NIH Training Grant Fellow: Irina Ushach

Irina Ushach

Irina Ushach is a Ph.D. candidate in the Zlotnik lab at UCI. Prior to joining the Zlotnik lab, Irina worked at various positions in a biotech company (Geron Corporation, Menlo Park, CA) where she worked on the development of human embryonic stem cell (hESC) derived therapies, focusing on oligodendrocyte and cardiomyocyte progenitor cells.

Irina’s thesis work in the Zlotnik lab has focused on the characterization of a novel cytokine called Meteorin-like (Metrnl), which is produced by activated macrophages, mucosal tissues and skin. Irina has determined that Metrnl is expressed in barrier tissues (skin and mucosa) and also investigated the conditions under which Metrnl is expressed in cells of the monocyte-macrophage lineage. Macrophages have been subdivided based on their activation state into classically activated macrophages (M1) or alternatively activated macrophages (AAM/M2). Bacterial products and type I cytokines such as IFNγ induce M1 macrophages, while the type II cytokine IL-4 induces M2 macrophages. Irina has demonstrated that Metrnl is specifically expressed by macrophages polarized under M2 conditions, because its expression is up-regulated by type II cytokines (IL-4 and IL-13) and suppressed by IFNγ. Culturing murine bone marrow cells with GM-CSF and M-CSF has been linked to the M1- or M2- activation states of macrophages, respectively. Consistent with the above observations, Metrnl is strongly up-regulated in M-CSF- generated macrophages.

In the skin Metrnl is expressed by fibroblasts and IFNγ-treated keratinocytes. A screen of human skin-associated diseases indicates that Metrnl is significantly over-expressed in psoriasis, prurigo nodularis, actinic keratosis and atopic dermatitis. Together, these results indicate that Metrnl encodes a novel cytokine involved in inflammatory responses and human diseases.

Irina’s current interests focus on investigating the biological functions of Metrnl. To this end, Irina has generated a Metrnl knockout mouse which she is using for phenotypic analysis of immune compartments as well as elucidating immune functions through various disease models.

Honors:

NIH NIAID T32 Immunology Research Training Program (5T32 AI 060573), UC Irvine (2013-2014)

Publications:

  1. Loss of TSC2 confers resistance to ceramide and nutrient deprivation. Guenther GG*, Liu G*, Ramirez MR, McMonigle RJ, Kim SM, McCracken AN, Joo Y, Ushach I, Nguyen NL, Edinger AL. 2013 Oncogene.
  2. Meteorin-like is a cytokine associated with barrier tissues and alternatively activated macrophages. Ushach I, Burkhardt AM, Martinez C, Hevezi PA, Gerber PA, Buhren BA, Schrumpf H, Valle-Rios R, Vazquez MI, Homey B, Zlotnik A. Clin Immunol. Dec 2104.
  3. Interleukin-40 is a novel B cell-associated cytokine. Monica I. Vazquez, Van Phi Luu, Peter A. Hevezi,  Maravillas-Montero, Irina Ushach, Clayton A. White, Egest J. Pone, Amanda M. Burkhardt, Paolo Casali and Albert Zlotnik (Submitted for publication).