Postdoctoral Fellow, 1999-2002, John J. Turchi's Lab, Wright State University, Dayton, OH.
 

Courses Taught:

CB7240 Principles of Cancer Therapy
CB7300 Special Topics F31 Grant Writing Course
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling
CB7890 Seminar (Course Co-Director)
 

Stephan Matthew Patrick

Oncology

Position Title:

Professor
Basic Science

Office Location:

Karmanos Cancer Institute
4100 John R.
Mail Code: HW05A2
Detroit, MI 48201

Office Phone: 313-576-8335
Office Fax: 313-576-8928
Education Training:

Education
(1994 - 1999)  Ph.D. Biochemistry & Molecular Biology, Wright State University, Dayton, OH
(1990 - 1994)  B.S. Comprehensive Science (Biology/Chemistry), Urbana University, Urbana, OH

Postgraduate Training
(1999 - 2002)  Postdoctoral Fellow, Biochemistry & Molecular Biology, Wright State University, Dayton, OH

Professional Experience:

Faculty Appointments
(2020 - Present) Professor (with Tenure), Molecular Therapeutics & Cancer Biology, Department of Oncology, Wayne State University School of Medicine, Detroit, MI
(2014 - 2020)  Associate Professor (with Tenure), Molecular Therapeutics & Cancer Biology, Department of Oncology, Wayne State University School of Medicine, Detroit, MI
(2011 - 2014)  Associate Professor (with Tenure), Biochemistry & Cancer Biology, University of Toledo College of Medicine (formerly Medical University of Ohio), Toledo, OH
(2006 - 2010)  Assistant Professor, Biochemistry & Cancer Biology, University of Toledo College of Medicine (formerly Medical University of Ohio), Toledo, OH
(2002 - 2006)  Assistant Professor, Depatment of Biochemistry & Molecular Biology, School of Medicine, Wright State University, Dayton, OH

Hospital or Other Professional Appointments
(2014 - Present)  Member, Karmanos Cancer Institute, Detroit, MI
(1995 - 1996)  Graduate Teaching Assistant, Department of Biochemistry & Molecular Biology, School of Medicine, Wright State University, Dayton, OH
(1994 - 1999)  Graduate Research Assistant, Department of Biochemistry & Molecular Biology, School of Medicine, Wright State University, Dayton, OH

Honors and Awards:

(2012)  College of Medicine and Life Sciences Dean's Award for Research
(2011)  Discover Award from the Ohio Cancer Research Associates
(2001)  Sigma Xi Award for Outstanding Postdoc Oral Presentation, Molecular Biology Retreat, Wright State University, Dayton, OH
(1998)  Outstanding Oral Presentation, Molecular Biology Retreat, Wright State University, Dayton, OH
(1996)  Sigma Xi Award for Outstanding Oral Presentation, Molecular Biology Retreat, Wright State University, Dayton, OH
(1995)  Sigma Xi Award for Outstanding Oral Presentation, Runner-up, Molecular Biology Retreat, Wright State University, Dayton, OH

Courses taught:

CB 7240: Cancer Chemotherapy
CB 7300 F31: Special Topics in Cancer Biology - Grant Writing
CB 7460: Mechanisms of Neoplasia - Alterations to Cellular Signaling
CB 7700: Cancer Biology Journal Club
CB 7890: Seminar Course in Cancer Biology

Research Interests:
  • Elucidating mechanisms of drug resistance in specific cancers with DNA repair defects
  • Targeting DNA repair pathways to enhance platinum based chemotherapy
  • Assessing the role of ERCC1 isoforms and p53 status in mediating platinum-based chemotherapy response
  • Assessing synthetic lethality with ATR inhibition for novel lung cancer treatment
  • Elucidating the role of the bystander effect in platinum resistance and how DNA damage and the DNA damage response pathway mediates the bystander effect
  • Elucidating the mechanism of how chromatin remodelers mediate cisplatin DNA repair and drug sensitivity.
Publications:

1. Akshada Sawant, Ashley M. Floyd, Mohan Dangeti, Wen Lei, Robert W. Sobol and Steve M. Patrick. (2016) Differential Role of Base Excision Repair Proteins in Mediating Cisplatin Cytotoxicity. DNA Repair, http://dx.doi.org/10.1016/j.dnarep.2017.01.002.

2. Sanjeevani Arora, Joshua Heyza, Hao Zhang, Vivian Kalman-Maltese, Kristin Tillison, Ashley M. Floyd, Elaine M. Chalfin, Gerold Bepler and Steve M. Patrick. (2016) Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells. Oncotarget, DOI: 10.18632/oncotarget.12072.

3. Akshada Sawant, Anbarasi Kothandapani, Anatoly Zhitkovich, Robert W. Sobol and Steve M. Patrick. (2015) Role of Mismatch Repair Proteins in the Processing of Cisplatin Interstrand Cross-Links. DNA Repair, 35, 126-136.

4. Gerold, Bepler, Wei Chen, Steve Patrick, Stephanie Astrow, Craig Stephens, David Gandara, Rafael Rosell, Jose Luis Ramirez, Giorgio Scagliotti, Simone Busso, Marco Volante, Silvia Novello. (2015) Validation of ERCC1 (E1) for response prediction to platinum-gemcitabine. Journal of Clinical Oncology, 33, 15, 8036.

5. Anbarasi Kothandapani, Akshada Sawant, Venkata Srinivas Mohan Nimai Dangeti, Robert W. Sobol and Steve M. Patrick. (2013) Epistatic role of base excision repair and mismatch repair pathways in mediating cisplatin cytotoxicity. Nucleic Acids Research, 41, 7332-7343. PMCID: PMC3753620

6. Anbarasi Kothandapani and Steve M. Patrick. (2013) Evidence for Base Excision Repair Processing of DNA Interstrand Crosslinks. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Invited Review Article, 743-744, 44-52. PMC3637959

7. Moises Serrano, Zhengke Li, Venkata Srinivas Mohan Nimai Dangeti, Phillip Musich, Steve M. Patrick, Marina Roginskaya, Brian Cartwright and Yue Zou. (2013) DNA-PK, ATM and ATR collaboratively regulate p53-RPA interaction to facilitate homologous recombination DNA repair. Oncogene, 32, 2452-2462. PMC3651755

8. Anbarasi Kothandapani, Kathirvel Gopalakrishnan, Bhaskar Kahali, David Reisman and Steve M. Patrick (2012) Downregulation of SWI/SNF chromatin remodeling factor subunits modulate cisplatin cytotoxicity. Experimental Cell Research, 318, 1973-1986. PMC3408789

9. Anbarasi Kothandapani, Venkata Srinivas Mohan Nimai Dangeti, Ashley R. Brown, Lauren A. Banze, Xiao-Hong Wang, Robert W. Sobol and Steve M. Patrick. (2011) Novel Role of Base Excision Repair (BER) in Mediating Cisplatin Cytotoxicity. Journal of Biological Chemistry, 286, 14564-14574. PMC3408789

10. Saravanan Kaliyaperumal, Steve M. Patrick and Kandace J. Williams. (2011) Phosphorylated hMSH6: DNA mismatch versus DNA damage recognition. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 706, 36-45. PMC3010429

Complete List of Published Work in MyBibliography

Faculty Status: Basic Science
Stephan Matthew Patrick

Courses taught by Stephan Matthew Patrick

Fall Term 2024 (future)

Winter Term 2024 (current)

Fall Term 2023

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Winter Term 2023

Fall Term 2022

Spring-Summer Term 2022

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