Shannon McCall

Overview:

As Vice Chair for Translational Research in the Department of Pathology, I am involved in numerous translational cancer research projects that rely on the study of human biological samples.  I am the director of the Duke BioRepository & Precision Pathology Center (Duke BRPC), a shared resource of the School of Medicine and the Duke Cancer Institute.  I serve as the PI for the National Cancer Institute's Cooperative Human Tissue Network Southern Division (a five-year UM1 grant), which lives in the Duke BRPC.  My own area of research interest is gastrointestinal tract metaplasias and their relationship to carcinogenesis, particularly in the upper GI tract.

Positions:

Associate Professor of Pathology

Pathology
School of Medicine

Associate Professor in Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1996

North Carolina State University

M.D. 2000

Duke University

Anatomic and Clinical Pathology, American Board of Pathology (ABPath)

American Board of Pathology

Clinical Informatics, American Board of Pathology (ABPath)

American Board of Pathology

Resident, Pathology

Duke University

Chief Resident, Pathology

Duke University

Grants:

Mutation analysis of pap smear samples and associated tissues for ovarian cancer diagnostics

Administered By
Pathology
Awarded By
Genendeavor LLC
Role
Principal Investigator
Start Date
End Date

Cooperative Human Tissue Network Support through Duke's BioRepository & Precision Pathology Center

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

The genetics of hepatosplenic T cell lymphoma

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Empowering Duke's Precision Pathology Center with Quantitative Image Analysis to Support Discovery, Diagnostic Assay Development, and Immune Cell Monitoring

Administered By
Pathology
Awarded By
North Carolina Biotechnology Center
Role
Principal Investigator
Start Date
End Date

Lung Squamous Cell Carcinoma: Validation of Molecular Signatures of Prognosis

Awarded By
University of Colorado - Denver
Role
Pathologist
Start Date
End Date

Publications:

Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients

© 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. Background: Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice. Methods: Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome. Results: For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%). Conclusions: Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings.
Authors
Zhang, T; Pabla, S; Lenzo, FL; Conroy, JM; Nesline, MK; Glenn, ST; Papanicolau-Sengos, A; Burgher, B; Giamo, V; Andreas, J; Wang, Y; Bshara, W; Madden, KG; Shirai, K; Dragnev, K; Tafe, LJ; Gupta, R; Zhu, J; Labriola, M; McCall, S; George, DJ; Ghatalia, P; Dayyani, F; Edwards, R; Park, MS; Singh, R; Jacob, R; George, S; Xu, B; Zibelman, M; Kurzrock, R; Morrison, C
MLA Citation
Zhang, T., et al. “Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients.” Oncoimmunology, vol. 9, no. 1, Jan. 2020. Scopus, doi:10.1080/2162402X.2020.1773200.
URI
https://scholars.duke.edu/individual/pub1449567
Source
scopus
Published In
Oncoimmunology
Volume
9
Published Date
DOI
10.1080/2162402X.2020.1773200

The Project Baseline Health Study: a step towards a broader mission to map human health.

The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.
Authors
Arges, K; Assimes, T; Bajaj, V; Balu, S; Bashir, MR; Beskow, L; Blanco, R; Califf, R; Campbell, P; Carin, L; Christian, V; Cousins, S; Das, M; Dockery, M; Douglas, PS; Dunham, A; Eckstrand, J; Fleischmann, D; Ford, E; Fraulo, E; French, J; Gambhir, SS; Ginsburg, GS; Green, RC; Haddad, F; Hernandez, A; Hernandez, J; Huang, ES; Jaffe, G; King, D; Koweek, LH; Langlotz, C; Liao, YJ; Mahaffey, KW; Marcom, K; Marks, WJ; Maron, D; McCabe, R; McCall, S; McCue, R; Mega, J; Miller, D; Muhlbaier, LH; Munshi, R; Newby, LK; Pak-Harvey, E; Patrick-Lake, B; Pencina, M; Peterson, ED; Rodriguez, F; Shore, S; Shah, S; Shipes, S; Sledge, G; Spielman, S; Spitler, R; Schaack, T; Swamy, G; Willemink, MJ; Wong, CA
MLA Citation
Arges, Kristine, et al. “The Project Baseline Health Study: a step towards a broader mission to map human health.Npj Digit Med, vol. 3, 2020, p. 84. Pubmed, doi:10.1038/s41746-020-0290-y.
URI
https://scholars.duke.edu/individual/pub1448045
PMID
32550652
Source
pubmed
Published In
Npj Digital Medicine
Volume
3
Published Date
Start Page
84
DOI
10.1038/s41746-020-0290-y

Prior tonsillectomy is associated with an increased risk of esophageal adenocarcinoma.

BACKGROUND: Esophageal cancer is a deadly cancer with 5-year survival <20%. Although multiple risk factors for esophageal adenocarcinoma (EAC) including obesity, GERD and smoking have been identified, these risk factors do not fully explain the rising incidence of EAC. In this study, we evaluated the association between prior history of tonsillectomy and EAC. Our goal was to determine whether tonsillectomies were more frequent in patients with EAC (cases) than in our thoracic surgery controls. METHODS: Cases included 452 esophagectomy cases, including 396 with EAC and 56 who underwent esophagectomy for Barrett's esophagus (BE) with high grade dysplasia (HGD). 1,102 thoracic surgery patients with surgical indications other than dysplastic BE or esophageal cancer represented the controls for our analysis. The association of tonsillectomy and HGD/EAC were primarily evaluated by using univariate tests and then verified by logistic regression analysis. Baseline demographics, medical history, and thoracic surgery controls were compared by using χ2 tests or 95% CIs. Significant risk factors were considered as covariates in the multivariate models while evaluating the association between tonsillectomy and HGD/EAC. P-values or odds ratios were estimated with 95% confidence limits to identify significances which was more appropriate. RESULTS: Tonsillectomy was more common in cases than controls and was found to have a significant association with esophageal cancer (19.9% vs. 12.7%; p-value = 0.0003). This significant association persisted after controlling for other known risk factors/covariates. CONCLUSION: A prior history of tonsillectomy was significantly associated with HGD/EAC and may represent an independent risk factor for the development of EAC. However, the underlying biology driving this association remains unclear.
Authors
Garman, KS; Ajayi, TA; Boutte, HJ; Chiu, S-T; von Furstenberg, RJ; Lloyd, BR; Zhang, C; Onaitis, MW; Chow, S-C; McCall, SJ
MLA Citation
Garman, Katherine S., et al. “Prior tonsillectomy is associated with an increased risk of esophageal adenocarcinoma.Plos One, vol. 15, no. 7, 2020, p. e0235906. Pubmed, doi:10.1371/journal.pone.0235906.
URI
https://scholars.duke.edu/individual/pub1452502
PMID
32697782
Source
pubmed
Published In
Plos One
Volume
15
Published Date
Start Page
e0235906
DOI
10.1371/journal.pone.0235906

Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer.

BACKGROUND: Metastatic colorectal cancer (CRC) continues to be a major health problem, and current treatments are primarily for disease control and palliation of symptoms. In this study, we developed a precision medicine strategy to discover novel therapeutics for patients with CRC. METHODS: Six matched low-passage cell lines and patient-derived xenografts (PDX) were established from CRC patients undergoing resection of their cancer. High-throughput drug screens using a 119 FDA-approved oncology drug library were performed on these cell lines, which were then validated in vivo in matched PDXs. RNA-Seq analysis was then performed to identify predictors of response. RESULTS: Our study revealed marked differences in response to standard-of-care agents across patients and pinpointed druggable pathways to treat CRC. Among these pathways co-targeting of fibroblast growth factor receptor (FGFR), SRC, platelet derived growth factor receptor (PDGFR), or vascular endothelial growth factor receptor (VEGFR) signaling was found to be an effective strategy. Molecular analyses revealed potential predictors of response to these druggable pathways. CONCLUSIONS: Our data suggests that the use of matched low-passage cell lines and PDXs is a promising strategy to identify new therapies and pathways to treat metastatic CRC.
Authors
Altunel, E; Roghani, RS; Chen, K-Y; Kim, SY; McCall, S; Ware, KE; Shen, X; Somarelli, JA; Hsu, DS
MLA Citation
Altunel, Erdem, et al. “Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer.Bmc Cancer, vol. 20, no. 1, June 2020, p. 592. Pubmed, doi:10.1186/s12885-020-07090-y.
URI
https://scholars.duke.edu/individual/pub1448846
PMID
32580713
Source
pubmed
Published In
Bmc Cancer
Volume
20
Published Date
Start Page
592
DOI
10.1186/s12885-020-07090-y

NanoString Gene Expression Profiling in Chronic Lung Allograft Dysfunction (CLAD)

Copyright © 2020. Published by Elsevier Inc. PURPOSE: CLAD, mainly manifest as bronchiolitis obliterans syndrome (BOS), is the leading cause of late death in lung recipients. BOS develops despite routine immunosuppression and its pathogenesis is poorly understood. The histological correlate of BOS is bronchiolitis obliterans (BO), or airways fibrosis. We quantified over 700 immune-related genes in BO affected airways to better understand immune responses active in end-stage BOS. METHODS: Formalin fixed paraffin embedded lung tissue was procured at retransplantation for BOS (n=6). Unused donor tissue was used as normal control (n=5). Histologies of interest were isolated using laser capture microdissection (LCMD). Within each BOS lung, airways histologically affected by BO pathology, defined as intraluminal fibrous expansion, were isolated. Additionally, airways unaffected by evident fibrosis were isolated. Within each donor lung, histologically normal airways were isolated. Cellular RNA was extracted and multiplex gene expression analysis was performed using the NanoString PanCancer Immune Profiling Panel. Linear regression was used to compare gene expression among groups. The primary comparison was differential expression in BO affected vs. normal donor airways. We also compared expression in BO affected vs. unaffected airways within BOS explant lungs. P-values were corrected for multiple comparisons using Benjamini-Hochberg. RESULTS: Sixty-seven genes were significantly different between BO affected vs. normal donor airways, of which 52 had a fold change (FC) <0.5 or >2. Along with genes in adaptive immunity, several genes related to innate and humoral activation were significantly increased in BO affected airways. Among the innate immune genes with increased expression in BO were toll-like receptor 1 (FC 2.31) and its adaptor molecule CD14 (FC 5.26) in addition to the complement subcomponent C1s (FC 3.06), while those in humoral immunity included bone marrow stromal antigen 2 (FC 3.41), important to the growth and development of B-cells. No genes were significantly differentially expressed between BO affected vs. unaffected airways within BOS explant lungs. CONCLUSION: Our results suggest innate and humoral immune responses are active in airways affected by BO pathology, and also in airways without evident fibrosis. Ongoing analyses of BO lesions through LCMD will provide new insights into CLAD pathogenesis.
Authors
Todd, JL; Kelly, FL; Neely, ML; Keslar, K; Pavlisko, EN; McCall, SJ; Fletcher, A; Chen, X; Frankel, CW; Singer, LG; Budev, M; Shah, PD; Belperio, JA; Snyder, LD; Reynolds, JM; Fairchild, RL; Palmer, SM
MLA Citation
Todd, J. L., et al. “NanoString Gene Expression Profiling in Chronic Lung Allograft Dysfunction (CLAD).” The Journal of Heart and Lung Transplantation : The Official Publication of the International Society for Heart Transplantation, vol. 39, no. 4, 2020, p. S113. Scopus, doi:10.1016/j.healun.2020.01.985.
URI
https://scholars.duke.edu/individual/pub1438058
Source
scopus
Published In
J Heart Lung Transplant
Volume
39
Published Date
Start Page
S113
DOI
10.1016/j.healun.2020.01.985

Research Areas:

Ampulla of Vater
Apoptosis
Bevacizumab
Bile Ducts
Biological Markers
Biopsy
Biopsy, Needle
Cell Differentiation
Cell Line
Cell Nucleus
Cell Proliferation
Cell Survival
Cells, Cultured
Colorectal Neoplasms
Colorectal Neoplasms, Hereditary Nonpolyposis
Cytochrome P-450 CYP2E1
Endocytosis
Epithelial Cells
Epithelial-Mesenchymal Transition
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
Hedgehog Proteins
Homeodomain Proteins
Humans
Hydroxyproline
Immunohistochemistry
Kruppel-Like Transcription Factors
Lasers
Mesenchymal Stromal Cells
Mesoderm
Microdissection
Mutation
Nuclear Proteins
Oligonucleotides, Antisense
Oligoribonucleotides, Antisense
Oncogenes
Organoplatinum Compounds
Pancreaticoduodenectomy
Pancreatitis
Pilot Projects
Prognosis
Protein Isoforms
Proteome
Proto-Oncogene Proteins
Proto-Oncogene Proteins B-raf
Pyrimidines
RNA, Messenger
Receptors, Cell Surface
Recombinant Proteins
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Stromal Cells
Thiazoles
Tissue Donors
Tumor Markers, Biological
Tumor Necrosis Factor-alpha
Wnt Proteins
Xenograft Model Antitumor Assays
ras Proteins