Department Head of Biomedical Engineering
Professor of Biomedical Engineering
My research centers in understanding the molecular mechanisms involved in axon guidance and target recognition and clinical neuromodulation of the PNS. Specific areas of interest include spinal cord injury, peripheral nerve gap repair, regenerative peripheral neural interfaces for the control and feel or robotic prosthetic limbs, and bioelectronics medical applications. Throughout my career, I served as PI and Co-I of several grants, securing nearly $20M in research funding from a host of federal, private and state agencies to make basic and translational contributions in the following areas:
Molecular Mechanisms of Neuron Migration and Axon Guidance
- During development, axons are guided to their targets via membrane bound and secreted molecular cues, which can be either attractive or repulsive. We uncovered the role of NT-3 in proper targeting of thalamic neurons projecting to the primary sensory cortex, defined the role of KIf7 in the regulation of nociceptive neuron development, and discovered that Ephrin B-3 plays a critical role in the proper targeting of axonal projections from the primary motor cortex to the ventral motor neurons in the spinal cord. We then observed that EB-3 is upregulated in oligodendrocytes during early postnatal and reported for the first time that this molecule is a myelin-associated inhibitor in the adult spinal cord (Benson et al., 2005 PNAS; 396 citations). More recently, we uncovered the role of the Ephrin ligands in guiding the migration of CA-3 hippocampal neurons from their birth site in the sub-ventricular zone, to their destination in the ventral hippocampus (Buche et al., 2013)
- Peripheral Nerve Regeneration: The repair of nerve gap injuries longer than 4 cm is limited by the need to sacrifice donor tissue and the morbidity associated with the autograft gold standard, while decellularized grafts and biodegradable conduits are effective only in short nerve defects. Peripheral nerve regeneration involves complex cellular and molecular mechanisms that mediate nerve growth, Schwann cell proliferation and re-myelination, blood vessel growth axon guidance and target re-innervation. While many growth factors have shown the potential for increasing nerve regeneration in the transected peripheral nerves, mounting recent evidence both in the injured PNS and CNS, supports the notion that combinations of different growth factors provide improved axonal regeneration and functional recovery. We developed a method that establish sustained 3D neurotrophic factors (NTF) gradients in the collagen-filled lumen of multi-luminal nerve guides, and pioneered the use NGF, BDNF, NT-3, and GDNF growth factors for the enticement of selective nerve growth, and to support nerve regeneration across long critical nerve gaps. We have shown that NGF is able to increase axonal regeneration in the injured spinal cord and developed a novel multi-luminal nerve scaffolds that successfully repairs a 3-4 cm nerve injury gap in a rabbit animal model (Alsmadi et al., 2018). Our recent work will report the important role of Neuroregulin I in increasing the number and activity of Shwann cells in long-gap conduit repair (In preparation).
Peripheral Neural Interfacing
- Advanced robotic prosthesis with up to 18 degrees of freedom, capable of performing complex movements and equipped with multiple proprioceptive and exteroceptive sensors and embedded controllers have the potential of delivering sensory feedback to amputees. Despite such progress, the development of neural interfacing technology needed to provide sensation to the user that would allow intuitive movement and natural feel of the prosthetic limb to amputee lags far behind.
- Molecular Guidance in Regenerative Multielectrode Interfacing (REMI):
- Novel electrodes for peripheral nerve interfacing:
- Intraneural ultramicroelectrode arrays for function-specific interfacing to the vagus nerve:
- Wireless stimulation nerve stimulation: Multi-channel and sub-millimeter:
- Bioelectronic Medical Applications:
- Hyptertension
- Stress Urinary Incontinence (SUI)
Representative Publications
Google Scholar
PubMed
Contact
romeroortega@arizona.edu