AD&T's Therapeutics theme focuses on medical treatments, largely in the areas of targeted drug delivery and wound healing. These often exploit multivalent avidity for molecular recognition and targeting in disease conditions, such as cancer, allergies, and inflammatory conditions, that are approaching a critical stage – for example, a multicomponent, specifically-targeted multiple myeloma therapy has been successful tested in animal trials.

Some current Therapeutics-related projects include:

Magnetoelectric nanoparticles (MENs) for minimally-invasive deep brain stimulation in a Parkinsonian mouse model
Over the past decade, a great deal of research has looked at using non-invasive brain stimulation as a lasting treatment for Parkinson’s disease, but the technique has several drawbacks. The intent of this study is to assess the feasibility of injecting magnetoelectric nanoparticles (MENs) as a neurostimulatory enhancement technology. It is hoped that decoding the information from neuromodulation signals generated by MENs in Parkinson’s disease models will increase our fundamental understanding of the treatment and prevention of neurodegenerative disorders. (PI: Stewart)

Magnetoelectric nanoparticles for cancer treatments
The goal of this partnership with Florida International University’s Wertheim College of Medicine and Notre Dame's Harper Cancer Research Institute is to develop extremely small, electrically charged particles that can selectively penetrate the membranes of cancer cells and deliver chemotherapy drugs right where they are needed. Though applicable to a wide range of cancers, this initial study focuses on improving the treatment of ovarian cancer using both human cell lines and mouse models. (PI: Bernstein)

Role of Macrophage‐derived EMAP II in Neovascular Recovery from Hindlimb Ischemia
This collaboration between Notre Dame and the Indiana University School of Medicine-South Bend examines the role that a biologically important protein known as EMAP II plays in the growth of new blood vessels and in wound repair. The researchers are looking at how control of EMAP II could reduce inflammation and speed recovery time from trauma and wounds. (PI: Boerckel)

Role of YAP and TAZ in mechanical control of vasculogenesis
The objective of this project, a collaboration between Notre Dame, Purdue University, and the Wells Center for Pediatric Research at Indiana University School of Medicine, is to understand the way two particular proteins, called YAP and TAZ, affect the body’s ability to grow new blood vessels and bone in response to wounds, traumatic injuries, or disease. The molecular mechanisms that underlie this growth are unclear, but these two factors are thought to play an important role in such “neovascular regeneration.” The findings of this work could have direct application to tissue engineering and the identification of novel therapeutic targets and regeneration strategies. (PI: Boerckel)

Characterization of Human METTL16 in Miller-Dieker Syndrome
This collaborative effort will bridge the fields of biochemistry and computational biology to investigate the potential role of human methyltransferase-like protein 16 (METTL 16) in Miller-Dieker Syndrome (MDS). The RNA targets of METTL16 may be directly involved in MDS, and thus it is important to understand its unique cellular role as a “writer”, “eraser” and “reader” associated with RNA modification. Since no therapeutic treatments are available for MDS patients, it is hoped that this study will reveal novel therapeutic targets for normal cellular function (PIs: Brown and Emrich)

Design and Development of New Therapeutics for Trisomy 21 Phenotypes 
Developmental alterations in brain morphology due to Down syndrome (DS) lead to cognitive and behavioral impairments such as memory deficiencies, motor dysfunction, altered synaptic plasticity and early occurrence of Alzheimer’s disease. The aims of this project are to design and synthesize a collection of inhibitors that are selective for the specific genes involved DS phenotypes, develop a viable antibody drug conjugate with these synthesized inhibitors, and create a low cost in vivo assay to enable the swift identification of specific inhibitors. (PIs: Ashfeld and Zartman)

For more information on this research, please contact Arnie Phifer, Associate Director, or the listed principal investigators.