Research Summary

I have extensive experience in the design and statistical analysis of genetic epidemiologic projects. My research program encompasses a synthesis of methodological and applied genetic epidemiology, with the overall aim of deciphering the mechanisms underlying complex diseases and traits. I have developed widely used methods and software for studying rare genetic variants, pathways, interactions, and genome-wide association studies. I am applying these methods to studies of cancer, birth defects, and pharmacogenomics. Current projects in my lab include developing methods for effectively evaluating pleiotropy, determining the germline and somatic basis of prostate cancer risk and aggressiveness, and detecting genes that impact drug / treatment response. We have also recently been evaluating the use of cell free DNA (liquid biopsies) for prediction of prostate cancer risk and progression. In addition, I direct an NIH-Funded post-Doctoral training grant in Genetic Cancer Epidemiology, and have mentored over 40 pre- and post-doctoral fellows.

Research Funding

  • June 16, 2021 - May 31, 2026 - Leveraging Diversity in Cancer Epidemiology Cohorts and Novel Methods to Improve Polygenic Risk Scores , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01CA261339
  • December 1, 2004 - June 30, 2025 - Training in the Molecular & Genetic Epidemiology of Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32CA112355
  • April 1, 2020 - March 31, 2024 - Precision Prostate Cancer Screening with Genetically Adjusted Prostate-Specific Antigen Levels , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA241410
  • August 5, 1999 - May 31, 2023 - Cancer Center Support Grant , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P30CA082103

Education

University of California, Santa Barbara, CA, BS, 1986, Mathematical Sciences
University of California, Berkeley, CA, MS, 1988, Industrial Engineering and Operations Research
University of California, Los Angeles, CA, PhD, 1994, Epidemiology

Honors & Awards

  • 1986
    Undergraduate Honors, University of California, Santa Barbara
  • 1989-1994
    National Research Service Award, NIH
  • 1994
    Ruth F. Richards Outstanding Student Award, UCLA School of Public Health Alumni Association
  • 1999-2000
    Glennan Fellow, Case Western Reserve University
  • 2002-2003
    Visiting Scientist Award, International Agency for Research on Cancer
  • 2010
    Directors Invited Lecture, NHGRI / NIH
  • 2011
    Stephen B. Hulley Award for Excellence In Teaching, UCSF Training in Clinical Research
  • 2016
    Up for a Challenge Grand Prize, National Cancer Institute
  • 2017
    Robert Millikan Symposium Memorial Lecture, Univ North Carolina Lineberger Comprehensive Cancer Center
  • 2018
    Leadership Award, International Genetic Epidemiology Society

Selected Publications

  1. Kachuri L, Chatterjee N, Hirbo J, Schaid DJ, Martin I, Kullo IJ, Kenny EE, Pasaniuc B, Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium Methods Working Group, Witte JS, Ge T. Principles and methods for transferring polygenic risk scores across global populations. Nat Rev Genet. 2023 Aug 24.  View on PubMed
  2. Huang M, Lyu C, Liu N, Nembhard WN, Witte JS, Hobbs CA, Li M, National Birth Defects Prevention Study. A gene-based association test of interactions for maternal-fetal genotypes identifies genes associated with nonsyndromic congenital heart defects. Genet Epidemiol. 2023 Jun 21.  View on PubMed
  3. Darst BF, Shen J, Madduri RK, Rodriguez AA, Xiao Y, Sheng X, Saunders EJ, Dadaev T, Brook MN, Hoffmann TJ, Muir K, Wan P, Le Marchand L, Wilkens L, Wang Y, Schleutker J, MacInnis RJ, Cybulski C, Neal DE, Nordestgaard BG, Nielsen SF, Batra J, Clements JA, Cancer BioResource AP, Grönberg H, Pashayan N, Travis RC, Park JY, Albanes D, Weinstein S, Mucci LA, Hunter DJ, Penney KL, Tangen CM, Hamilton RJ, Parent MÉ, Stanford JL, Koutros S, Wolk A, Sørensen KD, Blot WJ, Yeboah ED, Mensah JE, Lu YJ, Schaid DJ, Thibodeau SN, West CM, Maier C, Kibel AS, Cancel-Tassin G, Menegaux F, John EM, Grindedal EM, Khaw KT, Ingles SA, Vega A, Rosenstein BS, Teixeira MR, NC-LA PCaP Investigators, Kogevinas M, Cannon-Albright L, Huff C, Multigner L, Kaneva R, Leach RJ, Brenner H, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Neuhausen SL, Isaacs WB, Nemesure B, Hennis AJ, Carpten J, Pandha H, De Ruyck K, Xu J, Razack A, Teo SH, Canary PASS Investigators, Newcomb LF, Fowke JH, Neslund-Dudas C, Rybicki BA, Gamulin M, Usmani N, Claessens F, Gago-Dominguez M, Castelao JE, Townsend PA, Crawford DC, Petrovics G, Casey G, Roobol MJ, Hu JF, Berndt SI, Van Den Eeden SK, Easton DF, Chanock SJ, Cook MB, Wiklund F, Witte JS, Eeles RA, Kote-Jarai Z, Watya S, Gaziano JM, Justice AC, Conti DV, Haiman CA. Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry. Am J Hum Genet. 2023 Jul 06; 110(7):1200-1206.  View on PubMed
  4. Yee SW, Macdonald C, Mitrovic D, Zhou X, Koleske ML, Yang J, Silva DB, Grimes PR, Trinidad D, More SS, Kachuri L, Witte JS, Delemotte L, Giacomini KM, Coyote-Maestas W. The full spectrum of OCT1 (SLC22A1) mutations bridges transporter biophysics to drug pharmacogenomics. bioRxiv. 2023 Jun 07.  View on PubMed
  5. Kachuri L, Hoffmann TJ, Jiang Y, Berndt SI, Shelley JP, Schaffer KR, Machiela MJ, Freedman ND, Huang WY, Li SA, Easterlin R, Goodman PJ, Till C, Thompson I, Lilja H, Van Den Eeden SK, Chanock SJ, Haiman CA, Conti DV, Klein RJ, Mosley JD, Graff RE, Witte JS. Genetically adjusted PSA levels for prostate cancer screening. Nat Med. 2023 Jun; 29(6):1412-1423.  View on PubMed
  6. Hiatt RA, Worden L, Rehkopf D, Engmann N, Troester M, Witte JS, Balke K, Jackson C, Barlow J, Fenton SE, Gehlert S, Hammond RA, Kaplan G, Kornak J, Nishioka K, McKone T, Smith MT, Trasande L, Porco TC. A complex systems model of breast cancer etiology: The Paradigm II Model. PLoS One. 2023; 18(5):e0282878.  View on PubMed
  7. Shieh Y, Roger J, Yau C, Wolf DM, Hirst GL, Swigart LB, Huntsman S, Hu D, Nierenberg JL, Middha P, Heise RS, Shi Y, Kachuri L, Zhu Q, Yao S, Ambrosone CB, Kwan ML, Caan BJ, Witte JS, Kushi LH, 't Veer LV, Esserman LJ, Ziv E. Development and testing of a polygenic risk score for breast cancer aggressiveness. NPJ Precis Oncol. 2023 May 15; 7(1):42.  View on PubMed
  8. Darst BF, Shen J, Madduri RK, Rodriguez AA, Xiao Y, Sheng X, Saunders EJ, Dadaev T, Brook MN, Hoffmann TJ, Muir K, Wan P, Le Marchand L, Wilkens L, Wang Y, Schleutker J, MacInnis RJ, Cybulski C, Neal DE, Nordestgaard BG, Nielsen SF, Batra J, Clements JA, Australian Prostate Cancer BioResource, Grönberg H, Pashayan N, Travis RC, Park JY, Albanes D, Weinstein S, Mucci LA, Hunter DJ, Penney KL, Tangen CM, Hamilton RJ, Parent MÉ, Stanford JL, Koutros S, Wolk A, Sørensen KD, Blot WJ, Yeboah ED, Mensah JE, Lu YJ, Schaid DJ, Thibodeau SN, West CM, Maier C, Kibel AS, Cancel-Tassin G, Menegaux F, John EM, Grindedal EM, Khaw KT, Ingles SA, Vega A, Rosenstein BS, Teixeira MR, NC-LA PCaP Investigators, Kogevinas M, Cannon-Albright L, Huff C, Multigner L, Kaneva R, Leach RJ, Brenner H, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Neuhausen SL, Isaacs WB, Nemesure B, Hennis AJ, Carpten J, Pandha H, De Ruyck K, Xu J, Razack A, Teo SH, Canary PASS Investigators, Newcomb LF, Fowke JH, Neslund-Dudas C, Rybicki BA, Gamulin M, Usmani N, Claessens F, GagoDominguez M, Castelao JE, Townsend PA, Crawford DC, Petrovics G, Casey G, Roobol MJ, Hu JF, Berndt SI, Van Den Eeden SK, Easton DF, Chanock SJ, Cook MB, Wiklund F, Witte JS, Eeles RA, Kote-Jarai Z, Watya S, Gaziano JM, Justice AC, Conti DV, Haiman CA. Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry. medRxiv. 2023 May 15.  View on PubMed
  9. Chen DM, Dong R, Kachuri L, Hoffmann T, Jiang Y, Berndt SI, Shelley JP, Schaffer KR, Machiela MJ, Freedman ND, Huang WY, Li SA, Lilja H, Van Den Eeden SK, Chanock S, Haiman CA, Conti DV, Klein RJ, Mosley JD, Witte JS, Graff RE. Transcriptome-Wide Association Analysis Identifies Novel Candidate Susceptibility Genes for Prostate-Specific Antigen Levels in Men Without Prostate Cancer. medRxiv. 2023 May 05.  View on PubMed
  10. Schaffer KR, Shi M, Shelley JP, Tosoian JJ, Kachuri L, Witte JS, Mosley JD. A Polygenic Risk Score for Prostate Cancer Risk Prediction. JAMA Intern Med. 2023 04 01; 183(4):386-388.  View on PubMed
  11. Chen F, Madduri RK, Rodriguez AA, Darst BF, Chou A, Sheng X, Wang A, Shen J, Saunders EJ, Rhie SK, Bensen JT, Ingles SA, Kittles RA, Strom SS, Rybicki BA, Nemesure B, Isaacs WB, Stanford JL, Zheng W, Sanderson M, John EM, Park JY, Xu J, Wang Y, Berndt SI, Huff CD, Yeboah ED, Tettey Y, Lachance J, Tang W, Rentsch CT, Cho K, Mcmahon BH, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Sellers TA, Yamoah K, Murphy AB, Crawford DC, Patel AV, Bush WS, Aldrich MC, Cussenot O, Petrovics G, Cullen J, Neslund-Dudas CM, Stern MC, Kote-Jarai Z, Govindasami K, Cook MB, Chokkalingam AP, Hsing AW, Goodman PJ, Hoffmann TJ, Drake BF, Hu JJ, Keaton JM, Hellwege JN, Clark PE, Jalloh M, Gueye SM, Niang L, Ogunbiyi O, Idowu MO, Popoola O, Adebiyi AO, Aisuodionoe-Shadrach OI, Ajibola HO, Jamda MA, Oluwole OP, Nwegbu M, Adusei B, Mante S, Darkwa-Abrahams A, Mensah JE, Diop H, Van Den Eeden SK, Blanchet P, Fowke JH, Casey G, Hennis AJ, Lubwama A, Thompson IM, Leach R, Easton DF, Preuss MH, Loos RJ, Gundell SM, Wan P, Mohler JL, Fontham ET, Smith GJ, Taylor JA, Srivastava S, Eeles RA, Carpten JD, Kibel AS, Multigner L, Parent MÉ, Menegaux F, Cancel-Tassin G, Klein EA, Andrews C, Rebbeck TR, Brureau L, Ambs S, Edwards TL, Watya S, Chanock SJ, Witte JS, Blot WJ, Michael Gaziano J, Justice AC, Conti DV, Haiman CA. Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry. Eur Urol. 2023 07; 84(1):13-21.  View on PubMed
  12. Wand H, Martschenko DO, Smitherman A, Michelson S, Pun T, Witte JS, Scott SA, Cho MK, Ashley EA, Preventive Genomics Program Co-Design Working Group. Re-envisioning community genetics: community empowerment in preventive genomics. J Community Genet. 2023 Feb 11.  View on PubMed
  13. Leapman MS, Wang R, Loeb S, Seibert TM, Gaylis FD, Lowentritt B, Brown GA, Chen R, Lin D, Witte J, Cooperberg MR, Catalona WJ, Gross CP, Ma X. Use of Monitoring Tests Among Patients With Localized Prostate Cancer Managed With Observation. J Urol. 2023 04; 209(4):710-718.  View on PubMed
  14. Cavazos TB, Kachuri L, Graff RE, Nierenberg JL, Thai KK, Alexeeff S, Van Den Eeden S, Corley DA, Kushi LH, Regeneron Genetics Center, Hoffmann TJ, Ziv E, Habel LA, Jorgenson E, Sakoda LC, Witte JS. Assessment of genetic susceptibility to multiple primary cancers through whole-exome sequencing in two large multi-ancestry studies. BMC Med. 2022 10 06; 20(1):332.  View on PubMed
  15. Lyu C, Huang M, Liu N, Chen Z, Lupo PJ, Tycko B, Witte JS, Hobbs CA, Li M. Random field modeling of multi-trait multi-locus association for detecting methylation quantitative trait loci. Bioinformatics. 2022 08 10; 38(16):3853-3862.  View on PubMed
  16. Gabriel AAG, Atkins JR, Penha RCC, Smith-Byrne K, Gaborieau V, Voegele C, Abedi-Ardekani B, Milojevic M, Olaso R, Meyer V, Boland A, Deleuze JF, Zaridze D, Mukeriya A, Swiatkowska B, Janout V, Schejbalová M, Mates D, Stojšic J, Ognjanovic M, ILCCO consortium, Witte JS, Rashkin SR, Kachuri L, Hung RJ, Kar S, Brennan P, Sertier AS, Ferrari A, Viari A, Johansson M, Amos CI, Foll M, McKay JD. Genetic Analysis of Lung Cancer and the Germline Impact on Somatic Mutation Burden. J Natl Cancer Inst. 2022 08 08; 114(8):1159-1166.  View on PubMed
  17. Byun J, Han Y, Li Y, Xia J, Long E, Choi J, Xiao X, Zhu M, Zhou W, Sun R, Bossé Y, Song Z, Schwartz A, Lusk C, Rafnar T, Stefansson K, Zhang T, Zhao W, Pettit RW, Liu Y, Li X, Zhou H, Walsh KM, Gorlov I, Gorlova O, Zhu D, Rosenberg SM, Pinney S, Bailey-Wilson JE, Mandal D, de Andrade M, Gaba C, Willey JC, You M, Anderson M, Wiencke JK, Albanes D, Lam S, Tardon A, Chen C, Goodman G, Bojeson S, Brenner H, Landi MT, Chanock SJ, Johansson M, Muley T, Risch A, Wichmann HE, Bickeböller H, Christiani DC, Rennert G, Arnold S, Field JK, Shete S, Le Marchand L, Melander O, Brunnstrom H, Liu G, Andrew AS, Kiemeney LA, Shen H, Zienolddiny S, Grankvist K, Johansson M, Caporaso N, Cox A, Hong YC, Yuan JM, Lazarus P, Schabath MB, Aldrich MC, Patel A, Lan Q, Rothman N, Taylor F, Kachuri L, Witte JS, Sakoda LC, Spitz M, Brennan P, Lin X, McKay J, Hung RJ, Amos CI. Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer. Nat Genet. 2022 08; 54(8):1167-1177.  View on PubMed
  18. Mabry PL, Pronk NP, Amos CI, Witte JS, Wedlock PT, Bartsch SM, Lee BY. Cancer systems epidemiology: Overcoming misconceptions and integrating systems approaches into cancer research. PLoS Med. 2022 06; 19(6):e1004027.  View on PubMed
  19. Hayes-Larson E, Shaw C, Ackley SF, Zimmerman SC, Glymour MM, Graff RE, Witte JS, Kobayashi LC, Mayeda ER. The Role of Dementia Diagnostic Delay in the Inverse Cancer-Dementia Association. J Gerontol A Biol Sci Med Sci. 2022 06 01; 77(6):1254-1260.  View on PubMed
  20. Rashkin SR, Cleves M, Shaw GM, Nembhard WN, Nestoridi E, Jenkins MM, Romitti PA, Lou XY, Browne ML, Mitchell LE, Olshan AF, Lomangino K, Bhattacharyya S, Witte JS, Hobbs CA, National Birth Defects Prevention Study. A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study. Am J Med Genet A. 2022 08; 188(8):2303-2314.  View on PubMed

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