Kris Wood

Positions:

Associate Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Core Faculty in Innovation & Entrepreneurship

Duke Innovation & Entrepreneurship
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 2002

University of Kentucky at Lexington

Ph.D. 2007

Massachusetts Institute of Technology

Grants:

Pharmacology Industry Internships for Ph.D. Students

Administered By
Pharmacology & Cancer Biology
Awarded By
American Society for Pharmacology and Experimental Therapeutics
Role
Participating Faculty Member
Start Date
End Date

Medical Scientist Training Program

Administered By
School of Medicine
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Targeting the Hippo pathway in Ras-driven rhabdomyosarcoma

Administered By
Pediatrics, Hematology-Oncology
Awarded By
V Foundation for Cancer Research
Role
Collaborator
Start Date
End Date

Identification and validation of the PAX3-FOXO1 protein interactome

Administered By
Pediatrics, Hematology-Oncology
Role
Collaborator
Start Date
End Date

RalA signal transduction

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

Publications:

Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer.

Local adaptation directs populations towards environment-specific fitness maxima through acquisition of positively selected traits. However, rapid environmental changes can identify hidden fitness trade-offs that turn adaptation into maladaptation, resulting in evolutionary traps. Cancer, a disease that is prone to drug resistance, is in principle susceptible to such traps. We therefore performed pooled CRISPR-Cas9 knockout screens in acute myeloid leukemia (AML) cells treated with various chemotherapies to map the drug-dependent genetic basis of fitness trade-offs, a concept known as antagonistic pleiotropy (AP). We identified a PRC2-NSD2/3-mediated MYC regulatory axis as a drug-induced AP pathway whose ability to confer resistance to bromodomain inhibition and sensitivity to BCL-2 inhibition templates an evolutionary trap. Across diverse AML cell-line and patient-derived xenograft models, we find that acquisition of resistance to bromodomain inhibition through this pathway exposes coincident hypersensitivity to BCL-2 inhibition. Thus, drug-induced AP can be leveraged to design evolutionary traps that selectively target drug resistance in cancer.
Authors
Lin, KH; Rutter, JC; Xie, A; Pardieu, B; Winn, ET; Bello, RD; Forget, A; Itzykson, R; Ahn, Y-R; Dai, Z; Sobhan, RT; Anderson, GR; Singleton, KR; Decker, AE; Winter, PS; Locasale, JW; Crawford, L; Puissant, A; Wood, KC
MLA Citation
Lin, Kevin H., et al. “Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer.Nature Genetics, vol. 52, no. 4, Apr. 2020, pp. 408–17. Epmc, doi:10.1038/s41588-020-0590-9.
URI
https://scholars.duke.edu/individual/pub1435937
PMID
32203462
Source
epmc
Published In
Nature Genetics
Volume
52
Published Date
Start Page
408
End Page
417
DOI
10.1038/s41588-020-0590-9

Druggable Vulnerabilities in Therapy-Resistant Lung Cancers

Authors
MLA Citation
Wood, K. C. “Druggable Vulnerabilities in Therapy-Resistant Lung Cancers.” Journal of Thoracic Oncology, vol. 15, no. 2, ELSEVIER SCIENCE INC, 2020, pp. S6–S6.
URI
https://scholars.duke.edu/individual/pub1432972
Source
wos
Published In
Journal of Thoracic Oncology
Volume
15
Published Date
Start Page
S6
End Page
S6

Abstract PR18: Leveraging synthetic lethality to target convergent therapeutic resistance

Authors
MLA Citation
Wood, Kris C. “Abstract PR18: Leveraging synthetic lethality to target convergent therapeutic resistance.” Resistance Against Drug Combinations, American Association for Cancer Research, 2017. Crossref, doi:10.1158/1538-8514.synthleth-pr18.
URI
https://scholars.duke.edu/individual/pub1279811
Source
crossref
Published In
Resistance Against Drug Combinations
Published Date
DOI
10.1158/1538-8514.synthleth-pr18

Overcoming MCL-1-driven adaptive resistance to targeted therapies.

Authors
MLA Citation
Wood, Kris C. “Overcoming MCL-1-driven adaptive resistance to targeted therapies.Nat Commun, vol. 11, no. 1, Jan. 2020, p. 531. Pubmed, doi:10.1038/s41467-020-14392-z.
URI
https://scholars.duke.edu/individual/pub1428949
PMID
31988312
Source
pubmed
Published In
Nature Communications
Volume
11
Published Date
Start Page
531
DOI
10.1038/s41467-020-14392-z

Evolved resistance to partial GAPDH inhibition results in loss of the Warburg effect and in a different state of glycolysis.

Aerobic glycolysis or the Warburg effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although the WE is ubiquitous, its biological role remains controversial, and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, here we evolved resistance to koningic acid (KA), a natural product that specifically inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme, during the WE. We found that KA-resistant cells lose the WE but continue to conduct glycolysis and surprisingly remain dependent on glucose as a carbon source and also on central carbon metabolism. Consequently, this altered state of glycolysis led to differential metabolic activity and requirements, including emergent activities in and dependences on fatty acid metabolism. These findings reveal that aerobic glycolysis is a process functionally distinct from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.
Authors
Liberti, MV; Allen, AE; Ramesh, V; Dai, Z; Singleton, KR; Guo, Z; Liu, JO; Wood, KC; Locasale, JW
MLA Citation
Liberti, Maria V., et al. “Evolved resistance to partial GAPDH inhibition results in loss of the Warburg effect and in a different state of glycolysis.J Biol Chem, vol. 295, no. 1, Jan. 2020, pp. 111–24. Pubmed, doi:10.1074/jbc.RA119.010903.
URI
https://scholars.duke.edu/individual/pub1421761
PMID
31748414
Source
pubmed
Published In
The Journal of Biological Chemistry
Volume
295
Published Date
Start Page
111
End Page
124
DOI
10.1074/jbc.RA119.010903