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

Authors' Reply.

Authors' Reply to the Letter to the Editor by Montgomery et al (Identification of Germline Variants in Tumor Genomic Sequencing Analysis. J Mol Diagn 2017, 19:XXXX-XXXX).
Authors
Li, MM; Datto, M; Duncavage, EJ; Kulkarni, S; Lindeman, NI; Roy, S; Tsimberidou, AM; Vnencak-Jones, CL; Wolff, DJ; Younes, A; Nikiforova, MN
MLA Citation
Li, Marilyn M., et al. “Authors' Reply.J Mol Diagn, vol. 20, no. 1, Jan. 2018, pp. 125–26. Pubmed, doi:10.1016/j.jmoldx.2017.11.002.
URI
https://scholars.duke.edu/individual/pub1292939
PMID
29249244
Source
pubmed
Published In
J Mol Diagn
Volume
20
Published Date
Start Page
125
End Page
126
DOI
10.1016/j.jmoldx.2017.11.002

Donor cell-derived leukemias/myelodysplastic neoplasms in allogeneic hematopoietic stem cell transplant recipients: a clinicopathologic study of 10 cases and a comprehensive review of the literature.

We report 10 cases of donor cell leukemia (DCL). All cases except the case of chronic lymphocytic leukemia had anemia, neutropenia, and/or thrombocytopenia when DCL was diagnosed. Eight cases with sex-mismatched hematopoietic stem cell transplant (HCT) showed donor gonosomal complements, suggesting DCL. Clonal cytogenetic abnormalities were detected in 8 cases: 6 were monosomy 7/del(7q). In all 10 cases, engraftment studies confirmed donor cell origin. Retrospective fluorescence in situ hybridization in archived donor cells in 4 cases showed a low level of abnormalities in 2. Of 7 patients with clinical follow-up of 5 months or more, 1 (with acute myeloid leukemia) died of disease; 6 are alive, including 1 with myelodysplastic syndrome with spontaneous remission. Similar to reported cases, we found disproportional sex-mismatched HCTs, suggesting probable underdetection of DCL in sex-matched HCTs. The latency between HCT and DCL ranged from 1 to 193 months (median, 24 months), in keeping with the literature. Analyzing our cases, pooled with reported cases, with survival models showed much shorter latency for malignancy as primary disease, for T-cell large granular lymphocyte leukemia as type of DCL, and for umbilical cord blood as stem cell source.
Authors
Wang, E; Hutchinson, CB; Huang, Q; Lu, CM; Crow, J; Wang, FF; Sebastian, S; Rehder, C; Lagoo, A; Horwitz, M; Rizzieri, D; Yu, J; Goodman, B; Datto, M; Buckley, P
MLA Citation
URI
https://scholars.duke.edu/individual/pub743484
PMID
21411775
Source
pubmed
Published In
Am J Clin Pathol
Volume
135
Published Date
Start Page
525
End Page
540
DOI
10.1309/AJCPPJUQ9DNR1GHP

Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies.

We have observed an increasing number of autopsies on patients with chemotherapy-related complications. One complication is toxic leukoencephalopathy, which is due to a direct toxic effect of chemotherapeutic agents on the central nervous system white matter. Autopsies of four cases of toxic leukoencephalopathy were performed following standard protocols. The brain and spinal cord were examined routinely, and histological sections were taken for evaluation. We report here three patients with hematologic malignancies and one patient with metastatic carcinoma with chemotherapy-induced leukoencephalopathy. The first was a 56-year-old male treated with multiple chemotherapeutics for multiple myeloma. He presented with confusion and focal seizures with a rapid progression to coma and decerebrate posturing. The second was a 36-year-old male who developed mental status changes, ataxia and dysarthria following treatment for lymphoma. The third was a 16-year-old male who developed a profound peripheral and central neuropathy after chemotherapy treatment for T-cell acute lymphoblastic leukemia. The fourth was a 49-year-old female patient who was treated with multiple chemotherapeutics for Stage II breast carcinoma and subsequently developed visual acuity and field defects. The neuropathologic findings in these cases, although similar, varied in severity and distribution. The white matter was affected by severe myelin pallor, edema, and a prominent macrophage infiltrate in each of the cases. The location and extent of the central nervous system pathology correlated with the type and severity of clinical symptoms. These four cases, with their varied presenting symptoms, clinical courses, and degree of pathology, emphasize the importance of considering toxic leukoencephalopathy as an etiology of acute neurologic deterioration following high-dose chemotherapy.
Authors
Moore-Maxwell, CA; Datto, MB; Hulette, CM
MLA Citation
Moore-Maxwell, Crystal A., et al. “Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies.Mod Pathol, vol. 17, no. 2, Feb. 2004, pp. 241–47. Pubmed, doi:10.1038/modpathol.3800049.
URI
https://scholars.duke.edu/individual/pub663327
PMID
14704718
Source
pubmed
Published In
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Volume
17
Published Date
Start Page
241
End Page
247
DOI
10.1038/modpathol.3800049

TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein.

Smads are intermediate effector proteins that transduce the TGF-beta signal from the plasma membrane to the nucleus, where they participate in transactivation of downstream target genes. We have shown previously that coactivators p300/CREB-binding protein are involved in TGF-beta-mediated transactivation of two Cdk inhibitor genes, p21 and p15. Here we examined the possibility that Smads function to regulate transcription by directly interacting with p300/CREB-binding protein. We show that Smad3 can interact with a C-terminal fragment of p300 in a temporal and phosphorylation-dependent manner. TGF-beta-mediated phosphorylation of Smad3 potentiates the association between Smad3 and p300, likely because of an induced conformational change that removes the autoinhibitory interaction between the N- and C-terminal domains of Smad3. Consistent with a role for p300 in the transcription regulation of multiple genes, overexpression of a Smad3 C-terminal fragment causes a general squelching effect on multiple TGF-beta-responsive reporter constructs. The adenoviral oncoprotein E1A can partially block Smad-dependent transcriptional activation by directly competing for binding to p300. Taken together, these findings define a new role for phosphorylation of Smad3: in addition to facilitating complex formation with Smad4 and promoting nuclear translocation, the phosphorylation-induced conformational change of Smad3 modulates its interaction with coactivators, leading to transcriptional regulation.
Authors
Shen, X; Hu, PP; Liberati, NT; Datto, MB; Frederick, JP; Wang, XF
MLA Citation
Shen, X., et al. “TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein.Mol Biol Cell, vol. 9, no. 12, Dec. 1998, pp. 3309–19. Pubmed, doi:10.1091/mbc.9.12.3309.
URI
https://scholars.duke.edu/individual/pub656601
PMID
9843571
Source
pubmed
Published In
Molecular Biology of the Cell
Volume
9
Published Date
Start Page
3309
End Page
3319
DOI
10.1091/mbc.9.12.3309