Therapeutic nanoparticles for GBM
In collaboration with the Lahann and Castro/Lowenstein laboratories, we are studying synthetic protein nanoparticles (SPNPs) as a translational therapeutic in immunocompetent mice with intracranial (i.e., not flank) glioblastoma tumors. In this clinically relevant model, SPNPs loaded with a targeting peptide and STAT3 siRNA show remarkable therapeutic efficacy - including up to 80% long-term survival. Our priorities now are to better define the mechanism(s) of tumor accumulation and mode(s) of therapeutic action in anticipation of commercialization and clinical testing. The project is highly collaborative and combines quantitative radiotracing and multi-modal imaging techniques. We are actively seeking fellows and students to join our effort.
BBB shuttles for mAb delivery to the brain parenchyma
The high affinity, extreme specificity, and pharmacokinetic properties of monoclonal antibodies (mAbs) make them the fastest growing drug class. Their incredible potential has yet to be fully harnessed for treatment of brain disorders due to the inability of most IgGs to cross the BBB. A platform technology capable of delivering mAbs into the brain parenchyma in an efficient and predictable manner would have numerous potential applications. In collaboration with the Tessier laboratory, our group is developing and optimizing BBB shuttles for the treatment of neurodegenerative diseases, brain cancer, traumatic brain injury, and other CNS disorders.
Targeting IgG-mediated hemolysis
The destruction of red blood cells by cell-bound IgG occurs in both autoimmune disease (warm Autoimmune Hemolytic Anemia) and in certain types of hemolytic transfusion reactions. In both cases, acute and severe hemolysis can result in multi-organ failure or even death, and limited therapies exist for stopping hemolysis once it has begun. Our group is working to create novel, targeted biotherapeutics capable of intervening and improving patient outcomes. Students interested in working on this translational project should contact Dr. Greineder.
Targeting therapeutics to sites of bone resorption
Bone loss occurs when the rate of bone resorption exceeds that of bone formation. For decades, available therapies have sought to address this imbalance by eliminating bone degrading cells, a strategy which inadvertently decreases new bone formation. In collaboration with laboratories at the Mayo clinic and the U-M dental school, we have developed a series of small molecules and biotherapeutics aimed at changing the phenotype of bone degrading cells, rather than killing them. Students interested in working on this translational project should contact Dr. Greineder.
Implementing practice change in low-risk PE
Through a collaboration with Dr. Geoff Barnes and the Institute for Health Policy and Innovation, we have created and analyzed a registry of nearly 1,000 acute PEs diagnosed in the Emergency Department. Based on this work, we have designed and implemented a multi-component intervention to increase outpatient management of low risk PE at the University of Michigan. To extend the reach of this practice change, we have partnered with the MEDIC collaborative and proposed to design and implement tailored interventions at 10 sites across Michigan. Students, fellows, and residents interested in joining this highly collaborative project should contact Drs. Greineder or Barnes.
Targeted therapeutics for TBI
Thanks to an award from the Weil Institute and the Massey Grand Challenge, we have initiated a series of projects aimed at developing novel therapeutic approaches for traumatic brain injury (TBI). The first involves a neuroprotective BBB shuttle which enters the brain parencyhma and induces anti-apoptotic signaling in neurons. Our second approach involves targeting the cerebrovascular endothelium itself as a means of reducing disruption of the BBB and resulting edema, elevated intracranial pressure, and secondary brain ischemia.