Jack Krieger

Jack Krieger received a B.S. in engineering physics from the University of Illinois at Urbana-Champaign in 2012 and joined Dr. Botchwey’s lab at Georgia Tech later that fall. His research interest is manipulating inflammation to augment healing of injured tissues. To achieve this end, Jack is involved in collaborative work developing hydrogel materials that release immunomodulatory molecules at sites of injury. Jack’s recent studies demonstrate that pro-regenerative inflammation and microvascularization are achieved by hydrogel-mediated delivery of immunomodulatory proteins and synthetic sphingolipid analogs.

In ongoing work, Jack is focused on rotator cuff tears, specifically how post-injury inflammation affects rotator cuff muscle health and whether immunomodulatory strategies can improve muscle function.

In his spare time, Jack can be found outside or watching live music.

Molly Ogle, PhD

Claire Olingy

METABOLOMICS AND PATHOBIOLOGY

We have devoted significant attention in recent years to the role of sphingolipid metabolism in sickle red blood cells. We have recently identified a novel mechanism of feed-forward inflammatory signaling in SCD whereby sickled RBC membrane strain increases the activity of sphingomyelinase (SMase), which contributes to membrane lipid composition and budding of cellular vesicles. This dysregulation of sphingolipid metabolism leads to the aberrant production and release of cell-derived microparticles (SS MVs). MVs have been described as transcellular delivery vehicles that can transfer receptors, adhesion molecules, kinases, and lipids between cells. We are also investigating a potential pathogenic role of SS MVs in bone and joint disorders including osteonecrosis of the femoral head (ONFH). Read More

SMART BIOMATERIALS

An additional interest is the development of “immunologically smart” biomaterials that can tune the regenerative potential of subpopulations of leukocytes to the needs defined by the injury microenvironment. Our goal is to harness the phenotypic complexity and the division of labor among innate immune cell subsets to amplify endogenous mechanisms of tissue repair. In one recent example, we have shown that diverting circulating non-classical monocytes to injury sites using extracellular matrix (ECM)-derived hydrogels promotes healing and inflammation resolution in musculoskeletal injuries. Read More

ENDOGENOUS TISSUE ENGINEERING

Our interest is to understand the microenvironmental factors that govern healing outcomes in musculoskeletal tissues and skin in order to harness endogenous mechanisms of repair. Efficient wound healing requires the angiogenic and fibrogenic activity of macrophages, which are derived at least in part from circulating monocytes that undergo differentiation post-extravasation. We focus specifically on unlocking the therapeutic potential of pro-regenerative monocyte subsets and their progeny. Learn More

 

Dr. Botchwey on Monocytes

Therapeutic Angiogenesis and Bone Regeneration with Natural and Synthetic Small Molecules

Intravital Imaging

We have extensively utilized the dorsal skinfold window chamber model (a.k.a. “backpack”) for development of appropriate biomaterial-based biomolecular delivery strategies for targeted recruitment of MP populations and for assessing their contributions to microvascular growth and remodeling. This chronic window chamber model permits both systemic and localized in vivo assessment of dynamic interactions of engineered materials with surrounding tissues in repeated measures during the initial 2-3 weeks after implantation. Cellular and molecular mechanisms involved in microvascular remodeling and the early inflammatory host response to pro-angiogenic stimulation can be assessed by means of in situ intravital fluorescence microscopy and end point flow cytometry analysis of implanted materials as well as tissue compartments in direct contact with or at various distances from the biomaterial. For a recent example of how these approaches may be applied, please see our recent paper.

High-Throughput Molecular Lipidomics

We are using high-through-put lipid chromatography and mass spectrometry (LC-MS) analysis to investigate membrane metabolism and signaling through sphingolipids. We use sickle red blood cells and adult stem cells as model systems to gain insight into disease pathology and therapeutic cell potency respectively. We believe that our integrated systems-based research approach can compliment existing knowledge bases linking sphingolipids to wife range of biological processed, including cell death mechanisms, formation of inflammatory membrane microparticles, and secretion of soluble signals. For broader discussion of our interests in systems based approaches to understand pathogenic mechanisms and to find ways to induce pro-regenerative signaling, see our previous review paper.