Kyle Walsh PhD

Kyle Walsh PhDAssistant Professor in Residence of Neurological Surgery and Epidemiology and Biostatistics

 

 

 

 

Dr. Walsh’s research program is divided into two components: genetic epidemiology and functional genomics. The epidemiology component focuses on the use of genomic data from large population-based cohorts to identify the causes of cancer. This computational work stresses statistical methodologies for “gene hunting”, including GWAS, fine-mapping, admixture mapping, and whole-genome sequencing. This ongoing work has identified novel risk factors for glioma and childhood leukemia. The functional genomics component investigates the biological impact of genetic variants linked to cancer risk.

Dr. Walsh’s laboratory utilizes numerous techniques, including: digital droplet PCR, ChIP, FISH, and luciferase reporter assays. Special focus is given to the interface of the inherited genome and the tumor genome. Deregulation of tumor suppression mechanisms, such as telomere-induced cell senescence, are of particular interest. Dr. Walsh’s recent work with the UCSF Adult Glioma Study identified inherited genetic variants associated with longer telomere length and increased glioma risk, suggesting that heritable variation in telomere length or telomerase activity may underlie glioma susceptibility. Continuing research in Dr. Walsh’s laboratory is extremely collaborative, involving genomic analyses of adult glioma risk with UCSF and Mayo investigators, meningioma risk with UCSF and Yale investigators, and childhood leukemia risk with UCSF and Berkeley investigators.

Research in Dr. Walsh's laboratory is funded by the NIH, the NCI, the Sontag Foundation, the Pediatric Brain Tumor Foundation, and Alex's Lemonade Stand Foundation. 

Education, Training, and Previous Positions

2007: BS, Ohio State University
2011: PhD, Yale University School of Public Health
2011-2013: NCI Post-doctoral Scholar, Program in Cancer Genetics, Division of Cancer Epidemiology, The University of California, San Francisco
2013-present: Assistant Professor, Department of Neurological Surgery, UCSF

Selected Professional Memberships and Appointments

Society for Epidemiologic Research
The Brain Tumor Epidemiology Consortium
The American Society of Human Genetics
The Human Biology Association
The American Association of Anthropological Genetics

Selected Honors and Awards

2015: The Society for Neuro-Oncology Young Investigator Award for Clinical Research
2015: The Sontag Foundation Distinguished Scientist Award
2014: The Society for Neuro-Oncology Epidemiology Research Award
2013: UCSF Brain Tumor Research Center Marvin Barker Award
2013: The Brain Tumor Epidemiology Consortium (BTEC) Junior Investigator Award
2011: The Brain Tumor Epidemiology Consortium (BTEC) Junior Investigator Award
2009: M.Phil. awarded as “Distinguished”
2007: University Fellowship, Yale University School of Public Health
2007: American Association for Anthropological Genetics “Outstanding Student Presentation in Human Genetics (OSPHG)” Award
2005: Mayers Fellow, The Ohio State University College of Biological Sciences

Selected Recent Publications

Wiemels JL, de Smith AJ, Xiao J, Lee ST, Muench MO, Fomin ME, Zhou M, Hansen HM, Termuhlen A, Metayer C, Walsh KM. A functional polymorphism in the CEBPE gene promoter influences acute lymphoblastic leukemia risk through interaction with the hematopoietic transcription factor Ikaros. Leukemia. 2015 Sep 16. doi: 10.1038/leu.2015.251. [Epub ahead of print]

Walsh KM, de Smith AJ, Hansen HM, Smirnov IV, Gonseth S, Endicott AA, Xiao J, Rice T, Fu CH, McCoy LS, Lachance DH, Eckel-Passow JE, Wiencke JK, Jenkins RB, Wrensch MR, Ma X, Metayer C, Wiemels JL. A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution. Cancer Res. 2015 Nov 2. [Epub ahead of print]

Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, Pekmezci M, Rice T, Kosel ML, Smirnov IV, Sarkar G, Caron AA, Kollmeyer TM, Praska CE, Chada AR, Halder C, Hansen HM, McCoy LS, Bracci PM, Marshall R, Zheng S, Reis GF, Pico AR, O'Neill BP, Buckner JC, Giannini C, Huse JT, Perry A, Tihan T, Berger MS, Chang SM, Prados MD, Wiemels J, Wiencke JK, Wrensch MR, Jenkins RB. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med 2015;372(26):2499-508.

Bell RJ, Rube HT, Kreig A, Mancini A, Fouse SD, Nagarajan RP, Choi S, Hong C, He D, Pekmezci M, Wiencke JK, Wrensch MR, Chang SM, Walsh KM, Myong S, Song JS, Costello JF. Cancer. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer. Science 2015 May;348(6238):1036-9.

Walsh KM, Wiencke JK, Lachance DH, Wiemels JL, Molinaro AM, Eckel-Passow JE, Jenkins RB, Wrensch MR. Telomere maintenance and the etiology of adult glioma. Neuro Oncol 2015;17(11):1445-52.

Reis GF, Pekmezci M, Hansen HM, Rice T, Marshall RE, Molinaro AM, Phillips JJ, Vogel H, Wiencke JK, Wrensch MR, Walsh KM, Perry A. CDKN2A loss is associated with shortened overall survival in lower-grade (World Health Organization Grades II-III) astrocytomas. J Neuropathol Exp Neurol 2015;74(5):442-52.

Claus EB, Walsh KM, Wiencke JK, Molinaro AM, Wiemels JL, Schildkraut JM, Bondy ML, Berger M, Jenkins R, Wrensch M. Survival and low-grade glioma: the emergence of genetic information. Neurosurg Focus 2015;38(1):E6.

Osorio JA, Hervey-Jumper SL, Walsh KM, Clarke JL, Butowski NA, Prados MD, Berger MS. Familial gliomas: cases in two pairs of brothers. J Neurooncol 2015;121(1):135-40.

Hsu LI, Chokkalingam AP, Briggs FB, Walsh K, Crouse V, Fu C, Metayer C, Wiemels JL, Barcellos LF, Buffler PA. Association of genetic variation in IKZF1, ARID5B, and CEBPE and surrogates for early-life infections with the risk of acute lymphoblastic leukemia in Hispanic children. Cancer Causes Control 2015;26(4):609-19.

Bainbridge MN, Armstrong GN, Gramatges MM, Bertuch AA, Jhangiani SN, Doddapaneni H, Lewis L, Tombrello J, Tsavachidis S, Liu Y, Jalali A, Plon SE, Lau CC, Parsons DW, Claus EB, Barnholtz-Sloan J, Il'yasova D, Schildkraut J, Ali-Osman F, Sadetzki S, Johansen C, Houlston RS, Jenkins RB, Lachance D, Olson SH, Bernstein JL, Merrell RT, Wrensch MR, Walsh KM, Davis FG, Lai R, Shete S, Aldape K, Amos CI, Thompson PA, Muzny DM, Gibbs RA, Melin BS, Bondy ML; Gliogene Consortium. Germline mutations in shelterin complex genes are associated with familial glioma. J Natl Cancer Inst 2014;107(1):384.

Walsh KM, Codd V, Smirnov IV, Rice T, Decker PA, Hansen HM, Kollmeyer T, Kosel ML, Molinaro AM, McCoy LS, Bracci PM, Cabriga BS, Pekmezci M, Zheng S, Wiemels JL, Pico AR, Tihan T, Berger MS, Chang SM, Prados MD, Lachance DH, O’Neill BP, Sicotte H, Eckel-Passow JE, ENGAGE Consortium Telomere Group, van der Harst P, Wiencke JK, Samani NJ, Jenkins RB, Wrensch MR. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nature Genetics 2014;46(7):731-5.

Ostrom QT, Bauchet L, Davis F, Deltour I, Langer CE, Fisher J, Pekmezci M, Turner M, Schwartzbaum J, Walsh KM, Wrensch MR, Barnholtz-Sloan JS. The epidemiology of glioma in adults. Neuro-Oncology 2014;16(7):896-913.

Walsh KM, de Smith AJ, Welch TC, Smirnov I, Cunningham MJ, Ma X, Chokkalingam AP, Dahl GV, Roberts W, Barcellos LF, Buffler PA, Metayer C, Wiemels JL. Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B-cell ALL. American Journal of Hematology 2014;89(7):721-5.

de Smith AJ, Walsh KM, Ladner MB, Zhang S, Xiao C, Cohen F, Moore TB, Chokkalingam AP, Metayer C, Buffler PA, Trachtenberg EA, Wiemels JL. The role of KIR genes and their cognate HLA class I ligands in childhood acute lymphoblastic leukemia. Blood 2014;123(16):2497-503.

Walsh KM, de Smith AJ, Chokkalingam AP, Metayer C, Roberts W, Barcellos LF, Wiemels JL, Buffler PA. GATA3 risk alleles are associated with ancestral components in Hispanic children with ALL. Blood 2013;122(19):3385-7.

Walsh KM, Rice T, Decker PA, Kosel ML, Kollmeyer T, Hansen HM, Zheng S, McCoy LS, Bracci PM, Anderson E, Hsuang G, Wiemels JL, Pico AR, Smirnov I, Molinaro AM, Tihan T, Berger MS, Chang SM, Prados MD, Lachance DH, Sicotte H, Eckel-Passow JE, Wiencke JK , Jenkins RB, Wrensch MR. Genetic variants in telomerase-related genes are associated with an older age-at-diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis. Neuro-Oncology 2013;15(8):1041-7.

Walsh KM, Chokkalingam AP, Hsu L, Metayer C, de Smith AJ, Jacobs DI, Dahl GV, Loh ML, Smirnov I, Bartley K, Wiencke JK, Ma X, Barcellos LF, Wiemels JL, Buffler PA. Associations between genome-wide Native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children. Leukemia 2013;27(12):2416-9.

Walsh KM, de Smith AJ, Chokkalingam AP, Hsu L, Metayer C, Dahl GV, Barcellos LF, Wiemels JL, Buffler PA. Novel childhood ALL susceptibility locus BMI1-PIP4K2A is specifically associated with the hyperdiploid subtype. Blood 2013;121:4808-4809.

Walsh KM, Anderson E, Hansen HM, Decker PA, Kosel ML, Kollmeyer T, Rice T, Zheng S, Xiao Y, Chang J, McCoy LS, Bracci PM, Wiemels JL, Pico AR, Smirnov I, Lachance DH, Sicotte H, Eckel-Passow JE, Wiencke JK , Jenkins RB, Wrensch MR. Analysis of 60 reported glioma risk SNPs replicates published GWAS findings but fails to replicate associations from published candidate-gene studies. Genetic Epidemiology 2013;37(2):222-8.

Walsh KM, Gorlov IP, Hansen HM, Wu X, Spitz MR, Zhang H, Lu EY, Wenzlaff AS, Sison JD, Chen W, Seldin MF, Bierut LJ, Bracci PM, Wrensch MR, Schwartz AG, Wiencke JK, Amos CI: Fine-mapping of the 5p15.33, 6p22.1-p21.31 and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans. Cancer Epidemiol Biomarkers Prev 2013;22(2):251-60.

Rice T, Zheng S, Decker PA, Walsh KM, Bracci P, Xiao Y, McCoy LS, Smirnov I, Patoka JS, Hansen HM, Hsuang G, Wiemels JL, Tihan T, Pico A, Prados MD, Chang SM, Berger MS, Fink S, Kollmeyer T, Rynearson A, Voss J, Caron A, Kosel ML, Fridley BL, Lachance DH, Eckel-Passow JE, Sicotte H, O’Neill BP, Giannini C, Wiencke JK, Jenkins RB, Wrensch MR: Inherited variant on chromosome 11q23 increases susceptibility to IDH mutated but not IDH normal gliomas regardless of grade or histology. Neuro-Oncology 2013;15(5):535-41.

Walsh KM, Amos CI, Wenzlaff AS, Gorlov IP, Sison JD, Wu X, Spitz MR, Hansen HM, Lu EY, Lloyd SM, Zhang H, Chen W, Bracci PM, Seldin MF, Wrensch MR, Schwartz AG, Wiencke JK: Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans. Oncotarget 2012;3(11):1428-38.

Jenkins RB, Xiao Y, Sicotte H, Decker PA, Kollmeyer T, Hansen HM, Kosel ML, Zheng S, Walsh KM, Rice T, Bracci P, McCoy LS, Smirnov IS, Patoka JS, Hsuang G, Wiemels JL Tihan T, Pico AR, Prados MD, Chang SM, Berger MS, Caron A, Fink S, Rynearson A, Fridley BL, Buckner JC, O’Neill BP, Giannini C, Lachance DH, Wiencke JK, Eckel-Passow JE, Wrensch MR: A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation. Nat Genet 2012;44(10):1122-5.

DeWan AT, Egan K, Hellenbrand K, Sorrentino K, Pizzoferrato NM, Walsh KM, Bracken MB: Whole-exome sequencing of a pedigree segregating asthma. BMC Med Genet 2012;13(1):95.

Jacobs DI, Walsh KM, Wrensch MR, Jenkins RB, Houlston RS, Bondy ML, Simon M, Sanson M, DeWan AT, Dubrow R: Leveraging Ethnic Group Incidence Variation to Investigate Genetic Susceptibility to Glioma: A Novel Candidate SNP Approach. Front Genet 2012;3:203.

Zhao L, Triche EW, Walsh KM, Bracken MB, Saftlas AF, Hoh J, DeWan AT: Genome-wide association study identifies a maternal copy-number deletion in PSG11 enriched among preeclampsia patients. BMC Pregnancy and Childbirth 2012;12:61.

Claus EB, Walsh KM, Calvocoressi L, Bondy ML, Schildkraut JM, Wrensch M, Wiemels JL: Cigarette smoking and risk of meningioma: the effect of gender. Cancer Epidemiol Biomarkers Prev 2012;21(6):943-50.

Sebastiani P, Solovieff N, DeWan AT*, Walsh KM*, Puca A, Hartley SW, Melista E, Dworkis DD, Wilks JB, Meyers RH, Steinberg MH, Montano M, Baldwin CT, Hoh J*, Perls TT: Genetic signatures of exceptional longevity in humans. PLoS One 2012;7(1):e29848.

Bracci PM, Sison J, Hansen H, Walsh KM, Wrensch M, Wiencke JK: Cigarette smoking associated with lung adenocarcinoma in situ in a large case-control study (SFBALCS). J Thorac Oncol 2012;7(9):1352-60.

Walsh KM, Choi M, Kulke M, Yao J, Wu C, Jurkiewicz M, Hsu L, Vosburgh E, Sackler R, Lifton R, Hooshmand SM, Hassan M, Janson ET, Cunningham J, Oberg K, Dewan AT, Hoh J: A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum. Endocrine-Related Cancer 2011;8:171-180.

Walsh KM, Bracken MB: Copy-Number Variation in the Dosage-Sensitive 16p11.2 Interval Accounts for Only a Small Proportion of Autism Incidence: a Systematic Review and Meta-Analysis. Genetics in Medicine 2011;13(5): 377-384.

Wu C, Walsh KM, DeWan AT, Hoh J, Wang Z. Disease risk prediction with rare and common variants. BMC Proceedings 2011;5(Suppl 9): S61.

Murk WK, Walsh KM, Hsu L, Zhao L, Bracken MB, DeWan AT: Attempted replication of 50 reported asthma risk genes identifies SNPs in RAD50 and PTPRE as associated with childhood atopic asthma. Hum Hered 2011;71(2): 97-105.

Kochar R, Walsh KM, Jain A, Spalding SJ, Hashkes PJ. Decreased use of non-steroidal anti-inflammatory drugs for the treatment of juvenile idiopathic arthritis in the era of modern aggressive treatment. Rheumatol Int 2012;32(10):3055-60.

Walsh KM, Bracken MB, Murk WK, Hoh J, Dewan AT: Association between reduced copy-number at T-cell receptor gamma (TCRgamma) and childhood allergic asthma: A possible role for somatic mosaicism. Mutat Res 2010;90(1-2):89-94.

Clendenning M, Baze ME, Sun S, Walsh KM, Liyanarachchi S, Fix D, Schunemann V, Comeras I, Deacon M, Lynch JF, Gong G, Thomas BC, Thibodeau SN, Lynch HT, Hampel H, de la Chapelle A: Origins and prevalence of the American Founder Mutation of MSH2. Cancer Res 2008;68(7):2145-2153.