• Welcome to the Hollenhorst Lab at IU

  • Research

    About the Lab

    Transcription factors are proteins that bind to specific places in the genome and regulate which genes should be turned on or off. We focus on a type of transcription factor called an ETS transcription factor. There are 28 ETS transcription factors in the human genome. They all bind to DNA in a very similar way. However, they all have very different biological functions. We are interested in learning the molecular mechanisms behind these specific functions. In particular, some ETS proteins cause cancer (oncogenes), some inhibit cancer formation (tumor suppressors), and some have no role in cancer. We would like to discover why some ETS proteins cause cancer, and others do not so we can develop therapeutic strategies that target only the cancer causing ETS family members.

     

     

    In the Hollenhorst lab we use a variety of approaches to understand mechanisms of ETS protein specificity:

    1. We use chromatin-immunoprecipitation/next generation sequencing (ChIP-seq) to identify the genomic targets of ETS genes in vivo. Bioinformatics analysis of these results allows us to identify sequences important for both specific and redundant DNA binding within the ETS family.

    2. We use biochemical assays with purified proteins to validate the models of ETS protein/DNA interactions that are predicted by our bioinformatic work. This approach also allows us to dissect the mechanisms of these functions in greater detail.

    3. We express wild-type and mutant ETS genes in cell culture systems to test the function of these proteins on gene expression and to assess oncogenic potential.

     

    Understanding how ETS proteins target unique genes is important for understanding their critical role in cancer. Chromosomal rearrangements that alter the expression and/or function of ETS proteins are found in a number of cancers including more than half of prostate tumors, almost all cases of Ewing’s sarcoma, and occasionally in leukemia. However, only a subset of the ETS genes promote cancer. In fact some family members may act as tumor suppressors. Thus a major interest of the lab is to understand the mechanisms that allow specific oncogenic functions within the ETS family.

  • Join our group

    Graduate Students

    We accept graduate students through the following programs:

    Postdoctoral Fellows

    We sometimes have postdoctoral opportunities available. Contact Dr. Hollenhorst for details.

  • Lab Members

    Dr. Peter C. Hollenhorst

    Associate Professor of Biochemistry & Molecular Biology, Medical Sciences Program

    B.S. Chemistry and Biology, St. Norbert College

    Ph.D. Biomolecular Chemistry, University of Wisconsin-Madison

    American Cancer Society Postdoctoral Fellow, Huntsman Cancer Institute, University of Utah

    Mary Ferris

    Lab Manager

    B.S. Microbiology, Ohio State University

    Dr. Haihan Zhang

    Postdoctoral Fellow

    Ph.D. Virginia Tech

    Taylor Nicholas

    Genome, Cell and Developmental Biology Graduate Student

    B.S. Biology, Northern Illinois University

    Brady Strittmatter

    Biochemistry Graduate Student

    B.S. Biochemistry, University of Wisconsin

    Ben Greulich

    Cell, Molecular and Cancer Biology Graduate Student

    B.S. Biochemistry Indiana University

    Hannah Plunkett

    Undergraduate Researcher

     

    Haley Klimaszewski

    Undergraduate Researcher

     

    Peter Amezcua

    Undergraduate Researcher

     

    Barry Wei

    Undergraduate Researcher

     

  • Former Lab Members

     

    Nagarithinam Selvaraj (former postdoc) - Developmental Scientist II, Leidos Biomedical Research, Frederick MD

    Justin Budka (former graduate student) - Postdoctoral Fellow, Indiana University School of Medicine

    Josh Plotnik (former graduate student) - Senior Scientist, AbbVie, North Chicago IL

    Vivek Kedage (former graduate student) - Postdoctoral Fellow, Genentech, South San Francisco CA

    Paige Dausinas (former undergraduate researcher) - Ph.D. student, Indiana University School of Medicine

    Li Feiran (former undergraduate researcher) - Ph.D. student, Purdue University

    HongXin Gao (former undergraduate researcher) - Ph.D, Princeton University, now Procter and Gamble

    Megan (Hull) Altemus (former undergraduate researcher) - Ph.D. student, University of Michigan

    Linda Senbanjo (former undergraduate researcher) - Ph.D student, University of Maryland Medical School

  • Publications

     
     
    Budka, J.A., Ferris, M.W., Capone, M.J., and P.C. Hollenhorst. (2018) Common ELF1 deletion in prostate cancer bolsters oncogenic ETS function, inhibits senescence and promotes docetaxel resistance. Genes and Cancer 9:198-214.
     
    Madison, B.J., Clark, K.A., Bhachech, N., Hollenhorst, P., Graves, B.J., and S.L. Currie. (2018) Electrostatic repulsion causes anticooperative DNA binding between tumor suppressor ETS transcription factors and JUN-FOS at composite DNA sites. Journal of Biological Chemistry
     
    Damayanti, N.P., Budka, J.A., Khella, H.W.Z., Ferris, M.W., Ku, S.Y., Kauffman, E., Wood, A.C., Ahmed, K., Chintala, V.N., Adelaiye-Ogala, R., Elbanna, M., Orillion, A., Chintala, S., Kao, C., Linehan, W.M., Yousef, G.M., Hollenhorst, P.C., and R. Pili. (2018). Therapeutic targeting of TFE3/IRS-1/PI3K/mTOR axis in translocation renal cell carcinoma. Clinical Cancer Research
     
    Tomar, S., Plotnik, J.P., Haley, J., Scantland, J., Dasari, S., Sheikh, Z., Emerson, R., Lenz, D., Hollenhorst, P.C., and A.K. Mitra. (2017). ETS1 induction by the microenvironment promotes ovarian cancer metastasis through focal adhesion kinase. Cancer Letters 414:190-204
     
    Adelaiye-Ogala, R., Budka, J., Damayanti, N.P., Arrington, J., Ferris, M.W., Hsu, C.C., Chintala, S., Orillion, A.R., Miles, K.M., Shen, L., Elbanna, M., Ciamporcero, E., Arisa, S., Pettazzoni, P., Draetta, G.F., Seshadri, M., Hancock, B.A., Radovich, M., Kota, J., Buck, M., Keilhack, H., McCarthy, B.P., Persohn, S.A., Territo, P.R., Zang, Y., Irudayaraj, J., Tao, A.W., Hollenhorst, P., and R. Pili. (2017). EZH2 modifies sunitinib resistance in renal cell carcinoma by kinome reprogramming. Cancer Research 77(23): 6651-6666
     
    Kedage, V., Strittmatter, B.G., Dausinas, P.B., and P.C. Hollenhorst. (2017). Phosphorylation of the oncogenic transcription factor ERG in prostate cells dissociates polycomb repressive complex 2 allowing target gene activation. Journal of Biological Chemistry 292(42): 17225-17235
     
    Potu, H., Peterson, L.F., Kandarpa, M., Pal, A., Sun, H., Durham, A., Harms, P.W., Hollenhorst, P.C., Eskiocak, U., Talpaz, M., and N.J. Donato. (2017). Usp9x regulates Ets-1 ubiquitination and stability to control NRAS expression and tumorigenicity in melanoma. Nature Communications 8:14449.
     
    Plotnik, J.P. and P.C. Hollenhorst. (2017). Genome-wide analysis of RAS/ERK signaling targets. Methods in Molecular Biology 1487:277-288.
       
    Plotnik, J.P. and P.C. Hollenhorst. (2017). Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2. Nucleic Acids Research 45(8):4452-4462
     
    Kedage, V., Selvaraj, N., Nicholas, T.R., Budka, J.A., Plotnik, J.P., Jerde, T.J., and P.C. Hollenhorst. (2016). An interaction with Ewing's sarcoma breakpoint protein EWS defines a specific oncogenic mechanism of ETS factors rearranged in prostate cancer. Cell Reports 17(5): 1289-1301.
     
    Selvaraj, N., Kedage, V., and P.C. Hollenhorst. (2015). Comparison of MAPK specificity across the ETS transcription factor family identifies a high-affinity ERK interaction required for ERG function in prostate cells.Cell Communication and Signaling 13:12.
     
    Selvaraj, N., Budka, J.A., Ferris, M.W., Plotnik, J.P., and P.C. Hollenhorst. (2015). Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration. Molecular and Cellular Biology 35(1): 88-100.
     
    Plotnik, J.P., Budka, J.A., Ferris, M.W., and P.C. Hollenhorst. (2014). ETS1 is a genome-wide effector of RAS/ERK signaling in epithelial cells. Nucleic Acids Research 42(19): 11928-40.
     
    Selvaraj, N., Budka, J.A., Ferris, M.W., Jerde, T.J., and P.C. Hollenhorst. (2014). Prostate cancer ETS rearrangements switch a cell migration gene expression program from RAS/ERK to PI3K/AKT regulation.Molecular Cancer 13:61.
     
     

     

  • News

    April 2019

    Brady Strittmatter presented his research at the AACR Annual Meeting in Atlanta GA

    October 2018

    Taylor Nicholas presented her research at the ASBMB Transcription meeting in Snowbird UT

    June 2018

    Justin Budka published his paper on the role of ELF1 in prostate cancer and successfully defended his thesis, congrats Dr. Budka!

    April 2018

    Ben Greulich was awarded an Indiana CTSI predoctoral fellowship to support his work. Congrats Ben!

    Jan 2018

    Taylor Nicholas received the Medical Sciences Program Doane and Eunice Wright fellowship to support her work in lab. Congrats Taylor!

    Jan 2018

    Brady Strittmatter received the Peglow Award for outstanding performance in the Biochemistry Preliminary Examination. Congrats Brady!

    Oct 2016

    See the press release for our recent work linking molecular mechanism of ETS factors in prostate cancer and Ewing’s sarcoma

    http://archive.news.indiana.edu/releases/iu/2016/10/prostate-cancer-ewings-sarcoma-study.shtml

  • Contact Us

    We are located in Jordan Hall,

    Indiana University

    Bloomington, Indiana

    Peter's email is pchollen@indiana.edu

    Peter's office phone: 812-855-1151

    Hollenhorst lab phone: 812-856-7608

  • Funding

    Research in the Hollenhorst Lab is supported by...

    Genitourinary Malignancies Pilot Funding

    Funding for Brady Strittmatter

    Funding for Taylor Nicholas

    National Cancer Institute R01