Kyle Walsh

Overview:

Dr. Walsh’s research program focuses on genetic and epigenetic factors contributing to cancer predisposition in children and adults, with a special interest in brain tumors. This research is informed by both epidemiology and anthropological genetics, with computational work stressing statistical methodologies for “gene hunting” (e.g. GWAS, fine-mapping, admixture mapping, whole-genome sequencing). The laboratory engages in functional genomics research, investigating the biological impact of genetic variants linked to cancer risk, with a particular focus on regulation of telomere maintenance in pre-malignant cells. 

Positions:

Associate Professor of Neurosurgery

Neurosurgery
School of Medicine

Associate Professor in Population Health Sciences

Population Health Sciences
School of Medicine

Associate Professor in Pediatrics

Pediatrics, Children's Health Discovery Institute
School of Medicine

Associate Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2011

Yale University School of Medicine

Grants:

My Childhood Cancer: Survey Series

Administered By
Neurosurgery
Awarded By
Alex's Lemonade Stand
Role
Principal Investigator
Start Date
End Date

Genetic Susceptibility to Pediatric Glioma in Individuals and Diverse populations

Administered By
Neurosurgery
Awarded By
University of Southern California
Role
Principal Investigator
Start Date
End Date

The role of rare and common variants in genetic predisposition to medulloblastoma

Administered By
Neurosurgery
Awarded By
Sontag Foundation
Role
Principal Investigator
Start Date
End Date

Genetic Susceptibility to pediatric Osteosarcoma and Interaction with Measures of Childhood Growth

Administered By
Neurosurgery
Awarded By
Alex's Lemonade Stand
Role
Principal Investigator
Start Date
End Date

Immune Correlates and Mechanisms of Perinatal Cytomegalovirus Infection and Later Life ALL Development

Administered By
Pediatrics, Children's Health Discovery Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Epidemiology of meningiomas.

More than 70,000 primary central nervous system tumors are diagnosed in the United States each year. Approximately 36% of these are meningiomas, making it the most common primary brain tumor. Because meningioma risk increases dramatically with age, the healthcare burden of meningioma in the developed world will continue to rise as demographics shift toward an older population. In addition to demographic factors associated with increased meningioma risk (i.e., older age, female sex, African American ethnicity), increased body mass index is a strong risk factor. A history of atopic allergies, eczema, and increased serum IgE are all consistently associated with reduced meningioma risk, suggesting a potential role for immunosurveillance. Although ionizing radiation is a strong meningioma risk factor, it accounts for very few cases at the population level. Recent studies suggest that diagnostic radiation (e.g., dental X-rays) increases meningioma risk. Because radiation dosages associated with medical imaging have decreased dramatically, the public health impact of this exposure is likely in decline. Genome-wide association studies have identified common inherited variants in the gene MLLT10 and RIC8A as low-penetrance meningioma risk alleles. To provide further insight into the etiology of meningioma, future studies will need to simultaneously examine genetic and environmental risk factors, while also stratifying analyses by subject sex.
Authors
MLA Citation
Walsh, Kyle M. Epidemiology of meningiomas. Vol. 169, 2020, pp. 3–15. Pubmed, doi:10.1016/B978-0-12-804280-9.00001-9.
URI
https://scholars.duke.edu/individual/pub1448334
PMID
32553297
Source
pubmed
Volume
169
Published Date
Start Page
3
End Page
15
DOI
10.1016/B978-0-12-804280-9.00001-9

Opportunities-and hard work-ahead.

Authors
Hoover, RN; Chanock, SJ
MLA Citation
Hoover, Robert N., and Stephen J. Chanock. “Opportunities-and hard work-ahead.Journal of the National Cancer Institute, vol. 107, no. 1, Jan. 2015, p. 398. Epmc, doi:10.1093/jnci/dju398.
URI
https://scholars.duke.edu/individual/pub1454881
PMID
25515231
Source
epmc
Published In
Journal of the National Cancer Institute
Volume
107
Published Date
Start Page
398
DOI
10.1093/jnci/dju398

Cytomegalovirus as an immunomodulator across the lifespan

© 2020 Elsevier B.V. Human cytomegalovirus (HCMV) is a nearly ubiquitous β-herpesvirus that establishes latent infection in the majority of the world's population. HCMV infection profoundly influences the host immune system and, perhaps more than any other human pathogen, has been shown to create a lasting imprint on human T and NK cell compartments. HCMV-seropositivity has been associated with both beneficial effects, such as increased vaccine responsiveness or heterologous protection against infections, and deleterious effects, such as pathological neurodevelopmental sequelae from congenital infection in utero and cumulative damage from chronic lifelong latency into old age. The significance of many of these associations is unclear, as studies into the causal mechanisms linking HCMV and these disease outcomes are lacking; however, HCMV-mediated changes to the immune system may play a key role. This review examines how HCMV impacts the host immune system in an age-dependent manner with important implications for human immunophenotypes and long-term disease risk.
Authors
Semmes, EC; Hurst, JH; Walsh, KM; Permar, SR
MLA Citation
Semmes, E. C., et al. “Cytomegalovirus as an immunomodulator across the lifespan.” Current Opinion in Virology, vol. 44, Oct. 2020, pp. 112–20. Scopus, doi:10.1016/j.coviro.2020.07.013.
URI
https://scholars.duke.edu/individual/pub1456251
Source
scopus
Published In
Current Opinion in Virology
Volume
44
Published Date
Start Page
112
End Page
120
DOI
10.1016/j.coviro.2020.07.013

Leveraging Genome and Phenome-Wide Association Studies to Investigate Genetic Risk of Acute Lymphoblastic Leukemia.

BACKGROUND: Genome-wide association studies (GWAS) of childhood cancers remain limited, highlighting the need for novel analytic strategies. We describe a hybrid GWAS and phenome-wide association study (PheWAS) approach to uncover genotype-phenotype relationships and candidate risk loci, applying it to acute lymphoblastic leukemia (ALL). METHODS: PheWAS was performed for 12 ALL SNPs identified by prior GWAS and two control SNP-sets using UK Biobank data. PheWAS-traits significantly associated with ALL SNPs compared with control SNPs were assessed for association with ALL risk (959 cases, 2,624 controls) using polygenic score and Mendelian randomization analyses. Trait-associated SNPs were tested for association with ALL risk in single-SNP analyses, with replication in an independent case-control dataset (1,618 cases, 9,409 controls). RESULTS: Platelet count was the trait most enriched for association with known ALL risk loci. A polygenic score for platelet count (223 SNPs) was not associated with ALL risk (P = 0.82) and Mendelian randomization did not suggest a causal relationship. However, twelve platelet count-associated SNPs were nominally associated with ALL risk in COG data and three were replicated in UK data (rs10058074, rs210142, rs2836441). CONCLUSIONS: In our hybrid GWAS-PheWAS approach, we identify pleiotropic genetic variation contributing to ALL risk and platelet count. Three SNPs known to influence platelet count were reproducibly associated with ALL risk, implicating genomic regions containing IRF1, proapoptotic protein BAK1, and ERG in platelet production and leukemogenesis. IMPACT: Incorporating PheWAS data into association studies can leverage genetic pleiotropy to identify cancer risk loci, highlighting the utility of our novel approach.
Authors
Semmes, EC; Vijayakrishnan, J; Zhang, C; Hurst, JH; Houlston, RS; Walsh, KM
MLA Citation
Semmes, Eleanor C., et al. “Leveraging Genome and Phenome-Wide Association Studies to Investigate Genetic Risk of Acute Lymphoblastic Leukemia.Cancer Epidemiol Biomarkers Prev, vol. 29, no. 8, Aug. 2020, pp. 1606–14. Pubmed, doi:10.1158/1055-9965.EPI-20-0113.
URI
https://scholars.duke.edu/individual/pub1446756
PMID
32467347
Source
pubmed
Published In
Cancer Epidemiol Biomarkers Prev
Volume
29
Published Date
Start Page
1606
End Page
1614
DOI
10.1158/1055-9965.EPI-20-0113

Highlights of the inaugural ten - the launch of Neuro-Oncology Advances.

Authors
Nassiri, F; Aldape, K; Alhuwalia, M; Brastianos, P; Ducray, F; Galldiks, N; Kim, A; Lamszus, K; Mitchell, D; Nabors, LB; Nam, D-H; Natsume, A; Ng, H-K; Niclou, S; Sahm, F; Short, S; Walsh, K; Wick, W; Zadeh, G
MLA Citation
Nassiri, Farshad, et al. “Highlights of the inaugural ten - the launch of Neuro-Oncology Advances.Neurooncol Adv, vol. 1, no. 1, May 2019, p. vdz016. Pubmed, doi:10.1093/noajnl/vdz016.
URI
https://scholars.duke.edu/individual/pub1450818
PMID
32642652
Source
pubmed
Published In
Neuro Oncology Advances
Volume
1
Published Date
Start Page
vdz016
DOI
10.1093/noajnl/vdz016