Jack Krieger

Ph.D. Defense Presentation

Date: Tuesday, 23 May 2017

Time: 1pm

Location: IBB 1128 (Suddath Seminar Room)

Committee Members:

Edward A. Botchwey, PhD (Thesis Advisor)

Johnna S. Temenoff, Ph.D.

Gabe A. Kwong, Ph.D.

Luke J. Mortensen, Ph.D.

Steven L. Goudy, M.D.

Biosynthetic materials for pro-regenerative immune modulation

The mononuclear phagocyte system underlies the host response to myriad tissue injuries and represents a powerful therapeutic target to potentially augment healing in numerous clinical indications with unmet need. Although alternatively-activated “M2” macrophages have received attention as regenerative mediators, non-classical monocytes are a novel cellular target for regenerative therapies. Our overarching goal is to effectively control the trafficking and function of circulating non-classical monocytes to enhance tissue repair. In Aim 1, we develop PEGDA-based hydrogels functionalized with DNA aptamers or heparin to control distinct chemokine signals locally within murine skin wounds to recruit non-classical monocytes and enhance tissue vascularization. In Aim 2, we use dual affinity heparin-functionalized PEGDA hydrogels to investigate synergy between chemokine and sphingolipid signals in mononuclear phagocyte recruitment and vascularization. In Aim 3, we investigate the relationship between mononuclear phagocyte infiltration and rotator cuff injury-induced muscle degeneration in a murine model. First, we quantitatively analyze immune cell infiltration and cytokine production in supraspinatus muscle and assess the role of circulating monocytes in degeneration. Then, we evaluate local delivery of chemokine and sphingolipid signals as a strategy to achieve pro-regenerative immune modulation and protect against supraspinatus degeneration.