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:

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
Awarded By
The Farrah Fawcett Foundation
Role
Collaborator
Start Date
End Date

The role of ATM in Metabolic Stress Responses

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

The role of ATM in Metabolic Stress Responses

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Metabolic Sensing and Stress Response Deficit in Ataxia Telangiectasia

Administered By
Pharmacology & Cancer Biology
Awarded By
A-T Children's Project
Role
Principal Investigator
Start Date
End Date

Publications:

ATM Regulation of the Cohesin Complex is Required for Repression of DNA Replication and Transcription in the Vicinity of DNA Double Strand Breaks.

ATM is an apical regulator of responses to DNA double strand breaks (DSBs). Using two complementary unbiased proteomic screens, we identified the cohesin complex proteins PDS5A, PDS5B, RAD21, NIPBL, and WAPL as apparent novel ATM interactors and substrates. ATM-dependent phosphorylation of PDS5A on Ser1278 following treatment with ionizing radiation (IR) is required for optimal cell survival, cell cycle checkpoint activation, and chromosomal stability. Using a system that introduces site-specific DNA breaks, we found that ATM phosphorylation of cohesin proteins SMC1A, SMC3, and PDS5A are all required for repression of both RNA transcription and DNA replication within the vicinity of a DSB, the latter insight based on development of a novel localized S-phase cell cycle checkpoint assay. These findings highlight the significance of interactions between ATM and cohesin in the regulation of DNA metabolic processes by altering the chromatin environment surrounding a DSB. Implications: Multiple members of the cohesin complex are involved in the regulation of DNA replication and transcription in the vicinity of DNA double strand breaks and their role(s) are regulated by the ATM kinase.
Authors
Bass, TE; Fleenor, DE; Burrell, PE; Kastan, MB
MLA Citation
Bass, Thomas E., et al. “ATM Regulation of the Cohesin Complex is Required for Repression of DNA Replication and Transcription in the Vicinity of DNA Double Strand Breaks.Mol Cancer Res, Dec. 2022. Pubmed, doi:10.1158/1541-7786.MCR-22-0399.
URI
https://scholars.duke.edu/individual/pub1559401
PMID
36469004
Source
pubmed
Published In
Mol Cancer Res
Published Date
DOI
10.1158/1541-7786.MCR-22-0399

Abeloff’s Clinical Oncology

Easily accessible and clinically focused, Abeloff’s Clinical Oncology, 6th Edition, covers recent advances in our understanding of the pathophysiology of cancer, cellular and molecular causes of cancer initiation and progression, new and emerging therapies, current trials, and much more. Masterfully authored by an international team of leading cancer experts, it offers clear, practical coverage of everything from basic science to multidisciplinary collaboration on diagnosis, staging, treatment and follow up.
Authors
Niederhuber, JE; Armitage, JO; Doroshow, JH; Kastan, MB; Tepper, JE
MLA Citation
Niederhuber, J. E., et al. Abeloff’s Clinical Oncology. 2019, pp. 1–2037. Scopus, doi:10.1016/B978-0-323-47674-4.00124-9.
URI
https://scholars.duke.edu/individual/pub1509808
Source
scopus
Published Date
Start Page
1
End Page
2037
DOI
10.1016/B978-0-323-47674-4.00124-9

Preface

Authors
Niederhuber, JE; Armitage, JO; Doroshow, JH; Kastan, MB; Tepper, JE
MLA Citation
Niederhuber, J. E., et al. Preface. 2019, pp. xxvii–xxvii. Scopus, doi:10.1016/B978-0-323-47674-4.00129-8.
URI
https://scholars.duke.edu/individual/pub1509809
Source
scopus
Published Date
Start Page
xxvii
End Page
xxvii
DOI
10.1016/B978-0-323-47674-4.00129-8

DNA Damage Response Pathways and Cancer

DNA repair and the cellular response to DNA damage are critical for maintaining genomic stability. Defects in DNA repair or the response to DNA damage encountered from endogenous or external sources results in an increased rate of genetic mutations, often leading to the development of cancer. Inherited mutations in DNA damage response pathway genes often result in cancer susceptibility. The major active pathways for DNA repair in humans are nucleotide excision repair, base excision repair, mismatch DNA repair, translesional DNA synthesis, and homologous recombination or nonhomologous end joining processes for double-strand break repair.
Authors
Ford, JM; Kastan, MB
MLA Citation
Ford, J. M., and M. B. Kastan. “DNA Damage Response Pathways and Cancer.” Abeloff’s Clinical Oncology, 2019, pp. 154-164.e4. Scopus, doi:10.1016/B978-0-323-47674-4.00011-6.
URI
https://scholars.duke.edu/individual/pub1509810
Source
scopus
Published Date
Start Page
154
End Page
164.e4
DOI
10.1016/B978-0-323-47674-4.00011-6

Impaired Endoplasmic Reticulum (ER)-Mitochondrial Signaling in Ataxia-Telangiectasia Contributes to Mitochondrial Dysfunction

Authors
Yeo, AJ; Kok, CL; Gatei, M; Zou, D; Stewart, R; Withey, S; Wolvetang, E; Parton, RG; Brown, AD; Kastan, MB; Coman, D; Lavin, MF
URI
https://scholars.duke.edu/individual/pub1454292
Source
ssrn