Steven Patierno

Overview:

Patierno's current translational research interests are focused on the genomics molecular biology of cancer disparities, cancer biology, molecular pharmacology and targeted experimental therapeutics to control prostate, breast and lung tumor aggressiveness. He is an internationally recognized expert in cancer control, cancer causation and molecular carcinogenesis, which includes a broad spectrum of laboratory and population level research.   Patierno is also actively engaged in cancer health disparities and healthcare delivery research focused on patient navigation, survivorship, community-based interventions, mHealth, implementation sciences, cancer care economics, and policy.

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Professor in Family Medicine and Community Health

Family Medicine and Community Health
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1981

University of Connecticut

Ph.D. 1985

University of Texas Medical School at Houston

Postdoctoral Training, Norris Comprehensive Cancer

University of Southern California

Grants:

2/2 NCCU-DUKE Cancer Disparities Translational Research Partnership

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Detection of Novel Alternative Splicing Biomarkers of Hypoxia in Breast and Lung Tumors

Administered By
Radiation Oncology
Role
Mentor
Start Date
End Date

2/2 NCCU-DUKE Cancer Disparities Translational Research Partnership

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Non-CME Educational Oncological Immersion Experience

Administered By
Medicine, Medical Oncology
Role
Principal Investigator
Start Date
End Date

Publications:

Perspectives on Inflammatory Breast Cancer (IBC) Research, Clinical Management and Community Engagement from the Duke IBC Consortium.

Inflammatory breast cancer (IBC) is an understudied and aggressive form of breast cancer with a poor prognosis, accounting for 2-6% of new breast cancer diagnoses but 10% of all breast cancer-related deaths in the United States. Currently there are no therapeutic regimens developed specifically for IBC, and it is critical to recognize that all aspects of treating IBC - including staging, diagnosis, and therapy - are vastly different than other breast cancers. In December 2014, under the umbrella of an interdisciplinary initiative supported by the Duke School of Medicine, researchers, clinicians, research administrators, and patient advocates formed the Duke Consortium for IBC to address the needs of patients in North Carolina (an ethnically and economically diverse state with 100 counties) and across the Southeastern United States. The primary goal of this group is to translate research into action and improve both awareness and patient care through collaborations with local, national and international IBC programs. The consortium held its inaugural meeting on Feb 28, 2018, which also marked Rare Disease Day and convened national research experts, clinicians, patients, advocates, government representatives, foundation leaders, staff, and trainees. The meeting focused on new developments and challenges in the clinical management of IBC, research challenges and opportunities, and an interactive session to garner input from patients, advocates, and community partners that would inform a strategic plan toward continuing improvements in IBC patient care, research, and education.
Authors
Devi, GR; Hough, H; Barrett, N; Cristofanilli, M; Overmoyer, B; Spector, N; Ueno, NT; Woodward, W; Kirkpatrick, J; Vincent, B; Williams, KP; Finley, C; Duff, B; Worthy, V; McCall, S; Hollister, BA; Palmer, G; Force, J; Westbrook, K; Fayanju, O; Suneja, G; Dent, SF; Hwang, ES; Patierno, SR; Marcom, PK
MLA Citation
Devi, Gayathri R., et al. “Perspectives on Inflammatory Breast Cancer (IBC) Research, Clinical Management and Community Engagement from the Duke IBC Consortium..” J Cancer, vol. 10, no. 15, 2019, pp. 3344–51. Pubmed, doi:10.7150/jca.31176.
URI
https://scholars.duke.edu/individual/pub1395729
PMID
31293637
Source
pubmed
Published In
Journal of Cancer
Volume
10
Published Date
Start Page
3344
End Page
3351
DOI
10.7150/jca.31176

Race-related differential splicing of the insulin receptor: A novel target underlying prostate cancer disparities

Authors
Deveaux, A; Wang, B-D; Lacroix, B; Patierno, B; Zhang, D; Owzar, K; Lee, N; George, D; Freedman, J; Patierno, S
MLA Citation
Deveaux, April, et al. “Race-related differential splicing of the insulin receptor: A novel target underlying prostate cancer disparities.” Cancer Epidemiology Biomarkers & Prevention, vol. 27, no. 7, AMER ASSOC CANCER RESEARCH, 2018, pp. 138–39.
URI
https://scholars.duke.edu/individual/pub1333238
Source
wos
Published In
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Volume
27
Published Date
Start Page
138
End Page
139

Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.

PURPOSE: African Americans (AA) exhibit higher rates of prostate cancer incidence and mortality compared with European American (EA) men. In addition to socioeconomic influences, biologic factors are believed to play a critical role in prostate cancer disparities. We investigated whether population-specific and -enriched miRNA-mRNA interactions might contribute to prostate cancer disparities. EXPERIMENTAL DESIGN: Integrative genomics was used, combining miRNA and mRNA profiling, miRNA target prediction, pathway analysis, and functional validation, to map miRNA-mRNA interactions associated with prostate cancer disparities. RESULTS: We identified 22 AA-specific and 18 EA-specific miRNAs in prostate cancer versus patient-matched normal prostate, and 10 "AA-enriched/-depleted" miRNAs in AA prostate cancer versus EA prostate cancer comparisons. Many of these population-specific/-enriched miRNAs could be paired with target mRNAs that exhibited an inverse pattern of differential expression. Pathway analysis revealed EGFR (or ERBB) signaling as a critical pathway significantly regulated by AA-specific/-enriched mRNAs and miRNA-mRNA pairings. Novel miRNA-mRNA pairings were validated by qRT-PCR, Western blot, and/or IHC analyses in prostate cancer specimens. Loss/gain of function assays performed in population-specific prostate cancer cell lines confirmed miR-133a/MCL1, miR-513c/STAT1, miR-96/FOXO3A, miR-145/ITPR2, and miR-34a/PPP2R2A as critical miRNA-mRNA pairings driving oncogenesis. Manipulating the balance of these pairings resulted in decreased proliferation and invasion, and enhanced sensitization to docetaxel-induced cytotoxicity in AA prostate cancer cells. CONCLUSIONS: Our data suggest that AA-specific/-enriched miRNA-mRNA pairings may play a critical role in the activation of oncogenic pathways in AA prostate cancer. Our findings also suggest that miR-133a/MCL1, miR-513c/STAT1, and miR-96/FOXO3A may have clinical significance in the development of novel strategies for treating aggressive prostate cancer.
Authors
Wang, B-D; Ceniccola, K; Yang, Q; Andrawis, R; Patel, V; Ji, Y; Rhim, J; Olender, J; Popratiloff, A; Latham, P; Lai, Y; Patierno, SR; Lee, NH
MLA Citation
Wang, Bi-Dar, et al. “Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities..” Clin Cancer Res, vol. 21, no. 21, Nov. 2015, pp. 4970–84. Pubmed, doi:10.1158/1078-0432.CCR-14-1566.
URI
https://scholars.duke.edu/individual/pub1099172
PMID
26089375
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
21
Published Date
Start Page
4970
End Page
4984
DOI
10.1158/1078-0432.CCR-14-1566

Protein tyrosine phosphatase (PTP) inhibition enhances chromosomal stability after genotoxic stress: decreased chromosomal instability (CIN) at the expense of enhanced genomic instability (GIN)?

Inappropriate survival signaling after DNA damage may facilitate clonal expansion of genetically compromised cells, and it is known that protein tyrosine phosphatase (PTP) inhibitors activate key survival pathways. In this study we employed the genotoxicant, hexavalent chromium [Cr(VI)], which is a well-documented carcinogen of occupational and environmental concern. Cr(VI) induces a complex array of DNA damage, including DNA double strand breaks (DSBs). We recently reported that PTP inhibition bypassed cell cycle arrest and abrogated Cr(VI)-induced clonogenic lethality. Notably, PTP inhibition resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of DNA damage may lead to genomic instability (GIN), via cell cycle checkpoint bypass. The aim of the present study was to determine the effect of PTP inhibition on DNA DSB formation and chromosomal integrity after Cr(VI) exposure. Diploid human lung fibroblasts were treated with Cr(VI) in the presence or absence of the PTP inhibitor, sodium orthovanadate, for up to 24h, and cells were analyzed for DNA DSBs and chromosomal damage. Cr(VI) treatment induced a rapid increase in DNA DSBs, and a significant increase in total chromosomal damage (chromatid breaks and gaps) after 24h. In sharp contrast, PTP inhibition abrogated both DNA DSBs and chromosomal damage after Cr(VI) treatment. In summary, PTP inhibition in the face of Cr(VI) genotoxic stress decreases chromosomal instability (CIN) but increases mutagenesis, which we postulate to be a result of error-prone DNA repair.
Authors
Kost, GC; Patierno, SR; Wise, SS; Holmes, AL; Wise, JP; Ceryak, S
MLA Citation
URI
https://scholars.duke.edu/individual/pub985010
PMID
22583656
Source
pubmed
Published In
Mutation Research
Volume
735
Published Date
Start Page
51
End Page
55
DOI
10.1016/j.mrfmmm.2012.05.001

AKT1 mediates bypass of the G1/S checkpoint after genotoxic stress in normal human cells.

Certain forms of hexavalent chromium [Cr(VI)] are human carcinogens. Our recent work has shown that a broad range protein tyrosine phosphatase (PTP) inhibitor, sodium orthovanadate (SOV), abrogated both Cr(VI)-induced growth arrest and clonogenic lethality. Notably, SOV enhanced Cr(VI) mutation frequency, ostensibly through forced survival of genetically damaged cells. In the present study, co-treatment with this PTP inhibitor bypassed the Cr(VI)-induced G(1)/S checkpoint arrest in diploid human lung fibroblasts (HLF). Moreover, the PTP inhibitor abrogated the Cr(VI)-induced decrease in the expression of key effectors of the G(1)/S checkpoint [Cyclin D1, phospho Ser 807/811 Rb (pRB), p27]. Cr(VI)-induced G(1) arrest was associated with the cytoplasmic appearance of pRb and the nuclear localization of p27, both of which were reversed by the PTP inhibitor. The PTP inhibitor's reversal of G(1)/S checkpoint effector localization after Cr exposure was found to be Akt1-dependent, as this was abrogated by transfection with either akt1 siRNA or an Akt1-kinase dead plasmid. Furthermore, Akt1 activation alone was sufficient to induce G(1)/S checkpoint bypass and to prevent Cr(VI)-induced changes in pRb and p27 localization. In conclusion, this work establishes Akt1 activation to be both sufficient to bypass the Cr(VI)-induced G(1)/S checkpoint, as well as necessary for the observed PTP inhibitor effects on key mediators of the G(1)/S transition. The potential for Akt to bypass G(1)/S checkpoint arrest in the face of genotoxic damage could increase genomic instability, which is a hallmark of neoplastic progression.
Authors
Lal, MA; Bae, D; Camilli, TC; Patierno, SR; Ceryak, S
MLA Citation
Lal, Madhu A., et al. “AKT1 mediates bypass of the G1/S checkpoint after genotoxic stress in normal human cells..” Cell Cycle, vol. 8, no. 10, May 2009, pp. 1589–602. Pubmed, doi:10.4161/cc.8.10.8547.
URI
https://scholars.duke.edu/individual/pub985024
PMID
19377290
Source
pubmed
Published In
Cell Cycle
Volume
8
Published Date
Start Page
1589
End Page
1602
DOI
10.4161/cc.8.10.8547