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:

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

Impaired endoplasmic reticulum-mitochondrial signaling in ataxia-telangiectasia.

There is evidence that ATM mutated in ataxia-telangiectasia (A-T) plays a key role in protecting against mitochondrial dysfunction, the mechanism for which remains unresolved. We demonstrate here that ATM-deficient cells are exquisitely sensitive to nutrient deprivation, which can be explained by defective cross talk between the endoplasmic reticulum (ER) and the mitochondrion. Tethering between these two organelles in response to stress was reduced in cells lacking ATM, and consistent with this, Ca2+ release and transfer between ER and mitochondria was reduced dramatically when compared with control cells. The impact of this on mitochondrial function was evident from an increase in oxygen consumption rates and a defect in mitophagy in ATM-deficient cells. Our findings reveal that ER-mitochondrial connectivity through IP3R1-GRP75-VDAC1, to maintain Ca2+ homeostasis, as well as an abnormality in mitochondrial fusion defective in response to nutrient stress, can account for at least part of the mitochondrial dysfunction observed in A-T cells.
Authors
Yeo, AJ; Chong, KL; Gatei, M; Zou, D; Stewart, R; Withey, S; Wolvetang, E; Parton, RG; Brown, AD; Kastan, MB; Coman, D; Lavin, MF
MLA Citation
Yeo, Abrey J., et al. “Impaired endoplasmic reticulum-mitochondrial signaling in ataxia-telangiectasia.Iscience, vol. 24, no. 1, Jan. 2021, p. 101972. Pubmed, doi:10.1016/j.isci.2020.101972.
URI
https://scholars.duke.edu/individual/pub1470998
PMID
33437944
Source
pubmed
Published In
Iscience
Volume
24
Published Date
Start Page
101972
DOI
10.1016/j.isci.2020.101972