Joseph Geradts

East Carolina University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Charles M. Perou

University of North Carolina at Chapel Hill

Melissa A. Troester

University of North Carolina at Chapel Hill

Robert C. Millikan

University of North Carolina at Chapel Hill

Lisa A. Carey

University of North Carolina at Chapel Hill

Andrew F. Olshan

University of North Carolina at Chapel Hill

Xuezheng Sun

Triangle

Chiu‐Kit Tse

University of North Carolina at Chapel Hill

Kathleen Conway

University of North Carolina at Chapel Hill

Lynn G. Dressler

University of North Carolina at Chapel Hill

Chad Livasy

Levine Cancer Institute

Cooperative Institutions

Duke University

240

Duke Medical Center

209

University of North Carolina at Chapel Hill

165

Dana-Farber Cancer Institute

139

Duke University Hospital

138

Harvard University

108

Roswell Park Comprehensive Cancer Center

UNC Lineberger Comprehensive Cancer Center

National Institutes of Health

Johns Hopkins University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Supplementary Figure S1 from CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer

Mahmoud A. Alfaqih Erik R. Nelson Wen Liu Rachid Safi Jeffery S. Jasper

<p>LDL enhances PC cell growth and assessment of CYP27A1 expression levels in different stages of PC</p>

CYP27A1

Homeostasis

10.1158/0008-5472.22416114

Cite

Citations (0)

Inverse association between MDM2 and HUWE1 protein expression levels in human breast cancer and liposarcoma.

PubMed (2016)

Kaleigh Canfield Wendy A. Wells Joseph Geradts William B. Kinlaw Chao Cheng

The ubiquitin E3 ligase MDM2 is best known for its ability to suppress the tumor suppressor p53. However, MDM2 also targets other proteins for proteasomal degradation and accumulating evidence strongly suggests p53-independent roles of MDM2 in cancer. We previously reported that MDM2 promotes degradation of another ubiquitin E3 ligase HUWE1 by ubiquitination, particularly, which confers HER2+ breast cancer cells resistance to the HER2 inhibitor lapatinib. However, it remains unclear whether such a mechanism can operate in other cell types, independently of HER2 inhibitors. Moreover, in vivo evidence that supports HUWE1 degradation by MDM2 is missing. In the current study, we performed immunohistochemistry (IHC) to analyze expression levels of MDM2 and HUWE1 in normal organs, two breast cancer cohorts (A, n = 137 and B, n = 27), and a liposarcoma cohort (n = 45). Our results show that HUWE1 is ubiquitously expressed in healthy organs, where the oncoprotein MDM2 is undetectable. Likewise, in the majority of breast cancers regardless of their subtypes, MDM2 is below detectable levels, while HUWE1 is highly expressed. In contrast, in a subset of liposarcoma that is characterized by MDM2 overexpression, only 40% of these showed detectable HUWE1 protein. Importantly, despite the inverse association between MDM2 and HUWE1 protein levels, gene expression analysis in independent datasets revealed no such correlation at the mRNA level. Our results demonstrate the first in vivo evidence to support the hypothesis of MDM2-mediated HUWE1 degradation, which may help to understand the regulation of HUWE1 as well as p53-independent roles of MDM2.

Protein Degradation

Source

Cite

Citations (9)

Supplementary Materials and Methods. Immunohistochemical staining and automated analysis methods from Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium

Emma H. Allott Stephanie M. Cohen Joseph Geradts Xuezheng Sun Thaer Khoury

<p>This file describes immunohistochemistry staining for ER, PR and HERs in tissue microarrays, in addition to automated quantification of staining.</p>

Subtyping

Tissue microarray

10.1158/1055-9965.22436335

Cite

Citations (0)

Nuclear Snail1 and nuclear ZEB1 protein expression in invasive and intraductal human breast carcinomas

Human Pathology (2011)

Joseph Geradts Antonio Garcı́a de Herreros Zuowei Su James L. Burchette Gloria Broadwater

Breast carcinoma

Tumor progression

Progesterone receptor

10.1016/j.humpath.2010.11.004

Cite

Citations (48)

Expression of the candidate tumor suppressor gene hSRBC is frequently lost in primary lung cancers with and without DNA methylation

Oncogene (2005)

Sabine Zöchbauer‐Müller Kwun M. Fong Joseph Geradts Xie L. Xu Sonja Seidl

Demethylating agent

Bisulfite sequencing

10.1038/sj.onc.1208775

Cite

Citations (42)

A randomized phase II trial evaluating the performance of genomic expression profiles to direct the use of preoperative chemotherapy for early-stage breast cancer.

Journal of Clinical Oncology (2010)

P. Kelly Marcom WT Barry M. B. Datto Joseph Geradts John A. Olson

TPS102 Background: Genomic assays have been shown to provide the potential for personalized approaches to breast cancer therapy. Full-transcriptome assays using microarrays are challenging, but have the advantage of providing multiple prognostic and predictive signatures in one assay. We have developed genomic predictive signatures for various clinically relevant cancer characteristics, including sensitivity to cytotoxic chemotherapies. We have investigated the analytic performance of these signatures in biologic replicates, and begun applying them in this prospective randomized clinical trial. Methods: Eligible patients have intact HER2 negative primary breast cancers with tumor size over 1.5 cm and any clinical lymph node status. A fresh frozen sample of the primary tumor must be obtained. After pathology assessment, RNA is analyzed on an Affymetrix H133 Plus 2.0 microarray. The expression data is used to predict doxorubicin (A) and docetaxel (T) sensitivity using previously defined signatures and analytic techniques developed to make one-at-a-time predictions from microarray data. Patients are then assigned to four cycles of standard doxorubicin/cyclophosphamide (AC) or docetaxel/cyclphosphamide (TC) chemotherapy in a blinded process randomizing in a 1:2 ratio to a control arm (random assignment to either AC or TC) or a genomically guided (GG) chemotherapy arm. In the GG arm, patients are assigned to AC or TC treatment if the predicted sensitivity is over 0.6 for A or T, respectively. If predictions for both agents are over 0.6, the higher score is used; if both scores are below 0.6, patients are randomly assigned to AC or TC. The primary endpoint is pathologic complete response (pCR) in the breast, with the primary objectives: 1) determine whether genomic profiling for drug-sensitivity can improve the pCR rate as compared to randomly assigned therapy; and 2) determine whether genomic profiling can identify drug-sensitive and drug-resistant patients including a comparison of subgroups for the two individual regimens. The accrual goal is 270 patients randomized; currently, 42 patients have been consented and 32 randomized. No significant financial relationships to disclose.

10.1200/jco.2010.28.15_suppl.tps102

Cite

Citations (2)

Prostate-derived Ets factor, an oncogenic driver in breast cancer

Tumor Biology (2017)

Ashwani Sood Joseph Geradts Jessica Young

Prostate-derived Ets factor (PDEF), a member of the Ets family of transcription factors, differs from other family members in its restricted expression in normal tissues and its unique DNA-binding motif. These interesting attributes coupled with its aberrant expression in cancer have rendered PDEF a focus of increasing interest by tumor biologists. This review provides a current understanding of the characteristics of PDEF expression and its role in breast cancer. The bulk of the evidence is consistent with PDEF overexpression in most breast tumors and an oncogenic role for this transcription factor in breast cancer. In addition, high PDEF expression in estrogen receptor–positive breast tumors showed significant correlation with poor overall survival in several independent cohorts of breast cancer patients. Together, these findings demonstrate PDEF to be an oncogenic driver of breast cancer and a biomarker of poor prognosis in this cancer. Based on this understanding and the limited expression of PDEF in normal human tissues, the development of PDEF–based therapeutics for prevention and treatment of breast cancer is also discussed.

10.1177/1010428317691688

Cite

Citations (12)

JOINT AND INDIVIDUAL ANALYSIS OF BREAST CANCER HISTOLOGIC IMAGES AND GENOMIC COVARIATES

Carolina Digital Repository (University of North Carolina at Chapel Hill) (2021)

I Carmichael B.C Calhoun Katherine A. Hoadley M.A Troester Joseph Geradts

10.17615/59fa-j629

Cite

Citations (0)

Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma

Journal of Gastrointestinal Surgery (2004)

Neal Wilkinson Jennifer D. Black Elena V. Roukhadze Deborah A. Driscoll Shannon Smiley

Lymphadenectomy

Esophagectomy

10.1016/j.gassur.2004.01.006

Cite

Citations (90)

The comprehensive role of E-cadherin in maintaining prostatic epithelial integrity during oncogenic transformation and tumor progression

PLoS Genetics (2019)

Adam W. Olson Vien Le Joseph Aldahl Eun‐Jeong Yu Erika Hooker

E-cadherin complexes with the actin cytoskeleton via cytoplasmic catenins and maintains the functional characteristics and integrity of the epithelia in normal epithelial tissues. Lost expression of E-cadherin disrupts this complex resulting in loss of cell polarity, epithelial denudation and increased epithelial permeability in a variety of tissues. Decreased expression of E-cadherin has also been observed in invasive and metastatic human tumors. In this study, we investigated the effect of E-cadherin loss in prostatic epithelium using newly developed genetically engineered mouse models. Deletion of E-cadherin in prostatic luminal epithelial cells with modified probasin promoter driven Cre (PB-Cre4) induced the development of mouse prostatic intraepithelial neoplasia (PIN). An increase in levels of cytoplasmic and nuclear β-catenin appeared in E-cadherin deleted atypical cells within PIN lesions. Using various experimental approaches, we further demonstrated that the knockdown of E-cadherin expression elevated free cytoplasmic and nuclear β-catenin and enhanced androgen-induced transcription and cell growth. Intriguingly, pathological changes representing prostatic epithelial cell denudation and increased apoptosis accompanied the above PIN lesions. The essential role of E-cadherin in maintaining prostatic epithelial integrity and organization was further demonstrated using organoid culture approaches. To directly assess the role of loss of E-cadherin in prostate tumor progression, we generated a new mouse model with bigenic Cdh1 and Pten deletion in prostate epithelium. Early onset, aggressive tumor phenotypes presented in the compound mice. Strikingly, goblet cell metaplasia was observed, intermixed within prostatic tumor lesions of the compound mice. This study provides multiple lines of novel evidence demonstrating a comprehensive role of E-cadherin in maintaining epithelial integrity during the course of prostate oncogenic transformation, tumor initiation and progression.

Organoid

10.1371/journal.pgen.1008451

Cite

Citations (24)