Michael Kastan

Positions:

William and Jane Shingleton Distinguished Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Director of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Professor of Pediatrics

Pediatrics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1984

Washington University in St. Louis

Ph.D. 1984

Washington University in St. Louis

Grants:

Kastan Gray Foundation Project

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Using bacterial CRISPR/Cas endonucleases to selectively eliminate HPV-transformed cells in vivo

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Development and Validation of Novel Therapeutic Targets in Anal Cancer

Administered By
Medicine, Medical Oncology
Role
Collaborator
Start Date
End Date

Administrative Supplements for P30 CCSG

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

Duke Cancer Institute Application for Administrative Supplement for the P30 Cancer Center Support Grant to Develop Tobacco Cessation Treatment Capacity and Infrastructure for Cancer Patients

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

Publications:

Retrospective Diagnosis of Ataxia-Telangiectasia in an Adolescent Patient With a Remote History of T-Cell Leukemia.

Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder characterized by progressive cerebellar degeneration that is typically diagnosed in early childhood. A-T is associated with a predisposition to malignancies, particularly lymphoid tumors in childhood and early adulthood. An adolescent girl with minimal neurological symptoms was diagnosed with A-T 8 years after completing therapy for T-cell acute lymphoblastic leukemia, following a diagnosis of ATM-mutated breast cancer in her mother. We highlight the importance of recognizing ATM mutations in T-cell acute lymphoblastic leukemia, appreciating the phenotypic heterogeneity of A-T, and defining optimal cancer screening in A-T patients.
Authors
Sze, S-GK; Lederman, HM; Crawford, TO; Wangler, MF; Lewis, AM; Kastan, MB; Dibra, HK; Taylor, AMR; Wechsler, DS
MLA Citation
Sze, Sei-Gyung K., et al. “Retrospective Diagnosis of Ataxia-Telangiectasia in an Adolescent Patient With a Remote History of T-Cell Leukemia..” J Pediatr Hematol Oncol, Nov. 2019. Pubmed, doi:10.1097/MPH.0000000000001672.
URI
https://scholars.duke.edu/individual/pub1421634
PMID
31743320
Source
pubmed
Published In
Journal of Pediatric Hematology/Oncology
Published Date
DOI
10.1097/MPH.0000000000001672

Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness.

Background: Metabolic syndrome, an obesity-related condition associated with insulin resistance and low-grade inflammation, leads to diabetes, cardiovascular diseases, cancer, osteoarthritis, and other disorders. Optimal therapy is unknown. The antimalarial drug chloroquine activates the kinase ataxia telangiectasia mutated (ATM), improves metabolic syndrome and reduces atherosclerosis in mice. To translate this observation to humans, we conducted two clinical trials of chloroquine in people with the metabolic syndrome. Methods: Eligibility included adults with at least 3 criteria of metabolic syndrome but who did not have diabetes. Subjects were studied in the setting of a single academic health center. The specific hypothesis: chloroquine improves insulin sensitivity and decreases atherosclerosis. In Trial 1, the intervention was chloroquine dose escalations in 3-week intervals followed by hyperinsulinemic euglycemic clamps. Trial 2 was a parallel design randomized clinical trial, and the intervention was chloroquine, 80 mg/day, or placebo for 1 year. The primary outcomes were clamp determined-insulin sensitivity for Trial 1, and carotid intima-media thickness (CIMT) for Trial 2. For Trial 2, subjects were allocated based on a randomization sequence using a protocol in blocks of 8. Participants, care givers, and those assessing outcomes were blinded to group assignment. Results: For Trial 1, 25 patients were studied. Chloroquine increased hepatic insulin sensitivity without affecting glucose disposal, and improved serum lipids. For Trial 2, 116 patients were randomized, 59 to chloroquine (56 analyzed) and 57 to placebo (51 analyzed). Chloroquine had no effect on CIMT or carotid contrast enhancement by MRI, a pre-specified secondary outcome. The pre-specified secondary outcomes of blood pressure, lipids, and activation of JNK (a stress kinase implicated in diabetes and atherosclerosis) were decreased by chloroquine. Adverse events were similar between groups. Conclusions: These findings suggest that low dose chloroquine, which improves the metabolic syndrome through ATM-dependent mechanisms in mice, modestly improves components of the metabolic syndrome in humans but is unlikely to be clinically useful in this setting.Trial registration ClinicalTrials.gov (NCT00455325, NCT00455403), both posted 03 April 2007.
Authors
McGill, JB; Johnson, M; Hurst, S; Cade, WT; Yarasheski, KE; Ostlund, RE; Schechtman, KB; Razani, B; Kastan, MB; McClain, DA; de Las Fuentes, L; Davila-Roman, VG; Ory, DS; Wickline, SA; Semenkovich, CF
MLA Citation
McGill, Janet B., et al. “Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness..” Diabetol Metab Syndr, vol. 11, 2019. Pubmed, doi:10.1186/s13098-019-0456-4.
URI
https://scholars.duke.edu/individual/pub1404051
PMID
31384309
Source
pubmed
Published In
Diabetol Metab Syndr
Volume
11
Published Date
Start Page
61
DOI
10.1186/s13098-019-0456-4

Commentary on "Participation of p53 Protein in the Cellular Response to DNA Damage".

Authors
MLA Citation
Kastan, Michael B. “Commentary on "Participation of p53 Protein in the Cellular Response to DNA Damage"..” Cancer Res, vol. 76, no. 13, July 2016, pp. 3663–65. Pubmed, doi:10.1158/0008-5472.CAN-16-1560.
URI
https://scholars.duke.edu/individual/pub1136098
PMID
27371738
Source
pubmed
Published In
Cancer Res
Volume
76
Published Date
Start Page
3663
End Page
3665
DOI
10.1158/0008-5472.CAN-16-1560

Erratum: Development of a cell-based, high-throughput screening assay for atm kinase inhibitors (Journal of Biomolecular Screening (2014) 19:4 (538-546) DOI:10.1177/1087057113520325)

Authors
Guo, K; Anang, A; Shelat, R; Guy, K; Kastan, MB
MLA Citation
Guo, K., et al. “Erratum: Development of a cell-based, high-throughput screening assay for atm kinase inhibitors (Journal of Biomolecular Screening (2014) 19:4 (538-546) DOI:10.1177/1087057113520325).” Journal of Biomolecular Screening, vol. 19, no. 10, Jan. 2014. Scopus, doi:10.1177/1087057114559509.
URI
https://scholars.duke.edu/individual/pub1053579
Source
scopus
Published In
J Biomol Screen
Volume
19
Published Date
Start Page
1418
DOI
10.1177/1087057114559509

Chloroquine Activates ATM and Improves Hematopoietic Recovery and Survival of Mice following Low Dose-rate Radiation

Authors
DeWeese, TL; Lim, Y; Hedayati, M; Merchant, A; Zhang, Y; Yu, HM; Kastan, MB; Matsui, W
MLA Citation
DeWeese, T. L., et al. “Chloroquine Activates ATM and Improves Hematopoietic Recovery and Survival of Mice following Low Dose-rate Radiation.” International Journal of Radiation Oncology*Biology*Physics, vol. 81, no. 2, Elsevier BV, Oct. 2011, pp. S191–92. Crossref, doi:10.1016/j.ijrobp.2011.06.343.
URI
https://scholars.duke.edu/individual/pub888480
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Published Date
Start Page
S191
End Page
S192
DOI
10.1016/j.ijrobp.2011.06.343