Denise Skrombolas

Award

  • 2011 - Boris Albini Award - This award is presented to a graduate student for a poster presentation at the Fall immunology meeting sponsored by the Witebsky Center for Microbial Pathogenesis and Immunology.

Bio

Denise Skrombolas graduated from the University of Rochester with a Bachelors of Science degree in Biochemistry. She entered the graduate program in the department Photo of Denise Skrombolasof Microbiology and Immunology in the fall of 2008 and subsequently joined the laboratory of Dr. John Frelinger. Denise earned her Master of Science degree in the spring of 2011 and recently received the Boris Albini student award for research excellence created by the Buffalo Collegium of Immunology and the Witebesky Center for Microbial Pathogenesis and Immunology.

Research Description

T cells are intimately involved in many aspects of the adaptive immune response and play a prominent role in the response to pathogens, autoimmunity, and in tumor immunity. Denise’s work has dealt with various aspects of T cells responses. Her current efforts are focused on modulating immune responses using novel fusion proteins that could be used to shape immune responses in a variety of contexts. The strategy she is developing involves constructing an inactive cytokine fusion protein that can be preferentially activated by proteases. This strategy is now being tested in the context of tumor immunity, as certain proteases are often dramatically over-expressed at the site of growing tumors. The overall hypothesis is that changing the cytokine balance at the tumor site towards an immunostimulatory setting could enhance the cellular immune response against the tumor. The fusion protein she is developing consists of a cytokine joined to a specific binding moiety (inhibitor) separated by a protease cleavage sequence. Active proteases expressed by tumor and host cells within the tumor would cleave the fusion protein, resulting in an increased local concentration of the cytokine at the tumor site, thereby tipping the balance from an immunosuppressive environment to one conducive for an ongoing immune response. She has provided proof of principle of this strategy using IL-2 and matrix metalloproteinases. She has analyzed the fusion protein in vitro biochemically and functionally and has developed an in vivo peritoneal tumor model to study the effects of the fusion protein on tumor growth and the immune response. She has also taken an alternative genetic approach to deliver the fusion protein in vivo to examine the effects of sustained delivery of the fusion protein as well as its ability to enhance anti-tumor responses in a variety of settings.

Articles Published

  1. J Puskas, D Skrombolas, A Sedlacek, E Lord, M Sullivan, J Frelinger: Development of an attenuated interleukin-2 fusion protein that can be activated by tumour-expressed proteases. Immunology 2011, 133:206-20.
  2. MD Valentino, CS Abdul-Alim, ZJ Maben, D Skrombolas, LL Hensley, TH Kawula, M Dziejman, EM Lord, JA Frelinger, JG Frelinger: A broadly applicable approach to T cell epitope identification: Application to improving tumor associated epitopes and identifying epitopes in complex pathogens. J Immunol Methods 2011.
  3. J Li, I Kuzin, S Moshkani, ST Proulx, L Xing, D Skrombolas, R Dunn, I Sanz, EM Schwarz, A Bottaro: Expanded CD23(+)/CD21(hi) B cells in inflamed lymph nodes are associated with the onset of inflammatory-erosive arthritis in TNF-transgenic mice and are targets of anti-CD20 therapy. J Immunol 2010, 184:6142-50.
  4. MD Valentino, LL Hensley, D Skrombolas, PL McPherson, MD Woolard, TH Kawula, JA Frelinger, JG Frelinger: Identification of a dominant CD4 T cell epitope in the membrane lipoprotein Tul4 from Francisella tularensis LVS. Mol Immunol 2009, 46:1830-8.

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