Ziv lab at UCSF

Our research:  We are interested in understanding cancer from susceptibility, to progression, to response to therapy. We use a human genetics approach, focusing mainly on the germline (both common and rare variation) but also occasionally studying the tumor at the level of somatic mutation/copy number, and gene expression.  We primarily study breast cancer, but also have projects in multiple myeloma and non-small cell lung cancer.

A special emphasis in our lab is the study of populations underrepresented in medical research.  We are motivated to study these populations for two related reasons: (1) We believe that the discoveries from human genetics will help improve medical care. For all populations to benefit, discovery and validation need to be performed in each population. (2) Since the study of human genetics focuses on human genetic variation, enhancing genetic variation by studying new populations is clearly beneficial.

News:

6/30/2019: Yiwey's K08 application has been funded.  Congratulations Yiwey!

6/24/2019: Our paper with Jeffrey Weitzel and Susan Neuhausen on founder mutations in CHEK2 and PALB2 in Latinas is published in Cancer

5/1/2019:  Elad, Niharika Dixit from ZSFG, Laura Fejerman from UCSF, Susan Neuhausen from City of Hope and Luis Carvajal-Carmona from UC Davis visit Sacramento for the kickoff of the California Initiative to Advance Precision Medicine on genetics of breast cancer in Latinas.

 

Current Projects:

Genetics of Breast Cancer in Latinas: 

Breast cancer is the most common non-skin cancer affecting women of all racial/ethnic groups in the U.S. and the most common cause of cancer mortality in Latinas.  One of the major goals of our lab is to understand genetic risk for breast cancer susceptibility in Latina women.  We are pursuing this goal using a variety of approaches including genome wide association and whole exome sequencing.

GWAS: We have an ongoing effort with several colleagues to identify common variants associated with breast cancer in Latinas in the U.S. As part of this project, we identified 6q25 as a locus associated with risk in this population. Specifically, we found an allele which originates from Indigenous American ancestors and, is therefore only common among Latinas with Indigenous ancestry, and which is highly protective for breast cancer risk. Women with one copy of the allele (~20% of Latinas from Mexico or Central America) have ~40% lower risk of breast cancer; women with 2 copies of this allele are even more protected. Of note, this allele is even more protective against estrogen receptor-negative breast cancer, which tends to be a higher risk subset of breast cancer. 

Germline Exome Sequencing: We are using whole exome sequencing to identify genes and rare variants in those genes which are associated with breast cancer in Latinas.  This project is a collaboration with Susan Neuhuasen at City of Hope and funded by NCI and the California Initiative to Advance Precision Medicine. 

Analysis of Breast Tumors from Latina women:  We are using paired tumor/normal whole exome sequencing to identify the genomic loci, and the genes which are frequently amplified, deleted and/or mutated in breast tumors from Latinas. We are also working with RNA-seq data to understand how particular pathways may be contributing to the progression of breast cancer in Latina women.  This project is a collaboration with Susan Neuhuasen at City of Hope and funded by NCI and the California Initiative to Advance Precision Medicine. 

Genetics of Multiple Myeloma:  

Multiple myeloma is a malignancy of plasma cells (antibody producing cells) and is among the most common hematological malignancies (cancers affecting components of the blood or lymph system).  Although substantial improvements have been made in treatment of myeloma, it remains a disease for which there is no cure.  We are studying how germline genetic variants contribute to multiple myeloma susceptibility and progression.  

Genetics of Immunotherapy: 

The immune system is increasingly being recognized as an important predictor of survival among patients with many different types of cancer.  In addition, therapies that target the immune system are routinely being used now to treat (and in some cases achieve long-term complete remissinons) across many cancer types.  However, not all patients respond to immunotherapy and many patients also get immune related adverse events (irAEs), which, in many cases resemble autoimmune diseases.  We are studying how germline genetic variation may affect tumor immune response and irAEs.

People:

Principal Investigator:

Elad Ziv, MD

Junior Faculty:

Yiwey Shieh, MD

Staff:

Donglei Hu, PhD, Statistical Geneticist

Scott Huntsman, MS, Programmer

Min Li, Laboratory Technician

Eduardo Cardenas, Clinical Research Coordinator

Students:

Simrin Bain, BS, Visiting Student 

Caroline Face, BS, UCSF Medical Student

Kyle Roter, BS, UCSF Medical Student

 

Selected Publications:

Genetics of Breast Cancer in Latinas:

Weitzel JN, Neuhausen SL, Adamson A, Tao S, Ricker C, Maoz A, Rosenblatt M, Nehoray B, Sand S, Steele L, Unzeitig G, Feldman N, Blanco AM, Hu D, Huntsman S, Castillo D, Haiman C, Slavin T, Ziv E. Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA-negative Hispanics with breast cancer. Cancer. 2019. Epub 2019/06/18. doi: 10.1002/cncr.32083. PubMed PMID: 31206626.

Hoffman J, Fejerman L, Hu D, Huntsman S, Li M, John EM, Torres-Mejia G, Kushi L, Ding YC, Weitzel J, Neuhausen SL, Lott P, Consortium C, Echeverry M, Carvajal-Carmona L, Burchard E, Eng C, Long J, Zheng W, Olopade O, Huo D, Haiman C, Ziv E. Identification of novel common breast cancer risk variants at the 6q25 locus among Latinas. Breast Cancer Res. 2019;21(1):3. Epub 2019/01/16. doi: 10.1186/s13058-018-1085-9. PubMed PMID: 30642363; PMCID: PMC6332913.

Fejerman L, Ahmadiyeh N, Hu D, Huntsman S, Beckman KB, Caswell JL, Tsung K, John EM, Torres-Mejia G, Carvajal-Carmona L, Echeverry MM, Tuazon AM, Ramirez C, Consortium C, Gignoux CR, Eng C, Gonzalez-Burchard E, Henderson B, Le Marchand L, Kooperberg C, Hou L, Agalliu I, Kraft P, Lindstrom S, Perez-Stable EJ, Haiman CA, Ziv E. Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25. Nat Commun. 2014;5:5260. Epub 2014/10/21. doi: 10.1038/ncomms6260. PubMed PMID: 25327703; PMCID: PMC4204111.

Fejerman L, Hu D, Huntsman S, John EM, Stern MC, Haiman CA, Perez-Stable EJ, Ziv E. Genetic ancestry and risk of mortality among U.S. Latinas with breast cancer. Cancer research. 2013;73(24):7243-53. doi: 10.1158/0008-5472.CAN-13-2014. PubMed PMID: 24177181; PMCID: 3881587.

Fejerman L, Chen GK, Eng C, Huntsman S, Hu D, Williams A, Pasaniuc B, John EM, Via M, Gignoux C, Ingles S, Monroe KR, Kolonel LN, Torres-Mejia G, Perez-Stable EJ, Burchard EG, Henderson BE, Haiman CA, Ziv E. Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas. Human molecular genetics. 2012;21(8):1907-17. doi: 10.1093/hmg/ddr617. PubMed PMID: 22228098; PMCID: 3313799.

Other Breast Cancer:

Shieh Y, Hu D, Ma L, Huntsman S, Gard CC, Leung JWT, Tice JA, Ziv E, Kerlikowske K, Cummings SR. Joint relative risks for estrogen receptor-positive breast cancer from a clinical model, polygenic risk score, and sex hormones. Breast cancer research and treatment. 2017;166(2):603-12. doi: 10.1007/s10549-017-4430-2. PubMed PMID: 28791495; PMCID: PMC5669824.

Ziv E, Tice JA, Sprague B, Vachon CM, Cummings SR, Kerlikowske K. Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention. PloS one. 2017;12(1):e0168601. doi: 10.1371/journal.pone.0168601. PubMed PMID: 28107349; PMCID: PMC5249071.

Shieh Y, Hu D, Ma L, Huntsman S, Gard CC, Leung JW, Tice JA, Vachon CM, Cummings SR, Kerlikowske K, Ziv E. Breast cancer risk prediction using a clinical risk model and polygenic risk score. Breast cancer research and treatment. 2016;159(3):513-25. doi: 10.1007/s10549-016-3953-2. PubMed PMID: 27565998; PMCID: PMC5033764.

Hoffman JD, Graff RE, Emami NC, et al. Cis-eQTL-based trans-ethnic meta-analysis reveals novel genes associated with breast cancer risk. PLoS Genet. 2017;13(3):e1006690.

Caswell JL, Camarda R, Zhou AY, Huntsman S, Hu D, Brenner SE, Zaitlen N, Goga A, Ziv E. Multiple breast cancer risk variants are associated with differential transcript isoform expression in tumors. Human molecular genetics. 2015;24(25):7421-31. doi: 10.1093/hmg/ddv432. PubMed PMID: 26472073; PMCID: 4664170

Caswell JL, Kerlikowske K, Shepherd JA, Cummings SR, Hu D, Huntsman S, Ziv E. High mammographic density in women of Ashkenazi Jewish descent. Breast cancer research : BCR. 2013;15(3):R40. doi: 10.1186/bcr3424. PubMed PMID: 23668689.

Genetics of Multiple Myeloma:

Ziv E, Dean E, Hu D, et al. Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients. Nat Commun. 2015;6:7539.

Rand KA, Song C, Dean E, et al. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci. Cancer Epidemiol Biomarkers Prev. 2016;25(12):1609-1618.

Datasets:

San Francisco Bay Area Cancer Study:  dbGaP Study Accession: phs000912.v1.p1 

California Pacific Medical Center Research Institute Breast Health Cohort: dbGaP Study Accession: phs000395.v1.p1