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) 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 aims at the characterization of a novel cytokine (tentatively named IL-41) which is produced by activated macrophages, mucosal tissues and skin. Irina studied the regulation of IL-41 expression in peritoneal exudate macrophages and P388D1 cells (mouse macrophage cell line). She has found that IL-41 is strongly induced in alternatively activated macrophages (also known as M2) because its expression is up-regulated in response to type II cytokines (IL-4 and IL-13) and parallels the expression of other type II chemokines such as CCL17 and CCL22 as well as M2 marker Arginase I. Irina has confirmed that IL-41 is a secreted protein produced by alternatively activated macrophages at the protein level by ELISA.

Given that IL-41 is highly expressed in skin, Irina was also interested in determining which cells in the skin produce IL-41. We measured IL-41 expression in human keratinocytes, fibroblasts, PBMCs and endothelial cells. We found that, under resting conditions, IL-41 is expressed in fibroblasts but not in keratinocytes, PBMSs or endothelial cells. However, when we cultured keratinocytes in the presence of a range of stimulating agents, we have found that IL-41 was highly up-regulated in response to TNFα. In addition, we also investigated the expression of IL-41 in various human skin diseases including psoriasis, atopic dermatitis, actinic keratosis, basal cell carcinoma and others. We determined that IL-41 is significantly over-expressed in psoriasis. Taken together, these observations indicate that IL-41 represents a novel cytokine that is likely involved in both innate and acquired immune responses, and has functional roles under both homeostatic and inflammatory conditions. IL-41 is also likely to be involved in the pathogenesis of various human diseases, including psoriasis. Currently, Irina is working on the first report identifying IL-41 as a novel cytokine associated with the immune system.  

Irina’s current interests focus on investigating the biological functions of IL-41. To study the role of IL-41 in vivo, Irina is generating an IL-41 knockout mouse which she will use to perform phenotypic analysis of immune compartments as well as to determine immune functions though various disease models. To this end, she already has generated IL-41+/- mouse which she is currently breeding in order to obtain an IL-41-/- mouse colony. This mouse will be instrumental to understanding the physiology of IL-41.

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. Interleukin-40 is a novel B cell-associated cytokine. Van Phi Luu, Peter A. Hevezi, Monica I. Vazquez, Jose L. Maravillas-Montero, Irina Ushach, Clayton A. White, Egest J. Pone, Amanda M. Burkhardt, Paolo Casali and Albert Zlotnik (Submitted on April 2014).