Kristine Yoder, PhD

Current OSU Appointment

Assistant Professor, SBS-Molec Vir, Imm & Med Gen

Biographical

I am deeply intrigued by the duality retroviruses offer the field of medicine: debilitating disease exemplified by HIV and miraculous cures via retroviral gene therapy. As a young scientist in the early 1990s at Stanford University in the lab of David Relman, MD, I used PCR and sequencing of rDNA genes of unrecognizable pathogens in AIDS patients from San Francisco which led to several co-author publications as well as a first author book chapter. Retroviruses, including HIV, are distinguished by their enzymes reverse transcription and integration. I studied HIV integration as a graduate student at the Salk Institute in the lab of Rick Bushman, PhD, from 1996 to 2000. My major goal was to determine which host DNA repair pathway completes the integration reaction. My research suggested that redundant pathways likely serve this function for which I was first author of a paper in Journal of Virology. Dissatisfied with that ambiguous conclusion, I went on to investigate the roles of DNA repair pathways during retroviral infection as a postdoctoral fellow at the Kimmel Cancer Center and at OSUMC with Rick Fishel, PhD, from 2001 to 2006. I found that the host DNA repair proteins XPB and XPD are part of an evolutionarily ancient host defense pathway that protects the genome from integrative assault. These findings led to a first author publication in Proceedings of the National Academy of Sciences. In 2006 I was appointed a Research Assistant Professor at OSUMC and began a collaboration with basic science researchers at Merck Pharmaceuticals led by Daria Hazuda, PhD. That group discovered through an siRNA screen that the host DNA base excision repair pathway was important for efficient HIV infection. I was able to show that proteins of the base excision repair pathway specifically enhance the integration of lentiviruses, such as HIV, but have no effect on other retroviruses. As a Research Assistant Professor I published 4 first/corresponding author papers and was awarded an NIH R21 grant. I was appointed a tenure track Assistant Professor in September, 2012 and since that time have been awarded an NIH R21 with an impact score of 11. While my graduate and post-graduate work focused on the interactions of host DNA repair pathways with invading retroviral cDNA, I am shifting my focus to dissecting the rules of chromatin that govern integration and targeting integration to sequence specific sites. These studies have implications for HIV disease and better targeting of retroviral gene therapy vectors.

Advising Narrative

Undergraduate

Research advisor: Molly Osterhage (Jan 2013 – present)

Mayers Summer Research Scholarship (Summer 2013)



Undergraduate, honors

Research co-advisor: Geoffrey Bennett (2009-2012)

SOLAR Foundation Research Fund (2010)

Mayers Summer Research Scholarship (Summer 2011)

OSU Arts and Sciences Honors Undergraduate Research Scholarship (2011)

OSU Honors Senior Thesis Research Scholarship (2011)

First author of a manuscript in preparation

Senior Thesis “Effects of OGG1 and MYH glycosylases on HIV-1 integration site preference”

Postdoctoral / Researcher Advising

Paula Vivas-Basto, May, 2013 - present

American Heart Association Postdoctoral Fellowship

Published Works

As a Research Assistant Professor working with only undergraduates, I published 4 papers as the first and corresponding author. I was co-author on an additional 3 papers.



A collaboration with Merck Pharmaceuticals led to joint publication of 2 papers in PLoS ONE. These studies showed that HIV pirates the host oxidative base excision repair pathway during integration. Subsequent work in my lab indicates that HIV interactions with the proteins of this DNA repair pathway are not responsible for enhanced integration; in fact, the DNA intermediates of the repair pathway are targeted by HIV integrase. Two papers are in preparation describing this preference of HIV integrase for DNA oxidative repair intermediates. This realization has clinical implications as HIV infection as well as anti-retroviral therapies that lead to increased oxidative stress and reactive oxygen species in patients.



As a tenure track Assistant Professor I currently have 3 papers in preparation as corresponding author: experiments of Bennett et al and Simon et al (HIV integrase) are complete leaving only the manuscript composition remaining before submission; one experiment remains for Simon et al (PFV integrase), but the manuscript has already been written for submission.

Chapters in Books

Yoder, KE, Sethabutr, O, and Relman, DA. "PCR-based detection of the intestinal pathogen Cyclospora." In PCR Protocols for Emerging Infectious Diseases. Edited by Persing, DH. -. Washington, DC, US|USA: ASM Press, January 1996.

Journal Articles

Relman,D,A; Schmidt,T,M; Gajadhar,A; Sogin,M; Cross,J; Yoder,K; SETHABUTR,O; Echeverria,P. "Molecular phylogenetic analysis of Cyclospora, the human intestinal pathogen, suggests that it is closely related to Eimeria species." JOURNAL OF INFECTIOUS DISEASES. Vol. 173, no. 2. (February 1996.): 440-445.

Relman, DA; Schmidt, TM; Gajadhar, A; Sogin, M; Cross, J; Yoder, K; Sethabutr, O; Echeverria, P. "Molecular phylogenetic analysis of Cyclospora, the human intestinal pathogen, suggests that it is closely related to Eimeria species." JOURNAL OF INFECTIOUS DISEASES. Vol. 173, no. 2. (February 1996.): 440-445.

Fortunato, EA; Sommer, MH; Yoder, K; Spector, DH. "Identification of domains within the human cytomegalovirus major immediate-early 86-kilodalton protein and the retinoblastoma protein required for physical and functional interaction with each other." JOURNAL OF VIROLOGY. Vol. 71, no. 11. (November 1997.): 8176-8185.

Fortunato,E,A; Sommer,M,H; Yoder,K; Spector,D,H. "Identification of domains within the human cytomegalovirus major immediate-early 86-kilodalton protein and the retinoblastoma protein required for physical and functional interaction with each other." JOURNAL OF VIROLOGY. Vol. 71, no. 11. (November 1997.): 8176-8185.

Relman, D.A., D.N. Fredericks, K.E. Yoder, G. Mirowski, T. Berger, and J.E. Koehler.. "Absence of Kaposi's sarcoma-associated herpesvirus DNA in bacillary angiomatosis-peliosis lesions.." Journal of Infectious Diseases. Vol. 180, (January 1999.): 1386-1389.

Yoder,K,E; Bushman,F,D. "Repair of gaps in retroviral DNA integration intermediates." JOURNAL OF VIROLOGY. Vol. 74, no. 23. (December 2000.): 11191-11200.

Yoder, KE; Bushman, FD. "Repair of gaps in retroviral DNA integration intermediates." JOURNAL OF VIROLOGY. Vol. 74, no. 23. (December 2000.): 11191-11200.

Li, L; Yoder, K; Hansen, MST; Olvera, J; Miller, MD; Bushman, FD. "Retroviral cDNA integration: Stimulation by HMG I family proteins." JOURNAL OF VIROLOGY. Vol. 74, no. 23. (December 2000.): 10965-10974.

Li,L; Yoder,K; Hansen,M,ST; Olvera,J; Miller,M,D; Bushman,F,D. "Retroviral cDNA integration: Stimulation by HMG I family proteins." JOURNAL OF VIROLOGY. Vol. 74, no. 23. (December 2000.): 10965-10974.

Li, L; Olvera, JM; Yoder, KE; Mitchell, RS; Butler, SL; Lieber, M; Martin, SL; Bushman, FD. "Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection." EMBO JOURNAL. Vol. 20, no. 12. (June 2001.): 3272-3281.

Li,L; Olvera,J,M; Yoder,K,E; Mitchell,R,S; Butler,S,L; Lieber,M; Martin,S,L; Bushman,F,D. "Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection." EMBO JOURNAL. Vol. 20, no. 12. (June 2001.): 3272-3281.

Olivier, C; van de Pas, S; Lepp, PW; Yoder, K; Relman, DA. "Sequence variability in the first internal transcribed spacer region within and among Cyclospora species is consistent with polyparasitism." INTERNATIONAL JOURNAL FOR PARASITOLOGY. Vol. 31, no. 13. (November 2001.): 1475-1487.

Olivier,C; van de Pas,S; Lepp,P,W; Yoder,K; Relman,D,A. "Sequence variability in the first internal transcribed spacer region within and among Cyclospora species is consistent with polyparasitism." INTERNATIONAL JOURNAL FOR PARASITOLOGY. Vol. 31, no. 13. (November 2001.): 1475-1487.

Olson, PD; Yoder, K; Fajardo, LF; Marty, AM; van de Pas, S; Olivier, C; Relman, DA. "Lethal invasive cestodiasis in immunosuppressed patients." JOURNAL OF INFECTIOUS DISEASES. Vol. 187, no. 12. (June 2003.): 1962-1966.

Martin, ES; Cesari, R; Pentimalli, F; Yoder, K; Fishel, R; Himelstein, AL; Martin, SE; Godwin, AK; Negrini, M; Croce, CM. "The BCSC-1 locus at chromosome 11q23-q24 is a candidate tumor suppressor gene." PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. Vol. 100, no. 20. (September 2003.): 11517-11522.

Martin,E,S; Cesari,R; Pentimalli,F; Yoder,K; Fishel,R; Himelstein,A,L; Martin,S,E; Godwin,A,K; Negrini,M; Croce,C,M. "The BCSC-1 locus at chromosome 11q23-q24 is a candidate tumor suppressor gene." PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. Vol. 100, no. 20. (September 2003.): 11517-11522.

Picchio, MC; Martin, ES; Cesari, R; Calin, GA; Yendamuri, S; Kuroki, T; Pentimalli, F; Sarti, M; Yoder, K; Kaiser, LR; Fishel, R; Croce, CM. "Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer." CLINICAL CANCER RESEARCH. Vol. 10, no. 8. (April 2004.): 2720-2724.

Picchio,M,C; Martin,E,S; Cesari,R; Calin,G,A; Yendamuri,S; Kuroki,T; Pentimalli,F; Sarti,M; Yoder,K; Kaiser,L,R; Fishel,R; Croce,C,M. "Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer." CLINICAL CANCER RESEARCH. Vol. 10, no. 8. (April 2004.): 2720-2724.

Yoder, K., A. Sarasin, K. Kraemer, M. McIlhatton, F. Bushman, and R. Fishel.. "The DNA repair genes XPB and XPD defend cells from retroviral infection.." Proc Natl Acad Sci U S A. Vol. 103, (January 2006.): 4622-4627.

Yoder, K. E., and R. Fishel.. "PCR-based detection is unable to consistently distinguish HIV 1LTR circles.." J Virol Methods. Vol. 138, (January 2006.): 201-206.

Yoder,Kristine,E; Fishel,Richard. "PCR-based detection is unable to consistently distinguish HIV 1LTR circles." JOURNAL OF VIROLOGICAL METHODS. Vol. 138, no. 1-2. (December 2006.): 201-206.

Shim, K. S., C. Schmutte, K. Yoder, and R. Fishel.. "Defining the salt effect on human RAD51 activities.." DNA Repair (Amst). Vol. 5, (January 2006.): 718-730.

Yoder,K; Sarasin,A; Kraemer,K; McIlhatton,M; Bushman,F; Fishel,R. "The DNA repair genes XPB and XPD defend cells from retroviral infection." PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. Vol. 103, no. 12. (March 2006.): 4622-4627.

Shim,Kang-Sup; Schmutte,Christoph; Yoder,Kristine; Fishel,Richard. "Defining the salt effect on human RAD51 activities." DNA REPAIR. Vol. 5, no. 6. (June 2006.): 718-730.

Ikura, T; Tashiro, S; Kakino, A; Shima, H; Jacob, N; Amunugama, R; Yoder, K; Izumi, S; Kuraoka, I; Tanaka, K; Kimura, H; Ikura, M; Nishikubo, S; Ito, T; Muto, A; Miyagawa, K; Takeda, S; Fishel, R; Igarashi, K; Kamiya, K. "DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics." Molecular and Cellular Biology. (January 2007.): -.

Ikura,Tsuyoshi; Tashiro,Satoshi; Kakino,Akemi; Shima,Hiroki; Jacob,Naduparambil; Amunugarna,Ravindra; Yoder,Kristine; Izumi,Shunsuke; Kuraoka,Isao; Tanaka,Kiyoji; Kimura,Hiroshi; Tkura,Masae; Nishikubo,Shuichi; Ito,Takashi; Muto,Akihiko; Miyagawa,Kiyoshi; Takeda,Shunichi; Fishel,Richard; Igarashi,Kazuhiko; Kamiya,Kenji. "DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics." MOLECULAR AND CELLULAR BIOLOGY. Vol. 27, no. 20. (October 2007.): 7028-7040.

Yoder, K. E.Fishel, R.. "Real-time quantitative PCR and fast QPCR have similar sensitivity and accuracy with HIV cDNA late reverse transcripts and 2-LTR circles.." J Virol Methods. Vol. 153, (January 2008.): 253-256.

Yoder,Kristine,E; Fishel,Richard. "Real-time quantitative PCR and fast QPCR have similar sensitivity and accuracy with HIV cDNA late reverse transcripts and 2-LTR circles." JOURNAL OF VIROLOGICAL METHODS. Vol. 153, no. 2. (November 2008.): 253-256.

Charbonneau, N., R. Amunugama, C. Schmutte, K. Yoder, and R. Fishel. "Evidence that hMLH3 functions primarily in meiosis and in hMSH2-hMSH3 mismatch repair." Cancer Biology and Therapy. Vol. 8, no. 14. (January 2009.): 1411-1420.

Charbonneau,Nicole; Amunugama,Ravindra; Schmutte,Christoph; Yoder,Kristine; Fishel,Richard. "Evidence that hMLH3 functions primarily in meiosis and in hMSH2-hMSH3 mismatch repair." CANCER BIOLOGY & THERAPY. Vol. 8, no. 14. (July 2009.): 1411-1420.

Yoder, K.E.*, W. Roddick, P. Hoellerbauer, and R. Fishel.. "XPB mediated retroviral cDNA degradation coincides with entry to the nucleus.." Virology. Vol. 410, (January 2011.): 291-298.

Yoder, K.E.*, A. Espeseth, X. Wang, Q. Fang, M.T. Russo, R.S. Lloyd, D. Hazuda, R.W. Sobol, and R. Fishel.. "The host base excision repair pathway is required for efficient lentivirus integration.." PLoS ONE. (January 2011.): -.

Espeseth,Amy,S; Fishel,Rick; Hazuda,Daria; Huang,Qian; Xu,Min; Yoder,Kristine; Zhou,Honglin. "siRNA Screening of a Targeted Library of DNA Repair Factors in HIV Infection Reveals a Role for Base Excision Repair in HIV Integration." PLOS ONE. Vol. 6, no. 3. (March 2011.): e17612-.

Yoder,Kristine,E; Roddick,William; Hoellerbauer,Pia; Fishel,Richard. "XPB mediated retroviral cDNA degradation coincides with entry to the nucleus." VIROLOGY. Vol. 410, no. 2. (February 2011.): 291-298.

Yoder,Kristine,E; Espeseth,Amy; Wang,Xiao-hong; Fang,Qingming; Russo,Maria,Teresa; Lloyd,R,Stephen; Hazuda,Daria; Sobol,Robert,W; Fishel,Richard. "The Base Excision Repair Pathway Is Required for Efficient Lentivirus Integration." PLOS ONE. Vol. 6, no. 3. (March 2011.): e17862-.

Espeseth, A.S., R. Fishel, D. Hazuda, Q. Huang, M. Xu, K. Yoder, and H. Zhou.. "siRNA screening of a targeted library of DNA repair factors in HIV infection reveals a role for base excision repair in HIV integration.." PLoS ONE. (January 2011.): -.

Reference Works

November 1995	Yoder, K, Kroes, I, Fredericks, D, Relman, D."Exploring the diversity of uncultivated microbial pathogens with amplified ribosomal DNA sequences" Palo Alto.
November 1999	Yoder, K, Bushman, F."Gap repair following retroviral integration" Hilton Head.
May 2000	Yoder, K, Bushman, F."Gap repair following retroviral integration" Cold Spring Harbor.
November 2004	Yoder, K, Sarasain, A, Kraemer, K, McIlhatton, M, Bushman, F, Fishel, R."Host DNA repair proteins affect HIV cDNA stability" Hamilton.
January 2005	Yoder, K, Sarasain, A, Kraemer, K, McIlhatton, M, Bushman, F, Fishel, R."The DNA repair genes XPB and XPD defend cells from HIV integration" Columbus.
May 2006	Yoder, K, Fishel, R."The DNA repair genes XPB and XPD participate in the degradation of retroviral cDNA" Cold Spring Harbor.
May 2007	Yoder, K, Roddick, W, Sarasin, A, Kraemer, K, Fishel, R."The host DNA repair proteins XPB an XPD medicate a novel host nuclear defense against retroviruses" Columbus.
April 2010	McNulty, M, Bennett, G, Fishel, R, Yoder, K."Effects of OGG1 and MYH glycosylases on HIV-1 integration site preference" Columbus.
May 2010	Yoder, K, Hoellerbauer, P, Roddick, W, Fishel, R."XPB/XPD participate in degradation of retroviral cDNA in the nucleus" Cold Spring Harbor.
May 2011	Bennett, G, McNulty, M, Peters, R, Naydinkiy, A, Fishel, R, Yoder, K."The role of base excison repair proteins during HIV infection" Columbus.

Presentations

"Gap repair following retroviral integration." Presented at CFAR Research Workshop, . (September 1999)

"Gap repair following retroviral integration." Presented at West Coast Retrovirus Meeting, Newport Beach, CA, US|USA. (October 2000)

"DNA repair proteins and HIV integration." Presented at Research in Progress Seminar Series, Philadelphia, PA, US|USA. (October 2002)

"DNA repair as a host defense against retroviral infection." Presented at Seminar Series, National Cancer Institute, Frederick, MD, US|USA. (September 2004)

"The DNA repair genes XPB and XPD defend cells from HIV integration." Presented at Retroviruses, Cold Spring Harbor, NY, US|USA. (May 2005)

"DNA repair as a host defense against retroviral infection." Presented at Center for Retrovirus Research Seminar Series, . (June 2006)

"DNA repair pathways defend the host genome from HIV integration." Presented at MVIMG Faculty Seminar Series, . (November 2007)

"Metabolism of retroviral cDNA." Presented at Center for Retrovirus Research Seminar Series, . (May 2007)

"Double strand break repair proteins and retroviruses." Presented at Center for Retrovirus Research Seminar Series, . (March 2008)

"Host DNA repair pathways and retroviral cDNA." Presented at CMIB Work in progress discussion group, . (April 2008)

"Host DNA repair pathways and retroviral cDNA." Presented at University of Idaho Department of Biological Sciences Seminar Series, Moscow, ID, US|USA. (April 2008)

"Retroviruses and DNA repair." Presented at Center for Retrovirus Research Seminar Series, . (February 2009)

"DNA repair and HIV: Novel targets for therapy." Presented at MVIMG Faculty Seminar Series, . (March 2009)

"Base excision repair and HIV integration." Presented at Center for Retrovirus Research Seminar Series, . (January 2010)

"The base excision repair pathway is required for efficient lentivirus integration." Presented at Retroviruses, Cold Spring Harbor, NY, US|USA. (May 2011)

"Host DNA repair and HIV: Viral agony and ecstasy." Presented at Microbial Infection and Immunity Seminar, . (June 2012)

"HIV integration and chromatin: Looking for a nice place to settle down." Presented at MVIMG Faculty Seminar Series, . (May 2012)

"Host DNA repair and HIV: Viral agony and ecstasy." Presented at University of South Florida Cell Biology, Microbiology, and Molecular Biology Department Seminar Series, Tampa Bay, FL, US|USA. (February 2012)

Unpublished Works

Simon, M, North, J, Bundschuh, R, Poirier, M, Yoder, K. HIV integration to unmodified chromatin favors nucleosome bound DNA and is dependent on the AT hooks of LEDGF.

Simon, M, North, J, Bernier, M, Skinner, C, Poirier, M, Yoder, K. Prototype foamy virus integrase shows preference for flexible or bent DNA.

Bennett, G, Peters, R, Bundschuh, R, Fishel, R, Yoder, K. Oxidative damage glycosylases determine the sequence specificity of HIV integration sites.