Michael Datto

Overview:

Dr. Datto is an AP/CP/MGP board certified pathologist who specializes in molecular pathology. He is the Associate Vice President for Duke University Health System Clinical Laboratories, the Vice Chair for Clinical Pathology and Medical Director for Duke University Health System Clinical Laboratories.  

In these roles, he is responsible for maintaining the standards of the College of American Pathologists and CLIA/CMS within all Clinical Laboratories at Duke.  Specifically, Dr. Datto oversees clinical testing and reporting, develops quality management systems and proficiency testing programs, provides consultation with ordering physicians, ensures educational programs, develops strategic plans that are in line with the needs of our patient population, physicians and health system leadership, coordinates research and development, ensures adequate and appropriately trained personnel, and provides profession interpretation for molecular diagnostic testing including the wide range of PCR, quantitative PCR, sequencing and FISH based tests for inherited genetic diseases, hematologic malignancies, solid tumors and infectious diseases.

Dr. Datto also serves as the chair of the Accreditation Committee (AC) for the College of American Pathologists (CAP).  The CAP is the largest accreditor of hospital based laboratories in the US and serves as a ‘deemed entity’ by the Center for Medicare Services. In his role of chair of the AC, Dr. Datto oversees the committee that makes clinical accreditation decisions for approximately 7,000 clinical domestic and international laboratories.

Finally, Dr. Datto has an active academic program developing data system to aggregate, normalize and utilize high complexity and high volume laboratory data.  Dr. Datto and his team have developed the Molecular Registry of Tumors; a software solutions that currently supports clinical trials matching, engagement with the AACR GENIE Project and the Molecular Tumor Board for Duke University Health System.  The ultimate goal of this work is to ensure that the vast amount of laboratory data (including next generation sequencing data) can be made useful and actually used to improve patient care.

Positions:

Associate Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.A. 1991

Johns Hopkins University

Ph.D. 1998

Duke University

M.D. 1999

Duke University

Post-Doctoral Fellow, Pharmacology

Duke University

Resident, Pathology

Duke University

Grants:

Non Muscle Myosin II Contractility Putatively Regulates Scar Contracture

Administered By
Surgery
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Publications:

Therapeutic outcomes in non-small cell lung cancer with BRAF mutations: a single institution, retrospective cohort study.

Background: Data describing therapeutic outcomes in patients with non-small cell lung cancers (NSCLC) with BRAF mutations remains limited. Methods: We conducted a retrospective cohort study of 31 patients with metastatic NSCLC treated at Duke University Hospital who had been identified by next-generation sequencing methods to bear a BRAF mutation in their tumor in order to evaluate clinical response to immunotherapy and chemotherapy. Results: Sixty-five percent of patients identified in this cohort were current or former smokers. Fourteen (45.2%) of patients had a BRAF V600E mutation and 17 (54.8%) had a non-V600E mutation. Median progression-free survival (PFS) in the 23 patients who received first-line chemotherapy was 6.4 months [95% confidence interval (CI), 2.3 to 13.0]. Overall survival (OS) in patients who received first-line chemotherapy showed a median survival of 18 months (95% CI, 7.4 to 28.6). OS comparing patients who had never received immunotherapy at any point was 18.4 months (95% CI, 4.1 to NE) compared to 19.0 months (95% CI, 9.9 to 28.6) in those who had received immunotherapy. We did not find a statistically significant difference in OS in patients with BRAF V600E, BRAF amplification, or non-V600E mutations. There was also no difference in OS in patients treated with targeted BRAF inhibitors compared to those who were not treated with targeted BRAF inhibitors. Conclusions: We describe therapeutic outcomes for patients with metastatic NSCLC with BRAF mutations treated with either cytotoxic chemotherapy or immunotherapy. Although the sample size is small, the survival curves do not suggest improved clinical activity in this population when treated with immunotherapy.
Authors
Tan, I; Stinchcombe, TE; Ready, NE; Crawford, J; Datto, MB; Nagy, RJ; Lanman, RB; Gu, L; Clarke, JM
MLA Citation
Tan, Irena, et al. “Therapeutic outcomes in non-small cell lung cancer with BRAF mutations: a single institution, retrospective cohort study.Transl Lung Cancer Res, vol. 8, no. 3, June 2019, pp. 258–67. Pubmed, doi:10.21037/tlcr.2019.04.03.
URI
https://scholars.duke.edu/individual/pub1397860
PMID
31367539
Source
pubmed
Published In
Translational Lung Cancer Research
Volume
8
Published Date
Start Page
258
End Page
267
DOI
10.21037/tlcr.2019.04.03

Young Investigator Challenge: Molecular testing in noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

BACKGROUND: Molecular testing provides an important ancillary study for thyroid nodules with indeterminate cytology. The nomenclature shift to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) will impact the performance of molecular tests. For the current study, the authors reviewed the performance of the Afirma gene-expression classifier (GEC) and the University of Pittsburgh Medical Center (UPMC) targeted mutation panel tests in thyroid nodules that were subsequently diagnosed as NIFTP on surgical resection. METHODS: In total, 302 nodules were sent for molecular testing between June 2012 and June 2016. These cases were retrospectively reviewed to identify patients who underwent subsequent surgical resection and were diagnosed with follicular variant of papillary thyroid carcinoma (FVPTC). Twenty-five nodules that were diagnosed as FVPTC met the initial inclusion criteria. These cases were reviewed using strict criteria to identify NIFTP. RESULTS: Eight cases met criteria for NIFTP, and 4 NIFTPs underwent Afirma testing. Cytology diagnoses were all Bethesda category III, with 3 diagnosed as atypia of undetermined significance (AUS) and 1 diagnosed as follicular lesion of undetermined significance (FLUS). All of these nodules were identified as "suspicious" using GEC. Four NIFTPs underwent testing at UPMC, all using ThyroSeq V2. The cytology diagnoses for these nodules also were category III, with the exception of 1 nodule that was category IV, suspicious for follicular neoplasm. All NIFTPs were positive for mutations, all of which were RAS mutations (NRAS, KRAS). One patient who had a nodule classified as NIFTP had metastatic carcinoma identified in a lymph node. Another who had a 6-cm tumor had coexisting NRAS and TERT mutations. CONCLUSIONS: The current results indicate that NIFTP is a rare tumor if defined by strict criteria, that both the GEC and UPMC methods indicate abnormalities in NIFTP, and further independent study will be needed to better characterize the molecular and clinical characteristics of NIFTP. Cancer Cytopathol 2016;124:893-900. © 2016 American Cancer Society.
MLA Citation
Jiang, Xiaoyin Sara, et al. “Young Investigator Challenge: Molecular testing in noninvasive follicular thyroid neoplasm with papillary-like nuclear features.Cancer Cytopathol, vol. 124, no. 12, Dec. 2016, pp. 893–900. Pubmed, doi:10.1002/cncy.21802.
URI
https://scholars.duke.edu/individual/pub1160319
PMID
27893191
Source
pubmed
Published In
Cancer Cytopathol
Volume
124
Published Date
Start Page
893
End Page
900
DOI
10.1002/cncy.21802

Utilization of genomic signatures for chemotherapy response in prospective clinical studies.

Authors
Barry, W; Acharya, C; Datto, MB; Dressman, HK; Marcom, PK; Ready, N; Ginsburg, GS; Potti, A; Nevins, JR
MLA Citation
Barry, W., et al. “Utilization of genomic signatures for chemotherapy response in prospective clinical studies.Journal of Clinical Oncology, vol. 28, no. 15_suppl, American Society of Clinical Oncology (ASCO), May 2010, pp. 10513–10513. Crossref, doi:10.1200/jco.2010.28.15_suppl.10513.
URI
https://scholars.duke.edu/individual/pub1024928
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
28
Published Date
Start Page
10513
End Page
10513
DOI
10.1200/jco.2010.28.15_suppl.10513

Chemotherapy induced leukoencephalopathy causes a wide range of symptoms: A series of three autopsies

Authors
Datto, MB; Moore-Maxwell, CA; Hulette, C
MLA Citation
Datto, M. B., et al. “Chemotherapy induced leukoencephalopathy causes a wide range of symptoms: A series of three autopsies.” Modern Pathology, vol. 15, no. 1, NATURE PUBLISHING GROUP, Jan. 2002, pp. 5A-5A.
URI
https://scholars.duke.edu/individual/pub873932
Source
wos
Published In
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Volume
15
Published Date
Start Page
5A
End Page
5A

Tumor suppressor Smad4 is a transforming growth factor beta-inducible DNA binding protein.

Members of the Smad family of proteins are thought to play important roles in transforming growth factor beta (TGF-beta)-mediated signal transduction. In response to TGF-beta, specific Smads become inducibly phosphorylated, form heteromers with Smad4, and undergo nuclear accumulation. In addition, overexpression of specific Smad combinations can mimic the transcriptional effect of TGF-beta on both the plasminogen activator inhibitor 1 (PAI-1) promoter and the reporter construct p3TP-Lux. Although these data suggest a role for Smads in regulating transcription, the precise nuclear function of these heteromeric Smad complexes remains largely unknown. Here we show that in Mv1Lu cells Smad3 and Smad4 form a TGF-beta-induced, phosphorylation-dependent, DNA binding complex that specifically recognizes a bipartite binding site within p3TP-Lux. Furthermore, we demonstrate that Smad4 itself is a DNA binding protein which recognizes the same sequence. Interestingly, mutations which eliminate the Smad DNA binding site do not interfere with either TGF-beta-dependent transcriptional activation or activation by Smad3/Smad4 cooverexpression. In contrast, mutation of adjacent AP1 sites within this context eliminates both TGF-beta-dependent transcriptional activation and activation in response to Smad3/Smad4 cooverexpression. Furthermore, concatemerized AP1 sites, in isolation, are activated by Smad3/Smad4 cooverexpression and, to a certain extent, by TGF-beta. Taken together, these data suggest that the Smad3/Smad4 complex has at least two separable nuclear functions: it forms a rapid, yet transient sequence-specific DNA binding complex, and it potentiates AP1-dependent transcriptional activation.
Authors
Yingling, JM; Datto, MB; Wong, C; Frederick, JP; Liberati, NT; Wang, XF
MLA Citation
Yingling, J. M., et al. “Tumor suppressor Smad4 is a transforming growth factor beta-inducible DNA binding protein.Mol Cell Biol, vol. 17, no. 12, Dec. 1997, pp. 7019–28. Pubmed, doi:10.1128/mcb.17.12.7019.
URI
https://scholars.duke.edu/individual/pub656598
PMID
9372933
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
17
Published Date
Start Page
7019
End Page
7028
DOI
10.1128/mcb.17.12.7019