Abstract

We have developed a new method to discover microbial causes of human disease, sequence-based computational subtraction. In this method, sequences from diseased tissue are compared to the human genome computationally, and the filtered sequences are highly enriched for non- human nucleic acids. I propose to apply computational subtraction to discovery viruses that cause human cutaneous T-cell lymphoma (CTCL). Specifically, we plan to generate cDNA libraries from CTCL biopsy specimens, to sequence a sampling of these libraries, and then to subtract the sequences computationally and experimentally against the human genome. Filtered sequences will be tested further for specific association with CTCL using the polymerase chain reaction. When we identify CTCL-associated sequences, we will then attempt to generate molecular clones of the entire putative viruses and begin to characterize the protein products of their genomes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR042689-09
Application #
6659409
Study Section
Special Emphasis Panel (ZAR1)
Project Start
2002-04-01
Project End
2004-03-31
Budget Start
Budget End
Support Year
9
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Tian, Tian; Jin, Michelle Qiushuang; Dubin, Krista et al. (2017) IL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection. J Immunol 198:4341-4351
Pan, Youdong; Tian, Tian; Park, Chang Ook et al. (2017) Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature 543:252-256
Volpicelli, Elgida R; Lezcano, Cecilia; Zhan, Qian et al. (2014) The multidrug-resistance transporter ABCB5 is expressed in human placenta. Int J Gynecol Pathol 33:45-51
Guenova, Emmanuella; Watanabe, Rei; Teague, Jessica E et al. (2013) TH2 cytokines from malignant cells suppress TH1 responses and enforce a global TH2 bias in leukemic cutaneous T-cell lymphoma. Clin Cancer Res 19:3755-63
Majewska-Szczepanik, Monika; Paust, Silke; von Andrian, Ulrich H et al. (2013) Natural killer cell-mediated contact sensitivity develops rapidly and depends on interferon-?, interferon-? and interleukin-12. Immunology 140:98-110
Zadran, Sohila; McMickle, Robert; Shackelford, David et al. (2013) Monitoring extra-vascular migratory metastasis (EVMM) of migrating cancer cells using an in vitro co-culture system. Protoc exch 2013:
Burkhardt, Ute E; Hainz, Ursula; Stevenson, Kristen et al. (2013) Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells. J Clin Invest 123:3756-65
Dowlatshahi, Mitra; Huang, Victor; Gehad, Ahmed E et al. (2013) Tumor-specific T cells in human Merkel cell carcinomas: a possible role for Tregs and T-cell exhaustion in reducing T-cell responses. J Invest Dermatol 133:1879-89
Degen, Martin; Natarajan, Easwar; Barron, Patricia et al. (2012) MAPK/ERK-dependent translation factor hyperactivation and dysregulated laminin ýý2 expression in oral dysplasia and squamous cell carcinoma. Am J Pathol 180:2462-78
Tian, Tian; Dubin, Krista; Jin, Qiushuang et al. (2012) Disruption of TNF-?/TNFR1 function in resident skin cells impairs host immune response against cutaneous vaccinia virus infection. J Invest Dermatol 132:1425-34

Showing the most recent 10 out of 113 publications