Assistant Professor in Neurosurgery
The Waitkus Laboratory is a team of researchers focused on understanding the molecular biology of malignant brain tumors. We work alongside clinician-scientists in the Preston Robert Tisch Brain Tumor Center at Duke to investigate the mechanisms by which brain tumors arise, progress, and recur.
Adult and pediatric malignant gliomas are caused by specific sets of genetic mutations that allow tumor cells to (1) proliferate indefinitely, (2) obtain and utilize nutrients to grow, and (3) evade normal anti-tumor protective mechanisms, such as programed cell death and immune surveillance. In the Waitkus Laboratory, our overarching goal is to better understand the mechanisms underlying the pathogenesis and progression of malignant gliomas. We aim to use this knowledge to develop improved methods for glioma diagnosis, prognostication, and treatment
Current Research Interests
Our laboratory is focused on understanding the genetic alterations and molecular mechanisms underlying telomere maintenance and cellular immortalization in gliomas and other cancers. Our previous work identified loss-of-function mutations in SMARCAL1 and ATRX as drivers of the Alternative Lengthening of Telomeres phenotype in adults whose tumors are wildtype for other glioma driver genes, such as IDH1/2 and the TERT promoter (TERTp). Our current work aims to understand how SMARCAL1 and ATRX loss-of-function mutations lead to ALT in cancer and to understand the role of specific DNA damage response proteins and replication fork remodeling enzymes in glioma cell proliferation and response to DNA damaging agents.
Role of IDH1/2 Mutations in Gliomagenesis and Therapy Response
We are interested in better understanding brain tumor cell metabolism and the metabolic consequences of glioma-associated IDH1/2 mutations. In particular, we seek to better understand the impact of IDH1/2 mutations on tumor progression, therapeutic response, and modulation of the tumor microenvironment. Our previous studies revealed that expression of IDH1-R132H mutation causes widespread metabolic reprogramming in brain tumor cells, including alterations in amino acid metabolism and glutaminolysis. We are currently investigating the extent to which mutant IDH-mediated metabolic alterations influence the sensitivity of glioma cells to radiation and chemotherapies. Additionally, we are using genetically engineered cell lines and in vivo models to identify and exploit IDH mutant-dependent metabolic sensitivities for glioma therapy.
Modern genomics approaches have revealed the genetic mutations underlying the pathogenesis of gliomas but more work is needed to link specific mutational signatures to highly efficacious therapies. In the Waitkus laboratory, we seek to identify novel drug targets and develop new biomarker-guided therapeutic strategies for patients with brain tumors. We are particularly interested in cancers that use the Alternative Lengthening of Telomeres (ALT) as a mechanism of cellular immortalization. We are currently conducting studies to identify synthetic lethal vulnerabilities that are associated with the ALT phenotype in both pediatric and adult malignant gliomas.
Current Appointments & Affiliations
- Assistant Professor in Neurosurgery, Neurosurgery, Neurosurgery 2021
- Assistant Professor of Pathology, Pathology, Clinical Science Departments 2021
- Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 2020
- 203 Research Drive, Durham, NC 27705
- DUMC 2600, 203 Research Drive, Room 155, Durham, NC 27710
- firstname.lastname@example.org (919) 684-1339
- The Waitkus Lab at Duke
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